Psychotogenic potential of prescribed drugs

Abstract

Australian & New Zealand Journal of Psychiatry, 57(6) Interest in prescribing psychoactive drugs as treatments for mental health conditions has been highlighted recently by the decision by the Therapeutic Goods Administration (TGA) to permit, from 1 July 2023, authorised psychiatrists to prescribe medicines containing psilocybin for treatment-resistant depression and 3,4-methylenedioxy-methamphetamine (MDMA) for the treatment of post-traumatic stress disorder (PTSD). A range of psychoactive substances may unmask or trigger psychotic symptoms or a psychotic episode in individuals with a vulnerability to psychosis (Lappin et al., 2017). People with substance-related psychoses associated with amphetamines, hallucinogens (including psychedelics and other compounds) and cannabis show heightened risks of transition to schizophrenia (Murrie et al., 2020), resulting in long-term clinical and functional impairment. Our group demonstrated in a large metaanalysis that the proportion of transition from substance-related psychosis to schizophrenia was highest for cannabis at 34% with high rates also observed for hallucinogens/psychedelics (26%) and for amphetamines (22%) (Murrie et al., 2020). We argue here that the risk for development of psychotic symptoms and episodes in the context of substance use is present whether the drug is prescribed or illicit. The harms associated with use are from the active effects of the drug itself, not the legal status of the substance. While it is true that illicit drug use is associated with additional harms (such as contamination with other substances, injecting-related harms or polysubstance ingestion), these substances have significant harmful psychomimetic effects, whether prescribed or illicitly sourced. Most evidence is available for amphetamines, which are commonly prescribed for attention-deficit/hyperactivity disorder (ADHD) and for other indications, including sleep conditions. Over recent years, we have witnessed increasing interest in the potential health benefits of hallucinogens/psychedelics and cannabis. We call for caution in therapeutic use of these three major drug classes without first, making a rigorous assessment of potential risk factors for the future development of psychosis and second, regular monitoring for emerging symptoms of psychosis.