Psychedelics: A new era of treatment?

Psychedelics such as LSD, psilocybin, DMT, ayahuasca, and mescaline have a long history of use across civilizations and briefly entered psychiatry after LSD's discovery in 1950 before being prohibited due to recreational use in the mid-1960s. Renewed scientific interest over the last decade, termed the 'Psychedelic Renaissance', has led to a review of their pharmacology and therapeutic potential. These drugs act as agonists on 5-HT2A receptors in brain regions involved in mood and emotion, increasing glutamatergic tone and neuroplasticity while reducing amygdala activity. Experimental, open-label, and randomized controlled trials show anxiolytic, antidepressive, and antiaddictive effects, including reduced anxiety and depression in cancer patients and reduced alcohol and tobacco dependence. Evidence remains preliminary, pending larger long-term studies.

Study at a glance

Abstract

Introduction Psychedelics - including LSD (lysergic acid diethylamide), psilocybin, DMT (N, N-dimethyltryptamine), ayahuasca and mescaline - have an ancient history across various civilizations. In 1950, after LSD’s discovery by Hofmann, psychedelics enjoyed a short-lived relationship with psychiatry, before prohibitive legislature emerging in response to the recreational use in the mid-1960s. However, the last decade has witnessed a renewed scientific interest in psychedelics - a phenomenon referred to as the ‘Psychedelic Renaissance’. Objectives Review the pharmacology of psychedelic drugs and the latest evidence of its therapeutic potentials in anxiety, mood and addictive disorders. Methods Literature review performed on PubMed and Google Scholar databases, using the keywords “psychedelics”, “hallucinogens”, “d-lysergic acid diethylamide (LSD)”, “psilocybin”, “ayahuasca”, “mescaline”, “DMT (N,N-dimethyltryptamine)”. Results The psychedelics or “classic hallucinogens” can be subdivided into three sub-classes: the plant-derived tryptamines (psilocybin and ibogaine) and phenethylamines (mescaline), and the semisynthetic ergolines (LSD). The therapeutic potentials are mediated by an agonist action on 5-HT2A receptors expressed in frontal and paralimbic structures involved in mood and emotion regulation, introspection, interoception and self-consciousness. Stimulation of 5-HT2ARincreases the glutamatergic tone and neuroplasticity and is accompanied by reduced amygdala activity, reducing anxiety. Experimental, open-label, and RCTs showed anxiolytic, antidepressive, and antiaddictive effects with psychedelics. As examples, psilocybin and LSD reduced anxiety and depression in cancer patients and symptoms of alcohol and tobacco dependence, and ayahuasca reduced depression in treatment-resistant depression. Conclusions Despite the promising effects of psychedelics on anxiety, depression and addiction, the evidence is still preliminary, waiting for long-term studies with bigger samples. Conflict of interest No significant relationships.