Psilocybin, a naturally occurring hallucinogen, is the main psychoactive component of psilocybe and other hallucinogenic mushrooms (so called “magic mushrooms”). Like other classic hallucinogens, such as d-lysergic acid diethylamide (LSD) and mescaline, psilocybin exerts its psychoactive effects through a sub-type of serotonin receptors (called 5-HT2a) in the brain. In some cultures, psilocybin has historically been used in religious contexts — likely for millennia. Psilocybin has a number of effects, including changes in perception, cognition, affect, and decision-making. Clinical research on psilocybin dates back to at least the 1950s, with variable effects on the perceived affective character of the experience. Research on psilocybin administration in humans has occurred in psychotherapeutic contexts in terminally ill cancer patients dating back to the 1970s and continues today. A surprising new study reveals that, under specific conditions, acute exposure to psilocybin can elicit long-lasting positive changes and increases in mystical-type experience.

A research team headed by Rolland R. Griffiths, PhD, professor of neuroscience in the Department of Neuroscience at Johns Hopkins University School of Medicine, performed the study in collaboration with Robert Jesse, founder of The Council on Spiritual Practices in San Francisco. The study was published in a recent issue of Psychopharmacology.

To investigate, the researchers sought study volunteers from the local community through flyers announcing a study of states of consciousness induced by psilocybin. Two-hundred seventy-nine people were screened by telephone and 31 were further screened in person. Eighteen study volunteers, eight of which were males, were tested for physical and mental health prior to initiation of the study. Volunteers were tested for common drugs of abuse and those with current alcohol or drug dependence (including nicotine) were excluded, as were those with a past history within the past 20 years of alcohol or drug dependence (excluding nicotine). Study volunteers had never used a hallucinogenic drug, except for one who had used psilocybin mushrooms on two occasions over 20 years previously. Study volunteers did not receive monetary compensation for participation in the study. Rather, their only motivation was curiosity about the effects of psilocybin and the opportunity for extensive self-reflection within the context of the study.

The double-blind study involved the administration of multiple doses of psilocybin (0, 5, 10, 20, and 30 mg for every 70 kilograms) during five 8-hour sessions conducted at 1-month intervals and a 14-month follow-up. Study volunteers were randomly assigned to receive either increasing or decreasing doses of psilocybin (in capsule form), with nine volunteers in each group. Drug sessions occurred in an aesthetic living room-like environment in the presence of two study “monitors,” who were present throughout all drug exposure periods for a given study volunteer but were unaware of the drug dose sequences. For most of the time during the drug sessions, volunteers were encouraged to lie down on the couch, use an eye mask to block external visual stimuli, and use headphones through which a music program was played. Volunteers were encouraged to focus their attention on their inner experiences throughout the drug sessions. At multiple time points throughout the study, blood pressure and heart rate were recorded for each volunteer. In addition, at the same time points, study monitors rated each volunteer’s mood and behavior. At seven hours after initial drug exposure (when drug effects had worn off), volunteers completed three questionnaires designed to assess subjective aspects of the hallucinogenic experiences, as well as two questionnaires to assess mystical experience.

At 14 months after the last drug session, study volunteers were interviewed to gain information about their study experiences and life situation. At this time, the volunteers filled out a questionnaire (which included some items related to mystical experience) and were also asked to provide written descriptions about the drug sessions, including how their behavior changed in response to the drug experiences. As an additional measure, three adults having regular contact with each study volunteer (“community observers”) were interviewed multiple times after the study to rate different aspects of the study volunteer’s behavior. At the conclusion of the study, the study monitors were asked to rate any enduring changes in the volunteer’s attitude and behavior they believed resulted directly from the drug sessions.

The research team reports that psilocybin produced significant dose- and time-related effects on blood pressure and heart rate in study volunteers over a six-hour period after initial drug exposure. During this time, monitors rated significant changes in study volunteers due to overall drug effects, including, stimulation/arousal, peace/harmony, distance from ordinary reality, and joy/intense happiness. For about 39% of study volunteers, monitors rated a significant, psilocybin-induced, unpredictable course of extreme anxiety or fearfulness, mostly at the higher drug doses. About 44% of study volunteers reported transient delusional or paranoid thinking, mostly at the higher doses, including some of those who experienced anxiety or fear. However, as noted by Dr. Griffiths, “if we reduce the dose a little, we have just as much of the same positive effects and the properties of the mystical experience remain the same, but there is a five-fold decrease in anxiety and fearfulness.”

At seven hours after initial drug exposure, study volunteers filled out three questionnaires about the drug experience, in which they reported a variety of significant dose-related effects typical of hallucinogens. These included perceptual changes (eg., visual pseudo-hallucinations and illusions), labile moods (eg., feelings of transcendence, grief, joy, and/or anxiety), and cognitive changes (eg., sense of meaning or insight). At this time, study volunteers also reported significant dose-related effects on measures of states of consciousness (eg., internal and external unity, sacredness, transcendence of time and space, and deeply felt positive mood) and mystical experience.

The long-term effects of the psilocybin sessions are perhaps even more striking. At 14 months after initial drug exposure, study volunteers rated significant dose-related effects of the drug sessions. These included positive ratings of attitudes about life and the self, mood, social and behavioral effects, well-being, life satisfaction, spirituality, a sense of continuity after death, as well as the personal and spiritual meaningfulness of the drug experience. In addition, at this time, the positive ratings reported about states of consciousness and mystical experience at seven hours after initial drug exposure were still present. Interestingly, at this time, most volunteer questionnaires about the drug experience indicated increased physical and psychological self-care, as well as increased spiritual practice. Post-study ratings of study volunteers by study monitors and community observers at 14 months after initial drug exposure were consistent with all of the aforementioned changes. Importantly, clinical interviews with study volunteers indicated that none reported clinically significant post-study adverse events or non-study hallucinogen use since study enrollment. At this time, all of the study volunteers appeared to be psychologically healthy, high-functioning, productive members of society.

Remarkably, most of the study volunteers (including the volunteer who experienced the highest level of transient psilocybin-induced anxiety) rated the highest dose drug sessions as the single most personally meaningful and spiritually significant event of their lives. This psilocybin-induced spirituality appears similar to that reported in case studies of individuals reporting spontaneous mystical experience. The authors suggest that, based on these and other studies, therapeutic use of psilocybin may be clinically useful in psychiatric settings when administered under specific, controlled conditions, but acknowledge that this is controversial.

“The important point here is that we found the sweet spot where we can optimize the positive effects of psilocybin while avoiding the fear and anxiety,” said Griffiths. Jerome H. Jaffe, MD, clinical professor of psychiatry at the University of Maryland School of Medicine, who served as the first White House “Drug Czar” but was not involved in the study, said “the Hopkins psilocybin studies clearly demonstrate significant and lasting benefits, but this route to the mystical is not to be walked alone.”

Griffiths and colleagues do warn against casual use of psilocybin (especially at high doses) and caution that the present results may be limited to the study population — a group of hallucinogen-naïve, well-educated, psychologically stable, mostly middle-aged adults, most of whom participate in religious or spiritual activities on a weekly basis. The authors conclude by highlighting that 70% of study volunteers reported having a “complete” psilocybin-induced mystical experience, which is considerable in comparison to what they refer to as “the rarity of spontaneous mystical experiences in the general population.”

References

Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, & Jesse R (2011). Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology, 218 (4), 649-65 PMID: 21674151

Griffiths R, Richards W, Johnson M, McCann U, & Jesse R (2008). Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. Journal of psychopharmacology (Oxford, England), 22 (6), 621-32 PMID: 18593735

Griffiths RR, Richards WA, McCann U, & Jesse R (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology, 187 (3) PMID: 16826400

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Johnson, M., Richards, W., & Griffiths, R. (2008). Human hallucinogen research: guidelines for safety Journal of Psychopharmacology, 22 (6), 603-620 DOI: 10.1177/0269881108093587

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Richards WA, Grof S, Goodman LE, and Kurland AA (1972). LSD-assisted psychotherapy and the human encounter with death. Journal of Transpersonal Psychology 4:121–150.

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