Does psilocybin cause changes in personality? Maybe, but not so fast

This morning I came across a news article about a new study claiming that psilocybin (the active ingredient in hallucinogenic mushrooms) causes lasting changes in personality, specifically the Big Five factor of openness to experience.

It was hard to make out methodological details from the press report, so I looked up the journal article (gated). The study, by Katherine MacLean, Matthew Johnson, and Roland Griffiths, was published in the Journal of Psychopharmacology. When I read the abstract I got excited. Double blind! Experimentally manipulated! Damn, I thought, this looks a lot better than I thought it was going to be.

The results section was a little bit of a letdown.

Here’s the short version: Everybody came in for 2 to 5 sessions. In session 1 some people got psilocybin and some got a placebo (the placebo was methylphenidate, a.k.a., Ritalin; they also counted as “placebos” some people who got a very low dose of psilocybin in their first session). What the authors report is a significant increase in NEO Openness from pretest to after the last session. That analysis is based on the entire sample of N=52 (everybody got an active dose of psilocybin at least once before the study was over). In a separate analysis they report no significant change from pretest to after session 1 for the n=32 people who got the placebo first. So they are basing a causal inference on the difference between significant and not significant. D’oh!

To make it (even) worse, the “control” analysis had fewer subjects, hence less power, than the “treatment” analysis. So it’s possible that openness increased as much or even more in the placebo contrast as it did in the psilocybin contrast. (My hunch is that’s not what happened, but it’s not ruled out. They didn’t report the means.)

None of this means there is definitely no effect of psilocybin on Openness; it just means that the published paper doesn’t report an analysis that would answer that question. I hope the authors, or somebody else, come back with a better analysis. (A simple one would be a 2×2 ANOVA comparing pretest versus post-session-1 for the placebo-first versus psilocybin-first subjects. A slightly more involved analysis might involve a multilevel model that could take advantage of the fact that some subjects had multiple post-psilocybin measurements.)

Aside from the statistics, I had a few observations.

One thing you’d worry about with this kind of study – where the main DV is self-reported – is demand or expectancy effects on the part of subjects. I know it was double-blind, but they might have a good idea about whether they got psilocybin. My guess is that they have some pretty strong expectations about how shrooms are supposed to affect them. And these are people who volunteered to get dosed with psilocybin, so they probably had pretty positive expectations. I wouldn’t call the self-report issue a dealbreaker, but in a followup I’d love to see some corroborating data (like peer reports, ecological momentary assessments, or a structured behavioral observation of some kind).

On the other hand, they didn’t find changes in other personality traits. If the subjects had a broad expectation that psilocybin would make them better people, you would expect to see changes across the board. If their expectations were focused around Openness-related traits, that’s less relevant.

If you accept the validity of the measures, it’s also noteworthy that they didn’t get higher in neuroticism — which is not consistent with what the government tells you will happen if you take shrooms.

One of the most striking numbers in the paper is the baseline sample mean on NEO Openness — about 64. That is a T-score (normed [such as it is] to have a mean = 50, SD = 10). So that means that in comparison to the NEO norming sample, the average person in this sample was about 1.4 SDs above the mean — which is above the 90th percentile — in Openness. I find that to be a fascinating peek into who volunteers for a psilocybin study. (It does raise questions about generalizability though.)

Finally, because psilocybin was manipulated within subjects, the long-term (one year-ish) followup analysis did not have a control group. Everybody had been dosed. They predicted Openness at one year out based on the kinds of trip people reported (people who had a “complete mystical experience” also had the sustained increase in openness). For a much stronger inference, of course, you’d want to manipulate psilocybin between subjects.