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Also known as: Magic Mushrooms, Psilocybe, Shrooms
Psilocybin is a naturally occurring psychedelic compound found in over 200 species of mushrooms. When ingested, it converts to psilocin, which activates serotonin receptors in the brain, particularly the 5-HT2A receptor. This leads to altered perception, enhanced emotional processing, and increased ...
Applications
7
Clinical Trials
7
Evidence Tier
strong
Duration
4-6 hours peak effects, with afterglow lasting 6-12 hours
Gabriel Brain Score
Strong Evidence
Psilocybin is a naturally occurring psychedelic compound found in over 200 species of mushrooms. When ingested, it converts to psilocin, which activates serotonin receptors in the brain, particularly the 5-HT2A receptor. This leads to altered perception, enhanced emotional processing, and increased neuroplasticity. Research shows psilocybin creates rapid and durable antidepressant effects, with single doses producing symptom reductions lasting weeks to months. Compass Pathways' COMP360, a synthetic psilocybin formulation, successfully met primary endpoints in two Phase 3 trials for treatment-resistant depression in 2026, showing a 3.8-point MADRS reduction compared to control doses. The compound appears to work by disrupting rigid thought patterns and promoting cognitive flexibility, while simultaneously reducing activity in the brain's default mode network, which is often hyperactive in depression. Johns Hopkins, Imperial College London, and other leading institutions have published groundbreaking studies demonstrating psilocybin's efficacy for depression, anxiety in cancer patients, addiction, and obsessive-compulsive disorder. The therapeutic effects appear enhanced when combined with psychotherapy and intention-setting.
Indigenous Mesoamerican cultures, particularly the Mazatec people of Mexico, have used psilocybin mushrooms in spiritual and healing ceremonies for thousands of years. These "sacred mushrooms" or "flesh of the gods" were central to religious rituals before Spanish colonization attempted to suppress their use.
0.1-0.3g dried mushrooms (100-300mg)
25mg synthetic psilocybin or 3-5g dried mushrooms
5g+ dried mushrooms (Terence McKenna's "heroic dose")
* Dosing should be individualized. Always consult with a qualified healthcare practitioner.
Schedule I federally; decriminalized in Oregon, Colorado, and several cities. Legal supervised therapy in Oregon since 2023.
Legal for supervised therapy in Oregon (US), Jamaica (unregulated), Netherlands (truffles only). Illegal in most countries under UN conventions.
Baltimore, United States
London, United Kingdom
New York City, United States
Berkeley, United States
Portland, Eugene, Bend, United States
San Francisco, United States
DMT (N,N-Dimethyltryptamine) and its close relative 5-MeO-DMT are among the most potent psychedelics known, producing intense but brief experiences. N,N-DMT, found in many plants and the active component of ayahuasca, creates vivid geometric patterns, encounters with seemingly autonomous entities, and profound shifts in consciousness lasting 15-30 minutes when smoked or vaporized. 5-MeO-DMT, found naturally in certain plants and the venom of the Sonoran Desert toad (Incilius alvarius), produces a more unified, often ineffable "white light" experience characterized by ego dissolution and feelings of cosmic unity. Clinical research on 5-MeO-DMT has accelerated dramatically, with multiple Phase 1/2 trials active in 2024-2025. Beckley Psytech's Phase 2b trial of intranasal 5-MeO-DMT (BPL-003) for treatment-resistant depression showed rapid, durable antidepressant effects with MADRS reductions of 10.8-11.1 points at day 8, generally well-tolerated with no serious adverse events. Sublingual formulations are also in trials for anxiety and depression. Imperial College London reported that a single dose of ayahuasca's DMT compound produced significant and lasting depression relief in 2026 research. The rapid onset and short duration make DMT particularly interesting for clinical settings, as the entire experience can occur within a supervised session.
LSD (lysergic acid diethylamide) is a potent semi-synthetic psychedelic first synthesized by Albert Hofmann at Sandoz Laboratories in 1938. It activates serotonin 5-HT2A receptors, producing profound alterations in consciousness, perception, mood, and cognition lasting 8-12 hours. During the 1950s-60s, LSD showed remarkable promise in psychiatric research for treating alcoholism, anxiety, and enhancing psychotherapy before political backlash led to prohibition. Modern neuroscience reveals LSD increases brain network connectivity, particularly between regions that don't normally communicate, promoting cognitive flexibility and creative problem-solving. Unlike psilocybin, LSD has a longer duration and tends toward more geometric and abstract visual experiences. Recent clinical trials on LSD microdosing (10-20 μg doses, sub-perceptual) show it is safe in outpatient settings but lacks proven efficacy beyond placebo for core ADHD symptoms in a 2025 phase 2A trial. However, ongoing research explores LSD's potential for anxiety, depression, and cluster headaches. The compound's ability to induce ego dissolution and mystical experiences correlates with therapeutic benefits. Imperial College London pioneered modern LSD neuroimaging, revealing how it temporarily dissolves the brain's default mode network, allowing for psychological flexibility and new perspectives on entrenched problems.