Psychedelics and hallucinogens such as ayahuasca, LSD, and psilocybin show promise for treating several psychiatric disorders. Evidence supports their use in depression, including treatment-resistant depression, with psilocybin and ayahuasca showing good results. In randomized controlled trials, psilocybin and LSD improved symptoms in anxious patients, and psilocybin reduced obsessive-compulsive symptoms in a small sample. Evidence for substance use disorders is less robust but suggests a possible role for LSD and psilocybin in alcohol use disorders and for psilocybin in tobacco addiction. These substances appear safe and well-tolerated in clinical settings. Their mechanisms involve 5-HT2A receptor agonism and changes in brain connectivity, though not fully understood. However, studies have small samples and heterogeneous methods, so more research is needed.
Treatment-resistant depression (TRD) shows minimal improvement after two or more antidepressant trials. Ketamine-assisted psychotherapy (KAP) combines the rapid antidepressant effects of ketamine with psychotherapy to improve and sustain outcomes. A systematic review of eight studies involving 421 participants found that KAP significantly reduces depressive symptoms compared to ketamine alone. Preliminary evidence also suggests KAP may help with PTSD, anxiety, and chronic pain. However, small sample sizes, varying protocols, short follow-ups, and risk of bias limit firm conclusions. The findings indicate KAP is promising for TRD, but larger, high-quality trials are needed to confirm effectiveness and establish standard protocols.