REPORT 04.15.19 Marijuana as Medicine

William Martin, Ph.D., Director, Drug Policy Program Katharine Neill Harris, Ph.D., Alfred C. Glassell, III, Fellow in Drug Policy

Several of these bills follow a recent INTRODUCTION trend of laws that allow for access to strains Thirty-four states have laws permiting of marijuana that are high in CBD, the the use of marijuana—properly called nonpsychoactive compound touted for its cannabis—for specified medical purposes. medical properties, but with little or no THC, Currently more than half the U.S. the component that causes the “high.” These population has access to marijuana for laws have attracted support, particularly in medical use, and an estimated 2.6 million southern states, because they are seen as people are using it for relief.1 States differ a way to provide patients with some of the in stipulating what medical cannabis is, main medicinal qualities of the marijuana who can use it, and how they can get it. plant but without any psychoactive effects. Most states with legal medical cannabis As one observer put it, “They don’t mind authorize licensed dispensaries. States that if you take medicine, as long as it doesn’t do not have dispensaries—as well as many make you happy.” A key drawback of CBD- that do—allow patients to grow their own only laws is that they typically place strict marijuana plants. limits on the number and types of qualifying A June 2018 University of Texas/Texas medical conditions. In 2015, Texas passed the Tribune poll indicated that 53 percent of Compassionate Use Act (CUA), which allows Texans would legalize it for any purpose, at Texans with intractable epilepsy to access It is necessary to least in small amounts, and 31 percent would low-THC (less than .5 percent) CBD oil, but understand what legalize it for medical purposes only. Only 16 that law has been criticized for its narrow makes cannabis serious scope (see below). Several bills introduced percent say marijuana should remain illegal medicine, not just a under any circumstance.2 this session are attempts to expand the CUA. In the summer of 2018, both The two drawing most attention are House stage on the road to major Texas political parties passed by Bill 1365,4 authored by Rep. Eddie Lucio III, full legalization of a overwhelming majorities platform planks D-Brownsville, and Senate Bill 90,5 authored recreational drug. that reflect these views. The Republican by Sen. José Menéndez, D-San Antonio. version calls on legislators “to allow doctors Though differing in some respects, both add to determine the appropriate use of cannabis substantially to the number of diseases or to certified patients” and its Democratic conditions that qualify for treatment, remove counterpart urges “the immediate the cap on the amount of THC than can be legalization of medical cannabis use.”3 legally dispensed or possessed, and provide Texas legislators have heard the call detailed regulation of dispensaries and testing and are considering 64 cannabis bills facilities, and myriad other details that are in the current session, 17 dealing only necessary parts of the lawmaking process. with medical cannabis, so many that To appreciate what these bills can Rep. Senfronia Thompson, D-Houston, accomplish, it is necessary to understand chairwoman of the Public Health Committee, what makes cannabis serious medicine, not has created a Subcommittee on Medical just a stage on the road to full legalization of a Marijuana just to deal with these bills. recreational drug. BAKER INSTITUTE REPORT // 04.15.19

receptor is not formed in the brain for the THE ENDOCANNABINOID SYSTEM sake of a plant constituent.”8 Therefore, they The chemical structure of cocaine, derived inferred and through careful experimentation from the coca plant, was understood and demonstrated that the human body produces described in the 1890s; that of morphine, its own (endogenous) cannabinoids, derived from opium, came in the 1920s. The molecules that act as “ligands” (from the first serious attempt to analyze the structure Latin legere, to bind) that activate and bind to and components of cannabis did not begin appropriate bimolecular receptors to produce until the early 1960s, when Dr. Raphael physiological effects. They called this happy Mechoulam, then an organic chemist bond anandamide, from the Sanskrit word at the Weizmann Institute of Science in for “bliss” or “supreme joy.” Less spiritually, Rehovot, Israel, applied to the U.S. National the scientific literature often uses images of a Institutes of Health for a grant to isolate key (the “endocannabinoid”) and a lock (the and identify the psychoactive component CB receptor) or a bullet and a target. “Essentially every of the marijuana plant. That first attempt Five years later (1993), a second receptor (CB2), different from the one in the brain physiological system was rejected, with the explanation that marijuana was used mostly in Mexico and and central nervous system, was found identified in our South America and was not a problem in the throughout the immune and gastrointestinal bodies is in some way United States. A year later, as the buds of the systems. In 1995, the Mechoulam team modulated by eCBs 1960s began to flower in profusion, the NIH reported a new endocannabinoid, 2-arachidonoyl glycerol (2-AG), similar to [endocannabinoids].” called back, beginning decades of support that would enable Mechoulam to gain anandamide. Over the past quarter century, the unofficial title of “Father of Cannabis they have identified at least 100 others. Research.” More than 50 years later, at Together, these receptors and age 88, he is still on the case and under his cannabinoids constitute the leadership Israel has been called “The Holy “endocannabinoid system” (ECS). Though Land of Medical Marijuana,” attracting a much is still to be learned, a key reason concentration of cannabis research and top- the ECS exists is to maintain homeostasis— level researchers unmatched anywhere else keeping things on an even keel by offering in the world.6 relief from pain, reduction of inflammation, In fewer than five years, Mechoulam control of nausea, uplift from depression and his colleagues isolated many of the and anxiety, and preventing, moderating, more than 100 of the plant’s components, or curing some diseases. As one article put which they dubbed “cannabinoids” after it, “Essentially every physiological system marijuana’s scientific name, Cannabis sativa. identified in our bodies is in some way The most notable of these was Delta-9- modulated by eCBs [endocannabinoids].”9 Tetrahydrocannabinol (THC), responsible for The Scientist, the Canadian magazine the “high” that made marijuana famous. for life science professionals, put it more The other headliner, currently drawing even breezily: “Your Body is Teeming with Weed more public attention, was cannabidiol Receptors.”10 When the endogenous system (CBD), a substance capable of controlling or is not strong enough to handle such tasks on reducing inflammation, anxiety, epileptic its own, the use of exogenous cannabinoids— seizures, and pain, among numerous other extracted from cannabis plants or produced known or plausible beneficial effects.7 synthetically—can bind with CB1 or CB2 to Two decades later, Mechoulam’s team help restore order. gained a breakthrough understanding of Not surprisingly, pharmaceutical how and why cannabinoids do their work. companies have sought to meet these In 1988 came evidence that a type of needs by producing synthetic chemical cannabinoid receptor (CB1) exists in the brain equivalents of key cannabinoids or “limited and throughout the central nervous system, editions” of extracts from cannabis plants. ready for the appropriate cannabinoid to bind Prominent examples include dronabinol with it to produce its effect. As Mechoulam (trade name Marinol), a synthetic THC put it, “We assumed that a cannabinoid developed to control nausea produced by 2 MARIJUANA AS MEDICINE

chemotherapy. Its popularity has been sclerosis, and control or significantly limited because it lacks CBD and other ease neuropathic pain associated with chemicals that modulate the unpleasant migraines, diabetes, traumatic nerve injury, effects of the “high.” Nabiximols (trade chemotherapy, and other conditions. name Sativex), produced by the UK company Clearly, scientific research regarding GW Pharmaceuticals, combines THC and CBD cannabinoids is not being done to provide extracted from cannabis plants in a 1-to- healthy 20-somethings with justification 1 ratio, and works to reduce neuropathic for using an alleged knee pain as a way pain, spasticity, and other symptoms of to obtain legal pot. For additional proof multiple sclerosis and related conditions. of that, visit the website of the National Sativex has been moderately well received Cancer Institute15 for brief descriptions and in Canada and most European countries, but links to hundreds of research investigations is not available legally in the United States. of the demonstrated or potential effects Mechoulam places greater confidence in of cannabis and cannabinoids for cancer what he calls the “Entourage Effect”—the development and treatment, appetite many components of this complex plant stimulation, analgesia, anxiety, and sleep. work better together than in isolation of Much of the research involves rodents or only one or two ingredients.11 monkeys, but clinical studies and trials Increased understanding of the ECS with humans, long blocked by the Food and has generated an explosion of research Drug Administration (FDA), the National by thousands of scientists striving to Institute on Drug Abuse (NIDA), and the learn more about how it works and the Drug Enforcement Administration (DEA), Clearly, scientific therapeutic possibilities offered by the are slowly becoming more common. research regarding cannabis plant and medicines that could The justification for placing limits on mimic its processes. In fiscal year 2017, the cannabis research involves the Controlled cannabinoids is not NIH supported 330 projects totalling almost Substances Act, passed by Congress in being done to provide $140 million on cannabinoid research.12 1970, which placed various drugs into five healthy 20-somethings Inevitably, some efforts will prove more categories, or “schedules,” that ostensibly with justification for successful than others, and some will fail. indicate their relative benefits and dangers using an alleged knee A 2017 exhaustive review by an ad hoc as determined by the FDA and the DEA. committee of the National Academies of Schedule I contains substances deemed to pain as a way to obtain Sciences, Engineering, and Medicine found have “no currently accepted medical use legal pot. “conclusive or substantial evidence that in treatment in the United States” and “a cannabis or cannabinoids are effective for high potential for abuse.”16 The list includes the treatment of chronic pain in adults, heroin, LSD, Ecstasy, Quaaludes, and nausea and vomiting related to cancer cannabis.17 Schedule II drugs, which have chemotherapy, and symptoms of spasticity a high potential for abuse but also have associated with multiple sclerosis.”13 It also recognized medical uses, include morphine, indicated potential benefits for a variety of methadone, oxycodone, and fentanyl. other conditions and stressed the need for Used to treat acute “breakthrough” pain, more and better quality research. fentanyl is approximately 100 times more The 212-page January 2018 issue of potent than morphine and is the major Neuropsychopharmacology Reviews,14 contributor to the deadly spike in overdose an official publication of the American deaths in recent years. No one has ever College of Neuropsychopharmacology, died from an overdose of marijuana. comprised a series of articles summarizing Inexplicably, dronabinol (Marinol), the current understanding of cannabis and synthetic form of THC, the component most cannabinoids and their medical potential. vilified by marijuana’s critics, is in Schedule Among notable findings are the ability or III, deemed to have moderate potential for likelihood of these interactions to reduce abuse and dependence, but less dangerous inflammation and cartilage degradation than drugs in Schedules I and II. caused by rheumatoid and osteoarthritis, reduce the spasms of multiple 3 BAKER INSTITUTE REPORT // 04.15.19

To claim that cannabis poses more Intractable Epilepsy of a threat than heroin or oxycodone or Millions of people have watched CNN’s Dr. fentanyl defies reason. Given the voluminous Sanjay Gupta as he evolved from a critic and growing evidence that cannabis of cannabis to an ardent believer in its has substantial medicinal benefits and is therapeutic value. The turning point for “accepted medical treatment” in Israel, Gupta, and for hundreds of thousands who Canada, and several countries in both watched his August 2013 special,19 came Western and Eastern Europe and South when he tracked the story of Charlotte Figi, America, how can federal agencies continue a 5-year-old girl burdened from shortly 18 to assert that cannabis has no medical use? after her birth with Dravet’s Syndrome, an The answer is maddening: because those extreme form of epilepsy that was producing same agencies have for years refused to 300 seizures a week, at least two every permit the scientific research needed to prove Used to treat acute hour. After available pharmaceutical options that it does or might have such use. Obtaining failed and doctors recommended putting “breakthrough” a government grant to fund research into her into a coma to let her brain and body pain, fentanyl is the possible benefits of cannabis requires rest lest the seizures finally kill her, the Figis approximately 100 FDA approval, which is extremely difficult agreed to try a cannabis solution that was to get. And if permission is granted, the times more potent 21 percent CBD and less than 1 percent THC. cannabis used for such research must The results were immediate and seemed than morphine and is come from the DEA-licensed and federally miraculous. After the first dose, placed the major contributor run farm on the campus of the University under her tongue, Charlotte had no seizures to the deadly spike in of Mississippi. Access to the Ole Miss pot for three days. She was soon down to one farm is controlled by the National Institute seizure per week. When Gupta met her three overdose deaths in on Drug Abuse (NIDA), which rarely shares recent years. No one months later, she was walking, talking, its stash with anyone interested in finding riding a horse, and riding a bike on her own. has ever died from an beneficial uses for cannabis. The American Forty-one other children in Colorado were overdose of marijuana. Medical Association, the American College of using the solution, produced by the Stanley Physicians, the Institute of Medicine, and a Brothers farm and called Charlotte’s Web. host of other medical and scientific groups All were reporting far fewer seizures. Soon, in this country and internationally have families were moving to Colorado from called for more research into the therapeutic states where legal cannabis is not available benefits of cannabis. NIDA has consistently to them. As noted earlier, in 2015 the declined to participate. As one spokesperson legislature passed the Texas Compassionate put it, “Our focus is primarily on the Use Act, which authorized production of a negative consequences of marijuana use. CBD oil, trade name Epidiolex, to treat only We generally do not fund research focused one condition, intractable epilepsy, with on the potential beneficial medical effects of Dravet’s Syndrome the primary example. marijuana.” Some softening of that restriction That restriction was tightened even further has occurred quite recently, but the general by requiring that patients must first establish policy appears still to stand. that at least two FDA-approved drugs have failed to control their condition, then convince two of 18 neurologists certified by PROVEN OR PROMISING RESULTS the state to give them a prescription that For a better appreciation of marijuana’s can be filled in only three dispensaries in proven or promising therapeutic potential, the state, one in Schulenburg and two in 20 consider four conditions of interest to Austin, none in the 576 miles between Texans, many of whom have lobbied Austin and El Paso. This is a feeble effort to legislators and testified before committees ease the suffering of an estimated 160,000 in recent sessions. Texans with intractable epilepsy, of whom fewer than 600 have jumped through the hoops to receive the medicine they need. Both HB 1365 and SB 90 will greatly improve 4 these regulations. MARIJUANA AS MEDICINE

Post-traumatic Stress Disorder that it could not conduct research with an Cannabis offers—and according to abundant illegal substance or even refer veterans anecdotal testimony, delivers—substantial to research projects. In fact, before 2010, relief to people suffering from post-traumatic veterans would lose their right to VA health stress disorder. PTSD can be triggered by services if they were found to be using exposure to actual or threatened death, any illegal substance, including marijuana, serious injury, or sexual violation. Symptoms and VA physicians were not allowed even include re-experiencing the event through to discuss cannabis with their patients. flashbacks or nightmares, insomnia, That year, at the urging of groups such as depression, the inability to talk about the Veterans for Medical Cannabis Access, the memories, estrangement and isolation from VA issued a directive that vets who are family and friends, self-blame, irritability, registered patients in a state-sanctioned anxiety, fear, hypervigilance, anger, medical marijuana program can continue aggression, and reckless or self-destructive marijuana use without losing access to VA behavior. A variety of experiences—rape, treatment or other benefits. In states like fires, floods, and other traumatizing events— Texas that do not allow medical marijuana, 21 can give rise to PTSD, but none is more likely vets are out of luck. to produce its symptoms than war. One In March 2015, the FDA, DEA, and NIDA tragic consequence has been the alarming agreed, after long deliberation, to allow and number of veterans who have taken their provide cannabis for a “gold-standard” own lives, at a rate estimated to be more randomized controlled trial of whole plant than 20 per day. Polls have found that more cannabis as a treatment for PTSD symptoms. than 40 percent of Iraq and Afghanistan The study was funded by a $2.156 million veterans display signs of mental and grant from the Colorado Department of Public emotional health problems characteristic Health and Education to the Multidisciplinary of PTSD, often made worse by chronic pain. Association for Psychedelic Studies (MAPS) A 2013 Veterans Administration report said and led by Sue Sisley, M.D. Despite state that more than 300,000 veterans of those funding and federal authorization, approval, two wars had sought treatment for PTSD and oversight, the Ole Miss farm took two In varied ways, sizable in VA hospitals and Vet Centers. The typical years to provide Sisley with the requested numbers of veterans treatment options include opioid painkillers, drugs, and what she eventually received reminded her of “green talcum powder” began to find relief antidepressants, and sleeping pills, which from smoking cannabis, veterans known to the authors say were and was considerably less potent than what “handed out like Skittles,” turning them into veterans could obtain elsewhere, making many coming to find it “pilled-up zombies.” In varied ways, sizable it more difficult to extrapolate her findings not a gateway to using numbers of veterans began to find relief from beyond her study subjects. In addition, some samples were contaminated with mold. more dangerous illicit smoking cannabis, many coming to find it substances, but an not a gateway to using more dangerous illicit Rick Doblin, MAPS’ director, said the episode substances, but an exit route from serious “shows that NIDA is completely inadequate as exit route from serious overuse of alcohol and prescription drugs. a source of marijuana for drug development overuse of alcohol and Despite the risk it involved, they began to research. They’re in no way capable of prescription drugs. share their stories and press for legal access assuming the rights and responsibilities to their drug of choice. for handling a drug that we’re hoping to Despite being the ideal institution be approved by the FDA as prescription 22 to conduct research on the potential of medicine.” (The DEA said in 2016 that it cannabis to help with PTSD, given its would approve other qualified growers to access to veterans suffering from it, the produce cannabis for research purposes, but VA declined to do so. That decision drew as of this date, that has not happened.) Sisley a scathing response from the 2 million did, however, proceed with the study and member American Legion, which claimed 92 the results will be reported later this year. percent of veteran households favored such Meanwhile, research on cannabis and PTSD research, but the VA stood firm, explaining proceeds without hindrance in Israel and 5 BAKER INSTITUTE REPORT // 04.15.19

cannabis is available to treat PTSD through Studies in the 1960s and 1970s estimated medical marijuana programs in New Mexico, the prevalence of autism to be between 2 Oklahoma, Arkansas, and Louisiana, all four and 4 per 10,000 children. The rate currently states surrounding Texas. published by the CDC is about 1 in 59, with Texas Veterans for Medical Marijuana is boys outnumbering girls by 4 to 1.26 Nearly an active force in lobbying for legal access to 500,000 persons with autism live in Texas. the plant that has helped vets find surcease There is general agreement that a significant from the horrors of war. As Maj. Dave Bass, factor in this astonishing apparent explosion one of the group’s founders and effective is a widening of diagnostic criteria such that advocates, observed, “When a guy has children now described as “on the spectrum” done four tours in Iraq, like some of our might have been seen as odd, “slow,” or people, and been wounded in action, it’s difficult to control in earlier decades, but hard to look him in the eye and call him a there is no question that the prevalence of slacker pothead.”23 To mobilize veterans children (who eventually become adults) on and dramatize being denied the medicine the serious segment of the spectrum has they know has helped them instead of the greatly increased. pills provided by the VA, the group collected There is strong scientific consensus that one empty pill bottle from 500 vets, placing vaccines do not cause ASD, and no vaccine a toy soldier in each one, along with a slip exists to cure it. Antipsychotic drugs Abilify of paper that provided the name, branch, and Risperdal are given to autistic youth for dates of service, and service-connected “irritability” and are often prescribed for kids disabilities of each person. Dubbed Operation with tantrums, aggression, and self-injury “When a guy has done Trapped, these were displayed in custom- behavior, but both carry “black box warnings” four tours in Iraq, like made cases at veterans’ events and at the of devastating side effects, some fatal.27 some of our people, Capitol for a week during the 2016-17 Texas Other pharmaceuticals, developed to legislative session. In Operation Still Trapped, treat other conditions but used “off label” and been wounded in the campaign for the current session, the may bring some improvement for a time, but action, it’s hard to look bottles are displayed in a wooden coffin there are currently no FDA-approved drugs him in the eye and call made to resemble those common in the for treating ASD’s core symptoms. him a slacker pothead.” 1800s. Both efforts have drawn wide Much of the research about ASD and media coverage in Texas and nationally, cannabinoids has used dronabinol (synthetic leading more veterans to join their cause. THC) alone. Some has combined CBD as The group also reached Gov. Greg Abbott, a way to inhibit or modulate intoxication, who acknowledged in a debate during the tachycardia, and other effects associated 2018 election campaign that he had been in with THC while also increasing the overall “discussions with veterans [and others] who efficacy—the entourage effect—but lacking make a very strong, compelling case about the versatility of the whole plant. the legalization of medical marijuana.”24 Until recently, most research regarding cannabinoids and ASD has been preclinical Autism (using animal but not human subjects). These Another serious set of conditions with have indicated a correlation between ASD inadequate relief from existing medical and impairments of the ECS. New research, treatments but abundant anecdotal now conducted on humans, is clarifying that testimony is autism—more properly relationship. In 2018, Stanford University autism spectrum disorder (ASD). The scientists reported finding significantly lower “core symptoms” include communication concentrations of blissful anandamide in 60 difficulties, social awkwardness, persistent children with ASD than in a control group of difficulties with social communication, and 56 “neurotypical” children, all aged 3 to 12. restrictive, repetitive patterns of behavior, This first clinical test to confirm the findings interests, or activities. Hypersensitivity to of animal studies “suggests that impaired certain sounds is also common.25 anandamide signaling may be involved in the pathophysiology of ASD.”28 Even newer

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(2019) research from Israeli researchers Chronic Pain and Opioid Use Disorder found that serum levels of the major Less dramatic but of enormous importance endocannabinoid AEA and related compounds in considering medical cannabis is its were significantly lower in 93 children with established ability to diminish pain. The ASD than in a control group of 93 age- and Institute of Medicine has estimated that 29 gender-matched neurotypical children. “more than 100 million Americans suffer from Earlier preclinical research had chronic pain.” The aforementioned 2017 NAS already indicated that targeting various review said that THC, CBD, and cannabinol ECS deficiencies common to ASD with (CBN), a third major component of cannabis, phytocannabinoids (derived from cannabis are all known to help relieve pain.36 plants) shows encouraging potential for Though often effective in dealing treating ASD in humans, in keeping with the with chronic pain, cannabinoids alone are 30 anecdotal evidence. A 2017 Chilean study insufficient to handle acute pain such as using oral cannabis extracts found them that from surgery, burns, broken bones, to be “dramatically more effective than or advanced cancer, but there is strong conventional medicines” for ASD patients evidence that, used in combination with and called for large randomized controlled opioids, they can significantly reduce the trials. An Israeli study (January 2019) of data amounts needed for acute pain and thereby collected from 188 autistic patients treated lessen the chance of overdose.37 Several with medical cannabis oil between 2015 and studies have found that “when given access 2017 found substantial evidence of significant to cannabis, individuals currently using (30.1 percent) or moderate (53.7 percent) opioids for chronic pain decrease their use 32 improvement in common symptoms of ASD. of opioids by 40–60 percent and report that A second Israeli study, of children with ASD they prefer cannabis to opioids,” mentioning receiving oral cannabis under the direction of fewer side effects and a better quality of their physicians, reported a notable reduction life.38 Related to that finding, noted in in typical symptoms in about two-thirds the Summer 2017 issue of Neuroscience 33 of the cases. Worth mentioning is that Quarterly, is that CBD can significantly reduce the reported adverse side effects were mild the consumption of alcohol and also the sleepiness, reflux, and changes in appetite. No motivation to relapse and resume drinking.39 need for a black box warning. In addition to assisting patients and their In recent years, while federal agencies families, legal medical cannabis can help continue to thwart clinical studies in the U.S. states save money. Two studies by Ashley that might confirm such research, uncounted C. Bradford and W. David Bradford, a father- but substantial numbers of parents have daughter research team at the University of experimented with cannabis and found it to Georgia, found that use of prescription opioids bring quicker and longer-lasting relief and dropped by more than 3.7 million daily doses improvement to their children than anything among Medicare D enrollees from 2007 to else they have tried. Despite the legal risk, 2014 as patients substituted legal cannabis many have formed advocacy organizations to for FDA-approved prescription drugs. In a publicize the need and implore their legislators 2016 paper published in the journal Health to pass bills that will give their children legal Affairs, the authors estimated that if all states access to cannabis. The most prominent legalized medical cannabis, the savings to and vigorous of these groups in Texas is Medicare in 2014 would be ca. $468 million.40 Mothers Advocating Medical Marijuana for A 2018 paper in the Journal of the American Autism—MAMMA USA, founded and led Medical Association, Internal Medicine, by Austinites Thalia Michelle and AmyLou examining Medicaid data, estimated that all- Fawell, both of whom describe themselves as states medical legalization would produce “Bible-believing, Pro Life, 2nd Amendment national savings for fee-to-service Medicaid 34 Conservative Republican Voters.” of ca. $1.01 billion; if Medicaid managed care were included, the estimated savings would be ca. $3.89 billion.41 7 BAKER INSTITUTE REPORT // 04.15.19

teen use rates have remained stable or FEARS AND FACTS declined since the implementation of We favor prudent uses of medical cannabis medical marijuana programs.42 that are supported by careful research, but Peer-reviewed studies of the we acknowledge and want to respond to relationship between MMLs and use report some of the apprehensions and objections mixed findings depending on variations in raised by opponents, skeptics, and even study designs, such as survey data used, people simply worried about increased legal years examined, and states included in the use of a long-maligned drug. analysis. A well-designed study funded by NIDA and using data from Monitoring the Medical Marijuana Laws and Adolescent Use Future, an annual survey of roughly 50,000 high school students, compared adolescent Increased marijuana use, especially among (8th, 10th, and 12th graders) marijuana use adolescents, is one of the primary concerns and attitudes toward marijuana in states among opponents of medical marijuana that had legalized medical use and those reform. Medical marijuana laws (MMLs) that had not. Looking at survey data over could plausibly increase use rates in several a 24-year period (1991-2014), the authors ways: by increasing availability, especially found that adolescent use did not increase if state law allows dispensaries to become in states that passed MMLs. Adolescent use commonplace; by labeling marijuana a was higher in states that had passed MMLs medicine, thus increasing perceptions that compared to those that had not, but the it is a drug without risks; and by decreasing differences were present before the laws the stigma of marijuana use, thus signaling were passed, suggesting that they should that it is acceptable behavior. These not be attributed to the changes in the fears are exaggerated. Dispensaries are laws. Among 8th graders, marijuana use not allowed to sell to minors, and teens decreased and its perceived harmfulness have consistently reported that pot was Several studies have increased in states that passed MMLs. The easy to obtain over the four decades of authors hypothesize that this decline could found that “when given near-total prohibition. Emphasis on the be due to increased media attention to access to cannabis, medical use of marijuana could lead youth the harms of marijuana use and increased to perceive the drug as something for individuals currently efforts by parents to warn young teens sick people rather than something to be using opioids for about these risks.43 consumed recreationally; and legalization chronic pain decrease In contrast to these findings, a study could prompt schools, parents, the medical using data from the National Survey on their use of opioids by community, and the media to increase Drug Use and Health (NSDUH), a nationwide 40–60 percent and efforts to warn young people about the annual survey of approximately 70,000 risks of marijuana use. report that they prefer people ages 12 and older, for the time period Using data from the CDC’s Youth Risk cannabis to opioids.” 2004-2012 found that implementation of Behavior Survey to compare marijuana MMLs was “associated with a 4.72 percent use rates among high school students increase in the probability that young adults before and after the passage of MMLs in perceived no or low health risk related to several states suggests that the overall marijuana use.”44 Another study that relied impact on teen use so far is negligible on the NSDUH found that state adoption of or negative. In Nevada and Connecticut, MMLs was associated with an increase in current marijuana use among high- past-month marijuana use among 12- to school students (defined as having 17-year-olds in those states between 2004 smoked marijuana in the past 30 days) and 2011.45 They also found, however, that rose slightly in the first year or two after MMLs did not impact adolescent use of other medical legalization began, then dropped illicit drugs. Greater alcohol use, however, to levels significantly below where the was associated with higher use rates of both rates had been before the change. In marijuana and other illicit drugs, highlighting Arizona, Maryland, Massachusetts, New the central role alcohol plays in other drug Hampshire, Rhode Island, and Vermont, use behaviors. 8 MARIJUANA AS MEDICINE

Taken together, these findings make There is considerable evidence to it difficult to draw firm conclusions about suggest that marijuana, especially marijuana the relationship between MMLs and high in THC, can exacerbate schizophrenia. adolescent marijuana use. On balance, the (In contrast, some studies have shown that data available so far suggest that factors marijuana rich in CBD can help alleviate other than implementation of MMLs have some symptoms of schizophrenia.) Some greater influence on whether teens use researchers argue that heavy and early marijuana. Regardless of the relationship, use can actually cause schizophrenia in the fact remains that adolescent marijuana people who would not have developed use, especially when heavy and prolonged, it otherwise. Critics of that claim have can have significant adverse consequences countered that researchers have not been and cannot be dismissed. Still, this is not a able to rule out the possibility of a “shared reason to deny access to medical marijuana vulnerability,” by which people at risk for the millions of people who can benefit for schizophrenia are also more likely to from it. Instead, states can and should take use marijuana while young, due to other a long-term view of MMLs and implement mediating factors.47 Regardless, people them in such a way that addresses the with schizophrenia or a history of psychotic needs of patients without encouraging use episodes are a vulnerable population that among adolescents and young adults. This should be discouraged from marijuana use. may mean placing restrictions on medical This can be achieved through increasing marijuana programs, such as limiting the public awareness of the connection between Overall, cannabis is far number of dispensaries or the amount of psychosis and marijuana use, but it is not a THC a product may contain (though not so reason to deny access to marijuana for the safer than many widely low as to render the product ineffective), millions of Americans who do not have these advertised and used and increasing evidence-based public health vulnerabilities and would benefit from the drugs. Listen carefully campaigns to educate adolescents on the plant’s use. to the commercials for risks of marijuana use. Overall, cannabis is far safer than many widely advertised and used drugs. Listen almost any drug touted Marijuana Use and Adverse Health Effects carefully to the commercials for almost any on television, especially Like all drugs, marijuana carries some drug touted on television, especially the the words spoken risks and side effects. Available evidence words spoken swiftly at the end of the pitch. swiftly at the end of indicates that marijuana has fewer negative Or read the warnings that accompany the the pitch. physiological effects than more common prescriptions you pick up at your trusted recreational drugs such as alcohol and pharmacy. Or Google NSAIDs and discover tobacco, some adverse effects on short- they are responsible for thousands of deaths 48 term cognitive impairment, and potentially each year. You might be frightened, but negative effects on some mental health you are likely to take those drugs without outcomes, psychosis in particular. much hesitation, deciding that the potential The NAS review found limited to no benefits outweigh the risks. Parents of evidence for an association between children with Dravet’s Syndrome or autism marijuana use and development of may know that cannabis poses a risk for depression, anxiety, post-traumatic brains not fully formed, but few would stress, or bipolar disorder. It did, however, deny their children access to plant-derived find “substantial evidence of a statistical medicine whose safety and efficacy are association between cannabis use and the attested to by abundant anecdote, proven development of schizophrenia or other by scientific research, and sensibly regulated psychoses, with the highest risk among the in legal regimes. Neither should the Texas most frequent users.”46 Legislature, which by providing regulated and safe access to medical cannabis to people with demonstrated need can provided justified relief, help reduce the opioid epidemic, and save Texas millions of dollars.

9 BAKER INSTITUTE REPORT // 04.15.19

17. The chemical names are LSD– ENDNOTES lysergic acid diethylamide; ecstasy–MDMA, 1. Marijuana Policy Project, Medical or 4-methylenedioxymethamphetamine; Marijuana Patient Numbers, December 3, Quaaludes–methaqualone. 2018, http://bit.ly/2TUmwhH. 18. See countries approving medical 2. University of Texas/Texas Tribune marijuana at http://bit.ly/2U6VLXx. Poll, June 2018, http://bit.ly/2TbiFIV . 19. See a CNN special with Sanjay 3. Ibid. The Republican plank passed Gupta at https://www.youtube.com/ by 90 to 10 percent. The entire Democratic watch?v=XUwkLiciY6Q. platform was accepted on a voice vote. 20. Technically, one of the Austin- 4. HB 1365 available at https://capitol. area dispensaries is in Manchaca, an texas.gov/tlodocs/86R/billtext/html/ unincorporated community ca. 10 miles HB01365I.htm. southwest of downtown Austin. 5.SB 90 available at https://capitol. 21. These paragraphs draw heavily on texas.gov/tlodocs/86R/billtext/html/ William Martin, “War Without End,” Texas SB00090I.htm. Monthly, May 2014, http://bit.ly/2Y7zZSD. 6. See “The Holy Land of Medical 22. Caleb Hellerman, “Scientists say Marijuana” at https://bit.ly/2o95kSF. the government’s only pot farm has moldy 7. R. Gaoni and R. Mechoulam, samples,” https://to.pbs.org/2FcCnyU. “Isolation, Structure, and Partial Synthesis 23. Martin, “War Without End.” of an Active Constituent of Hashish,” Journal 24. See http://bit.ly/2Yiqujt, in which of the American Chemical Society, 86, no. Abbot is impressed by veterans. 8 (1964): 1646–1647. For Mechoulam’s own 25. For the core symptoms of autism, brief survey of his career, see R. Mechoulam see http://www.researchautism.net/ and Lumir Hanus, “Anandamide and More,” autism-issues/core-symptoms-of-autism. in Julie Holland, ed., The Pot Book—A 26. See CDC autism data at https:// Complete Guide to Cannabis (Rochester, www.cdc.gov/ncbddd/autism/data.html. Vermont: Park Street Press, 2010), 63-72. 27. See side effects Abilify [aripiprazole] 8. Mechoulam and Hanus, at http://bit.ly/2TSBMg2; side effects Anandamide, 70. of Risperdal [risperidone] at https:// 9. G. Gerdeman and J. Schechter, “The wb.md/2FjbGJ1. Endocannabinoid System,” in Julie Holland, 28. For more on lower anandamide in ed., The Pot Book—A Complete Guide to ASD children, see Karhson et al., Molecular Cannabis (Rochester, Vermont: Park Street Autism 9 (2018):18, https://doi.org/10.1186/ Press, 2010), 52-62. s13229-018-0203-y. 10. See “Your body is teeming with 29. For an Israeli study on lower EC weed receptors,” http://bit.ly/2TY8vzC. levels, see http://bit.ly/2HTiDmG. 11. Entourage Effect, http://bit. 30. For more on the role of cannabinoids ly/2UaVmnZ. in ASD therapy, see http://bit.ly/2OdAN3Y. 12. See NIH research on marijuana and 31. For the Chilean study, see http://bit. cannabinoids at http://bit.ly/2HLSFBG. ly/2Ol4gJ9. 13. See the National Academies’ 32. For the Israeli study of 188 patients, summary of a report on the health effects see https://www.nature.com/articles/ of cannabis and cannabinoids at https://bit. s41598-018-37570-y. ly/2V2ojyJ. 33. For more on parents administering 14. See 2018 Neuropsychopharmacology oral drops to children, see http://bit. Review at https://www.nature.com/ ly/2Yf6vT0. collections/pgzvtchpmq. 34. We gratefully acknowledge being 15. See National Cancer Institute studies guided to some of this research by Mses. at http://bit.ly/2JmOEWV. Michelle and Fawell and the MMAMMA’s 16. See a Scientific American account website, http://www.mammausa.org. Ms. of how cannabis was put into Schedule I at Fawell’s presentation at a Baker Institute http://bit.ly/2JxOhsC. 10 MARIJUANA AS MEDICINE

event can be viewed at https://www. 48. A commonly reported figure for bakerinstitute.org/videos/texas-ready- NSAID deaths is 16,500 per year, but that medical-marijuana/ beginning at ca. 51:00. is likely quite exaggerated (see http://bit. 35. For more on the 100 million in ly/2YiJQ8n ), but there is consensus that the chronic pain, see https://wb.md/2FsaDHW. number is in the thousands. 36. National Academies summary, https://bit.ly/2V2ojyJ. 37. “Legalizing Marijuana Decreases AUTHORS Fatal Opiate Overdoses, Study Shows,” see William Martin, Ph.D., is the director of the https://bit.ly/2lWSasa. Drug Policy Program. He is also the Harry 38. For more on the role of cannabis in and Hazel Chavanne Senior Fellow in opioid use, see https://www.ncbi.nlm.nih. gov/pmc/articles/PMC6135562/#B36. Religion and Public Policy at the Baker 39. “Inside Neuroscience: Tapping Institute and the Chavanne Emeritus into the Cannabinoid System,” http://bit. Professor of Sociology at Rice University. ly/2HIIFt8. His research and writing focus on two 40. See Ashley and David Bradford major areas: the political implications Medicare study at http://bit.ly/2CyAVpX. of religion and the importance of the 41. Ashley C. Bradford, et al., separation of religion and government, and “Association Between U.S. State Medical ways to reduce the harms associated with Cannabis Laws and Opioid Prescribing in drug abuse and drug policy. the Medicare Part D Population,” JAMA Internal Medicine, 2018, DOI: 10.1001/ Katharine Neill Harris, Ph.D., is the jamainternmed.2018.0266. Alfred C. Glassell, III, Fellow in Drug Policy. 42. Data for each these states regarding Her current research focuses on the adolescent use after medical cannabis availability of drug treatment for legalization can be found at https:// at-risk populations, the opioid epidemic, nccd.cdc.gov/YouthOnline/App/Results. and the legalization of medical and See more Baker Institute Reports at: aspx?LID=NV. Filter data by using choices in adult-use cannabis. www.bakerinstitute.org/baker-reports top box, “Choose Table Content.” This publication was written by a 43. Deborah S. Hasin, et al., “Medical researcher (or researchers) who Marijuana Laws and Adolescent Marijuana participated in a Baker Institute project. Use in the USA from 1991 to 2014: Results Wherever feasible, this research is from Annual, Repeated Cross-sectional reviewed by outside experts before it is Surveys,” Lancet Psychiatry 2 (2015): 601- released. However, the views expressed herein are those of the individual 608. author(s), and do not necessarily 44. Hefei Wen, Jason M. Hockenberry, represent the views of Rice University’s and Benjamin G. Druss, “The Effect of Baker Institute for Public Policy. Medical Marijuana Laws on Marijuana- Related Attitude and Perception among U.S. © 2019 Rice University’s Baker Institute for Public Policy Adolescents and Young Adults,” Prevention Science 20 (2019): 215-223. This material may be quoted or 45. Lisa Stolzenberg, Stewart J. reproduced without prior permission, D’Alessio, and Dustin Dariano, “The Effect of provided appropriate credit is given to Medical Cannabis Laws on Juvenile Cannabis the author and Rice University’s Baker Use,” International Journal of Drug Policy Institute for Public Policy.

(2015): 1-8. Cite as: 46. National Academies, https://bit. Martin, William and Katharine Harris ly/2V2ojyJ. Neill. 2019. Marijuana as Medicine. 47. Charles Ksir and Carl L. Hart, Baker Institute Report no. 04.15.19. “Cannabis and Psychosis: A Critical Overview Rice University’s Baker Institute for Public Policy, Houston, Texas. of the Relationship,” Current Psychiatry Report 18 (2016): 1-12. 11