This is one of the first (and key) double-blind, placebo-controlled studies (n=30) on psilocybin and its effect on ‘healthy normals’. It shows that a high (30mg/70kg) dose can occasion mystical (peak) experiences (participants did already have a spiritual/religious practice beforehand). The experience is rated as personally meaningful, the participants exhibit positive mood (and lower anxiety), immediately and after 2 months.
“Rationale Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects.
Objectives This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions.
Materials and methods The participants were hallucinogen-naïve adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers’ behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer’s attitudes and behavior.
Results Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers.
Conclusions When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.”
- The first double-blind, placebo-controlled study of a high-dose of psilocybin on hallucinogen-naïve healthy participants
- Psilocybin increased measures of mystical experience
- Effects persist after 2 months
Griffiths et al (2008) do a 14-month follow-up and find that the mystical experience mediates personal meaning and spiritual significance.
This paper is included in the meta-analytical review by Galvão-Coelho and colleagues (2021) that found psychedelics to improve mood (for those with mood disorders) both in the short and long-term (up to 60 days).
“The study compared psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) using a double-blind between-group, crossover design that involved two or three 8-h drug sessions conducted at 2-month intervals. Thirty-six volunteers were randomly assigned to receive either two sessions (N=30) or three sessions (N=6).” (only the data of the two-session group was used in analysis)
The participants were ‘healthy-normals’, many had enjoyed higher education, and none had a family history of schizophrenia. The placebo used was methylphenidate (Ritalin), so there was some blinding, but of course, not everyone was fooled by the active placebo.
“[P]silocybin produced significantly greater elevations in ratings of positive attitudes, mood, social effects, and behavior; the negative ratings of these same dimensions were very low and did not differ across the drug conditions. This questionnaire also included ratings of the personal meaningfulness and spiritual significance of the experience and whether the experience changed their sense of well-being or life satisfaction. Table 4 shows that these ratings were significantly higher after psilocybin than after methylphenidate. It is remarkable that 67% of the volunteers rated the experience with psilocybin to be either the single most meaningful experience of his or her life or among the top five most meaningful experiences of his or her life.”
Research consistently finds that participants rate the psychedelic experience as one of the most meaningful ones in their life. This is (at least in this case) without any further prompting/priming/preparations of the participant expect to tell them about what they can expect.
“In written comments about their answers, the volunteers often described aspects of the experience related to a sense of unity without content (pure consciousness) and/or unity of all things.”
“None of the factors on the two widely used questionnaires assessing five factors of personality (NEO and PI-R) and measures of general positive and negative affect (PANAS-X) was differentially affected by psilocybin. At screening and at 2 months after session 1, there were no significant differences between the group that received psilocybin on the first session (N=15) and the group that received methylphenidate on the first session (N=15). Furthermore, within the latter group, there were no significant changes from post-session 1 to postsession 2.”
Although the sessions were impactful, they did not elicit changes in personality or positive/negative affect. This is a different result from a later study by Griffiths et al (2011) that found increases in the personality measure openness.
“An important finding of the present study is that, with careful volunteer screening and preparation and when sessions are conducted in a comfortable, well-supervised setting, a high dose of 30 mg/70 kg psilocybin can be administered safely. It is also noteworthy that, despite meetings and prior sessions with monitors ranging from 8 h (when psilocybin was administered on the first session) up to 24 h (when psilocybin was administered on the third session) of contact time, 22% (8 of 36) of the volunteers experienced a period of notable anxiety/dysphoria during the session, sometimes including transient ideas of reference/ paranoia.”
So, although about 1 in 5 does experience anxiety, there were no (pharmacological) interventions needed. The authors also report that in the follow-up, none of the participants have reported negative (psychological) outcomes.
“To date, there have been no reports of persisting perceptional phenomena sometimes attributed to hallucinogen use or of recreational abuse of hallucinogens, and all participants appear to continue to be high-functioning, productive members of society.”
Find this paper
Journal of Psychopharmacology
July 7, 2006
The psychedelics given at which dose and how many timesPsilocybin 20 - 30
mg | 3x