Natural hallucinogens such as psilocybin, ayahuasca, ibogaine, and mescaline show therapeutic potential for treatment-resistant depression, PTSD, existential anxiety, and substance addictions. Psilocybin has the best-documented evidence, with controlled trials indicating rapid and lasting improvement in treatment-resistant depression, reduction of existential anxiety, easing of obsessive-compulsive symptoms, and support for addiction therapy, alongside a favorable safety profile. Ayahuasca exhibits antidepressant and anxiolytic effects and potential in addiction treatment. Ibogaine reduces withdrawal and drug craving in opioid addiction and PTSD symptoms in war veterans but requires caution due to cardiotoxic side effects.
Hallucinogens from fungi and animals, such as psilocybin, ergot alkaloids, and bufotenine, have been used traditionally for centuries and are now being studied for therapeutic applications. These compounds vary widely in chemical structure and mechanism, affecting neurotransmitter systems to alter perception, cognition, and mood. A review of literature from 1983 to 2025 indicates that preclinical and limited clinical data suggest benefits for mood and anxiety disorders, treatment-resistant depression, pain, and possibly neurodegenerative diseases. Some compounds may serve as leads for new drugs. Further research is needed to understand their mechanisms, safety, and therapeutic potential in neuropsychiatry.