Safety issues of psilocybin and LSD as potential rapid acting antidepressants and potential challenges

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.

KEYWORDS:

• Psilocybin
• LSD
• adverse events
• depression
• rapid acting antidepressants
• psychedelics

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.

Additional information

Funding

GN Rossi received funding from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). JEC Hallak is recipient of CNPq 1A productivity fellowship. RG dos Santos is Fellow of the Programa Nacional de Pós-Doutorado, Braz il (PNPD/CAPES).