This Phase I RCT indicates that 10mg and 25mg doses of psilocybin are generally well-tolerated when administered to up to 6 participants simultaneously. Participants (n=89) each received one-to-one psychological support during the sessions. 511 treatment adverse events (TEAEs) were reported, 67% of which were resolved on the day of administration in the largest published trial with psilocybin to date.
“Background: Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin’s effects on cognitive function have not been widely or systematically studied.
Aim: The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date. Primary and secondary endpoints assessed the short- and longer-term change in cognitive functioning, as assessed by a Cambridge Neuropsychological Test Automated Battery (CANTAB) Panel, and emotional processing scales. Safety was assessed via endpoints which included cognitive function, assessed by CANTAB global composite score, and treatment-emergent adverse event (TEAE) monitoring.
Methods: In this phase 1, randomised, double-blind, placebo-controlled study, healthy participants (n = 89; mean age 36.1 years; 41 females, 48 males) were randomised to receive a single oral dose of 10 or 25 mg psilocybin, or placebo, administered simultaneously to up to six participants, with one-to-one psychological support – each participant having an assigned, dedicated therapist available throughout the session.
Results: In total, 511 TEAEs were reported, with a median duration of 1.0 day; 67% of all TEAEs started and resolved on the day of administration. There were no serious TEAEs, and none led to study withdrawal. There were no clinically relevant between-group differences in CANTAB global composite score, CANTAB cognitive domain scores, or emotional processing scale scores.
Conclusions: These results indicate that 10 mg and 25 mg doses of psilocybin were generally well tolerated when given to up to six participants simultaneously and did not have any detrimental short- or long-term effects on cognitive functioning or emotional processing.”
Authors: James Rucker, Lindsey Marwood, Riikka-Liisa J. Ajantaival, Catherine Bird, Hans Eriksson, John Harrison, Molly Lennard-Jones, Sunil Mistry, Francesco Saldarini, Susan Stansfield, Sara J. Tai, Sam Williams, Neil Watson, Ekaterina Malievskaia & Allan H. Young
Ensuring drugs are safe for human consumption is one of the most important parts of the drug development process. Alongside proving their effectiveness in treating their target disorder, researchers must prove that their new drugs do not possess any threat to human health. To do so, new drug candidates must undergo rigorous testing in what is known as the clinical trial process. This process consists of various phases, with each phase having different requirements the drug under study must meet. Randomized-controlled trials (RCTs) have become the gold standard of this process. These trials tend to consist of large sample sizes to enhance the statistical significance and the overall generalizability of trial results.
In the realm of psychedelic research, the criterion set out by the gold standard RCTs is proving difficult to meet. Firstly, sample sizes in trials tend to be low given that psychedelics remain as Schedule I substances making them difficult and expensive to procure. Blinding and randomization are also difficult given the potency and effects psychedelics have once consumed. Despite these difficulties, as psychedelic research is progressing it slowly becoming more compliant with these gold-standard RCTs which are favoured by regulatory agencies like the FDA and EMA.
The present study is the largest study with psilocybin published in a peer-reviewed journal to date. One of the many trials sponsored by Compass Pathways, the overall aim of this study was to assess the safety and feasibility of the simultaneous administration of single doses of either 10 or 25 mg doses of psilocybin compared with placebo in healthy participants. The study also assessed the effects of psilocybin on some key aspects of cognitive function. This Phase I study saw 89 healthy participants being administered either 10mg or 25mg of psilocybin or a placebo simultaneously in groups of up to six people. Dosing took place in a controlled environment and each participant had one-to-one psychological support.
The main findings:
- 10mg and 25mg of doses of psilocybin were generally well tolerated by trial participants given their willingnes to undergo simulatenous administration and group preperation sessions.
- 511 treatment emergent adverse events (TEAEs) were reported during th 12 week study period: 217 in the 25mg psilocybin arm, 203 in the 10mg psilocybin arm and 91 in the placebo arm. 67% of TEAEs were resolved on the day of administration while no serious TEAEs were reported.
- The Cambridge Neuropsychological Test Automated Battery (CANTAB) Panel assesseed measures of congitive function. Small differences in congitive measures were obsereved between groups but no clinically relevant negatvie findings were identified.
- Psilocybin was found to have no consistent short- or long-term effects on any measures of social cognition.
Overall, the findings of this study support the use of psilocybin for the treatment of mental health disorders such as depression. Furthermore, given that the administration of psilocybin took place in a group setting, the findings also support the use of psilocybin in this context providing there is adequate preparation and psychological support given in a supportive environment. If psilocybin-assisted therapies are to become available, the group context may prove to be both a cost- and time-effective method.
The authors do acknowledge several limitations to their study. Given that the efficacy of blinding was not assessed, it is not possible to rule out the unblinding of participants (i.e guessing their treatment) did not impact results. 37% of trial participants had previously used psilocybin so it is plausible to assume that these participants could have determined their treatment group. Practice effects may also have influenced results as a familiarisation session with testing procedures took place prior to treatment administration. While psychedelic research as a whole must overcome limitations such as these, the overall results of this trial are a positive step toward realizing the therapeutic potential of psychedelics.
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The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation
Journal of Psychopharmacology
January 4, 2022
Authors associated with this publication with profiles on BlossomJames Rucker
James Rucker is a Senior Clinical Lecturer at The Institute of Psychiatry, Psychology & Neuroscience in King's College London.
Institutes associated with this publicationKing's College London
KCL is home to the Psychedleic Trials Group.
The psychedelics given at which dose and how many timesPsilocybin 10 - 25