ABSTRACT
Introduction
A limited number of preliminary open-label (n = 3) and placebo-controlled clinical trials (n = 5) have suggested psilocybin and LSD as potential rapid antidepressants. In this context, there is a growing need to verify and document their safety and tolerability as therapeutic agents, discuss the challenges associated with their administration, and develop safety protocols for their use as next-generation therapeutic agents.
Areas covered
We have analyzed all randomized, double-blind, and controlled trials that assessed the antidepressant effects of psilocybin and LSD in clinical populations to date, taking special attention to adverse events (AEs) related to their use. Prevalence, significance, and mechanisms of action related to AEs were systematically extracted, analyzed, and discussed.
Expert opinion
There were no serious AEs related to psilocybin and LSD administration. Most AEs were expected, manageable, and transient. Nevertheless, safety and tolerability concerns regarding some effects, such as dissociation, paranoia, and confusion, remain. Thus, randomized controlled trials with bigger samples are warranted to confirm their therapeutic effects and further investigate their safety and tolerability.
Article highlights
Psilocybin and LSD are being investigated as to treat mood disorders
While preliminary and nonconfirmatory research is promising, safety and tolerability associated with these drug’s administration needs further investigation
Current randomized clinical trials on the subject reported no serious adverse events
Most common adverse events associated with these drugs are headaches/migraines, nausea/vomiting, acute raises in cardiovascular variables, and emotional distress/psychological discomfort/anxiety
There is still concern with less common adverse events, such as dissociation, paranoia, and con fusion, and bigger trials with larger samples are needed to confirm the therapeutic effects of psilocybin and LSD and ascertain the side effects continue within acceptable parameters
Declaration of interests
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership, or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.