Serotonin toxicity of serotonergic psychedelics

Summary & key facts

This paper is a careful review of existing studies about whether psychedelic drugs that affect serotonin can cause dangerous ‘serotonin toxicity’ when used with other drugs that also change serotonin. The authors looked at how serotonin toxicity happens, what it looks like, and what combinations are most risky. They say that serious toxicity usually shows up after an overdose or when a serotonin‑raising drug is combined with a monoamine oxidase inhibitor, and that many psychedelic + antidepressant pairings that do not involve MAO inhibitors are likely low risk. The review also explains clear warning signs and stresses that risk depends on the exact drugs involved.

Key facts:

• This paper is a review of many scientific reports. It aims to judge the risk of serotonin toxicity when people mix serotonergic psychedelics with other serotonin‑acting psychiatric medicines like selective serotonin reuptake inhibitors (SSRIs).
• True serotonin toxicity (sometimes called serotonin syndrome) most often happens after a drug overdose or when a drug that raises serotonin is combined with a monoamine oxidase inhibitor (MAOI). An MAOI is a drug that blocks an enzyme that normally breaks down serotonin, so serotonin levels can rise a lot.
• Psychedelic drugs and psychiatric medicines that do not include MAOIs are generally low risk when used together, according to available evidence. That means many common combinations appear unlikely to cause true serotonin toxicity.
• Serotonin toxicity lies on a spectrum. Mild reactions can happen, but the most severe form — serotonin syndrome — includes very serious problems such as sudden muscle jerks, very unstable or swinging heart rate and blood pressure, extreme agitation or coma, very stiff muscles, very high fever, and seizures. These signs need immediate medical attention.
• Some psychedelics differ in exactly how they affect serotonin. Because of those different mechanisms, some specific drug combinations may carry a meaningful risk while others are probably safe. The authors stress that risk depends on which drugs are combined, not just on the broad label ‘psychedelic’ or ‘antidepressant’.
• The authors summarize possible ways to manage serotonin toxicity and give criteria used by clinicians to recognize it, but they note that available evidence varies and that risks must be judged case by case rather than assumed to be identical for all drugs.

Topics

Forensic Toxicology and Drug Analysis Pharmacology and Obesity Treatment Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Biochemistry Biology Enzyme Internal medicine Medicine Monoamine oxidase Monoamine oxidase inhibitor Pharmacology Psychiatry Psychology Receptor Serotonergic Serotonin Serotonin syndrome

Substances

Ayahuasca LSD MDMA Psilocybin

Conditions & symptoms

Anxiety Depression PTSD Anxiety or worry Panic