Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants
- PMID: 35076721
- PMCID: PMC9166883
- DOI: 10.1007/s00213-022-06066-z
Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants
Abstract
Background: LSD and psilocybin are increasingly used in phase I trials and evaluated as therapeutic agents for mental disorders. The phenomenon of reoccurring drug-like experiences after the acute substance effects have worn off was described for both substances and especially attributed to LSD. According to the DSM-V, the persisting and distressing manifestation of these experiences is called hallucinogen-persisting perception disorder (HPPD). Data on both conditions is very limited.
Objective: This study aims to provide descriptive data on reoccurring drug-like experiences after the administration of LSD and psilocybin in controlled studies with healthy participants.
Methods and materials: Data from 142 healthy subjects enrolled in six double-blinded, placebo-controlled, randomized cross-over studies were analyzed. In total, 60 subjects received LSD; 27 subjects received LSD, MDMA, and D-amphetamine; 31 subjects received LSD and psilocybin; and 25 subjects received psilocybin and escitalopram. At the end-of-study visit (mean 39.8 days after last study session, SD 37.2), subjects were asked for any reoccurring drug effects since the initial substance effects had worn off. Those reporting reoccurring perception changes more than 24 h after administration were contacted for follow-up (mean follow-up duration: 31.2 months, SD 28.6).
Results: Thirteen out of 142 subjects reported reoccurring drug-like experiences (LSD: seven, psilocybin: two, both: four). The reported phenomena were predominantly mild and perceived as neutral to pleasant. Flashbacks were mostly of visual nature, lasted for seconds to minutes, and occurred within a week after the last drug administration. Two subjects reported distressing experiences that subsided spontaneously. One subject reported brief and pleasant visual perception changes which reoccurred for 7 months. None of the subjects reported impairment in their daily lives. None of the cases met DSM-V criteria for HPPD.
Conclusion: Reoccurring drug-like experiences after the administration of LSD and psilocybin are a common phenomenon occurring in up to 9.2% of healthy subjects (7.8% for LSD, 8.3% for psilocybin and 14.3% if both substances are administered). Additionally, our work suggests that flashback phenomena are not a clinically relevant problem in controlled studies with healthy participants.
Keywords: Flashbacks; HPPD; Hallucinogen-persisting perception disorder; Hallucinogens; LSD; Psilocybin; Psychedelics.
© 2022. The Author(s).
Conflict of interest statement
Matthias E. Liechti is a consultant for Mind Medicine, Inc., and had no role in financing, planning, or conducting the present study or the present publication. The other authors declare no competing interests.
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References
-
- Abraham HD, David Abraham H (1983) Visual phenomenology of the LSD flashback. 40:884–889. 10.1001/archpsyc.1983.01790070074009 - PubMed
-
- American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders. Am Psychiatric Assoc. 10.1176/appi.books.9780890425596
-
- Becker AM, Holze F, Grandinetti T, Klaiber A, Toedtli VE, Kolaczynska KE, Duthaler U, Varghese N, Eckert A, Grünblatt E, Liechti ME (2021) Acute effects of psilocybin after escitalopram or placebo pretreatment in a randomized, double-blind, placebo-controlled, crossover study in healthy subjects. Clin Pharmacol Ther. 10.1002/cpt.2487 - PubMed
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