Psilocybin’s anti-depressant potential has been demonstrated again in a Phase 2 randomized, clinical trial.
After monitoring 104 participants with major depression – 50 of which had been given a single dose of psilocybin; 54 had been given the placebo niacin – the researchers behind the study found that those given the magic mushroom drug had significantly lower depression scores.
The researchers say their findings add to the growing body of evidence that psilocybin can be used in a clinical setting to treat depression.
The results were published in JAMA.
Psilocybin on trial
To get their findings, the researchers first recruited 104 participants with major depressive disorder from across the US. At 11 sites from December 2019 to June 2022, these participants were then given either 25 milligrams (mg) of synthetic psilocybin or 100 mg of niacin (vitamin B3).
The psilocybin was supplied by Usona Institute Inc., the research organization that funded the study.
The doses were administered under the supervision of study coordinators. During the sessions, both parties (the participants and the researchers) were blinded as to whether the substances given were psilocybin or the placebo.
Participants were then psychologically assessed five times following their dose over a period of six weeks.
However, not every participant made it to the last assessment. By week six of the study, one participant in the psilocybin group and nine in the niacin group had withdrawn. In their paper, the researchers speculate that more niacin-participants dropped out of the study as it became apparent (due to the lack of hallucinations) that they hadn’t received the genuine psychedelic.
After unblinding the data and comparing all the results of the two different trial groups (including the limited data of the drop-outs), the researchers found that the participants given the psychedelic compound experienced, on average, a greater reduction in their depression scores from their baselines (-19.1%) than the participants given the placebo (-6.8%).
This difference, however, only became pronounced at day eight post-dose; prior to that, the drop in depression scores in both groups was remarkably similar. Post-day eight, the greater anti-depressant effect of psilocybin was sustained until at least day 43 (the last day of assessment post-dose). Although, by the end of the trial, the 15.9% difference in sustained remission rates between the two groups wasn’t considered significantly different.
The benefits of psilocybin that were recorded also often came with unwelcome side effects. Participants in the psilocybin group reported significantly more headaches and nausea, but these effects resolved by the study’s conclusion.
Despite the limitations of the study (the drop-outs) and the somewhat mixed results, the researchers behind the study say their findings show psilocybin still holds “promise” as a novel treatment for major depressive disorder.
Psilocybin and depression
Previous research into psilocybin has suggested that the compound exerts its psychedelic effects by acting on the body’s serotonin 2A receptor (5-HT2AR). Through this mechanism, and the presence of a trained therapist, many psychedelic researchers believe that psilocybin can become a valuable drug for the treatment of depression.
And this notion has been evidenced several times now in trials.
A study published this year found that the drug’s antidepressant effects continued to last for at least 14 days after psychedelic-assisted therapy sessions.
Another study published last year found that the compound’s anti-depressive effects can last even longer, for at least a year. Most of trial’s 24 participants with a history of depression reported lower depression scores three months, six months, and 12 months after their psilocybin trip.