MEDIA REVIEW Dive into the public narrative around ATAI’s work to transform healthcare for hundreds of millions living with treatment resistant mental illnesses

Table of contents

Endpoints News: ATAI adds MDMA biotech to growing list of psychedelic makers ...... 2

FierceBiotech: From ‘party drug’ to PTSD treatment: EmpathBio to develop MDMA-based therapy ...... 3

Benzinga: ATAI Launches Subsidiary To Develop MDMA Derivatives ...... 5 pharmaphorum: Why the next blockbuster in mental health might be a video game ...... 9

Benzinga: ATAI Launches Subsidiary Focused On Active Ingredient In Hallucinogenic Brews ...... 12

FierceBiotech: Meet Viridia, the ATAI unit exploring ayahuasca-based treatments for mental illness ...... 13

Endpoints News: After psilocybin and ketamine, a biotech comes along developing a drug Scott Gottlieb fought ...... 15

Health Europa: Could ibogaine offer a revolutionary long-term solution to addiction? ...... 18

FierceBiotech: ATAI dives into digital therapeutics to boost mental health care ...... 21

Health Europa: Could arketamine be a breakthrough therapy for depression? ...... 23

UBS: Innovations in Mental Healthcare ...... 25

Forbes: Psychedelic Drugs Can Improve Quality Of Life - And Death - For Older Adults ...... 26

Endpoints News: Mushroom magic draws $80M injection for London-based mental health startup ...... 29

Forbes: Thiel Capital’s Jason Camm Discusses Joining Psychedelics Company ATAI Following $24 Million Raise ...... 31

Bloomberg: Thiel Backs Psychedelic-Drug Startup in Latest Funding Round ...... 33

The Sociable: Biotech startup wants to make new short-acting psychedelic drugs more scalable & accessible ...... 34

The European Pharmaceutical Manufacturer: How psychedelic medicine is being used to end opioid addiction ...... 37

Benzinga: Arketamine: A Fast-Acting Antidepressant Without Dissociative Effects? ...... 39

Endpoints: How do depressed rats respond to psychedelics? New data offer insight into the human experience ...... 42

Business Insider: Meet the top 9 startups raising millions to use psychedelics to treat depression, anxiety, and more...... 45

Business Insider: ATAI is courting pharma and biotech investors as it looks to raise millions ...... 47

The New York Times: The Capital That Ate Wellness Is Going to Eat Your Mushrooms ...... 51

Business Insider: Investors eyeing psychedelics as the next big trend in healthcare ...... 53

FierceBiotech: ATAI, DemeRx pursue 'neurochemical reset' for addiction in $22M JV ...... 56

Bloomberg: A Hallucinogenic Root Is Pitched to Davos Set as Treatment for Opioid Addiction ...... 58

FierceBiotech: ATAI backs Neuronasal's through-the-nose concussion treatment ...... 59

Benzinga: The Keys To Understanding Psilocybin's Medical Value, Market Potential ...... 61

FierceBiotech: ATAI Life Sciences, Cyclica team up for mental health JV ...... 66

WSJ: The Power of Combining 5G and AI ...... 68

Vice News: Can a Trip-Free Psychedelic Still Help People With Depression? ...... 69

The Economist: Investors hope psychedelics are the new cannabis. Are they high? ...... 70

WSJ Pro Venture: Atai Life Sciences Is Assembling a Mental-Health Drug Platform ...... 71

STAT News: A German financier wants to turn magic mushrooms into modern medicine ...... 73

Business Insider: Evidence is mounting that psychedelic drugs can help treat diseases ...... 79

CNBC: Investors are starting to bet big on psychedelic medicine ...... 82

ATAI adds MDMA biotech to growing list of psychedelic makers

Jason Mast | August 25, 2020

For years, the biggest push in psychedelic drug development has been around MDMA, a party drug long thought to have potential benefits for patients with PTSD. Rick Doblin, for years psychedelic therapy’s most prominent advocate and fundraiser, and his non-profit, MAPS, have raised millions to advance clinical trials, most recently raising $30 million to complete a Phase III study in veterans.

But ATAI, the German-born biotech that has quickly become the most prominent private promoter and driver of psychedelic therapy, still thinks they have something to offer. Yesterday, the portfolio announced their latest subsidiary: EmpathBio.

The idea behind EmpathBio is that Doblin’s approach, while promising, will only represent MDMA 1.0. In a a recent MAPS analysis of pooled Phase II studies – not a perfectly sound measure but good enough to support more studies – about half of the 100 patients who received the drug didn’t have the diagnostic symptoms for PTSD two months after their last dosing. The problem, said ATAI CSO Srinivas Rao, is that the drug has to be administered over multiple days in facilities where patients are supervised by trained professionals for hours.

“The challenge with MDMA as it’s envisioned by MAPS is that it’s difficult to deploy and to scale up,” Rao told Endpoints News. “What we want to do is transition this more to an outpatient, or day-therapy type of approach, so we’re looking at compounds that are potentially safer.”

The company remains far from the clinic, but they will work on MDMA-like compounds that they say have a better profile. With at least one other company, notably Kures, ATAI and its subsidiaries have tweaked generic, plant or other non-patentable molecules in large part to make them patentable, ensuring there’s a viable commercial pathway.

But EmpathBio CEO Glenn Short pointed to the potential for some of these tweaks to reduce hypertension of MDMA, allowing it to be given patients with co-morbidities, as well as allowing it to be given over shorter periods of time and in less controlled settings, allowing patients to receive the drug in rural and other areas.

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From ‘party drug’ to PTSD treatment: EmpathBio to develop MDMA-based therapy

Amirah al Idrus | August 24, 2020

Treatment for post-traumatic stress disorder (PTSD) varies from patient to patient and can combine different kinds of therapy and drugs, including anti-anxiety meds and antidepressants. Problem is, the only drugs approved for PTSD don’t work for everyone, and even when they do, they don’t work perfectly and come with side effects.

EmpathBio, ATAI Life Sciences’ latest company, is looking to fill that gap with treatments based on 3,4- methylenedioxymethamphetamine, better known as the “party drug” MDMA. The hope is that MDMA derivatives will work better as add-ons for patients with PTSD who are undergoing psychotherapy than antidepressants, such as Zoloft and Paxil, do.

Accelerate Clinical Operations Across Sponsors, CROs, and Partners

The most advanced life sciences organizations know that digital innovation and multi-platform integrations are essential for enabling product development. New platforms are providing the life sciences industry with an opportunity to improve the efficiency of clinical trials and reduce costs while remaining compliant and reducing risk.

MDMA is a psychedelic, but it's not a traditional one like N,N-dimethyltryptamine (DMT)—the active ingredient in ayahuasca—or psilocybin, which is found in magic mushrooms. Instead, it’s thought of as an entactogen, meaning it can reduce anxiety, evoke feelings of empathy and sympathy and promote a sense of psychological safety. This puts patients in a place where they can process the intrusive thoughts and memories that characterize PTSD.

“The idea is that this compound and compounds like it allow you to get some degree of comfort and also give you a better bond [with a therapist] to allow you to express these feelings and thus work through them,” said Srinivas Rao, M.D., Ph.D., chief scientific officer of ATAI Life Sciences.

Compare that approach with using with Zoloft and Paxil, which work by boosting levels of serotonin—sometimes called the “feel-good” hormone—in the brain. They can rein in the emotional ups and downs that come with PTSD, but they can also hinder patients’ progress when undergoing psychotherapy.

“When it comes to medically assisted therapy, they are not particularly great. They don’t really allow for opening up and facilitating a patient’s alliance with their therapist,” Rao said.

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The Multidisciplinary Association of Psychedelic Research (MAPS) is already testing the MDMA approach in PTSD. Phase 2 data published in June showed that after two months of MDMA-assisted psychotherapy, more than half of 100 patients no longer met the diagnostic criteria for PTSD. And just last week, the nonprofit announced it had raised $30 million to bankroll phase 3 studies and an FDA submission for MDMA-assisted therapy as a treatment for PTSD.

Unlike MAPS, which is running with MDMA itself, EmpathBio will develop derivatives of the compound with the goal of delivering its benefits without its downsides, such as increases in blood pressure or heart rate.

“There are other side effects associated with MDMA and those are very mild to moderate, including anxiety, dizziness, fatigue and headache. Jaw clenching is a big one,” Glenn Short, the early development lead at ATAI, said. Creating a safer, more tolerable version of MDMA could open up the treatment to more patients, such as those who suffer from hypertension and could do without a drug that elevates blood pressure, he added.

Throw in a digital therapeutic that can help doctors monitor patients and tailor their treatment, and MDMA-assisted therapy could reach patients who live far away from treatment centers. That would be an improvement over MDMA-based approaches in development, which would require patients to stay overnight while they are undergoing treatment.

EmpathBio is in the lead selection stage of discovery and aims to move an MDMA derivative into human trials as quickly as possible.

“We are obviously a number of years behind MAPS—they’re in phase 3 and that’s OK. We view this as a second-generation program,” Rao said.

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ATAI Launches Subsidiary To Develop MDMA Derivatives

Natan Ponieman | August 24, 2020

Psychedelics and biotech company ATAI Life Sciences announced on Monday the launch of a new subsidiary that will focus on the development of MDMA derivatives for the treatment of post-traumatic stress disorder and other indications. EmpathBio will be a wholly owned subsidiary of ATAI, led by CEO Glenn Short.

The news comes days after the Multidisciplinary Association for Psychedelic Studies (MAPS) completed a $30 million fundraising that puts it one step closer to achieving FDA approval for MDMA-assisted psychotherapy in the treatment of PTSD.

“MAPS’ program is groundbreaking and will transform the direction of mental healthcare forever,” Srinivas Rao, MD, PhD, chief scientific officer of ATAI, told Benzinga. “Our rationale for [EmpathBio] is only to scale, expand access to underserved populations, and improve the overall safety profile of MDMA-like therapy."

Novel MDMA Formulations: Safer Drugs and IP Possibilities

MDMA was first synthesized in 1912 by Merck, which makes it impossible to patent. However derivatives from the drug are apt to be patented, which opens a tremendous business opportunity for psychedelic research companies in sight of the upcoming legalization of MDMA-assisted therapy.

As a reward for completing MDMA clinical research, the FDA is expected to grant MAPS a five to seven year market exclusivity once the MDMA-assisted psychotherapy is approved. After that, any company is open to produce and distribute the “generic” drug with legal purposes.

By developing MDMA analogs, companies are able to secure patent rights. However, these derivatives need to offer an advantage against the generic in order to thrive in the competitive market.

EmpathBio’s goal for its drug research is to improve MDMA in its practicality, accessibility and scalability.

“MAPS’ program requires at least one overnight stay and three full sequential days of therapy involving two therapists, a process which is likely to be difficult for mental health providers to deliver,” said Srinivas Rao.

EmpathBio’s program is expected to be conducted on an outpatient basis and not require multiple back-to-back days of therapy. Additionally, the company expects to be able to develop formulations that allow for virtual sessions through a DTx platform.

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In a recent interview, MAPS’ spokesperson Brad Burge said that the organization supports the development of alternative IPs for MDMA.

“Because we're a nonprofit, we have the advantage of not needing to lock down any intellectual property around these drugs,” said Burge.

“When other companies come out and they develop other uses for these drugs or different variations of them, we support that and we will actually commit to helping them as long as they commit to doing it in an ethical way.”

How Can MDMA Be Improved?

MDMA-assisted psychotherapy is showing an unprecedented potential in the treatment of PTSD, a condition that is having devastating effects on the population, especially among army veterans.

A long-term follow-up study of MAPS’ trials from June 2020 showed that 67% of the patient volunteers who had PTSD for an average of 18 years no longer qualified for PTSD at least 12-months after the treatment.

MDMA is able to produce significant empathogenic effects. These are psychological feelings of calmness, emotional openness and empathy that promote a sense of psychological safety. When accompanied by psychotherapy, this altered state allows patients to address traumatic memories in order to treat unresolved traumas from the past.

However, MDMA is not perfect. The drug also produces a set of physiological effects called “sympathomimetic effects”, which include anxiety, dizziness, fatigue, headache, jaw clenching, lack of appetite and nausea.

“While being potentially well-tolerated by healthy individuals, others with comorbidities, such as hypertension, cardiovascular disease or history of stroke, may be at increased risk after MDMA treatment,” said Glenn Short, CEO of EmpathBio, in an interview.

Given that obesity and hypertension in individuals with PTSD are commonly reported comorbidities (additional conditions that often co-occur with the main condition), being able to remove these sympathomimetic effects from MDMA would allow the treatment to be available to a lot more patients.

“EmpathBio will be developing MDMA derivatives designed to minimize these sympathomimetic effects so that all individuals suffering from PTSD can be safely and effectively treated despite underlying comorbidities,” said Short.

The exec added that the company has already identified a lead compound for further development, and will continue to develop novel MDMA analogs with improved safety parameters.

“Given that EmpathBio's programs are not yet clinical stage, it is not likely that there will be any overlap with MAPS exclusivity runway,” said Short, who nonetheless showed enthusiasm, stating that the company is well beyond the discovery stage, having made significant progress with a lead compound in hand.

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Why the next blockbuster in mental health might be a video game

David Keene | August 20, 2020

David Keene looks at the difficulties faced in treating mental health patients and how digital technologies are changing the game.

In 1919 a young Dwight Eisenhower participated in a cross-country road trip to deliver tanks from Fort Meade in Maryland to San Francisco. Most of the roads on the journey were muddy, rut filled trails, and after 62 days at an average speed of 5 miles per hour, the convoy finally arrived. Forty years later President Eisenhower signed the Federal Aid Highway Act and created the United States’ interstate highway system. Today, the same trip can be easily completed in 4 days.

A highway is a wonderful example of an enabling technology, an underlying, general purpose entity that supports many – sometimes unexpected – innovations. For example, one could argue, that without a high-speed reliable interstate highway system, we wouldn’t have Amazon. Moreover, first mover advantage goes to those who see the maturation of enabling technologies and can build solutions at their intersection at the right moment. For digital therapeutics, that moment is now.

When I started in the video games industry, computer graphics were – at best – abstract representations of reality. Over the last 20 years, computer and graphics processors have improved astronomically. These improvements — measured by increased transistor count and power efficiency — have allowed for radical increases in graphic fidelity. To put it simply, my mother can’t tell the difference between real life and a computer image anymore. GPU speed and power efficiency has also accelerated machine learning techniques that were unheard of 10 years ago.

Likewise, the availability of high-speed internet has skyrocketed. Spurred on by the intense bandwidth requirements of digital entertainment, the average data rate in the western world has doubled every 18 months, in lockstep with Edholm’s law, the telecommunications equivalent of Moore’s law. Starlink, a network of satellites being launched by SpaceX, is 30% launched, and when complete will provide high speed internet to the entire planet.

“EndeavorRx has become the first ‘prscription video game’ for doctors to utilise, forcing focus for children with ADHD” In short, society has created machines with photorealistic graphics and machine learning capability, along with a blindingly fast network to connect them. Beyond video games, cat videos, and increased revenue, what else will we spend this tech treasure on?

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Mental health disorders affect one in four people, making them a leading cause of ill-health and disability worldwide. Economically speaking, Americans lose approximately $193.2 billion in annual earnings as a result of unmanaged mental illness, and depression alone cost the global market $1 trillion in lost productivity in 2013. According to a 2018 landmark report by the Lancet Commission, the growing mental health epidemic could cost the international economy up to $16 trillion by 2030, with a dramatic impact on productivity and quality of life.

After early wins in the mental health space in the 1950s and 60s with first generation antidepressants and antipsychotics, the industry has struggled to impact mental health at the same rate as other indications. With the exceptions of Spravato and Zulresso, the last major steps forward in the space were SSRIs and SNRIs in the 80s and 90s.

Why is mental health such a “hard attack surface”, to use a hacker’s analogy? The brain is the most complex system in the body, and we are only now starting to understand the complex mechanisms of communication within. It is as if we are standing at the doorway to a vast server farm of computers, but we don’t know the passwords, have only recently discovered electronics, and we don’t yet have a keyboard.

Luckily, our brains already have sensing and effector capabilities, including eyes, ears, a vestibular system to sense the world and many other ways to interact with the outside world. Our brains are highly optimized to use these systems not just as content to reason about, but also as source data to change how we reason, a sort of meta-cognition system.

The human brain is constantly rearranging how it filters, processes and reasons its input. For example, in 1897, George Stratton created a pair of goggles to invert his vision. After wearing them for several days, his brain adapted to the inverted signal from his eyes to his brain, allowing him to function normally and even ride a bike. This year, Akili received FDA clearance for their digital therapeutic for children with ADHD by forcing the brain to adapt with a cleverly designed video game that forces focus. Our brains are capable of responding to training with plasticity. This makes Akili’s product, EndeavorRx, the first ‘prescription video game’ for doctors to utilise. The game, recommended for children aged 8-12 years old, sees players piloting a small aircraft through a variety of challenging environments.

Due to their rapid development times, low risk and potential for synergistic effects, digital techniques are an ideal add on to existing pharmaceutical pipelines. Many existing drugs and therapies could see an efficacy or adherence boost by adding a digital combination therapy. Soon, integrated digital medicine will be like having a miniature interdisciplinary team accessible 24 hours a day in the patient’s pocket.

In some cases, a combination approach like this will give radically better outcomes. For example, Medically Assisted Therapy (MAT) in Substance Use Disorder (SUD) is more effective than medication intervention alone but is simply unavailable in many areas. A combination digital medicine approach will make high quality, standardised behavioural interventions available for everyone. In other cases, such as the emerging use of psychedelics for SUD or Treatment Resistant Depression, such after- care, as well as pre-care, is critical.

Perhaps now, more than any time in history, all the conditions are ripe for a massive leap forward in mental health. Who will take up the challenge? Who will invest in the basic science? Who will invest in the clinical trials? I would argue that the pharmaceutical industry is the prime candidate for taking up the mantle of taking on mental health with digital medicine. No other industry has the experience, budget, scientific rigour, and established commercialisation pathways to move quickly, ethically and powerfully into this green field of development.

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With every required enabling technology now mature, the next leap forward is imminent – and for the hundreds of millions living with debilitating mental illnesses, not a moment too soon.

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ATAI Launches Subsidiary Focused On Active Ingredient In Hallucinogenic Brews

Natan Ponieman | July 22, 2020

Psychedelics and biotech company ATAI Life Sciences announced Wednesday the launch of Viridia Life Sciences. This wholly-owned subsidiary will be dedicated to the study and production of the DMT molecule (N,N-Dimethyltryptamine).

DMT is a psychoactive alkaloid present in Ayahuasca, a hallucinogenic brew traditionally used by indigenous communities in South America. The compound has gained attention in recent decades in North America for its ability to induce psychedelic experiences with a rapid onset and shorter duration than other psychedelic drugs. While a typical LSD or psilocybin experience can last upwards of six hours, DMT’s hallucinogenic effects can reach a peak and extinguish in less than 15 minutes.

Exploring Alternative Routes Of Administration

Most common applications of DMT in clinical settings are done through intravenous administration, as it’s the case with MindMed (NEO: MMED), another psychedelic company that announced the launch of DMT trials last month.

ATAI said that Viridia is leveraging the platform’s own drug development experience to formulate DMT products based on alternative routes of administration.

“Viridia’s DMT products will be developed with the specific aim of controlling the rate of which the drug is released and absorbed, which has a direct impact on the onset and duration of the psychedelic experience,” said Glenn Short, PhD, CEO of Viridia Life Sciences to Benzinga.

DMT’s psychedelic onset is typically very rapid and intense, beginning within two minutes. Short said that ATAI aims to slow the onset and lengthen the duration of the experience slightly, so that the psychedelic onset is much more gradual and overall more gentle and agreeable to the patient.

Combining DMT Treatment With Digital Therapeutics

Short added that ATAI will explore ways of combining DMT drug developments with its recently-launched digital therapeutics platform, which was announced earlier this month.

“Treatment does not stop after a patient leaves the doctor’s office. A digital therapeutic can give direct lines of communication to the therapist, allow journal writing, allow for real time patient monitoring,” said the executive. These remote assessments will not only allow for the therapist to track progress toward the reduction and remission of specific symptoms, but also allow rapid intervention if necessary, or trigger a subsequent DMT-assisted psychotherapy session.

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Meet Viridia, the ATAI unit exploring ayahuasca-based treatments for mental illness

Amirah al Idrus | July 22, 2020

Can ayahuasca, a psychoactive brew used traditionally in South America, be used to treat depression and other mental illnesses? Biotech builder ATAI Life Sciences is setting up a subsidiary to find out: Viridia Life Sciences. The company aims to develop new formulations of t he brew’s active ingredient, N,N-dimethyltryptamine, or DMT, to use alongside talk therapy to treat “a variety of mental health disorders.” The idea is to take advantage of the neuroplasticity—the brain’s ability to change itself—brought about by a psychedelic experience to help patients overcome ailments such as depression. ATAI will also pair its DMT products with a digital therapeutic, which can help doctors monitor patients remotely and tailor treatment to each patient.

“Why DMT? DMT is a short-acting psychedelic,” Glenn Short, the early development lead at ATAI and CEO of Viridia, told Fierce Biotech. “The reason why it is short-acting is because it is rapidly metabolized by enzymes called oxidases.”

The most advanced life sciences organizations know that digital innovation and multi-platform integrations are essential for enabling product development. New platforms are providing the life sciences industry with an opportunity to improve the efficiency of clinical trials and reduce costs while remaining compliant and reducing risk.

Although DMT has a short half-life, the psychedelic effects of ayahuasca can last anywhere between two and six hours, Short said. That’s because it doesn’t just contain DMT—it also has monoamine oxidase inhibitors that, as their name suggests, block the enzymes that metabolize DMT.

Isolating DMT could result in a drug that triggers psychedelic experiences that are much shorter than what’s usual with ayahuasca and other substances, such as psilocybin, the active ingredient in magic mushrooms.

A shorter experience could open up psychedelic-assisted treatment to people who can’t or don’t want to undergo a longer psychedelic experience, said ATAI CEO Florian Brand in a statement.

“Patients might be able to, after a psychedelic experience, have a psychotherapy session immediately afterwards,” Short said, adding that this would be much different than, say, Johnson & Johnson’s Spravato, a tweaked form of ketamine approved last year with various restrictions. It carries a boxed warning for risk of sedation, risk of abuse and suicidal thoughts and behaviors and difficulty with attention or thinking.

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Patients can’t take Spravato at home but must take it under the watchful eye of a healthcare provider charged with monitoring their response for at least two hours. Patients start out with one month of treatment twice a week. After that, those who respond then receive treatment every week or every other week.

“[DMT] would be differentiated from that model,” Short said.

Others have tested intravenous forms of DMT in the clinic, but that delivery method has obvious drawbacks. For starters, it requires patients to undergo an intravenous infusion in the clinic.

“I think there are methods to consider for alternative routes, such as mucosal administration,” Short said. That could include delivering the drug to mucous membranes in the nose or mouth, but Short declined to discuss specifics. The company aims to start clinical trials in early 2021.

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After psilocybin and ketamine, a new biotech comes along developing a drug Scott Gottlieb fought

Jason Mast | July 10, 2020

Andrew Kruegel was six years into his chemistry work at Columbia University, when, one day in August 2016, he learned he might have only 30 days before the government made him destroy his research.

Kruegel had been studying kratom, a leaf long used in Southeast Asia as a stimulant or for pain. It had opioid-like properties, he found, but seemed to offer pain relief without the addictive potential or respiratory side effects of traditional opioids — a riddle that might help illuminate how human opioid receptors work.

The DEA, though, saw the “opioid-like” properties and, citing an “imminent threat to public safety,” announced on August 30, 2016 that in a month, they would make it a Schedule 1 drug, the same classification as LSD, heroin and marijuana. You can research Schedule I drugs, but you need a license and you can’t just order it online, as they had been doing.

“We would’ve had to destroy everything we have, and probably start over,” Kruegel told me. “I was scrambling.”

Kruegel started circulating letters among scientists at Columbia and elsewhere and sent them to regulators. He spoke to dozens of reporters, explaining how kratom was an “atypical opioid.” He wasn’t alone. Thousands of individual kratom users signed petitions and flooded public comments sections with stories about how the plant helped them manage pain or recover from addiction. The DEA reversed course in October, even as new FDA chief Scott Gottlieb took the mantle, repeatedly calling to regulate what he saw as a dangerous opioid with no proven benefit.

Before the controversy, Kruegel thought only a few internet enthusiasts knew about the drug; the outpouring from kratom users surprised him. It also gave him an idea: If the plant was helping so many patients with opioid abuse or pain, why not turn its main ingredient into a drug for a country desperate for alternatives to oxycontin and its opiate cousins?

So he founded a tiny biotech called Kures. Today, ATAI Life Sciences, the mental health biotech best known for their work on psychedelics such as psilocybin, announced they’ve acquired Kures in their latest attempt to turn an already widely used substance into an FDA-approved drug.

The plan is to develop a compound derived from kratom first as a treatment for acute pain, then as a treatment for opioid abuse disorder and, further down the road, possibly as an anti-depressant.

“I think it makes sense,” Christopher McCurdy, one of the first US researchers to study kratom and who is not involved with Kures, told me. But he points out that the idea is still largely untested: “You don’t know it until you try it.“

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Kruegel acknowledged an irony in his company’s founding; had Gottlieb and other officials not tried to ban kratom, he would never have learned how widespread it was and started a company. “Or at least kratom and the derivative we made might not be the focus of the company,” Kruegel said.

For ATAI, those thousands of people saying the drug bolstered their confidence, as similar reports did for their programs testing psilocybin and arketamine as treatments for depression. “It de-risks it,” CEO Florian Brand told me.

Kruegel looks how you imagine a chemist who studies plants popular among drug enthusiasts to look. He has a boyish face at 32, with the scratchy semblance of a beard, and he explains the science with readily apprehensible and occasionally humorous candor. Unlike some other researchers of psychoactive substances, he makes no pains to distance himself from recreational users, talking about his first experience as an undergraduate taking salvia, a plant known to give a powerful 20 minute high. (“It’s not really describable in English,” he says of the experience.)

When I ask him how he got interested in studying psychoactives, he gave an answer reminiscent of a stoner grasping at a genuinely fascinating concept. “The idea that you can so profoundly alter human consciousness, with the amount of material in some cases that you can fit on the head of a pin — like, for example, with LSD — is a pretty remarkable thing,” he said. “If you showed a lay person the amount of material that would cause them to have a psychedelic trip, they would laugh at you.”

Kratom is often served as tea, and if you’re looking for a hot cup in New York you can find it, at least before the pandemic, about 100 blocks south of Kruegel’s old Columbia lab at an East Village bar called Kavasutra, though Kruegel wouldn’t recommend it. (“Overpriced,” he says, recommending you buy the ground or dried stuff online or a local supplement shop.) The place also serves kava, a high-inducing Hawaiian root. Outside a yoga teacher in a Hawaiian shirt talks to a body builder about “You are the placebo!,” a book by a chiropractor that promises to show how the placebo effect can reverse cancer and Parkinson’s and, well, pretty much anything else. The kratom comes in a paper cup and tastes like very bitter ice tea.

All this is relatively new, at least to the US. Kratom was first described to the west by a British botanist in the 1870s, who wrote about how it was used in Southeast Asia as a stimulant and pain reliever. It’s still used that way, either when brewed into tea or chewed by day laborers. “It’s really used as a traditional medicine,” Oliver Grundmann, a University of Florida pharmacologist who has published with Kruegel, told me.

It’s not clear when Americans started using it. There’s evidence of folks growing kratom trees in the South in the 90s, Grundmann said, but research on it and widespread availability only goes back to the last decade. That’s when surveys began coming out showing that people were using it as a pain reliever and anti-depressant.

Midwestern University pharmacologist Walter Prozialeck attributed the use and the interest in the area to the burgeoning opioid crisis. Kratom attracted the hipsters and alternative health enthusiasts who frequent Kavasutra, but it also gained traction online and in some recovery centers as a treatment for those recovering from opioids.

“The area of kratom research just exploded. If you look at the publication data between 2014 and the present, the number of publications has just increased dramatically,” Prozialeck told me. “It’s pretty obvious that interest in kratom has increased as the opioid crisis has gotten worse.”

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Kratom exists in a “grey area,” Grundmann said, neither a drug nor a supplement and thus, for now, subject to few restrictions.

The DEA and later the FDA’s opposition to kratom came as a result of two things: research, including from Kruegel’s lab, showed that the most common alkaloid in kratom, called mitragynine, operated by activating the opioid receptor and the government was deeply cracking down on opioid use. And while labs could work with particular chemicals, the ground and dried leaves that many consumers were buying were unregulated and their quality — or possible contamination — was unclear, McCurdy said.

In a 2018 statement, Gottlieb said the “FDA’s concerns about kratom’s potential for abuse, addiction, and serious health consequence” came after an internal computational model found it operated on opioid receptors. They said they were particularly concerned about what had excited Kruegel: the accounts of people using it for opioid abuse disorder. “There is no reliable evidence to support the use of kratom as a treatment for opioid use disorder and significant safety issues exist,” Gottlieb wrote.

Kruegel by that point had been studying kratom for 8 years, McCurdy for 14 years. The problem, they and others say, is that while kratom does hit the same mu-opioid receptor that oxycontin and percocet does, it does so very differently. It’s what Kruegel calls a “partial agonist” or an “atypical opioid.”

They don’t turn on the receptor as fully as morphine might, Kruegel said, so you can’t get a better high from just increasing the dose. Additionally, McCurdy and Kruegel’s work suggests that the drug is metabolized in the liver into a slightly different compound before it has its effect, meaning you can’t get a better high from injecting it.

“No matter how much you take, you have a ceiling,” Kruegel said. “That’s probably a major explanation for people who are taking kratom and not dying in droves.”

Grundmann explained that the drug doesn’t hit the beta-arrestin pathway that other opioids do. That pathway is responsible for a lot of the negative side effects of the drugs, including respiratory depression and addiction. That means a less powerful pain reduction but it also means far fewer side effects. Other researchers pointed out at the time and since then that the people who Gottlieb listed as possibly dying of kratom either had other substances in the system or possibly died of other causes.

The DEA has not tried since to restrict the drug, and Kruegel is proceeding as if they won’t. Kures is now doing preclinical studies through outside labs, with plans to move in the clinic with mitragynine next year for acute pain. “We’d like to replace opioids for some people,” Kruegel said, while acknowledging that many will still need the more powerful drugs.

He’s not alone. McCurdy, with the help of the National Institute on Drug Abuse, is working on starting studies on the plant itself and a trial has already begun in Washington. For all the kratom researchers, though, a single question hangs indefinitely in the back of their minds. What happens if regulators change their minds and try again?

“We’re always in a state of limbo,” Kruegel said. “I think the FDA has it out for Kratom.”

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Could ibogaine offer a revolutionary long-term solution to addiction?

Stephanie Price | June 12, 2020

Derived from the iboga plant, ibogaine is a psychoactive compound that could have huge potential as a long-term solution to addiction. ATAI Life Sciences and DemeRx are soon initiating clinical trials to test its efficacy.

According to the World Health Organization around 3.3 million people die every year from alcohol addiction and around 31 million have substance use disorders, but there are currently no long-term solutions for treating addiction. ATAI Life Sciences hopes that the clinical trials can demonstrate that ibogaine could be a contender for helping people kick their addictive habits for good.

The bushy iboga plant, or Tabernanthe iboga, produces slender orange fruits and grows in parts of Africa such as Gabon and Cameroon, however, it is difficult to cultivate outside of the country. Its extract – ibogaine – is an entheogen used in religious Bwiti ceremonies of the Punu and Mitsogo peoples as an initiation rite and to help with psychological conditions.

Chief Scientific Officer at ATAI Life Sciences, Srini Rao, spoke to Health Europa editor Stephanie Price about the upcoming clinical trials which will be investigating whether ibogaine, in conjunction with digital support tools providing cognitive behavioural therapy (CBT), could offer a long-term solution for those battling with opioid addiction. What is ibogaine and how does it work?

Dr Deborah Mash, Chief Executive Officer and founder at DemeRx, is a visionary in the field of ibogaine research and has been studying the iboga plant and its medical benefits for thirty years. Through her research, she has demonstrated that purified ibogaine (the active moiety in iboga plant extracts) could have applications for treating substance use disorders, and in particular, opioid use disorder.

To date, there have been no double blind, placebo-controlled trials to test the efficacy of ibogaine for the long-term treatment of opioid use disorder, but open label studies and case series suggest that a single dose of ibogaine may result in long-term abstinence.

Rao, who will be supporting the clinical trials, said: “People suffering with opioid addiction tend to revert to taking their drugs relatively quickly, so the open label data is quite supportive. The results suggesting that a single ibogaine treatment may result in months of remission is surprising and, if replicated, would be revolutionary.”

Patients who are opioid dependent are currently treated with substances such as methadone and buprenorphine, both of which engage with opioid receptors in the brain differently to heroin, morphine, or oxycodone, thus blunting cravings. In individuals

18 who are not opioid dependent, compounds like naloxone or naltrexone may be used, to make getting a high off of an opioid of abuse more difficult.

Rao said: “However, neither class of drug addresses the underlying desire to take a drug in the first place. This is what ibogaine seems to be doing – which is why it is a potential gamechanger in this space.”

Ibogaine clinical trials

The aims of the upcoming clinical trials are three-fold: to understand the drug from pharmacokinetic and dosing perspectives, to understand the compound’s tolerability and safety (particularly with respect to cardiovascular impact), and finally, to determine ibogaine’s effects on short-term withdrawal and long-term abstinence in a robust, double-blind, placebo-controlled trial. This type of study is considered the ‘gold standard’ and is the first to be conducted with ibogaine to date for treating addiction.

Rao said: “Ibogaine has been used in iboga clinics with bad cardiovascular outcomes being noted. This is not surprising as drug administration is not well controlled, and the actual dosage of drug being delivered is often unknown. When ibogaine was tested by Deborah Mash in controlled circumstances, no significant cardiovascular events were observed.

“Right now, our plan is to administer the ibogaine once. One of the approaches that we are using to support and assess the patient after the ibogaine therapy involves a digital therapeutic, which will provide both behavioural therapy and social support via a virtual community of subjects in the trial. We do not expect much of a placebo response, even for the digital therapy, as this is not a population who tends to do very well unless CBT is used in conjunction with a drug. We will be closely monitoring the participants and if there are any signs that they are using drugs again we will have them appropriately treated.

“For this first phase of the trial, we are looking at a three-month post-dose observation period, but I would like to see, in future trials, what happens over six months and a year to help answer the question of when participants do need to be re-dosed.” Facing the root cause of our addictions

Many people who are battling addiction are dealing with deep rooted psychological and emotional problems or traumas – cloaking pain by using substances. For this reason, it can be difficult to find a long-term solution for addiction without addressing the root cause for using the drugs in the first place.

Rao said: “The pharmacology of ibogaine is incredibly complicated, and it is not obvious at this moment what is driving its effects. The extract clearly has an impact on neuroplasticity like psilocybin, though the psychedelic effect that it creates is subjectively very different to what you get with psilocybin. It is a lot more dreamlike and protracted and can last over 20 hours in some individuals.

“The psychedelic experience that is often described is that the drug takes you through all of the bad decisions you have made in your life in a chronological order and makes you confront them. Ibogaine is not generally thought of as a drug of abuse as most people don’t have a great experience overall – but one hypothesis for why ibogaine has such profound, long-lasting effects is that by making you confront and process previous traumas, you obviate the need to abuse opioids as you are no longer trying to placate some underlying pain.”

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America’s opioid epidemic and the search for a solution

The supporting digital CBT therapy will be an additional branch of the trial which aims to help address the opioid epidemic and standardise supportive care in America.

Rao said: “Standardising support is one of the challenges in the US today. There is such different levels of therapy and resources depending on where you live – if you live in a big city there are quite a lot of resources, but if you are out in a small town in rural America, the level of resources is likely considerably less. We want to standardise that to some degree across the US, ensuring that everybody has at least a basic level of support.

“Ibogaine could be a part of the solution, but when all is said and done, no drug is going to work for everybody. However, hopefully, a substantial amount of people will get a benefit from ibogaine. The need is even more pressing in light of the COVID-19 crisis, which appears to be exacerbating the opioid crisis in the US.”

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ATAI dives into digital therapeutics to boost mental health care

Amirah Al Idrus | June 22, 2020

ATAI Life Sciences aims to transform mental health care, backing companies working on new treatments for depression, anxiety and addiction. Now, it’s adding digital tools to the mix through a new company called IntroSpect Digital Therapeutics.

IntroSpect will create digital tools and devices that will “magnify” the effects of drugs in development at ATAI’s companies, David Keene, CEO of IntroSpect, told Fierce MedTech.

The use of digital biomarkers could help doctors tailor doses for each patient and improve their treatment: “With improved understanding of how individual biological phenotypes align with responses to certain interventions, clinicians will be better able to predict patients’ recovery pathways,” said Srinivas Rao, chief scientific officer of ATAI Life Sciences, in a statement. “This, in turn, will cut down trial and error and shorten the time to therapeutic impact. And for those with difficult to treat mental illnesses, time is absolutely critical.”

Another use case is remote monitoring, which could make psychedelic treatments available for patients who live far away from treatment centers. The technology could come in handy at Compass Pathways, for example, which is working on a psilocybin therapy for people with treatment-resistant depression.

“What separates apart a recreational psychedelic experience versus a clinical one is the clinical setting and aftercare therapy,” Keene said. “This type of aftercare can help patients take advantage of the neuroplasticity—the brain’s ability to change itself— that comes with a psychedelic experience and use it to make life changes, Keene said.

Digitizing aftercare can widen access to psychedelic treatment for ailments such as addiction or depression. But that’s not all— the digital tools could also be treatments themselves, helping patients learn new behaviors in the “window of opportunity” after psychedelics treatment.

“A lot of digital therapeutics are based on psychological education, like cognitive behavioral therapy … They are far more effective when the brain is in a state it can learn new things,” Keene said.

IntroSpect is working on a modular system so it can apply its digital tools to the various disease areas in ATAI’s portfolio. In addition to Compass Pathways, the company has backed Perception Neuroscience, which is working on a ketamine-like drug for depression, and Neuronasal, which is working on a treatment for concussion that is given through the nose. It’s also set up joint ventures aimed at developing a “neurochemical reset” for opioid addiction and artificial-intelligence-based drug discovery for illnesses such as depression, bipolar disorder and schizophrenia.

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The company is building the technology for substance use disorder and treatment-resistant depression, Keene said. It’s starting with two indications so it doesn’t end up making something that’s too specialized and can’t be adapted to other diseases.

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Could arketamine be a breakthrough therapy for depression?

Stephanie Price | May 29th, 2020

Clinical trials are being carried out to test the efficacy of arketamine as therapy for depression, with the aim of offering an alternative to classic antidepressants.

Ketamine has a fifty-year history in medicine. Discovered in 1962, ketamine is a psychoactive, dissociative drug that has commonly been used as a general anaesthetic and sedative. Enantiomers (molecules that are mirror images of one another) of ketamine are esketamine and arketamine, and esketamine has recently received approval from the FDA as a therapy for treatment-resistant depression. Yet, the two molecules have subtle but important differences in how they act on the body.

Both compounds appear to be good potential antidepressants – however, arketamine has received little attention for its efficacy for the treatment of depression, despite showing promise of fewer psychotomimetic side effects than esketamine in animal studies.

Health Europa editor, Stephanie Price, spoke to Dr Terence Kelly, CEO of Perception Neuroscience (an ATAI Life Sciences portfolio company), which is carrying out clinical trials to explore whether arketamine could offer a promising alternative to classic antidepressants.

The benefits of arketamine as therapy for depression

According to the World Health Organization, more than 264 million people across the globe suffer from depression, and around 800,000 people each year die due to suicide.

Through ATAI Life Sciences, which is committed to developing innovative treatments that address significant unmet medical needs in the mental health space, Perception has initiated clinical trials in New Zealand with the long-term aim to prove the efficacy of the arketamine enantiomer for treatment-resistant depression.

Dr Kelly said: “We are hoping that by the time we get through the clinical trials we can prove two things. Firstly, that arketamine is at least as good an antidepressant as esketamine, and by extension ketamine, and secondly, that it has a much gentler side effect profile, or a wider ‘therapeutic index’, which is the difference between the dose at which you see effects, and the dose at which you start seeing side effects.

“We are currently in a Phase I clinical trial and the goal is to establish the tolerability of the compound and to assess the pharmacokinetics, which is how much stays in the body and for how long. We start with a small dose which will be increased until we start seeing dose-limiting side effects – such as sedation. The trial was put on hold in March due to COVID-19, but we are hoping to be back online with the trial in early June.”

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Dr Kelly wants arketamine to work at low doses that do not induce side effects, and to move away from the typical and invasive intravenous therapy (IV) drip route of administration.

Arketamine’s comparison to classic antidepressants

Dr Kelly emphasised that the main gap in psychiatric medicine is that the amount of time it takes for classical antidepressants to kick in can sometimes be weeks or months.

He said: “If you have a case where someone is acutely suicidal, time is really important, and we know that the effects of ketamine can take hold quickly. We know from the trial that was run in Brazil that arketamine appears to show a rapidly acting antidepressant effect.

“Administration of arketamine would likely be two to three times a week for a certain amount of time – maybe two weeks or a month – and would be administered in conjunction with, or on top of, classic antidepressants.

“One dosing scenario would be that this is an induction therapy, then once the patient is stable and the classical antidepressants start working they can come off arketamine. It may also be that this is a long-term therapy which is something we are looking into in the trials.”

He continued: “What we know from animal ‘condition place preference’ tests is that arketamine does not have a strong abuse potential in these models, which is a big game changer for the entire ketamine field, as it makes arketamine the first ketamine derived product that could be used at home and not in a clinicians office.”

A game changer for psychiatric medicine

Arketamine is not currently approved for use yet anywhere, but Perception hopes that the drug could be a breakthrough therapy for depression and Opioid Use Disorder. If proven to be effective this could have a huge impact on America’s opioid epidemic, which saw the death of 46,802 people in 2018.

Dr Kelly added: “This is the first big step to finding an antidepressant that works within a matter of hours – which could be a gamechanger for psychiatric medicine.

“Some of these types of drugs have been around, in some cases like psilocybin, for thousands of years, and the prejudices that have been associated with them are starting to fall away. At the same time companies and governments are stepping in to evaluate them under the classic rigour of New Medicines Approval. These two things go hand in hand as these molecules have tremendous potential, but some also have tremendous abuse potential. That has to be part of the assessment of these compounds.

“As long as you can balance the medical need against the abuse potential I think that there is clearly a role for psychedelic medicines in the treatment of depression and other psychiatric diseases – this has to be explored and it has to be explored rigorously.”

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https://www.atai.life/wp-content/uploads/2020/05/UBS-Newsletter-May-2020.pdf

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Psychedelic Drugs Can Improve Quality Of Life - And Death - For Older Adults

Abbie Rosner | May 6, 2020

Even before COVID-19 set off a global tsunami of anxiety and depression, psychedelic drugs were already showing exciting promise for treating these and other intractable mental health conditions.

Compass Pathway’s recent raise of $80M to expand research into the clinical uses of psilocybin only affirms that no coronavirus is going to dampen efforts to make these treatments legal and widely accessible. If anything, the need for an effective answer to COVID-era angst makes this work even more urgent.

Especially for Baby Boomers and their elders, developments in the psychedelic space are worthwhile following, particularly because of their potential to radically improve quality of life, up to its inevitable end.

Older Americans suffer disproportionately from chronic pain and its attendant ailments, anxiety, depression and insomnia. In the search for relief, they consume more pharmaceutical drugs than perhaps any comparable cohort on this planet.

Psychedelic therapies to treat mental health conditions offer a radical departure from current pharmaceutical models that wed individuals in a lifelong bond of drug-taking. Instead, the psychedelic therapy modalities currently under investigation combine a limited number of treatment sessions with a psychedelic substance, sandwiched between intensive pre- and post-treatment therapy sessions. The ideal, and realistic, outcome from this course of treatment is not mere symptom control but durable remission.

Indeed, these studies are finding that, in clinically significant numbers, recipients of a single course of psychedelic therapy report the experience to be life-changing, and enduring over time.

Christian Angermayer, founder of ATAI Life Sciences which is the largest shareholder in Compass Pathways, envisions a day when psychedelic treatments are fully integrated into the healthcare system and covered by insurers. And if that seems like a hippie’s fantasy, the mainstreaming of psychedelics is actually well on its way to becoming a reality.

The right conditions

The study of psychedelic drugs has been ongoing since the 1940s, launched by Albert Hoffmann’s serendipitous discovery of LSD. Not knowing exactly what to do with this new drug, Hoffman and others began to investigate psychedelics to treat alcoholism and other mental health conditions, with very promising findings.

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But when dropping acid in the 1960s became a counterculture rite of passage, an enraged President Nixon lashed out with the War on Drugs, and psychedelic research became its collateral damage. After over a decade hiatus, researchers quietly picked the thread up once again, this time determined not to let cultural distractions derail their efforts.

Their success is now evident in the new green rush of non-profits and companies that are making impressive strides in developing and commercializing psychedelic drug-based therapies, mainly focused on mental health. For a traumatized world, this movement offers tangible hope that depression, anxiety, PTSD and other ubiquitous mental health issues may, for the first time, be treated in a meaningful and effective way.

The challenges for bringing psychedelic drugs like LSD and psilocybin, which are currently federally illegal substances, to patients are not trivial. Fortunately, this time around, the set and setting appear to be optimal for psychedelic drug development to move forward. Bolstered by strong preliminary research findings, the entities working to bring psychedelic drugs to market enjoy the cooperation of the FDA and a critical mass of philanthropic and investor funding.

The positive preliminary outcomes of clinical studies by MAPS using MDMA to treat PTSD, and Compass Pathways for psilocybin therapy for treatment-resistant depression, have convinced the FDA to grant them Breakthrough Therapy Designation, acknowledging that they “may demonstrate substantial improvement over existing therapies.” The enlistment of the FDA to the cause is a major milestone towards bringing psychedelic drugs to the mainstream.

Psychedelics for Depression

Psilocybin – a psychedelic compound produced by certain “magic” mushrooms – is the study material used by Compass Pathways in their multi-center Phase IIb study of treatment-resistant depression. Angermayer likens psilocybin to a broad- spectrum antibiotic because of its potentially wide-ranging effects, which could extend to treating anxiety and addiction, among other conditions.

Considered milder – and less controversial - than LSD, a psilocybin “trip” lasts around six hours, compared to what can be double that amount or longer with LSD. With two therapists accompanying the patient through the experience, this is already a weighty commitment of time, emotional and financial resources.

The Compass-sponsored study is currently recruiting participants at 20 sites around the world, including seven in the US and 1 in Canada.

Psychedelics for End-of-Life Anxiety

Already in the 1960s researchers were interested in seeing if psychedelic drug treatment could alleviate existential distress in terminal cancer patients. This line of research was picked up 35 years later by Dr. Charles Grob, whose 2011 pilot study of psilocybin treatment for terminal cancer patients found significant enduring reductions in anxiety and improvement in mood at a six-month follow up.

In the landmark book “How to Change Your Mind” author Michael Pollan movingly describes the insights of cancer patients who participated in a subsequent psilocybin study conducted at NYU:

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“I was being told (without words) not to worry about the cancer … it’s minor in the scheme of things … simply an imperfection of your humanity and that the more important matter … the real work to be done is before you. Again, love.”

Another participant described driving away her fear with anger, which was replaced by “overwhelming love” and that in spite of being “a solid atheist”, she felt “bathed in God’s love.”

We all face the end of life

Even if we aren’t coping with a life-threatening diagnosis, who wouldn’t want to have an experience that might help approach the inevitable end with equanimity and grace?

When international travel was still an option, psychedelic experiences could be arranged at retreat centers in Jamaica, the Netherlands, and even Peru. But even without travel restrictions, the high price tag for these mind-expanding trips left them out of reach for most.

Perhaps one day, when psilocybin therapies are FDA approved and covered by insurance, psychotherapists will have enough experience working with them that they become a routine form of treatment not only for depression, but for end-of-life distress as well.

In the meantime, the importance of access to this type of transformational experience cannot be underestimated. Just consider the insight of the NYU end-of-life study participant:

“…everyone deserved to have this experience… that if everyone did, no one could ever do harm to another again … wars would be impossible to wage.”

And if older adults with depression, end-of-life anxiety, and even just general malaise can replace those feelings with joy and a sense of purpose, leading up to a conscious transition, that can be a trip well worth taking.

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Mushroom magic draws $80M injection for London-based mental health startup

Natalie Grover | April 27, 2020

The coronavirus outbreak has interfered with a mid-stage depression trial testing its psilocybin compound, but the magic of the mushroom has scored Peter Thiel-backed Compass Pathways an $80 million injection in fresh funding.

Exasperated with the often-ineffective existing slate of antidepressants, the company set up shop in London in 2016 and made a beeline for psilocybin, the psychoactive ingredient in magic mushrooms. It received the FDA breakthrough therapy status for the compound for treatment-resistant depression in 2018.

The study, designed to recruit 216 patients across sites in North America and Europe, had begun recruiting when the coronavirus outbreak unfolded. “We decided to — with the Covid crisis — pause the study for now, until there’s better visibility on how the world will develop,” said co-founder and chief business officer Lars Christian Wilde in an interview. “The positive news is that we have a huge number of patients that have completed pre-screening and we’re ready to start over again when the world normalizes.”

Psilocybin is a substance that in most regions is classified as having no medicinal value, falling in the same category as chemicals such as LSD. The company’s man-made version of the chemical — which is illegal across geographies in its natural fungi form — had been well-tolerated in an early-stage, placebo-controlled trial in 89 healthy volunteers in December.

“I think one thing that stands out not only in our healthy volunteer’s study but also in the earlier trials, is that typically patients report a deep sense of gratefulness for the experience, a recontextualization of their suffering, and oftentimes insight into how and what led them to become depressed, and also seeing solutions on how to overcome their depression,” said Wilde, who claimed that one session with magic mushrooms had cured his anxiety disorder and depression, which led to the creation of Compass along with his co-founders.

The new funding round included the participation of ATAI Life Sciences (also co-founded by Wilde); as well as new investors, including the McQuade Center for Strategic Research and Development (a member of the global Otsuka family of pharmaceutical companies), Founders Fund, Able Partners, Camden Partners Nexus, Perceptive Advisors, Skyviews Life Science, and Soleus Capital.

Given global spikes in alcohol consumption and symptoms of loneliness due to isolation measures, in the coronavirus era mental health treatments are needed now more than ever, Wilde said, noting that the plan was to originally raise $70 million.

Psychoactive ingredients, whether derived from cannabis, LSD or magic mushrooms, have long captivated mental health researchers. Navigating the complex legal hurdles to access these compounds has thawed the pace of research but with motivated scientists and a growing burden of poorly treated mental health conditions, the ecosystem of psychedelic research

29 has exploded. In September, Johns Hopkins unveiled it had scored $17 million to open its very own center of psychedelic research to explore the impact of psychedelic compounds on creativity and well-being.

But the brimming enthusiasm comes with a healthy dose of skepticism. Critics worry that the burgeoning research could incentivize unbridled use of non-pharmaceutical versions of these drugs and that clinical trial data could be clouded by the fact that placebo-controlled studies are not necessarily double-blinded, because it is far too easy to determine which group of patients have been given a placebo.

In a bid to combat some of these challenges, the mid-stage trial has three arms — evaluating a 1 mg, 10 mg and 25 mg dose of psilocybin.

“Based on earlier clinical work at Johns Hopkins, and we’re very confident that the 1 mg dose doesn’t have any subjective effects and for the patient, but the benefit of such a design is that we can at least deal with expectancy bias — every patient will receive notice that they will receive psilocybin,” Wilde said, adding that the company is also using blinded raters, who have not partaken in the therapy session.

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Thiel Capital’s Jason Camm Discusses Joining Psychedelics Company ATAI Following $24 Million Raise

Javier Hasse | April 25, 2020

A couple days ago, ATAI Life Sciences, a biotech company developing psychedelic medicines for a variety of mental health indication, announced that it had raised $24 million in a convertible note financing round.

The company will reportedly use the additional funding on existing research programs – like its Phase II studies for the use of ibogaine to treat opioid use disorder, as well as to further expand its existing portfolio.

“This $24 million round demonstrates that interest in mental health solutions is not a trend,” said ATAI founder Christian Angermayer. “Rather, it reflects growing awareness that existing therapeutics are not meeting patients’ complex needs – and COVID-19 has only exacerbated the situation.”

Peter Thiel And Other Big Investors

The most recent, $24 million funding round saw new investment from the likes of Peter Thiel, and Steve Jurvetson and Maryanna Saenko of Future Ventures, as well as follow-on investments from Michael Novogratz, Thor Bjorgolfsson, Efrem Kamen, and ATAI founder Christian Angermayer.

During its prior funding round, a Series B, ATAI had managed to raise $43 million.

Asked about the potential of an IPO for ATAI, a company representative stated, “We’re exploring all avenues to act with impact and at scale for patients, but I can’t comment on IPO speculation.”

Jason Camm Gets On Board

In addition to announcing additional funding, ATAI said Thiel Capital’s Chief Medical Officer, Jason Camm, joined its Board of Directors. Camm will reportedly help guide the company’s future development strategy.

“Mental health is poised to become the world’s leading disease burden,” Camm said in an exclusive email. “ATAI is advancing an evidence-based approach across a portfolio of medicines, each aimed at the various mental health challenges we face across the world today.

“I’m excited to join the founders and management team to help the company scale and reach the many patients who could benefit from this approach,” he concluded.

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Last month, Camm was named as a “Young Global Leader” by the World Economic Forum, alongside Megan Rapinoe, co- captain of the US women’s soccer team, Sanna Marin; the 34-year-old Prime Minister of Finland; and Caroline Malcolm, Head of the Blockchain Policy Centre at the Organization for Economic Cooperation and Development.

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Thiel Backs Psychedelic-Drug Startup in Latest Funding Round

Tereza Pusca | April 24, 2020

• German biotech ATAI raises about $24 million from investors • Company is said to be working toward an IPO within 12 months

Billionaire investor Peter Thiel made his first investment in ATAI Life Sciences, a German startup that’s looking into ways of using magic mushrooms and other psychedelics to treat mental-health disorders.

Thiel was among several participants in a $24 million convertible-note sale that closed in March, ATAI said in a statement. Thiel Capital LLC Chief Medical Officer Jason Camm will become a director of the Munich-based biotech which, according to a person with knowledge of the situation, is working toward an initial public offering within 12 months.

ATAI is in talks with pharmaceutical companies and institutional biotech funds as psychedelic treatments gain traction. The company said the money raised by the bond sale will help it broaden its platform, potentially through acquisitions.

ATAI is studying how to use psychedelics to treat disorders including addiction, depression and anxiety. The company plans to start a mid-stage trial of ibogaine, a naturally-occurring psychoactive compound, with partner DemeRx to treat opioid addiction. It’s also investigating the use of arketamine for depression. The antidepressant drug market alone was valued at around $13.7 billion in 2018 and is projected to grow as much as 24% by this year.

“No single treatment will work for all,” Co-Founder and Chief Executive Officer Florian Brand said in an interview. “We look at treatments that at least have a long-lasting effect, if not curative potential.”

Future Ventures, Galaxy Investment Partners’ Michael Novogratz, Actavis Group’s Bjorgolfur Thor Bjorgolfsson, Efrem Kamen and ATAI co-founder Christian Angermayer also participated in the convertible-bond sale. Fellow psychedelic-drug company Mind Medicine recently closed a similarly sized funding round ahead of its IPO on Toronto’s NEO stock exchange.

ATAI confirmed that it’s aiming for an IPO, but declined to give a time frame.

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Biotech startup wants to make new short-acting psychedelic drugs more scalable & accessible

Tim Hinchliffe | April 24, 2020

As the mental health benefits of the magic mushroom-derived drug psilocybin become more mainstream, researchers and developers are looking for ways to make new drugs more accessible for clinical therapy.

Born out of the desire to create psychedelic compounds more scalable than psilocybin, biotech startup EntheogeniX wants to make new, short-acting drugs that are “pharmacologically cleaner” than magic mushrooms, so more patients and practitioners can benefit from their use.

The magic mushroom experience typically lasts between four to eight hours, and that is a lot of time to spend in a clinical setting for both the patient and the doctor.

Dr. Srinivas Rao, Co-Founder and CEO at EntheogeniX Biosciences, tells The Sociable that his biotech startup wants to cut the psychedelic experience down to 30-40 minutes for several reasons.

There And Back Again

First of all, a shorter “trip” would mean a shorter visit to the doctor’s office where patients could get in and out in about two hours when you factor in the preparation at the beginning and the integration process at the end.

Integration is crucial to these types of therapies because it helps patients make sense of what they just experienced, so they can incorporate their experiences as part of the healing process.

For many people, an intense, eight-hour psychedelic experience can leave them so exhausted and mentally battered, that they may dread their next session because they don’t want to go back and ride the seemingly never-ending emotional roller coaster often associated with the psychedelic experience.

The beauty of a psilocybin-like drug lasting less than an hour is that it helps ease anxiety because the user knows it will all be over in about a half an hour.

According to Dr. Rao, when therapeutic sessions are split up over multiple events, it allows the patient to get more comfortable with the treatment, so they are less anxious about the next one, and this helps with set and setting.

Streamlining Set and Setting

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Set refers to a person’s mindset before going into the experience and setting is where the actual experience takes place — like at a doctor’s office.

Having a positive mindset beforehand and having the experience in a comfortable setting is very conducive for obtaining optimal outcomes.

By allowing the patient to “have an experience. Integrate it. And then have another experience,” Dr. Rao believes that EntheogeniX will be able to “automate some aspects of set and setting.”

But making a drug more scalable for clinical therapy goes beyond reducing time and partially automating set and setting.

EntheogeniX wants to create entirely new drugs that don’t look anything like psilocybin in their chemical structures.

Specially Tailored Drugs: Out With the Bad, In With the Good

Last year, ATAI Life Sciences and AI drug discovery company Cyclica came together to form EntheogeniX. Through this joint venture, EntheogeniX hopes to “specially tailor drugs to target specific disease pathways related to mental health – all while mitigating off-target interactions.”

“Compounds we generate don’t look like anything you’ve ever seen before”

According to Dr. Rao, developing specially tailored drugs from magic mushrooms involves extracting what you need from the psilocybin, discarding any elements that could cause cardiovascular stress in some patients, and then synthetically adding whatever else is needed to create the desired effects.

“Compounds we generate don’t look like anything you’ve ever seen before,” said the CEO.

The resulting drugs could be considered “pharmacological cleaner” than psilocybin because they would “clean up the cardiovascular profile,” thus making the drugs even more accessible to a wider selection of patients.

But for the drugs to be truly accessible, they must be able to reach patients that live outside of urban areas following FDA approval.

Getting Treatment to Small Towns

People all over the world suffer from a wide range of mental health issues such as treatment-resistant depression, bipolar disorder, and schizophrenia, but currently there are very few places people in rural areas can go to receive psychedelic-assisted therapies.

“A lot of people are suffering. We’re looking at getting to the small towns”

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Psilocybin is a Schedule I drug in the US, meaning it is illegal to possess unless authorized by the government, and the only places the drug is clinically available for testing are research centers in major cities like Baltimore, San Francisco, Santa Fe, and New York.

These trials have limited spaces for applicants, and they require that the patients stay there for hours on end. However, an FDA-approved psychedelic drug that lasts less than an hour could be dispatched to clinicians in rural areas who could then administer the drugs, provide treatment, and send patients on their merry way back home in the span of a couple of hours.

“A lot of people are suffering,” said Dr. Rao, adding, “Psilocybin will be very successful, but we’re looking at getting to the small towns.”

On the Doorstep

Herein, we’ve seen how EntheogeniX has looked to psilocybin for inspiration in coming up with new drugs, but the biotech startup is looking at far more compounds than just those found in magic mushrooms. Derivatives of ketamine, iboga, and mescaline are all being studied, and more.

Dr. Rao tells The Sociable that EntheogeniX has created 100 compounds to date and is in the process of testing them against receptors.

If everything runs smoothly, and hardly anything ever does in drug development, we should be seeing some new drugs ready for trial in a little under three years, according to the CEO.

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How psychedelic medicine is being used in the fight to end opioid addiction

Florian Brand | March 27, 2020

No one wakes up one day and decides to become opioid dependent. You might have been warned against the risks - aware that there’s a chance of developing a tolerance or dependence on the drugs. At the start they block the pain and release that feel- good rush of dopamine in your brain, helping you function and go about daily life. But, after a while, that impulse - for a rush, for relief, for a shift in consciousness - can become all-consuming. What starts as a way to relieve stress and pain can become a full-blown dependency, or opioid use disorder (OUD).

Treatment options are limited. In 2018 alone, 2.1 million Americans met the diagnostic criteria for OUD. 47,600 people died from opioid overdoses.

Some may argue that this crisis is a result of big pharma’s overzealous marketing, but, whatever your view, there is little doubt that the industry has faltered in finding a solution. Until now, therapeutic approaches have focused on substituting opioid use for treatments that replace the drugs with milder substances. There’s a significant risk for adverse health effects, including long-term dependency, cognitive issues and drug interactions.

Results of treatments with currently available substitution therapies are variable, with relapse rates across substance use disorders estimated to be between 40 and 60%.

ATAI Life Sciences was formed to take a different approach. My fellow founders and I were inspired by our personal experiences of living with mental health disorders to create a company that leaves no stone unturned in our search for answers. We employ a decentralised, technology and data-driven platform model which includes eight companies working to responsibly accelerate the development of impactful and evidence-based therapies. Many of these companies use innovative technologies like artificial intelligence (AI) and computational biophysics to discover compounds that could hold therapeutic potential for people living with OUD as well as other disorders like treatment resistant depression and anxiety. ATAI’s focus is on patients who have already tried – and failed – to find relief with other therapeutics.

We aren’t alone in this thinking: Deborah Mash, CEO of one of ATAI’s close partners, DemeRx, has spent years investigating the therapeutic properties of the iboga plant in OUD. Together, we are now taking the next step for research by submitting Clinical Trial Applications for a Phase II study in opioid-dependent patients.

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Ibogaine has been used in traditional ceremonies in West Africa as part of Bwiti religious practices since the late 1800s. It is known for its oneirophrenic and hallucinogenic properties and works by affecting a variety of neurotransmitter systems, including serotonin, opioid, and NMDA receptors. The exact mechanisms behind ibogaine’s dissociative psychedelic effects are unclear, but it has been speculated that the dream-like state induced in patients leads to a kind of “brain reset”. We want to see whether this reset might provide patients with a clean slate, empowering them to reframe their understanding of their behavioural patterns and play a more active role in reducing opioid use.

Uncontrolled data from hundreds of patients supports this theory. The largest study of ibogaine to date, found that a single low, oral dose significantly reduced opioid withdrawal scores, the severity of cravings and concurrent depression. Importantly, these effects persisted at a one-month follow up.

Research into ibogaine is difficult to carry out. Ibogaine is a Schedule I drug. According to the US government, Schedule I substances have no currently accepted medical use and a high potential for abuse. Consequently, clinical investigation of ibogaine remains limited, outside of a few highly regulated centres around the world. Dr Mash found a way to continue her research at a patient-funded treatment centre called Healing Visions that operates on the West Indies island of St. Kitts. There she was able to treat over 300 people from 1996-2003 in a holistically person-centred setting while collecting and publishing data about ibogaine addiction treatment.

Dr. Mash stated: “If ibogaine stays in the underground, backdoors, and back alleys outside of mainstream medical use, it’s never going to get out of Schedule 1 or be approved as a therapeutic drug, and we’ll never be able to get it to the millions of people who are desperate.”

We are working with Deborah to start a revolutionary shift in the way mental illness and addiction is studied, diagnosed and treated.

Our partnership with Deborah and her team doesn’t mean that we are a “psychedelics” company; it just means that existing treatments just aren’t working and opioid users and their families are still suffering from this devastating disorder due to a shortfall in mental health innovation. And, perhaps, that a pharmaceutical industry - used to being at the cutting edge of science - might yet have a thing or two to learn from ancient medicines like ibogaine when it comes to taking on OUD.

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Arketamine: A Fast-Acting Antidepressant Without Dissociative Effects?

Natan Ponieman | March 26, 2020

In February 2020, scientists in Brazil performed an open-label study on arketamine, a variant of ketamine. The pilot trial, conducted by the Federal University of Bahia, was performed on seven subjects suffering from treatment- resistant depression. It found evidence that arketamine might produce “fast-onset and sustained antidepressant effects in humans” without the dissociative effects normally produced by Ketamine.

The combination of immediate antidepressant properties, with a favorable safety profile and fewer — or even no — psychoactive disturbances, has some companies placing bets on arketamine to eventually become available on an outpatient basis.

Ketamine as a Treatment for Depression

Now, is arketamine ketamine? Yes, and no.

Some chemical compounds have what chemists call "stereoisomers." There are compounds with the same atoms, but oriented differently in space.

Ketamine has two of them: esketamine and arketmine. While their composition might be the same, their effects on the body can differ.

Ketamine was introduced decades ago as an anesthetic and sedative, gaining widespread use as a surgical anesthetic and pain- management drug during the Vietnam War. Following an adoption by recreational users due to its dissociative and hallucinogenic effects, the drug became an FDA schedule III controlled substance in 1999.

Starting in the 2000s, researchers found that ketamine and its chemical mirror compound esketamine can have rapid-acting antidepressant effects.

A critical review paper published in 2018 stated that “intravenous ketamine shows a significant antidepressant and probably antisuicidal effect in the short term.”

Another historical review study stated that ketamine showed significant results in the treatment of Major Depressive Disorder in various clinical studies, with better results than a control group treated with the opioid Midazolam.

In 2019, the FDA approved an esketamine nasal-spray for adults with treatment-resistant depression.

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Arketamine: Ketamine Without Dissociation?

Both ketamine and esketamine produce dissociative effects. However, recent studies have found that arketamine can produce helpful results in the treatment of depression, with milder dissociative effects. In some cases, scientific literature suggests that arketamine could produce zero dissociation in some patients.

A 2014 study done on mice found that arketamine binds to certain receptors in the brain differently from both ketamine and esketamine, leading to the hypothesis that it could produce the same antidepressant effects, without the psychological disturbances of its sibling compounds.

According to Allan Malievsky, from Atai Life Sciences, depression affects 350 million people, over a third of which don’t respond to any treatment. The company decided to focus on psychedelics research as a possible gateway to treating this group.

Atai Life Sciences is developing experimental treatments with different psychedelics such as psilocybin and ibogaine through its portfolio companies Compass Pathways and DemeRx.

Perception Neurosciences is another company working on developing arketamine treatments and proving the hypotheses postulated by preliminary studies.

Srinivas Rao, Chief Scientific Officer at Atai, told me that in terms of developing drugs for treatment-resistant depression, arketamine is the opposite to psilocybin, since the latter is intended to produce psychedelic effects and arketamine’s benefits lay precisely on the fact that it doesn’t.

When Would Arketamine Be Useful?

Rao expanded on some of the cases in which arketamine could be the prefered alternative for patients with treatment-resistant depression.

“There are patients you cannot give a psychedelic drug to, so someone who has bipolar 1, you shouldn't probably be giving it to them,” Rao explained.

Other patients might not respond to psilocybin. Rao acknowledged that this remark can be viewed as “heretical” in some circles, given psilocybin’s recent jump to fame as an answer for treatment-resistant depression.

“Depression is not a unitary construct. There's many different forms of depression, many different pathophysiology that are kind of rolled into this one phenotype,” he added. Rao is positive that once big clinical studies are performed on psilocybin, some patients are bound to be left out of the success group. Those could find a solution in arketamine. Lastly, one of the main advantages is that arketamine could -presumably- be taken at home. This type of administration is not deemed possible with psilocybin or ketamine, which need to be given in a controlled environment.

Arketamine Versus Traditional Antidepressants

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“If we can formulate it the right way,” says Terrance Kelly, president and CEO of Perception Neurosciences, “and if the if the clinical trials prove the hypothesis, the main benefit is that it's rapidly acting”

Taking data from ketamine, antidepressant effects occur in one to four hours, which is not common with tradicional antidepressants.

“When you think about cases of acute suicidality, this time is really, really important,” says Kelly. The group is still working on proving these hypotheses. They estimate that, if the process works out smoothly, typical time for clinical development of the drug would take between four to five years, after which time the product could be out in the market.

Perception is currently in a Phase I study being carried out in New Zealand, in which 40 healthy volunteers are being tested with arketamine. The main focus of this study, aside from traditional Phase I protocol -which centers on safety, tolerability and pharmacokinetics- is finding out at which dosis subjects start to report perceptual disturbances.

“We want to get a sense of how much higher dose can we go to before we start seeing effects, and are these effects the same, or are they different [from esketamine].”

In a further study, the company will go into an early proof of concept to find out at what dose does the antidepressant effect start, and how long it lasts.

Potential for Abuse

Ketamine is used in recreational circles for its psychoactive properties. Presumably, getting rid of the compound’s dissociative effects should eliminate the abuse appeal of this drug.

However, arketamine’s abuse potential should be explored further. While arketamine is being presented as a treatment for patients with treatment-resistant depression, allowing the availability of a drug that can be taken from home without supervision, could lead to patients with less extreme forms of depression to use it as an alternative to psychological treatment.

In this regard, Malievsky told us that in a more advanced stage of development, a risk evaluation and mitigation strategy will be presented. This could include limiting the dose and supply available per prescription, thereby avoiding overuse and encouraging patients to continue to seek psychotherapy.

Nonetheless, if arketamine is proven to rapidly eliminate depression symptoms without any perceivable side effects, it could become a perfect tool for overscheduled psychiatrists to rapidly dispatch patients that could have solved their issues in psychotherapy.

For this reason, the entire medical and legal community should remain on the lookout for possible slips in the far-from-perfect space of psychopharmaceutical healthcare.

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How do depressed rats respond to psychedelics? New data offer insight into the human experience Natalie Grover | March 5, 2020

Despite tricky regulations, research evaluating the antidepressant potential of psychedelics in humans is mushrooming — and the FDA has already approved a nasal spray concoction of the cat tranquilizer ketamine for patients whose depression persists despite conventional therapy.

But scientists still don’t quite fully understand the antidepressant impact of psychedelics on the brain — are the effects purely biological or psychological? A new study looks into the degree and duration of antidepressant effects induced by these drugs — largely branded by governments as illegal hedonistic compounds with no therapeutic potential — in an animal model.

“You really can’t take the brain of a patient and grind it up and extract the genes and look at gene expression and see what’s changed in that brain — the best we have right now is imaging. But that’s still just a window into the black box — to get into the black box, we actually need the brain tissue to be able to analyze,” said Charles Nichols, the director of the study and professor of pharmacology at Louisiana State University (LSU).

“But to get that we have to have a model where the drug works and nobody had yet been able to recapitulate the long term effects or even antidepressants effects to a really convincing level in an animal model.”

Nichols, the son of longtime psychedelic research proponent David Nichols, has been studying the effects of psychedelics in the brain for nearly 25 years. In this study, Nichols and his team compared the impact of a one-time dose of psilocybin (the psychoactive ingredient in magic mushrooms), lysergic acid diethylamide (LSD, or acid as it is fondly known), and ketamine in a rat model for depression.

There are already emerging data suggesting the beneficial effects of psychedelics in humans — apart from the FDA-approved ketamine product, psilocybin is being tested as an antidepressant in a range of trials. Recently, a psychedelic research center was opened at Johns Hopkins.

Data from Nichols’ study — the first direct preclinical comparison of the antidepressant efficacy of ketamine and other psychedelics — showed that both psilocybin and LSD significantly reduces depressive-like behaviors five weeks after a single administration in rats, while only the lowest dose of ketamine evaluated (5 mg/kg) was efficacious in decreasing depressive-like behaviors. In addition, the associated antidepressant-like effects of ketamine were transient compared to psilocybin and LSD- treated rats — and lasted less than two weeks.

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“Because there’s so much political discussion tied up into the research, it’s great…this can be a much more data, evidence- based progress towards psychedelic therapies as opposed to a more political grassroots piece,” said Ronan Levy, executive chairman of Toronto-based company Field Trip Psychedelics that is opening up clinics to deliver psychedelic-based psychotherapy.

A WINDOW TO NEW COPING STRATEGIES

In order to see how the “depressed’ rats reacted to the psychedelic compounds, the animals were first put through what is commonly known as a ‘forced swim test’ to measure if they were depressed.

“The short story is you throw them in a bucket of water,” said Meghan Hibicke, the study’s lead author and postdoctoral researcher at LSU Health Sciences Center, Pharmacology and Experimental Therapeutics.

“You see how much they swim versus how much they float. And then you can measure that behavior — so that’s the planning and the passive coping strategy that can be kind of comparable to a depressed person in bed.”

Depressed people find it difficult to get up and brush their teeth — daily functioning is really hard and active, problem-solving is arduous, she said.

“So basically, what makes humans feel bad, makes a rat float, and what makes a human feel better, makes a rat swim … they are just different measures of passive versus active coping strategies — like getting shocked and freezing when you’re human would be a passive coping strategy versus running around and trying to get away.”

Conversely, if you give rats antidepressant medications that have been shown to be effective in humans, the same rats will start to behave more normally. They’ll start swimming in the water and exhibit food-seeking behaviors, Nichols added.

While conducting the study, Nichols and Hibicke were cautious in choosing the doses of the trifecta of psychedelic compounds, relying on literature reviews and consultations with David Nichols to hone in on optimal doses. “If you use too much, the rat is going to be basically super-stoned and it’s not going to be able to perform. And if you don’t use enough, you might not hit a therapeutic level,” Nichols said.

The study findings were significant on two levels. The researchers first accomplished their primary goal of generating a rodent experimental system that could be used to study the molecular, cellular effects with psilocybin as an antidepressant.

“So we now have an animal model, where psilocybin has long-lasting effects after a single dose and we can go and take the (rat) brains out and begin to ask questions on how is it (the drug) changing the brain to do this,” Nichols said.

The second goal was broader — gathering insight into whether the therapeutic benefit is purely psychological or biological.

“What our results have shown is that it’s really kind of neither — that at its core the antidepressant effects are biological because the rat doesn’t really have the existential angst — the same reasons for depression that a human would have. But what we did find was that we could shape the antidepressant effect by the environment that the rat was placed in after the treatment,” Nichols said.

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What the rats encountered during their first week after their psychedelic experience either reinforces a coping strategy that was already there, or it taught them a new coping strategy.

“So it seems like psilocybin at least is opening this kind of window where a new coping strategy is learnable which would be really really helpful for people who are suffering from chronic life problems like depression and anxiety and stress and drug addiction or gambling addiction — where there’s a period of time in which, after their psychedelic experience, they can learn a new way to behave under old circumstances or under challenging circumstances,” Hibicke said.

IMPLICATIONS FOR INDUSTRY

What does this mean for the explosion of companies and researchers looking into the therapeutic potential of different psychedelic compounds for a range of conditions?

“Being able to combine our digital health capabilities with the new insights into the biological mechanisms, giving rise to antidepressant-like effects will enhance our ability to identify why some patients may respond better to psilocybin or LSD versus ketamine…further justifying reimbursement for care,” said Shlomi Raz, the chief of Eleusis Benefit Corporation, which sponsored Nichols’ study.

“When you can make predictions that have a high degree of accuracy, the whole perspective on the use of these otherwise costly therapies will begin to change.”

For ATAI Life Sciences — an umbrella entity that is behind companies such as Compass Pathways (which currently has a mid- stage treatment-resistant depression study testing a psilocybin compound) and Perception Neuroscience (which took its ketamine derivative into clinical trials last year) — the study adds more robust evidence supporting the therapeutic use of psychedelics.

Previously, the animal models were largely in mice, Srinivas Rao, ATAI’s chief scientific officer noted. “With rats, you’re just going up the evolutionary ladder a little bit,” he said. “Rats have much more complex behavior than mice — it’s just more brain there.”

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Meet the top 9 startups raising millions to use psychedelics to treat depression, anxiety, and more

Yeji Jesse Lee | March 16, 2020

• Investment in psychedelics has ramped up in recent years and companies say that interest from traditional biotech and pharma investors has picked up as well. • Key investors, like former Canopy Growth CEO Bruce Linton, hail from the cannabis sector. Others, like PayPal co- founder Peter Thiel have been interested in the industry for years now. • Business Insider identified the top nine companies that are working to turn psychedelics into approved medicines, for conditions like depression and anxiety. We used a list provided by CB Insights, and reached out to the companies to confirm how much money they've raised. • This article was updated May 6 with the latest figures from the companies. • Click here for more BI Prime stories.

It's no secret that investors have been eyeing psychedelics in recent years.

Several cannabis investors have already made the jump, including former Canopy Growth CEO Bruce Linton, who sits on the board of directors at psychedelics company MindMed. Former cannabis entrepreneurs and investors Ronan Levy, Joseph del Moral, and Hannan Fleiman founded psychedelics company Field Trip Ventures last year.

Psychedelic companies say that interest from traditional biotech and pharma backers has been growing steadily and seriously picking up in 2020.

Helping boost the industry, Johnson & Johnson's ketamine-inspired drug Spravato was approved by the US Food and Drug Administration (FDA) in March 2019 to treat serious forms of depression that don't respond to other treatments. Ketamine is a somewhat psychedelic substance that's used as a surgical anesthetic.

In the midst of the investment rush, clinics aimed at administering psychedelic-based treatments for mental health have started to spring up. Mindbloom recently opened up its first clinic for psychedelic treatment in New York City and Field Trip Ventures, which started out as an investment vehicle for psychedelics companies, told Business Insider it plans to open 50 to 60 psychedelic clinics across Canada and the US by 2023.

Data provided by CB Insights shows that equity funding for psychedelic medicine has ramped up since 2017, when investors put $2.8 million into the sector. The following year saw a huge jump, with $70.5 million poured into the industry, and 2020 has already seen $32.7 million invested into the space.

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Based on data from CB Insights, Business Insider put together a list of the top startups in the psychedelics space. They range from companies working on drugs using the psychedelics psilocybin and ibogaine to firms setting up clinics across the country to administer the treatments. We contacted every startup to verify the information.

This article was updated on May 5 with the latest information on the companies and their funding.

(…)

ATAI Life Sciences — $109 million

Founded: 2018 Location: Munich, Germany Money raised: $109 million

Post money valuation: $240 million, according to a source familiar with the matter

What they're working on: ATAI is a biotech platform company that invests in and works closely with portfolio and subsidiary companies developing psychedelics like psilocybin, arketamine, and ibogaine into medicines.

CEO Florian Brand told Business Insider in February that he plans to raise another round of funding soon that is expected to equal or exceed ATAI's Series B round of $43 million. Its current and previous backers include Mike Novogratz, Peter Thiel, Thor Bjorgolfsson, and Steve Jurvetson. A spokesperson told Business Insider, as of early May, that the round is still upcoming. A company representative said that this time around, ATAI was "focused primarily on institutional and strategic investors."

Compass Pathways — $117 million

Founded: 2016 Location: London Money raised: $117 million

Post money valuation: A spokesperson told Business Insider in March that the company's valuation is "significantly higher" than the $99.95 million figure listed on PitchBook.

What they're working on: Founded in 2016, Compass Pathways is developing psilocybin as a medicine for treatment-resistant depression.

Cofounder Lars Wilde told Business Insider in February that he believes investors are interested in the world of psychedelics today because there has been a lack of innovation in depression treatments since the invention of major drugs in the 1980s and 1990s. According to ATAI Life Sciences CEO Florian Brand, psilocybin is currently undergoing a mid-stage trial in more than 200 patients in North American and Europe and could be available to patients in three to five years. Compass is one of ATAI's portfolio companies.

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ATAI is courting pharma and biotech investors as it looks to raise millions to turns psychedelics into approved medicines

Yeji Jesse Lee | February 27, 2020

• Florian Brand helped start ATAI Life Sciences with one vision in mind: to effectively treat mental-health disorders by turning psychedelics into medicines. • The way to do that? By bringing psychedelics through clinical trials and getting approval from regulatory agencies. • Prominent backers like Mike Novogratz, Peter Thiel, Thor Bjorgolfsson, and Steve Jurvetson have come on board with this vision, investing over $100 million in ATAI. More recently, traditional biotech and pharmaceutical investors have shown interest as well. • ATAI plans to raise a fresh round of funding, Brand said. The round is expected to equal or exceed ATAI's Series B round of $43 million.

Florian Brand was skeptical of psychedelics at first.

His longtime friend Lars Wilde was the first to bring them up with him. At the time, in late 2016, Wilde was considering taking a trip to the Netherlands to try taking the psychedelic psilocybin to treat his severe depression. Wilde says it was a desperate attempt to find a solution for his mental health after he tried many other treatments but didn't feel better. Psilocybin is the main psychoactive ingredient in hallucinogenic mushrooms.

Wilde went to the Netherlands and received a "high dose of psilocybin," or more than 5 grams of the compound, he recalled in a recent interview with Business Insider, and noticed improvement. Then Brand's wife, who had struggled with depression after losing her mother, also underwent treatment with psilocybin and saw the same effects. "It was fantastic, and I didn't expect that," Wilde told Business Insider. "I didn't really believe it because it sounded too good to be true."

Brand, Wilde, and their friend and business partner Christian Angermayer came together in 2018 to found ATAI Life Sciences, a company dedicated to turning psychedelics into medicines.

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ATAI calls itself a biotech platform company, meaning it invests in and works closely with companies looking to develop medicines for mental-health conditions from psychedelics like psilocybin, arketamine, and ibogaine. Wilde — who helped build up ATAI with Brand and Angermayer — now works as the president and chief business officer of Compass Pathways, one of ATAI's portfolio companies. Compass is studying the use of psilocybin for treatment-resistant depression.

ATAI has raised more than $100 million from prominent backers like Mike Novogratz, Peter Thiel, Thor Bjorgolfsson, and Steve Jurvetson. The company plans to raise more money to keep funding its research, Brand said.

Enthusiasm grows for turning magic mushrooms into medicines

A company representative told Business Insider the new funding round was expected to equal or exceed ATAI's $43 million Series B round. ATAI is "focused primarily on institutional and strategic investors" this time, the person said. The representative said the company had seen growing enthusiasm for medicine made from psychedelics over the past several years. ATAI presented one of its studies at the J.P. Morgan Healthcare Conference in January, for instance, and the company says it had meetings with numerous interested pharmaceutical companies and biotech investors. The company declined to identify any of them.

ATAI is testing several compounds as potential mental-health treatments through its portfolio companies, though many of the trials are in earlier stages and it could be years before any of the compounds yield medical treatments. The first treatment that ATAI thinks will be available for patients is Compass Pathways' psilocybin in three to five years.

Other compounds being tested include arketamine for treatment-resistant depression, ibogaine for opioid addiction, and etifoxine for anxiety disorder.

As someone who struggled with anxiety disorder, Brand said he recognized the potential that psychedelic medicine could have for those with treatment-resistant disorders. He said he also spent time reviewing the research himself. Matthew Johnson, a professor who studies psychedelics at Johns Hopkins University, said the main reason we hadn't seen many developments in the research on psychedelics in the past few decades was the professional marginalization that researchers faced when they expressed interest in the field.

But interest in psychedelics as mental-health treatments has been picking up in recent years. In the past year or two especially we've seen more research and witnessed companies like Johnson & Johnson release a ketamine-inspired nasal spray for treatment-resistant depression.

Johnson, who has worked with psilocybin for over 15 years, said that the most promising data he'd seen had been on psilocybin but that he was a "strong proponent of pursuing multiple promising avenues." "We need more tools in the toolbox," he told Business Insider.

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Why investors are backing psychedelics

Amanda Eilian, a cofounder and partner at Able Partners, an investment fund focused on mental health and wellness that has invested in ATAI, told Business Insider that Brand's perspective on the mental-health crisis was an important factor for her company in choosing to invest.

"He doesn't come from a traditional pharma background," Eilian said. "And he's younger than many biotech execs. That was also important because the current community has not been able to deliver us solutions to address mental- health crises."

Brand attributes the interest from his backers to what he sees as the strong evidence surrounding psychedelics as medicine.

"They looked at the data, following the evidence for what has potential as an innovation driver in the field," Brand said. "I think we were lucky to be at the right moment at the right time to identify the potential and onboard those compounds."

ATAI's background and future plans

Before ATAI, Brand did everything from heading a kitchen e-commerce company (where he met Wilde) to interning at organizations focused on clean water and preventing HIV in developing countries.

Heading a psychedelics company wasn't in his plans, but he attributes where he is today — from fresh college graduate to CEO of a multimillion-dollar biotech company in less than a decade — to his efforts to try out a plethora of experiences. Brand says he learned what he was good at and what he was interested in by going after "helpful experiences" where the work was interesting and there was a steep learning curve.

Wilde, who affectionately refers to Brand as "Flo," said that while both he and Brand loved to cook and eat and enjoyed their time heading the e-commerce kitchen company Springlane, they cared about mental health for personal reasons and wanted to contribute to improving it through ATAI.

"One thing we keep saying is that our success is really measured in the number of lives we can save," Wilde said, citing stark statistics for suicide. "We're both driven by that."

That and the little progress that's been made in mental-health treatments since the development of depression drugs like selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in the late-20th century motivated Brand to build up ATAI Life Sciences, alongside Wilde and Angermayer.

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They aim to bring psychedelics through clinical trials to get approval from regulatory agencies like the Food and Drug Administration in the US and the Medicines and Healthcare Products Regulatory Agency in the UK.

"There are more therapists interested in this space now and a paradigm shift in the medical and psychiatrist community that allows for these services," Brand said. He added that this openness would ultimately prepare both patients and professionals for an ecosystem in which ATAI's medicines — once approved — could be integrated into everyday healthcare.

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The Capital That Ate Wellness Is Going to Eat Your Mushrooms

Jonah Engel Bromwich | February 27, 2020

Goop, Moon Juice and Daily Harvest are women-led companies oriented toward wellness, that fuzzy intersection of health and well-being. They share an ethos — and also an investor, Able Partners.

“We probably are the first fund to focus exclusively on wellness,” said Amanda Eilian, 42, one of the firm’s two partners.

This focus makes Able a bellwether for the direction in which wellness is headed. So it’s useful to know that it has also invested in Sanctuary (an astrology app), the Coconut Cult (probiotic-infused coconut “yogurt”) and MUD\WTR (a coffee alternative that includes mushrooms).

Now, Able is getting into psychedelics.

Ms. Eilian and her partner, Lisa Blau, originally became interested in women-led wellness companies not because they saw them as sympathetic underdogs but because those companies were “an arbitrage opportunity” — a way of saying that start-ups that are run by women or oriented toward women were undervalued.

A similar calculus has led the firm to invest in so-called vice industries, looking for a market advantage over institutional investors that can’t or won’t support companies centered on sexual pleasure, cannabis or other stigmatized goods and services.

Laura Huang, a professor of business administration at Harvard Business School, who studies why investors invest, said that as venture capital firms proliferate, each grows increasingly specialized. It would make sense, she said, that such firms would progress from women-led businesses to other categories once seen as risky or potentially reputation damaging.

“It was women for a while, and now it’s these lifestyle brands,” Dr. Huang said. “There’s this internal competitive pressure to find that diamond in the rough. So there’s this constant pressure for people to be looking at what’s that next thing that’s undervalued.”

Able is unwilling to invest in cannabis; its partners believe that the risks of taking the drug recreationally have been understated. But it is now an early-stage investor in two companies that are involved in research of psychedelic compounds for medical use, Compass Pathways and Atai Life Sciences.

“Most institutional funds can’t invest in areas like psychedelics,” Ms. Eilian said. “So there was this white space for somewhat untraditional funds like ourselves to be able to look at the category.”

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Particularly because the psychoactive drug psilocybin was recently decriminalized in Denver and Oakland, Calif., it has started to look like a good bet.

Compass Pathways, which is in London, announced in January that it had been granted a patent in the United States. The patent covers a particular method of obtaining psilocybin in order to treat drug-resistant depression. The treatment is currently in a phase IIb clinical trial.

Atai, a German biotech company, is a major investor in Compass. Able became an investor in Atai in February 2019 and in Compass in August 2019.

Compass, which also received seed investment from Peter Thiel’s investment company Thiel Capital (a bellwether of an entirely different sort), said that there was interest in its progress because many people believe there haven’t been significant advancements in treatment for depression in recent decades.

Ms. Eilian said that it is important to her that any psychedelics company in which Able has invested is willing to work within the regulatory structure in the United States. Still, the through line between its investments in Compass and Atai and the wellness companies it has long supported is that all of them purportedly correct for the inadequacies of the medical establishment.

This year, Able has publicly dedicated itself to narrowing what its partners call “the wellness gap.” That’s how they describe the distance between standard economic measures of prosperity and how rotten everyone feels all the time.

“There are definitely a lot of people who are not well and are desperate and they want to believe, and then there are unscrupulous people who will sell them any cure that they want,” Ms. Eilian said. “One hundred percent we need to be really aware of that. But I also don’t believe that we’re always going to be able to have large double-blind placebo studies to validate everything that we’re doing.”

She said that institutionally accepted studies had, for years, focused on men at the expense of women. Someone like herself, she said, “a mother of four who grew up in rural Vermont near a leaking thermometer factory,” was unlikely to be represented in major studies.

Wellness companies, including several of those in which Able has invested, have made claims about their health benefits that either cannot be independently substantiated or have not yet been. Asked whether Able had an alternate standard for the companies in which it invests, Ms. Eilian said the first priority was transparency.

“Goop, and Moon Juice as well, have gotten much better about saying, ‘Here’s what’s in here,’ or, ‘Here’s the research that we’re referring to, or, ‘Here’s where the research is lacking,’” she said.

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Investors are eyeing psychedelics as the next big trend in healthcare as medical-grade treatments inch toward FDA approval

Yeji Jesse Lee | January 28, 2020

• Business Insider's Jeremy Berke talked to leaders in the medical-psychedelics field about who was investing in their companies, testing procedures, and the similarities and differences between this industry and the cannabis sector. • The investor base for companies creating psychedelic drugs can be categorized into three groups, Florian Brand of ATAI Life Sciences said: the visionaries, the "momentum investors," and more recently, pharmaceutical and biotech investors. • Companies such as MindMed, Eleusis, and ATAI Life Sciences are hoping that medical psychedelics will be able to tackle big issues like the opioid epidemic, the vaping crisis, adult ADHD, and chronic inflammation. • Business Insider sat down for an exclusive interview last year with MindMed to talk about how the company raised millions in funding from big names, such as "Shark Tank" host Kevin O'Leary and Canopy Growth's Bruce Linton. Read the article here.

Investors may be eyeing psychedelics as the next big trend in healthcare.

That's according to leaders in the medical-psychedelics field. They say there's a serious growing interest from established backers who have traditionally stayed away from companies that deal with federally illegal substances.

Once that interest manifests into investment — and a few asset managers begin to put money into medical-psychedelic companies — Shlomi Raz, the founder and CEO of the medical-psychedelics company Eleusis, said on Friday at the Economics of Psychedelic Investing conference that he expected the rest to quickly follow.

"Once the lead steer moves into this space, you'll see the whole herd moving in," he said.

The Epidiolex of psychedelics

The barriers to entry for medical psychedelics are even higher than they are for cannabis, said JR Rahn, the founder of MindMed, a company that develops psychedelics-based medication. That's because medical-psychedelics companies are looking to have their products approved by the US Food and Drug Administration.

In MindMed's case, the company is pushing to get FDA approval for a compound called 18-MC, which would effectively remove the hallucinogenic properties from ibogaine, a West African psychedelic drug, while preserving its medical properties.

The compound must undergo a series of clinical trials before it can be approved by the FDA to address opioid use disorder.

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"It's a very different industry," Rahn said, adding that the clinical testing is strenuous. Beyond addressing the opioid crisis, Rahn said on Friday he would want to look into addressing the teen-vaping crisis as well.

Raz told Business Insider's Jeremy Berke at the conference that he and his company were inspired by the example of GW Pharmaceuticals and its development of Epidiolex.

"That's where we're coming from — to take a stigmatized drug and make it a valuable medicine, develop it just like any other life-science company," Raz said.

Eleusis has clinically tested the effects of low doses of LSD on inflammation associated with aging, which would have deep implications for Alzheimer's.

Treatment versus policy

Several cities have already decriminalized psychedelic mushrooms, and though the topic of adult use came up at the conference, the companies seemed more focused on treatment and testing rather than getting involved in policy changes.

Because psychedelics are such powerful compounds, Florian Brand, the cofounder and CEO of ATAI Life Sciences, a biotech company that develops psychedelic medicine for mental health purposes, said he was generally skeptical of legalization for adult use.

"We're focused on getting better treatment for patients, not so much what could be happening from a policy perspective in 12 years," Brand said.

But there seems to be a lot of interest in the psychedelics field from those coming from the cannabis industry, where there is a heavier focus on policy changes to allow for adult use.

Business Insider previously reported on Field Trip Ventures, a psychedelics-focused venture-capital firm founded by people from the cannabis sector.

"There's no shortage of investment interest in the psychedelic space right now," Ronan Levy, the cofounder of Field Trip Ventures, told Business Insider last year. "Almost everybody who's been participating in the cannabis industry is looking at it."

The kinds of investors

The investor base for companies creating psychedelic drugs, according to Brand, can generally be categorized into three groups for ATAI Life Sciences. There are the visionaries, those who "believe there is something there that deserves to be backed."

The second group is the "momentum investors," the group that is looking for the next big trend. And finally, there is now serious interest from more traditional biotech and pharmaceutical investors who were so far staying far away from the psychedelics field. Interest from the third group is very recent, Brand said, seriously picking up only within the last month.

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Raz said he put a lot of his own assets into establishing Eleusis, and other early investors in the company were either individual investors or family offices.

But Raz said he expected the opportunity for these kinds of backers — who are not traditional life-science investors — to play a crucial role in companies like his was closing very quickly as interest from more established financiers picks up.

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ATAI, DemeRx pursue 'neurochemical reset' for addiction in $22M JV

Amirah al Idrus | January 24, 2020

People seeking treatment to overcome opioid addiction are often stymied by the treatment itself. Many don’t have access to drugs like methadone or buprenorphine or can’t make it to a clinic every day for a long enough time for the treatment to succeed. ATAI Life Sciences and DemeRx are setting up a joint venture to develop a one-and-done treatment for opioid dependence that works by giving people a “neurochemical reset.”

ATAI is investing up to $22 million in the JV, which will develop the drug, ibogaine. Derived from a West African plant called iboga, ibogaine has previously been sold as a stimulant and antidepressant in France and has been studied in other countries as a treatment for addiction. Those studies, including a large one led by DemeRx CEO Deborah Mash, Ph.D., turned up "very stunning anecdotal data” for ibogaine. Now, ATAI and DemeRx will bring the drug into phase 2 trials to prove its benefits in a controlled clinical setting.

First up, the team needs to get regulatory approval to start a clinical trial.

“We want to move quickly to an efficacy study so we can demonstrate what hundreds and hundreds of patients already know,” Mash said.

It wouldn’t be a cure, Mash told FierceBiotech. But it would be a “powerful first step on the road to recovery.”

Mash, a longtime drug abuse researcher, ran into ibogaine in her work three times before it got her attention, she said. She traveled to Amsterdam to witness firsthand what the drug could do. She remembers a young musician who had been “banging back an awful lot of heroin.”

“It was an absolutely gentle detox with no withdrawals. I saw immediately the efficacy of this treatment, that a single dose was able to get people through withdrawal, to have this kind of ‘aha’ moment about their self-destructive behavior. To gain insights on what was driving them and what got them into this addiction habit to begin with,” she said.

Mash went on to lead an open-label study testing ibogaine in 102 patients who were dependent on opioids and 89 who were dependent on cocaine. She found that one low, oral dose of the drug reduced opioid withdrawal scores 36 hours after treatment. It also tamped down on the severity of cravings and depression in both patient groups.

Ibogaine affects multiple neurotransmitter systems, including serotonin, opioid and NMDA receptors. Its exact mechanism is unclear, but it causes a dreamlike state in patients that plays a role in “interrupting addiction.” The idea is that this

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“neurochemical reset” gives patients a window during which they have no cravings or desire to use opioids and so have a better chance at recovery.

“It makes more patients treatment ready, so they will be ready to succeed with whatever therapy they choose—rehabilitative therapy, inpatient, outpatient, case management, 12-step groups, or other adjunct therapies,” Mash said.

The $22 million from ATAI should get ibogaine through its “critical milestones” such as a double-blind, placebo-controlled study and understanding what dosing will ultimately look like, said ATAI Chief Scientific Officer Srinivas Rao, M.D., Ph.D. The JV will also work on a treatment protocol that includes screening guidelines for patients, as ibogaine has been linked to heart side effects and may be unsuitable for people with cardiovascular issues.

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A Hallucinogenic Root Is Pitched to Davos Set as Treatment for Opioid Addiction

Eyk Henning | January 22, 2020

The World Economic Forum’s billionaire audience in Davos took a break from the problem of climate change to listen to the story of a company developing a hallucinogenic drug.

The fascination lay not in recreation, but for its potential as a treatment for addiction to opioids that have killed hundreds of thousands in the U.S. Modeled on an extract from the root of an African shrub and already used medically in a few countries, the experimental therapy is to soon be tested by Atai Life Sciences AG, a company studying other natural products, such as magic mushrooms to treat depression.

Atai, backed by billionaire investor Peter Thiel, and partner DemeRx Inc. are preparing for a mid-stage trial of a synthetic form of the substance, called ibogaine, for treatment of drug addiction. Interest in such therapies is high as an opioid epidemic rages in the U.S., the German firm’s founder Christian Angermayer said in the Swiss ski resort.

“In some circles, psychedelics are still associated with escape from the real world and irresponsible extravagance,” Thiel said in an email. “With FDA-controlled studies, we will come to see that their most powerful use brings people to mental health and sober sanity in a medical setting.”

Researchers and clinicians are searching for substance abuse treatments that aren’t addictive themselves. Unlike methadone, a substitute and therefore also an opioid, ibogaine is often referred to as addiction interrupter that appears to reset the brain chemistry involved in dependency.

Use of ibogaine traces back to an ancient ceremony marking young males’ entry to adulthood at the West African Bwiti tribe. Between 1930 and the 1960s, the compound was marketed as Lambarene in France, purporting efficacy as a stimulant.

The substance has already been used in some drug rehabilitation clinics to treat severe addiction. Studies over the past decade indicate that it can reduce the severity of opioid withdrawal scores, in some cases more efficiently than methadone.

Patients have described their experience as a sobering trip that visualizes the negative consequences of drug abuse, according to Deborah Mash, founder of DemeRx. The procedure requires 24 hours of clinical monitoring, she said, as ibogaine has been linked to heart side effects.

Since a generation of supposedly safer painkillers, introduced two decades ago, triggered an opioid epidemic, overdoses have killed about 400,000 Americans -- more deaths than the country’s military suffered in World War II.

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ATAI backs Neuronasal's through-the-nose concussion treatment

Amirah al Idrus | January 6, 2020

There is no medicine for people who suffer concussions. Instead, they are often told to avoid activities such as reading or watching TV, so their brains can rest and recover. Biotech builder ATAI Life Sciences and Neuronasal are looking to change that.

Pennsylvania-based Neuronasal is working on a treatment that can be given after a patient suffers brain trauma to stop a chain of processes, including inflammation and bleeding in the brain, that leads to concussion symptoms. In addition to short-term symptoms like headache, nausea and anxiety, concussions can also cause long-term effects, such as cognitive impairment and depression. ATAI is investing an undisclosed amount into Neuronasal to bankroll its work.

Neuronasal’s treatment is based on N-acetylcysteine, or NAC, a precursor of the amino acid cysteine that has been used for decades to treat other ailments. The U.S. Army has tested it in soldiers injured by explosions, finding in a 2013 study that soldiers who received NAC within 24 hours of their injury had an 86% chance of clearing their concussion symptoms compared to 42% of those who took placebo. But the soldiers had to take very high doses of the NAC pills to get the drug across the blood-brain barrier.

[This is] more than you can use in the general population, because you run the risk of having unacceptable side effects, like dizziness and nausea—the last thing you’d want in a cohort of concussion patients,” Neuronasal CEO Thomas Bradshaw told FierceBiotech.

Giving NAC intravenously rather than orally allows for “slightly lower doses,” the company says, but requires patients to stay in the hospital for several days. Neuronasal’s technology solves both problems by delivering drugs to the brain via—you guessed it—the nose. ATAI and Neuronasal hope to show that NAC can treat concussion symptoms with a “multilevel approach.”

“When you have a mild traumatic brain injury, you’ve got a bunch of things going on. The first event is a physical insult to the brain. If nothing else happened, it would probably result in relatively mild damage,” Bradshaw said. “But what is caused by [the brain] banging around is a biochemical cascade. Glutathione levels go down and you get microbleeds and swelling … when you have microbleeds, you’re having a reaction to that as well."

A derivative of cysteine, NAC is involved in synthesizing glutathione, an antioxidant that plays a role in preventing damage to cells after an injury. In concussions, increasing glutathione levels could protect brain cells from reactive oxygen species, which are oxygen-containing molecules that react easily with other molecules and can damage DNA, RNA and proteins.

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Neuronasal is testing the intranasal delivery of NAC in a pilot study slated to end in the first quarter. Then, it will move the treatment into a phase 1 study, which will wrap in 2021. The goal is to show that intranasal NAC can boost levels of glutathione in the brain. The study will also look at how glutathione increases in different parts of the brain such as the regions responsible for balance or for processing visual information.

“There is a noninvasive, MRI-based way to monitor an increase in brain glutathione. If we can increase brain glutathione from the introduction of intranasal NAC, then that’s a very positive way for us to go into phase 1 and phase 2 proof of concept,” Bradshaw said.

If all goes to plan, it could become a treatment people can take soon after a suspected concussion: “It’s a safe drug. If we’re able to show efficacy, we won’t have to worry about giving it to people who may or may not have had a concussion to stop potential secondary damage,” Bradshaw said.

What’s more, the intranasal approach might lead to the resurrection of NAC in other diseases.

“NAC has been tried for a couple other indications and shown no efficacy. High doses of oral NAC were tried in a trial for Parkinson’s and they showed no increase in brain glutathione,” Bradshaw said. It could also be useful in intracranial hemorrhage, or bleeding inside the skull, including certain types of strokes.

Neuronasal is just the latest project for mental health-focused ATAI. CEO Florian Brand founded the Berlin-based company alongside Christian Angermayer and Lars Wilde to "spearhead the renaissance of psychedelic medicine and to incubate innovative therapeutic approaches with the ultimate goal of curing mental health disorders," Brand said via email.

"To date, ATAI has raised more than $90 million and our $43 million series B funding round in March 2019 was the largest- ever private financing round for a psychedelic medicine biopharma company," he said.

ATAI has backed companies like Compass Pathways, which is developing the psychedelic psilocybin, and Perception Neuroscience, which is working on a ketamine-like drug, both for the treatment of depression. It has also set up a joint venture with Cyclica dubbed Entheogenix Biosciences that's using artificial intelligence to design new medicines based on psychedelics.

"EntheogeniX will expand access to emerging mental health therapeutics by first creating shorter-acting psychedelics (helping therapists treat more people) and then potentially removing hallucinogenic effects entirely (which could allow those with otherwise disqualifying contraindications to access the benefits of psychoactive compounds)," said ATAI Chief Scientific Officer Srinivas Rao, M.D., Ph.D., in an email.

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The Keys To Understanding Psilocybin's Medical Value, Market Potential

Natan Ponieman | December 4, 2019

With a growing public acceptance of cannabis in society, there's a natural instinct to wonder about the possible health benefits and market potential of other still-illegal substances.

“To me, all the psychedelic stuff, it's just prohibition 2.0,” Bruce Linton, cannabis entrepreneur and former CEO of Canopy Growth Corp CGC 0.08%, said in a recent conversation with Benzinga.

Linton recently invested in and joined the board of Mind Medicine Inc., a company doing FDA-approved trials on LSD and MC-18, a psychedelic molecule derived from ibogaine, to treat opioid addiction.

Cannabis might be a gateway drug after all, but not in the way it was presented during the war on drugs. The gateway might actually lead to the treatment of illnesses with naturally occurring compounds, and ultimately to commercial success.

Psilocybin's Real Medical Value

Over 200 species of mushrooms have been identified that contain psilocybin.

Although “magic mushrooms” have found traditional use by humankind for thousands of years, dating back as far as 9,000 B.C in North Africa and the Iberian Peninsula, they entered western society in the 1950 at the hand of scholars looking to research their therapeutic applications in psychiatry.

Swiss chemist Albert Hofmann, the “inventor” of LSD, first isolated the active molecule psilocybin from its natural state in 1957 while working at Sandoz Laboratories.

The first half of the 1960s saw a number of clinical studies, famously led by Timothy Leary at Harvard University, that began to explore the compound’s application in psychiatric treatment.

The research was halted in 1970 with the scheduling of the drug by the FDA, and formal research was not resumed until the late 1990s.

With researchers closing in on the third decade of the "second wave" of psilocybin research, a consensus on the strong clinical potential of the compound is building among experts in psychiatry and psychopharmacology.

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In the past decade, various universities and research institutes have published landmark studies depicting successful applications of psilocybin in the treatment of anxiety disorders such as OCD, addiction to alcohol, tobacco and opioids, treatment-resistant depression, PTSD and chronic migraines.

Psilocybin's Legal Status

Clinical research didn’t just sprout an understanding of psilocybin’s treatment benefits.

Last year, researchers at John Hopkins University released a study analyzing the compound’s abuse potential, concluding that it should be rescheduled to Schedule IV, where most prescription benzodiazepines can be found.

Psilocybin is a Schedule I narcotic, meaning the DEA considers it a drug with high abuse potential and no healing characteristics — the same category as heroin.

Despite its federal scheduling, some jurisdictions have started to decriminalize psilocybin and psilocybin mushrooms.

In May, Denver voted to make possession of mushrooms a low law enforcement priority and forbid the city from spending public resources on possession charges.

One month later, Oakland voted to end criminal penalties for the use and possession of psychoactive plants and fungi on the basis that the substances have valuable traditional and religious uses.

Chicago could soon be on track to becomethe next municipality to decriminalize psilocybin use.

Oregon could become the first state to end mushroom criminalization next year if the psi-2020 ballot passes. In June, U.S. Rep. Alexandria Ocasio-Cortez, a New York Democrat, introduced a House amendment that would have made it easier for research institutions to study the compound; the measure was rejected in a House vote.

Why Psilocybin And Not Other Psychedelics Like LSD, Mescaline?

To better understand psilocybin and its potential as an industry, Benzinga spoke with Matt Johnson. Ph.D, a professor and researcher at Johns Hopkins University who heads the university’s Center on Psychedelic and Consciousness Research. Johnson has been leading psychedelics research in psychiatry for more than 15 years and has collaborated in multiple clinical trials that served as the basis for the renaissance of psychedelics as a valid treatment option, along with Dr. Roland Griffiths and other experts.

“I don't really see psilocybin as special other than it's the first among equals,” Johnson said when asked if psilocybin has a significant advantage in psychiatric treatment over other psychedelics like LSD. While there are hundreds of known psychedelic substances, Johnson said only a handful have proven safe in humans.

When researchers resumed psychedelics research in the 1990s, they faced a choice: either spend millions of dollars testing animal and human toxicology work for new substances, or choose among the short list of compounds that had been proven safe in the 1950s and 1960s, which includes LSD, mescaline, DMT and psilocybin.

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Psilocybin was chosen because of its short duration effect — 2-4 hours versus the 12 average hours of an LSD trip — and the fact that it hadn’t been stigmatized as much as some of the other compounds popularized in the 1960s counterculture.

Although each psychedelic is expected to offer slightly different treatment, Johnson said he believes that they will form a class of compounds in the same way that benzodiazepines do today.

"That's where most of the work lies ahead, but it's going to be like every other drug class. They're all more similar than different. Maybe this one works a little better for sleep. And this one works a little better for anxiety, even if there's an overlap," he said.

"We really need to do head-to-head comparisons of these drugs. The last head-to-head research was mainly back in the early '60s."

Natural Mushrooms Or Synthesized Pharmaceuticals?

During the first period of psilocybin research, Swiss chemist Albert Hoffmann and psychedelics researcher R. Gordon Wasson visited María Sabina, a Mazatec curandera from Mexico who became famous in North America for leading mushroom-induced trips for hippie tourists.

The duo offered her and her family a pill of the freshly synthesized compound. The shaman is documented saying that the pills “really contained the spirit of the mushrooms.”

If psilocybin follows the path of cannabis in any way, the industry will invariably hit a point where consumers will wonder if a synthesized version of the compound is better than consuming the whole mushroom.

Srinivas Rao is chief scientific officer at ATAI Life Sciences, a biotech firm that is working on developing psilocybin therapy for patients with treatment-resistant depression through its portfolio company, Compass. A big difference exists between mushrooms and purified psilocybin as an approved drug, Rao said.

“The former is a natural product that contains many substances in varying quantities. The latter is a pharmaceutical product produced under exacting methods to ensure purity, stability and potency.”

In the context of achieving FDA approval, a synthesized version of the drug is far more likely to succeed, he said.

Big Pharma is already interested, said Johns Hopkins' Johnson.

The drug “is certainly more in the realm of standard FDA drug development which means pure compounds and well characterized chemical entities,” he said.

Aside from the regulatory framework, Johnson said a synthesized version of psilocybin could offer greater potential in psychiatric treatment.

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Plant- or fungus-based medicine has potential, but it's a far more difficult road in terms of developing a product for the medical industry because of its inconsistency or unpredictability, he said, giving a simple analogy to highlight the difference between a substance's ultimate source and its medicinal form.

“Aspirin ultimately comes from white willow bark, but you don't typically take capsules of white willow bark extract. You typically take aspirin: salicylic acid.”

One-Trip Sessions Vs. Microdosing

Microdosing psychedelics has become a viral phenomenon in recent years and received considerable publicity. Most of the evidence found online is purely anecdotal and self-reported, which leads experts to believe that the potential benefits of sub-psychoactive doses of psilocybin and other substances could be a placebo effect. Johnson, who delivers high doses of psilocybin to his patients at medical trials, said microdosing still needs more research in order to be accepted as a potential treatment.

“Very little is known about microdosing [and] we will be starting a study soon," he said. "Two laboratory studies that have conducted double-blind studies on microdosing have not shown benefits so far.”

Concerns exist within the medical community that microdosing substances like psilocybin and LSD on a daily basis could bring heart valve problems in the medium- to long-term, Johnson said.

Taking these facts into consideration, it’s likely the initial expansion of a possible psilocybin industry will be in high-dosage applications until proper research of microdosing has been conducted. Leaving The Realm Of 'The Last Resort'

Today, the few patients in psilocybin treatment in a legal medical context are those who have tried everything else.

Although both Johnson and Rao said the compound could eventually be part of a first-line treatment, more research is needed to understand its full potential.

"Right now, the infrastructure to use such therapies as a first-line treatment really doesn’t exist. In short, this is conceivable, but we will first need to build an ecosystem around psilocybin-assisted therapy that includes clinics, therapist training, and reimbursement strategies," Rao said.

The Birth Of A Service Industry

Psilocybin and other psychedelics will reach their true potential in a strict medical environment, said ATAI Life Sciences CEO Florian Brand.

“Unlike cannabis, psychedelics are a service, not a product. Without appropriate preparation, attention to medical well- being and a systematic approach to integration, there is great potential for harm to those with mental illness.”

Psychedelics offer the possibility of a different treatment model than the one proposed by today’s psychiatric paradigm.

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Patients undergoing psychedelic treatment have individual sessions with the objective of having a meaningful experience that will get to the root of the problem, instead of taking one pill a day to combat symptoms.

Although this kind of treatment dynamic is uncommon in today’s psychiatric landscape, it is normal in mainstream medicine: surgical interventions, for instance, fall into this category.

As psychedelics research moves forward, a whole new industry could emerge parallel to the development of psychedelic products: treatment centers or dedicated facilities.

Treatment guides who accompany a patient through the experience will be needed, and they in turn will need to be educated and credentialed.

Is There A Recreational Market For Psilocybin?

Johns Hopkins' Johnson said he doesn't believe a recreational market for psilocybin will arise in the way one has for recreational cannabis. Psilocybin is a strong substance that should not be consumed without the supervision of a qualified physician, he said.

ATAI's Brand agrees.

“Given the potency of the substance in question, self-medication bears significant risks, as individual responses and experiences are varied and complex," he said, particularly for those without mental health issues.

People should not go to jail for using these substances, Johnson said, but as a culture, "we’ll need significant time and robust education to truly understand the risks of these substances — of which there are many.” Madison Margolin, the managing editor and co-founder of the psychedelics-devoted magazine Double Blind, holds a different opinion.

“The beauty of psychedelics as medicine is that you don't necessarily need to have an ailment in order to benefit from them. Psychedelics inspire us to re-evaluate what it means to be well — individually and collectively as a society — and to that end, there's an argument to be made about psychedelics for the betterment of well people, as much as they are a tool for healing.”

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ATAI Life Sciences, Cyclica team up for mental health JV

Ben Adams | November 14, 2020

Biotech ATAI Life Sciences has partnered with artificial intelligence drug discovery specialist Cyclica to form a new joint venture aimed at battling mental health.

The two companies will use Cyclica’s AI approach and ATAI’s biotech and funding know-how to design and synthesize new compounds from psychoactive seed small molecule compounds (SMCs) to find the next generation of drugs to augment mental health care and combat diseases such as depression, bipolar disorder and schizophrenia.

To do that, the pair have created Entheogenix Biosciences, which will be based in Delaware, to discover and work on both traditional and nontraditional drug approaches—such as tapping into psychedelics—to create better therapies for an area pretty much abandoned by Big Pharma, alongside much of its neuroscience work, in favor of oncology and rare diseases.

Current drugs for the more severe types of depression and schizophrenia have been around for decades, but there has been relatively little new innovation, despite a growing burden of mental health issues.

These older drugs typically rely on single-targeted drug interventions that, ATAI says, often fall short. Patients are then required to take multiple medications, leading to drug cocktails that can up the risks of side effects or lower efficacy over administration issues. Combining with Cyclica could help find new and better ways.

Cyclica’s platforms, Ligand Design and Ligand Express, work together to allow researchers to visualize the complete polypharmacological profile of a compound and specially tailor drugs to target specific disease pathways related to mental health, all while mitigating off-target interactions.

Entheogenix will specifically use seed SMCs that range from existing synthetic compounds to classic psychedelics (e.g. psilocybin and mescaline) to identify and synthesize new chemical entities that have enhanced effectiveness in both in vitro and in vivo models for mental health disorders.

This could, the companies say, lead to medications “that offer the putative benefits of psilocybin for depression, but with enhanced properties such as faster drug release and absorption or an absence of the hallucinogenic effects common to psychedelics.”

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Speaking to FierceBiotech, ATAI Chief Scientific Officer Srinivas Rao, M.D., Ph.D., (who will also run the JV as its chief) was keen to stress that while this JV is working on psychedelics, they don’t want to be seen solely as a ‘psychedelic company’, but rather as one focused on mental health using the most efficacious therapies possible. Rao said the JV came together in a remarkably modern way: A fortuitous travel plan and a “back and forth” conversation over WhatsApp that led to its name.

“So, I was at an AI drug discovery conference back in May and Cyclica’s CEO [Naheed Kurji] was there; we talked a little at the conference, but you’re pretty busy at these things so not much. But it turned out our flights were leaving at the same time, so we decided to take the same car to the airport and it was really remarkable: We had a lot of interests in common.

“I told him what our interests were and talked about psychedelic compounds, and it turns out Cyclica was also interested in this area, and that they had been playing with some of these compounds already. Then it just became an obvious marriage at that point.”

Rao says that the good thing about the project is that it can get into clinical testing “relatively quickly” as it’s only looking at single doses: “So it’s a single ascending dose trial, then it’s a phase 2a that’s a single dose, so that’s really nice compared to what I’ve had to deal with in development terms in the past,” he said.

Specifics on targets aren’t fully out there yet, but treatment-resistant depression is one “obvious target,” Rao says. “You can take it in different directions from there, like substance abuse disorders; and outside of psychedelics you have a lot of options, so you can also think about bipolar depression and other similar conditions.”

The company will be funded via its parents and will not in the near future seek any kind financial offering, although collabs with companies further down the line, especially when it comes to potential commercialization, are in the cards.

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The Power of Combining 5G and AI

James Rundle | November 8, 2020

(…)

In hospitals

The world of medicine is immersed in emerging technologies. The possibility of remote surgery becomes far more achievable, for instance, as 5G gives doctors more reliable and robust connection speeds to control machines from afar. Pharmaceutical companies have released smart pills containing miniaturized computer chips to track patient health, with the data transmitted back to doctors by 5G.

Meanwhile, all of these new technologies could make a big impact on the process of drug development itself.

Creating drugs to treat mental-health disorders can take up to seven years, says Naheed Kurji, chief executive of Toronto- based biotechnology firm Cyclica Inc. Molecules in drugs can interact with the body’s proteins in any number of ways, which can, in turn, cause different reactions further on. Now artificial intelligence can handle the level of computation required to model all those interactions.

Cyclica is teaming up with Berlin-based biotechnology company ATAI Life Sciences AG on a joint venture, Entheogenix Biosciences Inc., to create an AI-powered laboratory that will seek to develop treatments for mental-health disorders that are derived from psychoactive substances, including psilocybin, commonly known as magic mushrooms.

The company is making “the whole process of developing drugs that cost $1.5 billion, and take 10 to 12 years, shorter and less costly. That’s the ambition,” says Florian Brand, ATAI’s chief executive.

(…)

Read full: https://www.wsj.com/articles/the-power-of-combining-5g-and-ai-11573234753

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Can a Trip-Free Psychedelic Still Help People With Depression?

Shayla Love | November 7, 2020

(…)

A more customizable psychedelic therapy like that is appealing to many—both patients who might not want the trip, as well as private companies and governmental groups tinkering with these drugs to make better versions of them, or using psychedelics' interactions with the brain as a launch point to make something entirely new.

One such effort is a new AI-enabled psychedelics lab called Entheogenix Biosciences, launched by two companies, ATAI Life Sciences and Cyclica. Srini Rao, the Chief Scientific Officer of ATAI and the CEO of Entheogenix, agreed that there are intersecting, and sometimes competing, theories of how psychedelics help people—experientially or biologically. Depending on which holds true, it will likely influence the ways psychedelic drugs are brought to market.

Entheogenix will be studying several psychedelics—ketamine and DMT as well as psilocybin—and evaluate which parts of their chemical structures are associated with mental health benefits. “Then we can start taking out those pieces associated with hallucinations, for example,” Rao said. “We can design new compounds that presumably don't hit those pieces but maybe maintain some of the other pieces of pharmacology that are critical, particularly those around neuroplasticity.”

They're not only seeking out non-hallucinogenic psychedelics (after all, the hallucination bit might be crucial) but also analyzing different chemical versions of psilocybin that could "improve" on the original model. These versions might retain the psychedelic element, but at much shorter durations. Instead of the normal six to eight hours, it could be condensed to 30 to 45 minutes. They could also potentially fix other issues with the drug, like one with another serotonin receptor that is associated with damage to the heart.

"If you’re going to design new molecules, you might as well make those as pristine as possible,” Rao said.

It's an approach that The Defense Advanced Research Projects Agency (DARPA), the U.S. military's research branch, will be attempting their own version of, too. In September, DARPA announced the launch of the Focused Pharma program which will develop new "neuropsychiatric" drugs loosely inspired by the results from various clinical trials of psychedelics. The goal of DARPA's program is to develop treatment for service members and veterans with PTSD, depression, and substance abuse.

Read full: https://www.vice.com/en_us/article/pa748k/psilocybin-for-depression-and-the-world-of-non-hallucinogenic- psychedelics

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Investors hope psychedelics are the new cannabis. Are they high?

Multiple authors | October 19, 2019

Christian Angermayer has never drunk alcohol nor smoked a cigarette. He is, however, a fan of ketamine. In January atai Life Sciences, the German biotech company he founded last year, acquired a majority stake in Perception Neuroscience, a biopharmaceutical firm from New York which is developing a medication for pyschiatric conditions like depression from the drug, which is illegal in parts of the world (though not in America). Along with Peter Thiel, a veteran Silicon Valley investor known for headline-grabbing bets, atai has also backed compass Pathways, a startup in London aiming to be the first legal provider of psilocybin, which gives mushrooms their magic.

Messrs Angermayer and Thiel are not alone in putting money into the medical application of psychedelics. A clutch of investors see these drugs going the way of cannabis, whose creeping decriminalisation has spurred commercial interest in the weed’s medical uses. In particular, backers think, psychedelic drugs could be used to treat mental-health disorders like depression, anxiety and addiction. In April Imperial College London, inaugurated the first research centre dedicated to psychedelics research. Last month Johns Hopkins University in Baltimore launched America’s first such scientific outfit.

The market for antidepressants is dispiritingly large. Over 300m people worldwide suffer from depression. A report last year by the Lancet Commission, a body of experts, estimated that mental-health disorders could cost the global economy $16trn by 2030. Sales of antidepressants were $14bn in 2017 and analysts expect them to grow to $16bn-19bn by the middle of the next decade.

In October last year America’s Food and Drug Administration granted compass “breakthrough therapy” designation, which fast-tracks the approval process. The company is using the $38m it has raised to run the largest clinical study of psilocybin ever. Ekaterina Malievskaia, its co-founder, hopes that the therapy could go on sale within five years “if everything works out”, including the science. Patients would receive carefully controlled doses in one-off, therapist-run sessions. These may last all day and cost $1,000 a pop. Field Trip Ventures, a Canadian startup, plans to open speciality clinics where they could be administered (and clinical trials conducted).

Sceptics doubt Compass can get its drug to market by 2024—if at all. Worries about psychedelics’ side-effects, which can include drug-induced psychosis, abound. And it is unclear their medical use can ever be more than a niche. Finicky treatments make psychedelics trickier to scale than cannabis, which can be self-administered in spliffs, cakes and other forms. Field Trip Ventures’ co-founder, Ronan Levy, concedes as much. Big Pharma has steered clear, preferring pills which can be manufactured cheaply once approved and need to be taken regularly rather than just once, providing steady revenue streams. That left an opening for startups like Compass. Time will tell if ushering people through the doors of perception is a hard- headed business proposition—or a trippy one.

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ATAI Life Sciences Is Assembling a Mental-Health Drug Platform

Heather Mack | September 19, 2019

A startup backed by $80 million from investors is striking deals with a range of drug companies in its bid to lead the next wave of mental-health treatments.

Munich-based Atai Life Sciences AG has formed and financed several companies creating new drugs from unusual and controversial substances including psilocybin, found in “magic mushrooms,” and ketamine, which is nicknamed “Special K” and sometimes used illicitly. But the company intends to play a much larger part in a recent flurry of activity in drug-development innovation in mental health following decades of inactivity.

Founded in 2017, Atai is riding a wave of renewed interest from researchers, investors and regulatory bodies in developing and commercializing new therapies from substances that might be controversial, overlooked or underused, such as the use of ketamine to treat depression, and MDMA, commonly known as ecstasy, to treat post-traumatic stress disorder.

Last October, the U.S.Food and Drug Administration gave one of Atai’s portfolio companies, Compass Pathways Inc., breakthrough therapy designation for its psilocybin treatment for depression. The agency also approved two new depression drugs—one based on ketamine—in March. Those drugs are the first new depression treatments approved in decades.

Atai’s long-term goal is to assemble a broader drug-development platform. This strategy informed its decision to form a new partnership with an antianxiety drug developer called Gaba Therapeutics.

Similar to the other startups in Atai’s portfolio, which includes psilocybin-focused Compass Pathways and ketamine-focused Perception Neuroscience, Gaba has tinkered with an existing compound and created a new, proprietary compound that it says outperforms available medications for psychiatric disorders like anxiety and depression. Gaba is working with Etifoxine, a drug that was first approved in France nearly 40 years ago but was never offered in the U.S.

Atai founder Christian Angermayer said his company’s approach is similar to that of Privateer Holdings, a cannabis-focused private-equity and holding company that is backed by Peter Thiel, who has also invested in Atai’s portfolio company Compass Pathways.

Atai generally makes investments with the intention of taking a majority stake. As a result, the company prefers to invest alongside individuals and small firms, including Subversive Capital and Able Partners, rather than veteran life-science investors with big funds that might want larger stakes, Mr. Angermayer said.

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Gaba Chief Executive Ian Massey said the partnership with Atai will allow the company to get to the next phase of clinical trials. Looking forward, Mr. Massey said, Gaba hopes to expand beyond anxiety treatment, and Atai’s platform could provide cross-pollination of ideas and resources with other companies working on conditions that affect the central nervous system.

Gaba, based in Newport Beach, Calif., is now one of five companies on Atai’s platform—built up through a mix of investments, acquisitions and in-house company creation. Atai aims to take majority ownership of as many novel mental-health therapies as possible, Mr. Angermayer said.

“We think there is a tremendous value in a platform model that shares resources, because this is a new market,” Atai Chief Executive Florian Brand said. “When we are developing a new class of therapies, we don’t want to have people working in silos. We need to share the knowledge that is crucial to achieve economies of scale.”

Atai plans to invest up to $15.5 million into Gaba, and has established a pathway to eventually own 51% of the company, Mr. Brand said. Atai declined to say how much it owns now.

Mr. Angermayer said Atai is considering an initial public offering in 2020.

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The psychedelics evangelist: A German financier wants to turn magic mushrooms into modern medicine

Meghana Keshavan | July 1, 2019

Christian Angermayer is an unlikely proselyte of psychedelia: The German financier didn’t drink so much as a sip of beer for the first three decades of his life.

But five years ago, after careful consideration (and the encouragement of a personal physician), Angermayer boarded a yacht with a handful of his closest friends. They sailed into the crystalline, tropical waters of a jurisdiction in which such substances are legal (he is very emphatic on this point), and had his very first psychedelic trip. His entire worldview was changed.

“It was the single most meaningful thing I’ve ever done or experienced in my life,” said Angermayer, 40. “Nothing has ever come close to it.”

The first thing Angermayer did after the experience was call his parents and tell them, with a newfound conviction, that he loved them. Then, being a consummate entrepreneur, he quickly identified a business opportunity: He would commercialize psychedelics.

Today, with a net worth of roughly $400 million accrued through various enterprises, Angermayer is one of the driving forces behind the movement to turn long-shunned psychoactive substances, like the psilocybin derived from so-called magic mushrooms, into approved medications for depression and other mental illnesses. Though he still resolutely won’t touch even a drop of alcohol, he has banded together a team of like-minded entrepreneurs — including Silicon Valley billionaire Peter Thiel — to invest in a handful of startups focused on developing psychedelics.

Perhaps the most closely watched is Compass Pathways, which has patented a method to develop psilocybin in a laboratory, so it doesn’t need to be extracted from mushrooms. The company has quietly gobbled up intellectual property related to psychedelic manufacturing. And, importantly, it has won Food and Drug Administration approval to run clinical trials testing psilocybin in patients with treatment-resistant depression.

In May, at the Milken Institute Global Conference in Los Angeles, Angermayer stood before an audience of policy wonks, industry leaders, Hollywood types, and the global financial elite to argue that, beyond its therapeutic potential, psilocybin is also poised to be a moneymaker.

Depression alone affects some 300 million people around the globe.

“Even if it takes just a single dose of psilocybin to treat depression — and I’d be very, very happy if that’s the case — the medical unmet need is huge,” Angermayer said. “The market is growing, for better or for worse.”

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Not everyone is convinced. There are ample scientific questions, to say nothing of the regulatory hurdles involved in any drug approval. There are also competing startups developing alternative therapies that could prove more effective or safer or simply easier to administer.

But Angermayer’s associates warn against underestimating him, even if he sometimes comes off as simply an “eager puppy,” as he himself puts it.

“His excitability is the thing that allows him to do his due diligence, and understand how various sectors work very quickly,” said Dr. Jason Camm, the chief medical officer of Thiel Capital Management. “He’s very authentic and very genuine… and very different from your standard institutional investor.”

Once considered a relic of 1960s counterculture, drugs like psilocybin, LSD, peyote, and even more esoteric hallucinogens like ayahuasca and ibogaine are experiencing a renaissance, both in pop culture and in the lab. They have been helped along the way by the steady emergence of careful, peer-reviewed research from respected institutions like Johns Hopkins University and New York University that have validated the therapeutic potential of psychedelic drugs.

Scientists have found that psychedelics could be particularly potent for conditions like treatment-resistant depression, post- traumatic stress disorder, and obsessive-compulsive disorder. In 2016, a landmark study from Johns Hopkins found that psilocybin helped patients with terminal cancer manage their depression and anxiety, and eased the psychological stress associated with those conditions. It also helped some of them make peace with their diagnoses; of roughly 50 patients, two out of three ranked their psychedelic trip as one of the five most meaningful experiences of their lives.

Other studies, however, have raised bigger questions about whether some claims surrounding psychedelics are more hopeful than truthful. While proponents, for instance, have argued that psilocybin helps enhance perception, a study last year in the Netherlands found that microdoses of the substance had no noticeable effect on certain forms of intelligence like problem- solving and abstract reasoning. It did, however, seem to improve two forms of thinking that underlie creativity.

Because psilocybin remains illegal in the U.S., research around it is still limited. In early June, Rep. Alexandria Ocasio-Cortez, the Democratic congresswoman from New York, introduced legislation that would have made it easier for scientists to obtain psychedelic substances for research. The amendment, which Ocasio-Cortez introduced to encourage research into the potential for the drugs to help veterans struggling with post-traumatic stress disorder and other mental illnesses, was rejected by the House.

But it might only be the start of a political push to accelerate access to psychedelics in U.S. labs. “These drugs show extreme promise in treating PTSD + more,” Ocasio-Cortez said on Twitter. “Let’s keep at it.”

Compass Pathways’s clinical trial protocol requires that psilocybin be administered in the presence of a psychotherapist trained to guide patients through the experience. Patients are led to a serene, spa-like environment, given the drug, and for several hours are accompanied by a professional who can help them face past traumas or personal insights gleaned from the experience. The therapist can also steer them away from the notorious “bad trips” sometimes associated with magic mushrooms.

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Scientists still don’t fully understand how psychedelics work on the brain. But, despite their differing chemical structures, most seem to work by binding to receptors for the neurotransmitter serotonin.

Brain imaging studies indicate that psychedelics lift the neurochemical dampers typically in place in our brains that allow us to maintain a certain level of control. With the brakes off, so to speak, the user might have an expanded sense of perception. The drugs also help connect neuronal networks, leading to a kaleidoscope of complex emotions, a higher state of consciousness, and deeper observations about the nature of reality and of the self.

Not all hallucinogens have the same effects on the brain. And not all are seen as having therapeutic potential. Developing medications that are enhanced versions of, say, LSD, or a compound that combines the qualities of several psychoactive drugs, would be quite time-consuming and costly.

But a handful of drugs that are considered “classic” psychedelics — lysergic acid, which is derived from the ergot fungus; dimethyltriptamine, the active ingredient in ayahuasca; psilocybin, found in magic mushrooms; and mescaline, found in the peyote cactus — are seen as possible treatments.

With those, “there’s no dose with observable organ damage or neurotoxicity. That’s pretty freakish,” said Matthew Johnson, an associate professor of psychiatry and behavioral sciences at Johns Hopkins University who studies psychedelics. “You’d be hard-pressed to find anything sold over-the-counter that you could say this about — including caffeine and aspirin.”

There are caveats, of course: Drugs like psilocybin have the potential to exacerbate psychiatric illnesses like schizophrenia in a small percentage of the population. The belief, according to Johnson, is that this subset of individuals would likely have developed some form of psychosis even had they not taken a drug like LSD or psilocybin. Psychedelics may just speed up the inevitable. The research is still early in terms of figuring out who would be a poor candidate for psychedelic therapy.

Angermayer is adamant that psychedelic drugs will never be for everyone. And, unlike, say, marijuana or alcohol, they should not be taken casually or for recreational use, in his view. But in some cases, he believes, psychedelic drugs can help certain individuals gain perspective and a kind of wholeness.

He also knows that his beliefs are just beliefs. And what he and Compass need now is science.

“We have a lot of anecdotal evidence, and a lot of basic research on psychedelics — but unfortunately, these various drugs haven’t been brought through the FDA or the [European Medical Agency] approval process,” Angermayer said. “So I was like, ‘OK, let’s do this.’”

Angermayer, whose unlined face and boyish good looks belie his 40 years, is fervent about guarding the sanctity of his body and his brain. But teetotalism made him a “weird kid” in the small Bavarian town where he grew up.

“I was super worried that my brain cells would die,” he said, grinning. “So I didn’t drink, never smoked a joint or a cigarette, nothing.”

Instead, he studied. The only child of a mild-mannered engineer and secretary, he went to University of Bayreuth in Germany on a full scholarship. He pursued economics as part of a multidisciplinary education that led him to work with two

75 biotechnology professors: Stefan Limmer and Roland Kreutzer. They were working on Nobel Prize-winning RNA interference technology, and Angermayer quickly saw commercial promise.

He helped his professors form a company, Ribopharma, with a sizable stake in the company himself, and brokered an all-stock deal in 2004 to sell the company to Alnylam, a Cambridge biotech that was buying up intellectual property related to RNAi science. (The country’s first RNAi-based drug, developed by Alynyam, was approved last year.) By age 20, Angermayer had made his first millions.

Being wealthy allowed Angermayer to pursue… well, whatever he wanted. He didn’t complete university. Instead, he looked into other sectors that he found intriguing. Along with his work in the life sciences, Angermayer has produced several Hollywood films, become something of a banking magnate in sub-Saharan Africa, and helped launch EOS, one of the top five cryptocurrencies in the world. Science, particularly science on the fringe, has been a persistent interest.

“But he has a good instinct for this stuff, and won’t invest in anything unless it has serious potential for profit,” said Ben Lipps, CEO of MagForce, an Angermayer investment that uses magnets to home in on difficult-to-treat tumor sites.

Psychedelics and mental health therapeutics make up about 15% of his current holdings, and he expects that figure to grow. He last year launched a company, ATAI Life Sciences, which owns about a quarter of the psilocybin-producing Compass Pathways, along with another startup that’s developing a depression drug that’s similar to ketamine, a common street drug. He’s on the verge of closing two more deals in that space — one of which aimed at providing an alternative therapy for the opioid epidemic. Angermayer said he is also interested in acquiring mental health clinics and other ancillary support services that might help buoy this psychotherapy-based model of psychedelics use.

Angermayer has a close-knit web of influential individuals whom he leans on heavily to make business decisions. And he doesn’t make a business decision until it has been vetted by someone he trusts.

“If one of my trusted friends recommends a person or a deal, I know this is ‘pre-screened’ — so every interesting person I meet, and every great deal I made — is made from my network,” Angermayer said.

The infectiously affable businessman counts among his closest friends Thiel, billionaire ex-hedge fund manager Mike Novogratz, and Rwandan president Paul Kagame — former commander of the rebel force that ended the country’s genocide. In 2007, Angermayer met Kagame when the latter was on a state visit to Germany — and the two immediately gelled. Kagame invited Angermayer to visit Rwanda, and he obliged.

“When I was in Rwanda for the first time, I realized the enormous opportunity Africa provides, and realized at the same time how back then the West had misjudged the economic potential of the continent,” Angermayer said. He privatized a bank there, which he sold to former Barclays CEO Bob Diamond.

Angermayer is plugged in to the German political scene, and is on good terms with German Chancellor Angela Merkel. He hops the globe, making new friends and business partners — though he does remain unmarried.

“Christian is endlessly interested in other people and relentlessly curious about new ideas,” Thiel said in a statement. “That combination makes him a perceptive investor.”

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Angermayer’s aggressive acquisition strategy and patent provisions have sparked fears of a mushroom monopoly in the industry.

Compass was initially launched as a charity in 2015. At the time, it was in discussions about a possible development partnership with the Usona Institute, a Wisconsin-based nonprofit that conducts its own pre-clinical and clinical research into psilocybin.

But after about a year, Compass was converted into a for-profit entity. It began recruiting scientists to develop and patent the psilocybin-synthesizing technology — and was accused of refusing to sell its product to Usona, hampering its own testing.

“The worry has been that Compass was leaping ahead, using data developed by nonprofit organizations,” said Rick Doblin, founder and executive director of the Multidisciplinary Association for Psychedelic Studies, a nonprofit focused on research and education around the substances. “But my perspective is: For-profits are supposed to do that. The nonprofit produces data for the world, and if people pick it up — that’s a sign of success.”

“I think the big concern is that Compass will try to block competitors from getting into the psychedelics business,” Doblin said.

Competitive issues aside, there are questions about Compass’s business model.

“Compass’s protocol for administering psychedelics is quite laborious, in terms of the amount of psychotherapist time necessary,” said Ronan Levy, founder of Field Trip Ventures, a Canadian venture firm focused exclusively on developing psychedelic-based therapies. “That creates both operational issues as well as an economic issue for people who want to experience or use this approach to medicine.”

Others argue the psilocybin production patent held by Compass is likely too broad, and could potentially be contested in the patent office.

“There are a whole bunch of different active molecules in magic mushrooms,” said Andrew Chadeayne, CEO of CaamTech, another startup in the psychedelics space who has been working on the “entourage effect” of mushrooms — learning about the chemical variability that might make different psychedelic mushroom varieties have different psychedelic effects. He’s patenting them, too.

Angermayer, interested in expanding his web of psychedelics holdings, recently asked Doblin this spring if he might invest in his nonprofit, MAPS — particularly its efforts to legalize therapeutic use of MDMA, commonly known as ecstasy. Doblin demurred. MAPS is purely donation-based, and unlike Compass, intends to stay that way.

But their talk shifted to one of the highest priority projects at the nonprofit: An exploration of psychedelics in conflict remediation.

Along with researchers at Imperial College London, MAPS plans on bringing Israelis and Palestinians together to take ayahuasca and, working with negotiation experts, sift through their respective traumas. The idea is that finding common ground in their spiritual and mystical experiences might help coax political reconciliation between the warring factions.

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“This is a project that’ll never be monetized,” Doblin said. Angermayer nevertheless wanted to fund the unconventional geopolitical study — so right then and there, he pledged about $250,000 to cover two years of the three-year effort to explore whether Israelis and Palestinians might, indeed, come to some kind of understanding.

“I’m not all about money,” Angermayer told Doblin. “I’m about peace, too.”

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Evidence is mounting that psychedelic drugs can help treat diseases. Here are the most promising uses.

Erin Brodwin | June 14, 2019

• There's been a recent resurgence of interest in psychedelic drugs' potential to address conditions like anxiety and depression. • Venture firms and researchers are on it. • This week, the world's first psychedelics-only VC launched in Canada, Business Insider reported exclusively. • Scientists are studying drugs including mushrooms, ecstasy (MDMA), and ketamine — and some are starting to turn into new, approved prescription drugs.

It's high time for psychedelic science.

Ever since drugs like psilocybin, the active ingredient in hallucinogenic mushrooms, appeared to help quell anxiety in cancer patients several years ago, the compounds have seen something of a resurgence of interest among scientists. Researchers are currently studying the potential of drugs ranging from ecstasy to ayahuasca to treat mental illnesses including depression and PTSD.

Investors are starting to join the bandwagon now, too. This week, Canadian entrepreneurs launched the world's first psychedelics-only venture firm, Business Insider reported exclusively. They hope to seed efforts to study the drugs' medical potential.

In the meantime, some psychedelic and semi-psychedelic drugs are turning into prescription medicines.

Last summer, federal regulators approved the first prescription drug made with marijuana, which many experts consider a psychedelic in high enough doses. Called Epidiolex, it is designed to treat rare forms of epilepsy. And this spring, regulators green-lit a drug inspired by ketamine and made by pharmaceutical giant Johnson & Johnson for severe forms of depression.

Other psychedelic drugs including ecstasy and psilocybin remain widely illegal, but that's beginning to change too.

In May, voters in Denver approved a measure to decriminalize psychedelic mushrooms, meaning that law enforcement would make policing their use a low priority. And recently, federal regulators assigned "breakthrough therapy" status to ecstasy, which could hasten its approval as a prescription drug for patients with PTSD.

A type of ecstasy might accelerate PTSD therapy

Researchers in October published the latest findings of a year-long study designed to assess if ecstasy or MDMA could play a role in treatment for PTSD. Their positive findings suggest that it could.

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After the treatment, in which patients were given MDMA alongside traditional talk therapy and compared with a group that got the same treatment only using a placebo instead of the drug, some three-quarters of the participants no longer met the criteria for a PTSD diagnosis. In other words, their symptoms had resolved.

That's a significant result. One of the chief problems with current talk therapy is that even when patients are able to afford and access the treatment, they grow tired of the painful process of rehashing traumatic events and sometimes disappear for months on end, according to psychiatrist Julie Holland, who currently serves as a medical observer for the MDMA study.

Still, the treatment was tied to some unpleasant side effects including insomnia, tiredness, and headaches. The drug, which amps up the activity of chemical messengers involved in mood regulation, can be dangerous when used without medical supervision because it raises body temperature and blood pressure.

MDMA also recently received a key federal designation designed to hasten the research and approval process. Some experts believe the drug will be approved as early as 2021.

A compound in magic mushrooms is showing promise for anxiety

Researchers studying psilocybin, the main psychoactive ingredient in hallucinogenic mushrooms, have likened its quick effects on cancer patients to a "surgical intervention" for depression.

Brain scan studies suggest that depression ramps up the activity in brain circuits linked with negative emotions, and weakens the activity in circuits linked with positive ones. Psilocybin appears to restore balance to that system.

Two for-profit companies are currently leading the research in the space. The first, called Compass Pathways, is backed by entrepreneur Peter Thiel and has recently began its own clinical trials of magic mushrooms for depression.

The second, a biotech startup called Atai, is focused on financing more of the kind of research that Compass is doing. Atai has raisedfunds from investors like ex-hedge fund manager Mike Novogratz and Icelandic entrepreneur Thor Bjorgolfsson. In late March, the biotech said it raised another $43 million.

Some researchers have high hopes that a psilocybin-inspired drug will get approved within a decade. David Nutt, director of the neuropsychopharmacology unit at Imperial College London, told Business Insider last year that he believed psilocybin would become an "accepted treatment" for depression before 2027.

The first prescription drug made from marijuana won federal approval last summer

The first prescription drug made from marijuana won federal approval last summer.

Called Epidiolex, the drug is designed to treat two rare forms of childhood epilepsy using a cannabis compound called cannabidiol (or CBD).

British-based GW Pharmaceuticals makes the drug. It does not contain THC, the well-known psychoactive component of marijuana responsible for the drug's characteristic high.

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The federal thumbs-up comes on the heels of several months of promising research results and a positive preliminary vote from the Food and Drug Administration this spring. Experts are hopeful that the approval will unleash a wave of new interest in the potential medical applications of CBD and other marijuana compounds to treat other psychiatric and neurological diseases.

Ketamine is inspiring novel treatments for depression

A widely used anesthetic that is also known as a party drug, ketamine was shown to have benefits as a rapid-fire antidepressant nearly a decade ago. Early studies suggested ketamine could help people who failed to respond to existing medications or were suicidal.

The authors of one paper called ketamine "the most important discovery in half a century."

In March, nasal spray called esketamine won approval from US regulators to treat severe forms of depression that don't respond to other medications. The brand name of the drug is Spravato, and it's taken as a nasal spray.

As opposed to existing antidepressants, ketamine appears to act on a brain mechanism that scientists have only recently begun to explore. Homing in on this channel appears to provide relief from depression that could arrive faster and work in more people than current drugs do.

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Investors are starting to bet big on psychedelic medicine

Chrissy Farr | March 27, 2019

KEY POINTS • Psychedelic substances were once viewed as “drugs of abuse,” but now regulators and investors are coming around to their potential therapeutic uses. • Federal regulators just approved a variant of ketamine to treat depression after years of clinical studies. • And now, a group of European investors have come together to fund new targets to treat mental health disorders, including arketamine (another variant of ketamine) and psychedelic mushrooms.

Psychedelic medicine is having a moment.

Just weeks after the U.S. Food and Drug Administration approved approved Johnson & Johnson’s ketamine-like nasal spray for depression, a group of European technology investors just got together for the largest-ever private financing round for a psychedelic medicine biotech company, ATAI.

Psychedelic medicine involves research and investigations into mind-altering substances to treat mental illnesses including addiction, depression and post-traumatic stress disorder. After recreational use of psychedelics became popular in the 1960s, the U.S. government classified most of them “drugs of abuse” with no real medical value. However, recent clinical studies show mounting evidence that some psychedelics can help patients with certain mental illnesses, either in combination with traditional therapies or in cases where nothing else has worked.

Now health and technology investors are paying attention.

German company ATAI Life Sciences announced on Tuesday that it has raised more than $40 million in new financing. The round valued the company at $240 million, according to a person familiar, making it both the biggest round and the most valuable company in the young space. (There are well established nonprofits, like MAPS in California, but relatively few for- profit ventures.) ATAI is also targeting a potential initial public offering for the end of this year, the person said, which would draw further attention.

ATAI is currently funding clinical trials for what it refers to as “formerly stigmatized compounds,” including psilocybin, the active compound in psychedelic mushrooms, and arketamine, a different variant of ketamine from the one Johnson & Johnson researched, as potential treatments for depression. Its portfolio also includes a technology arm called Innoplexus, which it describes as delivering “big data and AI solutions” to big pharma and biotech companies, as well as its own drug development.

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ATAI is also the largest investor in a start-up called Compass Pathways, which is setting itself up to be the first legal provider of psilocybin. ATAI invested alongside Peter Thiel, the iconoclastic Silicon Valley investor and Facebook board member who’s increasingly dabbling in health and biotech. ATAI co-founders Lars Wilde and Florian Brand are both affiliated with Compass; a third founder, Christian Angermayer, is a German entrepreneur and investor.

‘A regulatory path forward’

Biotech investors believe that psychedelic medicine will experience a revival in the wake of recent research studies as well as some early signals of support from regulators.

Last year, for example, the U.S. Food and Drug Administration (FDA) gave Compass a “Breakthrough Therapy” designation for its research into psilocybin for depression, allowing legal clinical trials to start. The FDA also expedited the approval process for esketamine, which is derived from the anesthetic ketamine, because many patients with depression don’t respond to normal treatments.

Adding further legitimacy to the space, Johnson & Johnson, the pharma giant, puts years of investment into studying into the benefits and potential side effects of esketamine. Its approval by the FDA represented the first new drug for depression in decades, although the medical establishment has stressed that more research is needed to better understand the long-term use of ketamine.

“A decision (like that) by FDA is the ultimate signal for investors,” said Brad Loncar, a biotech investor with Loncar Investments, who specializes in cancer and rare disease. “It shows that there’s a regulatory path forward for this class of drugs, which typically causes a flood of investment in the area.”

Others say that private investment in the space needs to be coupled with research into their social impact, as well as programs to support and guide patients.

“People are getting behind psychedelic-assisted therapies because they are desperate for real solutions that actually work, and for many, this treatment does,” said Liana Gillooly, a development officer at MAPS, a non-profit investigating the therapeutic uses of psychedelics, with an early focus on MDMA as a potential treatment for PTSD. But Gillooly said that funding needs to be set aside for “safe contexts” for these treatments to be administered, and not just for-profit drug development.

ATAI’s funding, which totals $43 million, comes from Michael Auerbach’s New York-based Subversive Capital, but also includes investors ranging from Apeiron Investment Group, which is Angermayer’s family office; Bail Capital, a private equity firm; and Efrem Kamen, founder of the health care fund Pura Vida Investments. Prior investors include billionaire investor Mike Novogratz and the Icelandic businessman Thor Bjorgolfsson.

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