Psilocybin: dosage

Effects scale with dose. Even the lowest doses tested produced measurable effects, and increasing the dose generally increased them rather than plateauing [1]. At 20 and/or 30 mg/70 kg, psilocybin produced extreme anxiety or fear in over a third of volunteers and a mystical-type experience in most [1]. A 15 mg psilocybin dose produced clearly weaker subjective effects than a 30 mg dose and than both LSD doses tested [2]. The 30 mg dose produced subjective effects comparable to 100 µg and 200 µg of LSD [2]. Psilocybin raised blood pressure more than LSD did in the same comparison, while LSD raised heart rate more [2].

In a clinical trial for treatment-resistant depression, a 25 mg dose lowered depression scores more than a 1 mg dose over three weeks; a 10 mg dose did not [3]. Headache, nausea, and dizziness occurred across all three dose levels tested (25, 10, and 1 mg), and suicidal ideation, behavior, or self-injury was reported in all three groups as well, including the lowest [3].

Free psilocin has a half-life of 1.8 hours, with a reported range of 1.1 to 2.2 hours [4].

What else changes the response: pretreatment with escitalopram for two weeks left the positive mood effects of a 25 mg dose unchanged but reduced bad drug effects, anxiety, and adverse cardiovascular effects [4]. Lithium is a different story — in online reports of psychedelic use (psilocybin or LSD) alongside lithium, nearly half involved seizures and another sizeable share involved bad trips, with over a third leading to medical attention [5]. Lamotrigine reports showed no seizures, and most were judged not to have changed the experience at all [5]. As with psychedelics generally, set and setting are significant determinants of harm [6].

References

1. Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects — Psychopharmacology (Springer)
2. Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects — Neuropsychopharmacology (Nature)
3. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression — New England Journal of Medicine
4. Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects — Clinical Pharmacology & Therapeutics (Wiley)
5. Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports — Pharmacopsychiatry (Thieme)
6. Hofmann vs. Paracelsus: Do Psychedelics Defy the Basics of Toxicology?—A Systematic Review — PMC / National Library of Medicine