Finding God in the Brain: That Psilocybin Study

Abel Pharmboy of Terra Sigillata has a recent post covering Sol Snyder’s NEJM commentary (currently free) on finding god in the brain, an overview of some neuroscience thinking on religiosity. Abel and Sol both touch on a 2006 study by Roland Griffiths and colleagues [available to all from the MAPS site here] which reported on a study of the “mystical-type” experiences of humans following a dose of psilocybin. I’ll try to expand a bit on this since it was a very interesting study in many ways. Even though this is a bit dated by now, I wasn’t blogging back then so I’ll give it a whack. It should be obvious where this touches on some of my own scientific interests.

Psilocybin, of course, is

“a naturally occurring tryptamine alkaloid with actions mediated primarily at serotonin 5-HT_2A/C receptor sites, is the principal psychoactive component of a genus of mushrooms (Psilocybe) (Presti and Nichols 2004, Biochemistry and neuropharmacology of psilocybin mushrooms. In: Metzner R, Darling DC (eds) Teonanacatl. Four Trees, El Verano, CA, pp 89–108).“.

In this it shares the presumed primary pharmacological action with the so-called “classical” hallucinogens such as LSD and mescaline. MDMA, by the by, is not a “classical” hallucinogen despite being an indirect serotonin (5-hydroxytryptamine, hence 5-HT) agonist (by virtue of releasing and blocking reuptake of serotonin) with some direct 5-HT agonist properties. There are some similarities in subjective effects but MDMA is sufficiently unique as to get people creating new subjective classifications such as “empathogen”, “entactogen” and the like.

The Hopkins group to which Griffiths belongs is one of the best, perhaps even the best, at conducting high quality, well-controlled and interpretable studies in humans on the effects of drugs (both recreational and therapeutic) which have primary or substantial effects on brain and behavior. For that reason alone this is worth a read, particularly for those that may be skeptical of either psychological experimental methods or what may be viewed as druggie “science”. This type of attitude may also be why the paper was accompanied by an editorial and four commentaries including from Sol Snyder, former NIDA director Charles Schuster and a prior ONDCP-er Herb Kleber [MAPS links for Kleber, Schuster, Snyder, Nichols].

The key elements for this study were

• 30 adult volunteers without prior hallucinogen use that were “medically and psychiatrically healthy). All had some degree of religious affiliation.
  • All 36 volunteers indicated at least intermittent participation in religious or spiritual activities such as religious services, prayer, meditation, church choir, or educational or discussion groups, with 56% (20 volunteers) reporting daily activities and an additional 39% (14 volunteers) reporting at least monthly activities.
• double-blind, cross-over design with two sessions conducted at 2-month interval. In human psychopharm studies, one often prefers a more “active” control condition than an inert capsule/tablet because effects are dramatic enough to immediately break the “blinding”. Meaning it would be obvious to subject and researcher whether they were getting a drug experience or not. So in this case, methylphenidate (aka, Ritalin, the ADHD medication) was the alternate dosing condition. There were two people monitoring the subjects during the drug sessions, these are relatively experienced individuals, familiar with human drug studies but blinded as to condition. They had an average 23% error rate in judging which drug had been administered and opined that multiple doses of psilocybin were employed (a fixed dose was used) which suggests blinding was as good as one might expect.
• a series of questionnaires regarding the drug experience were completed 7 hrs after dosing.
• to give a flavor for the “state of consciousness” and “mysticism” evaluations:
  • This questionnaire is based on the classic descriptive work on mystical experiences and the psychology of religion by Stace (1960; Mysticism and philosophy. Lippincott, Philadelphia), and it provides scale scores for each of seven domains of mystical experiences: internal unity (pure awareness; a merging with ultimate reality); external unity (unity of all things; all things are alive; all is one); transcendence of time and space; ineffability and paradoxicality (claim of difficulty in describing the experience in words); sense of sacredness (awe); noetic quality (claim of intuitive knowledge of ultimate reality); and deeply felt positive mood (joy, peace, and love).
  • The Mysticism Scale has been extensively studied, demonstrates cross-cultural generalizability, and is well regarded in the field of the psychology of religion (Hood et al. 2001, Quasi-experimental elicitation of the differential report of mystical experience among intrinsic indiscriminatively pro-religious types. J Sci Study Relig 29:164–172; Spilka et al. 2005, The psychology of religion: an empirical approach, 3rd edn. Guilford, New York) but has not previously been used to assess changes after a drug experience. A total score and three empirically derived factors are measured: interpretation (corresponding to three mystical dimensions described by Stace (1960): noetic quality, deeply felt positive mood, and sacredness); introvertive mysticism (corresponding to the Stace dimensions of internal unity, transcendence of time and space, and ineffability); and extrovertive mysticism (corresponding to the dimension of the unity of all things/all things are alive).
• two months after each session (i.e., before the second drug experience in the first case) subjects completed additional questionnaires focused on possible persisting effects.
• Three adult “community observers” designated in advance by the subject as having continual contact were interviewed about the subject 1 week and two months after each dosing.
  • The structured interview consisted of asking the rater to rate the volunteer’s behavior and attitudes … The rated dimensions were: inner peace, patience, good-natured humor/playfulness, mental flexibility, optimism, anxiety, interpersonal perceptiveness and caring, negative expression of anger, compassion/social concern, expression of positive emotions (e.g., joy, love, appreciation), and self-confidence.

So what happened?

At 7 h after capsule administration, … The total score and all three empirically derived factors of the Mysticism Scale and all seven scales on States of Consciousness Questionnaire were significantly higher after psilocybin than after methylphenidate. Based on a priori criteria, 22 of the total group of 36 volunteers had a “complete” mystical experience after psilocybin (ten, nine, and three participants in the first, second, and third session, respectively) while only 4 of 36 did so after methylphenidate (two participants each in the first and second sessions).

And at 2 months?

Figure 3 Percentage of volunteers who endorsed each of eight possible answers to the question “how personally meaningful was the experience?” on a questionnaire completed 2 months after the session (N=24)

The discussion gets a bit opaque for a number of reasons. The authors feel compelled to discuss the methodology and the context of prior (infamous) psychedelic research quite a bit for what should be obvious reasons. They soft pedal the implications for “mystical experience” quite a bit. It all boils down, however, to people having experiences quite consistent with other classical hallucinogens, that were rated as being “personally meaningful” two months later and that caused positive attitude, social and/or mood effects (by self report and with external verification).

Does this get us closer to a science of religion? Of understanding individual differences in religiosity? Perhaps. I certainly find it fascinating. It might give us a toehold on individual differences in, say 5-HT_2A/C receptor expression or function, that pre-dispose one to religion. To plasticity in such systems that might result from religious experience. To understanding the mechanism that are involved in the more flamboyant behavioral expressions of religious ferver.

Finally, because I am very nearly unable to post on science without talking about funding. It is interesting that this research group, which has a very long history of very high quality research publication and NIH funding, put out a letter to drum up private philanthropy to support this work. (It would appear that psychedelic research philanthropy outfit, the Heffter Research Insitute, has provided some support to the Griffiths group.) One might deduce the reasons for this from the immediate response from the NIDA director, Nora Volkow, M.D., which speaks volumes. NIDA isn’t interested in anything that might encourage people to use recreational drugs. Period. But this seems short sighted to me. After all, much of NIDA’s portfolio is about describing how much various drugs make one “feel good”. Why doesn’t that encourage drug use? Why is it different to explore higher levels of “feel good”?

NIDA isn’t necessary for funding, of course. One can see where this research might be of interest to the NIMH from a basic neuroscience of behavior perspective. Indeed it wouldn’t be a stretch to see this as linking into some therapeutic avenues. Nevertheless this whole thing illustrates a fairly concrete flaw in the system. The study was excellent work with some obvious avenues of interest to basic neuroscience and indeed the public at large. Yet funding of additional work is going to be hard to come by, NIH-wise, because of the rather rigid NIDA position. Seems a shame.