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.

中文翻译：

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5-羟色胺能迷幻药的5-羟色胺毒性

摘要

基本原理

近年来，具有血清素能机制的迷幻物质已经积累了大量证据，表明它们可能为患有精神症状的人提供治疗益处。这些迷幻辅助疗法所针对的精神疾病采用 5-羟色胺能药物（如选择性 5-羟色胺再摄取抑制剂 (SSRIs) 作为当前护理标准）进行管理，因此评估药物间相互作用和 5-羟色胺毒性 (ST) 之间的潜在风险非常重要这些代理。

目标

当迷幻药与可用的 5-羟色胺能药物治疗方案相结合时，有必要对科学文献进行批判性评估，以描述 ST 的风险。这篇综述文章描述了 ST 的体征和症状，描述了 ST 风险的机制，总结了关于 5-羟色胺能迷幻药物相互作用的已知信息，并概述了潜在的管理策略。

结果

真正的 ST 通常发生在 5-羟色胺能药物过量或可增加突触内 5-羟色胺的药物与单胺氧化酶抑制剂 (MAOI) 联合使用时。不含 MAOI 的 5-羟色胺能精神药物与同样不含 MAOI 的迷幻药合用风险较低。需要立即就医的体征和症状包括肌阵挛、极端和波动的生命体征、激动或昏迷的精神状态、肌肉僵硬、明显的高热（发烧）和/或癫痫发作。

结论

5-羟色胺相关的不良反应存在于一个范围内，5-羟色胺综合征是 ST 最严重的表现。由于迷幻药和精神药物的 5-羟色胺能机制不同，增加突触内 5-羟色胺的倾向不同，一些组合可能会带来 5-羟色胺毒性 (ST) 的显着风险，而其他组合可能是良性的。