Combining psychedelic substances with common psychiatric medications such as SSRIs carries varying risks of serotonin toxicity, a potentially severe reaction. True serotonin toxicity typically arises only from overdoses or combinations involving a monoamine oxidase inhibitor (MAOI). Serotonergic psychotropics without MAOIs pose low risk when combined with psychedelics that also lack MAOIs. Symptoms that require immediate medical attention include myoclonus, extreme and fluctuating vital signs, agitation or coma, muscle rigidity, pronounced fever, and seizures. The review concludes that some drug combinations present significant risk for serotonin toxicity while others are likely benign, depending on their specific serotonergic mechanisms.
Policymakers are increasingly using clinical trial data to justify deprioritizing, decriminalizing, or legalizing psychedelic substances, but personal possession limits written into law often lack scientific grounding. This commentary argues that allowable amounts should be based on moderate-high doses shown safe and effective in clinical trials, common naturalistic use, and dose-equivalence studies. The authors provide a table of evidence-informed moderate-high doses for seven psychedelics to guide consistent and equitable policy limits, aiming to replace arbitrary thresholds with scientifically justified ones.