Trip killers: Addressing a critical knowledge gap in psychedelic research.

Psychedelic drugs are being studied as treatments for mental health conditions and used recreationally, but they can cause intense psychological distress known as a "bad trip," which may lead to emergency care or psychiatric hospitalization. Managing these episodes should prioritize non-pharmacological strategies, but when those are insufficient, medications that can safely end the psychedelic state are needed. This review systematically evaluates candidate abortive agents, including serotonin antagonists, antipsychotics, and certain anxiety and depression drugs, considering their mechanisms, safety, and suitability for acute care. The authors propose a provisional framework for pharmacological management and identify priorities for future research.

Study at a glance

Abstract

Psychedelic drugs are increasingly under investigation as potential therapeutic agents for mental health conditions and are being increasingly used recreationally. Psychedelic use may result in an episode of intense psychological distress, commonly referred to as a "bad trip." Bad trips represent a potentially volatile, erratic, and dangerous situation, which may, in extreme cases, require presentation to accident and emergency departments and psychiatric hospital admission. Managing such cases requires careful consideration, with priority given to non-pharmacological strategies. When these measures prove insufficient, an alternative approach may be necessary, one that can effectively attenuate or terminate the psychedelic state and restore psychological stability. Despite clinical relevance, there is no systematic evaluation of pharmacological interventions to terminate such experiences. This review identifies and critically appraises candidate medications with potential utility as abortive agents, including serotonin antagonists, drugs for psychosis, and select drugs for anxiety and depression. We review these agents, their mechanisms of action, pharmacokinetics, safety profiles, and applicability in acute care settings. Binding strength at the molecular level, potency to functionally block receptor-mediated effects, and lack of side effects are key considerations. We conclude by proposing a provisional framework for the pharmacologic management of adverse psychedelic experiences and highlight key priorities for future research.