sign in sign up
<<
Home , Albert Hofmann, Alexander Shulgin, Amanda Feilding, Lysergamides, MDMA

Drugs Taking a medical trip Psychedelic show promise in treating conditions including post-traumatic stress disorder and Alzheimer’s, but stigma has excluded them from research for 35 years. Karen Harries-Rees uncovers the resurgence of medicinal PHOTO BY APOTHECARY, © .ORG © APOTHECARY, BY PHOTO

68 | World | September 2007 www.chemistryworld.org Forty years ago, MDMA to become a prescription 1970s for use in . invited a generation to ‘turn on, medicine. In short According to Doblin, MDMA tune in, drop out’. But the backlash Psychedelics have a long history  Research into the was considered to have remarkable against an LSD-using youth of use, starting in the late 1800s, therapeutic potential therapeutic potential due to its subculture led to it becoming before government agencies around of LSD and relatively short and gentle action impossible to gain approval for LSD the world put a stop to research in stopped in the early and the lack of major perceptual and ( diethylamide-25) the early 1970s. LSD was discovered 1970s, but is now cognitive alterations, that in other research, which has been stalled for in 1938, and used in research and re-emerging psychedelics can contribute to panic the last 35 years. therapy from the late 1940s (see  The effects of attacks and bad trips. ‘It’s difficult to prove that studies Chemistry World, January 2006, psychoactive drugs, ‘Many studies describe that are in the public interest and can be p30), with the CIA in the US such as LSD, MDMA MDMA can reduce stress, increase completed without undue risk to assessing it as a potential mind and psilocybin, include positive of self, increase sense participants – and without harming control during the 1950s and changes in perception of compassion for self and others the public image of collaborators,’ 1960s. and mood. This could be and reduce fear of discussing highly says John Halpern, assistant By the mid-1950s, LSD used with psychotherapy charged psychological material,’ professor of at McLean research was under way in the to treat post-traumatic adds Halpern. Hospital, Harvard Medical School US, Switzerland, Germany, Italy, stress syndrome and But by the early 1980s, MDMA too in the US. ‘But when it comes to France, Czechoslovakia, Canada related to had found its way underground and patients suffering from debilitating and several Scandinavian countries. advanced-stage cancer become a recreational drug so, once illness, surely our society can find Psychedelics showed the potential MDMA’s effects again, regulatory agencies moved to room to explore even the most to treat conditions that elude are the gentlest and it criminalise it. In 1985 it too became unlikely of drugs as potential drug treatment to this day, such could be available on a schedule 1 drug in the US – putting therapies.’ as , pain and anxiety in prescription within 10 an end to its use in psychotherapy. This exploration is finally cancer patients, and post-traumatic years Applications for studies involving happening – several studies stress disorder (PTSD). psychedelics were put on hold. involving psychedelics and humans In Switzerland between 1988 and have been approved in recent Going underground 1993, LSD and MDMA-assisted years. A few organisations have Then things began to change. By psychotherapy was still permitted, been instrumental in pushing the mid-1960s, LSD and other but, with the focus on treatment this research forward: the psychedelics were being used as – no research was carried out. In in the UK, an recreational drugs, triggering a the early 1990s, attitudes within independent trust that funds work regulatory backlash. In 1965, a law the FDA began to change. ‘The to advance the understanding of was passed in the US making it position changed to what it probably how the human brain functions and illegal to manufacture, compound, should have been in the first place,’ the nature of ; the process or sell any hallucinogenic says Dave Nichols, professor of Heffter Research Institute in the drugs. Medical research was eligible and molecular US, which supports and promotes for a permit excluding it from the at Purdue University, investigation into the medical uses ban but in practice, the US Food and US, and founding president of the of psychedelic hallucinogens; and Drug Administration (FDA) asked Heffter Research Institute. The the Multidisciplinary Association most researchers to stop their work FDA began to trust researchers – if for Psychedelic Studies (Maps), also and return any LSD being used in protocols were well designed and in the US. their labs. In 1970, the US classified the investigators qualified, there was most psychedelics as schedule 1 no reason why the study shouldn’t be Flying the psychedelic flag drugs, meaning that they had a approved. The FDA still maintains Maps describes itself as a non- high potential for abuse and no this approach. profit pharmaceutical company. recognised medical use. Funding As a result, approvals are now It focuses on the development dwindled and, by the early 1970s, steadily trickling through. MDMA of beneficial, socially sanctioned psychedelic research had stopped. research is the most advanced and uses of psychedelic drugs and After 1975, only three European the consensus among researchers marijuana – helping researchers studies of psychedelics for human is that there is less of a taboo get approval for studies and use were allowed to continue, says surrounding MDMA than LSD. funding many of them. It supports Doblin, one in Germany and two Phase I studies, in which MDMA research on MDMA, or ecstasy (3,4- in the Netherlands. Both of the was given to normal volunteers to methylenedioxymethamphetamine) Netherlands studies used LSD – one measure physiological effects and with the aim of it becoming available to treat neurotic patients and the , have been carried on prescription. This will be a long other, conducted by Jan Bastiaans, out in the US and Europe. There process, but the precedent has professor of psychiatry at the ‘When it comes are now four Phase II pilot trials already been set. ‘In the US we have University of Leiden, giving low underway looking into how MDMA found room to accept that drugs to moderate doses of the drug to a to debilitating could help those with PTSD and that are dangerous “on the street” small number of camp illness, surely anxiety related to advanced-stage may still be medicines approved for survivors. cancer. Maps is behind all of these prescription,’ says Halpern. Drugs Just as research into LSD and our society studies and plans to use the results such as , , other psychedelics stopped and can find room to design two large multi-site Phase tincture of and gamma- the drugs were criminalised, III trials. hydroxybutyrate (GHB) are MDMA arrived on the scene. It to explore currently legal to prescribe for was legal and similar to MDA (3,4- even the most Combating trauma specific conditions. But Maps methylenedioxyamphetamine), The first Phase II trial to get the president Rick Doblin estimates a schedule 1 drug that had shown unlikely of go-ahead was in Spain in 2000, that it could take five to 10 years for promise during the 1960s and early therapies’ looking at the potential of MDMA- www.chemistryworld.org Chemistry World | September 2007 | 69 Drugs Psychedelics – the facts

MDMA, 3,4-methylenedioxymethamphetamine, LSD, or lysergic acid diethylamide-25 was first eight to 12 hours. It alters perception, mood and also known as ecstasy, is a ring-substituted synthesised by in 1938. It is psychological processes. phenylisopropylamine derivative. It is a a chiral compound with two stereocentres at chemically similar to the carbon atoms C-5 and C-8, so four optical Psilocybin ,along with , is the primary the methamphetamine and the isomers of LSD could exist. The C-5 isomers of active ingredient of and do not exist in nature and are not are equally psychoactive. The ratio of psilocybin formed during synthesis from d-lysergic acid. to psilocin varies between species. Psilocin, H Of the two C-8 isomers, only one (the d-) LSD O N is psychoactive. LSD is one of the most potent OH mind-altering chemicals known. The current O PO– theory is that it works by inhibiting . O Its effects are very variable, are strongly O dependent on the setting and usually last for N+ . It was initially patented H by Merck in 1912 as an intermediary chemical used in the synthesis of hydrastinine. It was N O N rediscovered by chemist H in the 1970s. Some researchers say that MDMA should be in a separate , the the dephosphorylated of entactogens or empathogens. These reduce H psilocybin, is unstable and breaks down when fear associated with emotionally upsetting N the is dried, whereas psilocybin lasts thoughts, feelings or memories and generate much longer. They are part of the or enhance feelings of closeness to others. The family and closely resemble the effects of MDMA include feelings of openness, serotonin. Like LSD, they are thought to , , love and heightened self- N inhibit serotonin. The effects are also strongly awareness, lasting for three to five hours. H dependent on the setting and are similar to LSD.

assisted psychotherapy for women I study of psychologically healthy cancer. with chronic PTSD following people who have medical conditions Should MDMA prove helpful in sexual assault. Mounting political such as C, well controlled reducing anxiety associated with pressure meant that it was stopped and HIV to see if they cancer diagnosis, Halpern thinks in 2002, after just six of the 20 could be included in a Phase III trial. it could also help decrease the use patients were treated. Trial leader He then hopes to carry out a large, of and for Jose Carlos Bouso, psychologist and multicentre Phase III trial in the US. anxiety and pain control, which psychotherapist at the Autonomous In Israel, a Maps-sponsored have unpleasant side-effects. University of Madrid in Spain, says pilot study of MDMA use in war ‘Benzodiazepines are known to the trial showed that low doses of and terrorism-related PTSD is over sedate, cause coordination MDMA alongside psychotherapy being carried out by Moshe Kotler, problems, and are also associated was safe and that the drug showed a former chief psychiatrist for with cognitive problems such as promise in reducing PTSD the Israeli defence forces who is verbal memory deficits,’ he says. symptoms. now based at the department of MDMA could be used to This is a small study and any In March 2004, the first Phase psychiatry at the Sackler School of treat PTSD associated trends need to be interpreted with II trial to be approved in the US Medicine, Tel Aviv University. with war and terrorism caution. But if it shows that there began. This trial, being carried out Peter Oehen began studying could be significant benefits and that by psychiatrist Michael Mithoefer MDMA and PTSD in Switzerland MDMA can be administered safely, at his Charleston, South Carolina, in September last year and hopes Halpern plans to design a second, clinic, is studying 20 patients with to finish at the end of next year. larger pilot study. ‘We hope this treatment resistant PTSD resulting His study is co-sponsored by Maps experimental therapy might help a from sexual or criminal assault, and the Swiss Medical Association person face their issues and find new or from combat. The participants for Psycholytic Therapy. Oehen, a strength to attempt resolution and are patients who have already psychiatrist and psychotherapist, is acceptance,’ he says. tried psychotherapy and an SSRI getting similar results to Mithoefer, Doblin believes that due to (selective serotonin reuptake and is confident that MDMA will its gentle, yet profound effects, inhibitor) but prove a safe and efficient adjunct to MDMA is likely to be integrated continue to suffer symptoms. the psychotherapy of PTSD. into psychiatry before other, more The trial has one more year to run powerful, longer-lasting and but Mithoefer says the results are Tentative steps more psychologically challenging already very promising. ‘We can’t MDMA is also being studied for psychedelics such as LSD and draw any firm conclusions before its potential in treating anxiety. psilocybin. the study is completed but it seems Harvard Medical School’s Halpern Hopeful early results have extremely likely that our results will gained final approval in January stimulated speculation about the warrant the approval of larger Phase this year to study MDMA-assisted other circumstances in which III trials,’ he says. Following this psychotherapy for patients with these drugs could provide benefit.

CORBIS trial, he wants to start a small Phase anxiety related to advanced-stage Eating disorders could be one 70 | Chemistry World | September 2007 www.chemistryworld.org field worth investigating, says extension – in other words, the Oehen, since current treatments period of time between the cycles of are so ineffective. In addition, the attacks of episodic cluster headache Beckley Foundation is planning was increased,’ he says. Patients to look into the use of MDMA also reported termination of an in psychotherapy for couples in individual headache or cluster troubled relationships. series. ‘No approved standard

AJ PHOTO / SCIENCE PHOTO LIBRARY PHOTO SCIENCE / PHOTO AJ offer the same benefit. Tuning in again If this research confirms these The Beckley Foundation has also reports, it will be remarkable.’ gained the first approval for human Psilocybin is also being studied studies using LSD, for a US-based for its potential to treat obsessive study to look at dose-related compulsive disorder (OCD). changes in consciousness using Francisco Moreno, associate electroencephalography (EEG). A professor of psychiatry at the second phase of this study will use University of Arizona, US, has magnetoencephalography (MEG) completed the first FDA-approved to map changes in brain activity study in more than 25 years to and will also investigate the effects examine the use of psilocybin of LSD on creativity by measuring in a patient population. The insightful problem solving and investigators studied 10 patients visualisation in relation to other suffering from OCD and found cognitive functions. psilocybin reduced their symptoms, , director of the replicating the findings from Beckley Foundation, says this is a patients in case studies. very early study but it ‘opens the Meanwhile, Charles Grob, door to future research’. She is wary professor of psychiatry and of derailing the research and will biobehavioural sciences at not reveal the locations of the work. UCLA school of medicine, US, is Nichols is also cautious about LSD investigating whether psilocybin studies. ‘Everyone needs to tread might be effective in reducing carefully and do these studies for the anxiety, and physical right reasons, not to make a political pain in people with advanced cancer. splash, which is the motivation at His study started in April 2004. So least in some cases. There is so much far, 10 patients have been treated of a stigma, if anything goes wrong and one more is needed to finish the with a study it will hit the headlines,’ research. Two other groups in the he says. US are carrying out similar work, Feilding is discussing three but neither will release details at this further projects with institutions in The first therapeutic trial was LSD might help patients early stage. the UK and Europe. One will look at given approval in July. Peter Gasser, cope with the anxiety of ‘Psychedelics are an amazing the pharmacology of LSD in relation psychiatrist, psychotherapist and terminal illness category of substances,’ says to another closely related, but non- president of the Swiss Medical Feilding. ‘Only by understanding the hallucinogenic compound, . Association for Psycholytic Therapy, scientific neural and physiological Comparing fMRI (functional aims to discover if patients with correlates of what is happening magnetic resonance imaging) scans, anxiety related to advanced-stage underneath the experience will we using the two compounds, will illnesses can safely be given LSD- more easily be able to explain why indicate where in the brain LSD assisted psychotherapy and whether they could be therapeutic.’ elicits its hallucinogenic effects. it improves their anxiety symptoms. Research is already altering MRI will also be used to He hopes to start the trial by the end the perception of psychedelics investigate the of this year and is currently waiting – enabling them to come out of underlying the effects of LSD and for approval from SwissMedic, the the underground and be viewed as the changes in blood flow around Swiss drug regulation authority. possible treatments. In less than 10 the brain. Feilding is particularly LSD, along with psilocybin, is also years time, patients with a series interested in the hypothesis that the being studied for its potential to of distressing disorders for which changes in consciousness associated treat cluster headaches. In the 1950s, current treatments fall far short, with psychedelics are closely linked several research studies commented could be receiving psychedelics to an increased supply of blood to the that LSD reduced migraine on prescription. Leary may have brain, enabling billions more brain headaches but no clinical research been an unwitting advocate of a cells to function simultaneously. has been carried out for cluster ‘We need to psychiatric wonder drug. ‘We are beginning to see through headaches. Halpern is designing a tread carefully our studies of Alzheimer’s disease trial and hopes to put it forward to Karen Harries-Rees is a science that it is accompanied by diminished a review board later this year, with with these journalist based in Melbourne, blood supply in certain parts of the the aim of starting the trial in 2008. studies. If Australia brain, as is depression,’ she says. ‘If He and his colleagues published a LSD creates greater profusion [blood case series of people with cluster anything goes Further reading flow], it could be very useful at a headaches who had used psilocybin wrong, it will hit Maps: www.maps.org sub-hallucinogenic dose to improve or LSD to treat their condition. Beckley Foundation: www.beckleyfoundation.org cerebral circulation.’ ‘Most people reported remission the headlines’ Heffter Research Institute: www.heffter.org

www.chemistryworld.org Chemistry World | September 2007 | 71