Psychedelics and suicidality: A double-edged sword - risks, mechanisms, and moving forward

Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, and dimethyltryptamine (DMT), have re-emerged as promising treatments for psychiatric conditions linked to suicidality. However, rare reports of increased suicidality potentially associated with psychedelic use have raised safety concerns. This article examines the complex relationship between psychedelics and suicidality and develops a theoretical mechanistic model: the double-edge sword. We first summarise available data on suicide-related outcomes associated with psychedelic use reported in recreational settings and in first and second waves of clinical research. Several deaths have occurred following non-medical psychedelic use, where unsafe contexts led to accidents or presumed suicides, with unclear suicidal intent. Though less frequent, rare cases of increased suicidal ideation and behaviours have also been reported in clinical settings, without significant differences from placebo groups or established causality. We then offer a theoretical mechanistic framework encompassing both anti- and pro- suicidality mechanisms. Specifically, we propose three key psychological mechanisms - reduced fear of death, altered representations of the world and reduced experiential avoidance - constituting a double-edged sword: the same processes that facilitate healing may, in vulnerable individuals or unsupportive contexts, precipitate destabilisation and suicidal crises. Then, we turn to clinical practice recommendations aimed at harnessing these mechanisms for therapeutic benefit while mitigating suicide risk. Adequate therapeutic support, spanning screening, preparation, in-session guidance, and integration, seems essential to shifting outcomes toward benefit. Finally, we discuss future directions regarding potential psychedelic use in suicidal crises and propose guidelines to better study and characterise the underlying mechanisms driving this complex relationship.