Serotonin toxicity of serotonergic psychedelics
Benjamin Malcolm, Kelan Thomas
Psychopharmacology July 12, 2021 DOI: 10.1007/s00213-021-05876-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Serotonin |
| Citations | 131 |
| Key findings | True serotonin toxicity typically occurs with a serotonergic drug overdose or in combinations involving an MAOI; serotonergic psychotropics without MAOIs are low risk in combination with psychedelics that also do not contain MAOIs. |
Abstract
RationaleIn 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.ObjectivesA 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.ResultsTrue 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.ConclusionsSerotonin-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.
Comparable studies
Other narrative reviews on serotonin, most cited first.
Citations in the library
Cited by 104
- Adverse effects of psychedelics: From anecdotes and misinformation to systematic science. Journal of Psychopharmacology February 2, 2022
- Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double‐Blind, Placebo‐Controlled, Crossover Study in Healthy Subjects Clinical Pharmacology & Therapeutics November 7, 2021
- Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial Journal of Psychopharmacology March 20, 2023
- Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review Psychopharmacology March 7, 2022
- Assessing the risk–benefit profile of classical psychedelics: a clinical review of second-wave psychedelic research Psychopharmacology January 13, 2022
and 99 more in the library
Cites 44
- The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology July 19, 2010
- Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology May 20, 2016
- MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology September 1, 2019
- Carrier‐Mediated Release of Serotonin by 3,4‐Methylenedioxymethamphetamine: Implications for Serotonin‐Dopamine Interactions Journal of Neurochemistry 1996
- Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids Addiction December 20, 2006
and 39 more in the library