Research on Psychedelics Making a Comeback


In 1993, Charles Grob, MD, professor of psychiatry and pediatrics at the University of California, Los Angeles (UCLA) School of Medicine, and a research team were invited to study the physical and psychological effects of ayahuasca, a plant mixture that produces psychedelic effects.

In 1993, Charles Grob, MD, professor of psychiatry and pediatrics at the University of California, Los Angeles (UCLA) School of Medicine, and a research team were invited to study the physical and psychological effects of ayahuasca, a plant mixture that produces psychedelic effects. The invitation came from a syncretic church established during the 20th century called the Brazilian União do Vegetal (UDV), which used ayahuasca-long ingested by the indigenous people of South America for purposes of healing, religious ritual, and magic-as a sacrament.

Grob is among a handful of investigators who, after an imposed research hiatus of nearly 4 decades, are taking a second look at the clinical effects of some remarkable-and potentially useful-compounds. He is now working out of the Harbor-UCLA Medical Center in Los Angeles, where he is studying the effects of another psychedelic substance, psilocybin, in patients with terminal cancer.

In the 1950s and early 1960s, clinical studies of LSD and related compounds stood on the cutting edge of neuropsychiatric research. These compounds promised to elucidate the nature of psychosis, to facilitate psychotherapy, and to relieve a wide range of psychological ills. Early studies in patients with terminal cancer suggested that LSD relieved both their physical pain and psychological suffering. But when psychedelic drugs moved out of clinics and laboratory settings to become a centerpiece of the 1960s counterculture, the debacle that followed left a collective trauma that still resonates.

Some experts-and many users-claimed that these drugs had the power to transform both personal lives and society; other experts declared that these drugs were a menace. The medical establishment dismissed claims that psychedelics might have therapeutic uses on the grounds that data on them were based largely on anecdote.

By 1970, the medical profession and the United States government had joined forces to outlaw these drugs. They were classified as Schedule 1 (no medical use and high abuse potential), and it became illegal to either possess psychedelic drugs or use them for clinical purposes.

Studies on them required, in addition to local institutional review board approval, authorization from both the FDA and Drug Enforcement Agency, which could not be expected to be forthcoming. According to Grob, not only did research on psychedelics come to an end at this time but so did any dialogue about these compounds.

The silence came to an end with the August 2006 issue of Psychopharmacology. In it, a controlled study showing that psilocybin evokes a mystical-type experience with lasting personal meaning was published.1

The study was conducted by Roland Griffiths, PhD, and colleagues at Johns Hopkins University in Baltimore. Griffiths, professor of neuroscience at Johns Hopkins with 30 years of National Institute of Drug Abuse-funded comparative pharmacology research behind him, gave meticulous attention to the study's design, which was rigorously controlled, double-blind, and safe.

Thirty-six volunteers received either psilocybin (30 mg/70 kg) or, for comparison, methylphenidate. The volunteers were psychologically and medically healthy middle-aged adults without histories of hallucinogen use. All participated in religious or spiritual activities.

Volunteers were prepared for the experience by a research team member and were attended by 2 team members during their experience. They remained under observation for 8 hours following drug administration and underwent follow-up interviews 2 and 14 months later. At 2 months, 3 familiars of each volunteer also provided observations about the volunteer's attitudes and behavior.

Sixty-one percent of the participants who received psilocybin experienced a profound change in perception and consciousness that met the research team's a priori criteria for a "complete mystical experience." Only 11% of participants who received methylphenidate reported such an experience. The mystical experience defied ready description but volunteers spoke of a sense of unity, transcendence of space and time, sacredness, and of encountering ultimate truth, according to Griffiths.

When questioned 2 and 14 months later, 69% and 67% of the volunteers, respectively, rated the psilocybin experience as among the 5 most spiritually significant events of their lives. Fifty-nine and 58%, respectively, rated it as among the 5 most personally mean- ingful events, comparable to the birth of a first child or the death of a parent.1,2

Important as these findings are, even more so are the long-term effects of the psilocybin experience. Fourteen months after the psilocybin-induced experience, 64% of the participants reported that the event had increased their personal well-being or life satisfaction. The majority reported changes in their attitudes and behavior that Griffiths categorizes as "prosocial"; they were more tolerant, more loving, and less judgmental. Their contacts confirmed these changes.2


In the past decade, research groups in Switzerland and Germany have examined the acute effects of psilocybin on humans.3,4 Richard Strassman at the University of New Mexico has studied the acute physical and psychological effects of dimethyltryptamine, another hallucinogen.5 Griffiths' study, however, garnered singular notice. Grob speculated that this special attention came, in part, because of Johns Hopkins' reputation and Griffiths' impeccable scientific credentials. But Griffiths' study also was noteworthy for the attention given to controlled study design and for its focus on the mystical experience, said Grob. In addition, Griffiths' study went beyond the standard acute-effects design to include examination of long-term effects.

Does Griffith's study represent a resurgence of scientific interest in psychedelic compounds? Herbert Kleber, MD, professor of psychiatry at Columbia University in New York and former deputy director in the Office of National Drug Control Policy, thinks it's "too soon to tell." Yet, there are signs, in addition to Griffiths' study, of a thaw in both the self-imposed and government bans on such research.

The FDA seems more likely now than in the past to approve such studies. David Nichols, PhD, professor of medicinal chemistry and molecular pharmacology at Purdue University in West Lafayette, Indiana, credits a change in FDA personnel and the fact that the current generation of regulators were not on the job in the 1960s during the mess of unrestrained psychedelic drug use.

The FDA has approved several protocols, in addition to Grob's, for controlled studies of psilocybin in terminally ill cancer patients. Although it is not yet clear whether the NIH will fund these sorts of studies, 2 private foundations, the Multidisciplinary Association for Psychedelic Studies and the Heffter Research Institute, do provide such funding. Nichols started the Heffter Institute in 1993. He says that the institute's name reflects its purpose. Arthur Heffter was an eminent German pharmacologist who in the 1890s identified mescaline as the active compound in peyote. Heffter embodied the responsible, scientifically rigorous research on psychedelics that the institute aims to support, said Nichols.


In addition to Griffith's study, several reports have appeared in the past year suggesting that psychedelics may offer unique benefit in some difficult-to-treat conditions. In the June 27, 2006, issue of Neurology, John Halpern, MD, and colleagues at McLean Hospital in Belmont, Masssachusetts, reported the results of their survey of psilocybin and LSD use in 53 persons with cluster headaches.6

Prompted by a group of cluster headache patients who had discovered on their own that psilocybin-containing mushrooms and LSD provided singular relief, Halpern and colleagues, assisted by Clusterbusters (a support group for people with cluster headache), conducted a systematic survey of psilocybin and LSD among persons with cluster headaches.

Nine of the 53 persons surveyed had tried both LSD and psilocybin; the remainder had only tried psilocybin. Psilocybin aborted single headaches in 85% of those surveyed, terminated a cluster period in 52%, and extended the remission period in 91%. Results were similar for LSD.

The study was uncontrolled and subject to all the biases of a retrospective survey. Halpern and his colleagues are planning some follow-up work.

In November 2006, Moreno and colleagues7 at the University of Arizona reported the results of their study of psilocybin in treatment-resistant obsessive-compulsive disorder (OCD). All 9 subjects experienced substantial relief of OCD symptoms during at least 1 of the 4 testing sessions. The relief lasted throughout the 24-hour observation period. Like the cluster headache study, this one was prompted by anecdotal reports from patients who had discovered the benefits of psilocybin on their own.

Several lines of inquiry suggest that psilocybin and related hallucinogens may be of value in the treatment of addictions, particularly alcoholism. Grob found that all 11 of the Brazilians in his study who drank heavily before joining the UDV church achieved abstinence shortly after joining the church and participating in the ingestion of ayahuasca.8 Five of them had met diagnostic criteria for alcohol abuse. Consistent with these observations, peyote, when used as a sacrament in the Native American Church, has been reported to alleviate alcoholism. Although church participation itself may account for these benefits, it is conceivable that long-term use of these substances might have a "direct positive and therapeutic effect," according to Grob.8

However promising these substances might be, both as research tools and as treatments, strong cultural barriers remain in place. Psychedelic substances do have their dangers: 31% of the volunteers in Griffiths' study experienced transient fear during the psilocybin session, and experts agree that these substances should be administered only to carefully selected persons under controlled conditions. Experts also agree, however, that research on these agents should go forward.9


REFERENCES1. Griffiths RR, Richards WA, McCann U, et al. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology. 2006;187:268-283.
2. Griffiths RR. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance: 14-month follow-up. Proceedings of the 2007 Annual Meeting of the American Psychiatric Association. 2007:157.
3. Hasler F, Grimberg U, Benz MA, et al. Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose-effect study. Psychopharmacology. 2004;172:145-156.
4. Gouzoulis-Mayfrank E, Thelen B, Habermeyer E, et al. Psychopathological, neuroendocrine and autonomic effects of 3,4-methylenedioxethylamphetamine (MDE), psilocybin and D-methamphetamine in healthy volunteers. Results of an experimental double-blind placebo-controlled study. Psychopharmacology. 1999;142:41-50.
5. Strassman RJ, Qualls CR, Uhlenhuth EH, et al. Dose-response study of N,N-dimethyltryptamine in humans, II: subjective effects and preliminary results of a new rating scale. Arch Gen Psychiatry. 1994;51:98-108.
6. Sewell RA, Halpern JH, Pope HG. Response of cluster headache to psilocybin and LSD. Neurology. 2006;66:1920-1922.
7. Moreno FA, Wiegand CB, Taitano EK, et al. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry. 2006;67:1735-1740.
8. Grob CS, McKenna DJ, Callaway JC, et al. Human psychopharmacology of hoasca, a plant hallucinogen used in ritual context in Brazil. J Nerv Men Dis. 1996;184:86-94.
9. Schuster S. Commentary on: psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance by Griffiths et al. Psychopharmacology. 2006;187:289-290.

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