Serotonin toxicity of serotonergic psychedelics
- PMID: 34251464
- DOI: 10.1007/s00213-021-05876-x
Serotonin toxicity of serotonergic psychedelics
Abstract
Rationale: In recent years, psychedelic substances with serotonergic mechanisms have accumulated substantial evidence that they may provide therapeutic benefits for people suffering with psychiatric symptoms. Psychiatric disorders targeted by these psychedelic-assisted therapies are managed with serotonergic drugs like selective serotonin reuptake inhibitors (SSRIs) as the current standard of care, so it is important to evaluate the potential risks of drug-drug interactions and serotonin toxicity (ST) between these agents.
Objectives: A critical evaluation of the scientific literature is necessary to delineate the risks of ST when combining psychedelics with available serotonergic pharmacotherapy options. This review article describes signs and symptoms of ST, characterizes mechanisms of ST risk, summarizes what is known about serotonergic psychedelic drug interactions, and outlines potential management strategies.
Results: True ST typically occurs with a serotonergic drug overdose or in combinations in which a drug that can increase intrasynaptic serotonin is combined with a monoamine oxidase inhibitor (MAOI). Serotonergic psychotropics that do not contain MAOIs are low risk in combination with psychedelics that also do not contain MAOIs. Signs and symptoms warranting immediate medical attention include myoclonus, extreme and fluctuating vital signs, agitation or comatose mental state, muscle rigidity, pronounced hyperthermia (fever), and/or seizure activity.
Conclusions: Serotonin-related adverse reactions exist along a spectrum with serotonin syndrome being the most severe manifestations of ST. Due to varying serotonergic mechanisms of psychedelics and psychotropics, with varying propensities to increase intrasynaptic serotonin, some combinations may present a significant risk for serotonin toxicity (ST) while others are likely benign.
Keywords: Hallucinogen; MDMA; Monoamine oxidase inhibitor; Psilocybin; Psychedelic; Selective serotonin reuptake inhibitors; Serotonin syndrome; Serotonin toxicity.
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Similar articles
-
Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity.Br J Anaesth. 2005 Oct;95(4):434-41. doi: 10.1093/bja/aei210. Epub 2005 Jul 28. Br J Anaesth. 2005. PMID: 16051647 Review.
-
The serotonin syndrome. Implicated drugs, pathophysiology and management.Drug Saf. 1995 Aug;13(2):94-104. doi: 10.2165/00002018-199513020-00004. Drug Saf. 1995. PMID: 7576268 Review.
-
The serotonin toxidrome: shortfalls of current diagnostic criteria for related syndromes.Clin Toxicol (Phila). 2022 Feb;60(2):143-158. doi: 10.1080/15563650.2021.1993242. Epub 2021 Nov 22. Clin Toxicol (Phila). 2022. PMID: 34806513 Review.
-
[Serotonin syndrome associated with linezolid use: a case report].Turk Psikiyatri Derg. 2009 Winter;20(4):398-402. Turk Psikiyatri Derg. 2009. PMID: 20013432 Turkish.
-
Serotonin syndrome-A focused review.Basic Clin Pharmacol Toxicol. 2023 Aug;133(2):124-129. doi: 10.1111/bcpt.13912. Epub 2023 Jun 20. Basic Clin Pharmacol Toxicol. 2023. PMID: 37309284 Review.
Cited by
-
Content analysis of Reddit posts about coadministration of selective serotonin reuptake inhibitors and psilocybin mushrooms.Psychopharmacology (Berl). 2024 Apr 30. doi: 10.1007/s00213-024-06585-x. Online ahead of print. Psychopharmacology (Berl). 2024. PMID: 38687360
-
Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial.Sci Rep. 2024 Apr 17;14(1):8833. doi: 10.1038/s41598-024-58318-x. Sci Rep. 2024. PMID: 38632313 Free PMC article. Clinical Trial.
-
Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression.J Psychopharmacol. 2024 May;38(5):458-470. doi: 10.1177/02698811241237870. Epub 2024 Mar 22. J Psychopharmacol. 2024. PMID: 38520045 Free PMC article. Clinical Trial.
-
PAM trial protocol: a randomised feasibility study of psychedelic microdosing-assisted meaning-centred psychotherapy in advanced stage cancer patients.Pilot Feasibility Stud. 2024 Feb 12;10(1):29. doi: 10.1186/s40814-024-01449-9. Pilot Feasibility Stud. 2024. PMID: 38347582 Free PMC article.
-
Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study.J Psychopharmacol. 2024 Feb;38(2):145-155. doi: 10.1177/02698811231224217. Epub 2024 Jan 27. J Psychopharmacol. 2024. PMID: 38281075 Free PMC article.
References
-
- American Psychiatric Association (2010) Practice guideline for the treatment of patients with major depressive disorder. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/...
-
- Bonson KR, Murphy DL (1996) Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, monoamine oxidase inhibitors or lithium. Behav Brain Res 73(1–2):229–233 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources