Psychedelics

Substances that profoundly alter perception, cognition, and mood via 5-HT2A receptor agonism. From therapeutic psilocybin to sacred ayahuasca.

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LSD (Lysergic Acid Diethylamide)

Mechanism: 5-HT2A agonist | Duration: 8-12 hours | Dose: 100-200 ug (typical tab)

Risks: HPPD (rare), psychotic episodes (rare, predisposition), anxiety/panic during trip. No physical dependence. No organ toxicity.

Therapeutic potential: Depression, anxiety, addiction (early research, not FDA approved)

Psilocybin (Magic Mushrooms)

Mechanism: 5-HT2A agonist (via psilocin) | Duration: 4-6 hours | Dose: 1-5g dried mushrooms

Risks: Nausea (common), anxiety, confusion. Very safe physiologically. Cannot overdose lethally on mushrooms alone.

Therapeutic potential: Treatment-resistant depression (COMPASS Phase III), cancer anxiety (NYU/JHU — 80% improvement at 6.5 months), addiction

DMT (N,N-Dimethyltryptamine)

Mechanism: 5-HT2A agonist | Duration: Smoked: 5-20 min. Ayahuasca: 3-6 hours | Dose: Smoked: 20-60mg. Ayahuasca: varies

Risks: Intense experience. Ayahuasca: dangerous MAOI interaction with SSRIs, stimulants, tyramine-rich foods.

Therapeutic potential: Depression, PTSD, addiction (early research)

Mescaline (Peyote/San Pedro)

Mechanism: 5-HT2A agonist (phenethylamine) | Duration: 8-12 hours | Dose: 200-400mg (synthetic)

Risks: Nausea (significant with peyote), prolonged experience. Peyote endangered.

Therapeutic potential: NAC religious exemption. Cultural significance to indigenous peoples.

Ibogaine

Mechanism: Complex: kappa opioid, NMDA antagonist, serotonin transporter | Duration: 24-72 hours | Dose: 10-25 mg/kg

Risks: CARDIAC: QT prolongation, fatal arrhythmias reported. Requires medical supervision. NEVER self-administer.

Therapeutic potential: Anti-addiction properties (opioid, stimulant). Treatment centers in Mexico, Brazil, New Zealand.

MDMA (Ecstasy/Molly)

Mechanism: Serotonin/dopamine/norepinephrine releaser (empathogen) | Duration: 3-5 hours | Dose: 75-125mg

Risks: Neurotoxicity (debated), serotonin syndrome (with SSRIs/MAOIs), hyperthermia, hyponatremia.

Therapeutic potential: PTSD therapy (FDA rejected Lykos 2024, field continuing). VA-funded studies underway.

Clinical Trials

Study	Substance	Results
Johns Hopkins MDD (2020)	Psilocybin	71% response rate, 54% remission at 4 weeks. Sustained at 12-month follow-up.
COMPASS COMP360 Phase IIb	Psilocybin 25mg	Significant improvement vs control in treatment-resistant depression.
NYU Cancer Anxiety (2016)	Psilocybin	80% showed clinically significant decreases in depression/anxiety at 6.5 months.
MAPS MDMA-PTSD (Lykos)	MDMA	67% no longer met PTSD criteria (vs 32% placebo). FDA rejected Sept 2024.