Psilocybin is only administered orally and is a prodrug which means that the digestive tract metabolizes psilocybin into psilocin which is the molecule causing the effects on the body and mind.
As previously mentioned, mushrooms are not administered during psilocybin-assisted therapy because of the inconsistency with dosing. The dose ranges for pure psilocybin is provided as a result.
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The following doses have been used in clinical trials to date.
Psycholytic Dose |
15mg (Kuypers et al., 2019) |
---|---|
Psychedelic Dose |
25mg (Kuypers et al., 2019) |
FDA approval and more empirical evidence are needed to provide a recommended dosing mechanism.
Psilocin has a 2.5-hour half-life in blood plasma after oral ingestion, and a half-life of 1.23 hours after intravenous administration; both psilocybin and psilocin are excreted in urine, where they are detectable by chemical analysis and have an elimination half-life of 50 minutes (Hasler et al., 1997; Kamata et al., 2006; Lindenblatt et al., 1998; Passie et al., 2002). The majority is excreted within 3 hours after oral administration, and within 24 hours, all psilocybin and psilocin is eliminated from the human body (Hasler et al., 2002; Holzmann, 1995).
Unlike MDMA or ketamine, psilocybin tolerance must be taken into account when scheduling psilocybin Medicine Sessions. It is also an especially important consideration if clients have consumed psilocybin or LSD recreationally within the two weeks prior to the Medicine Session. With psilocybin and LSD, clients will develop a tolerance even after just one session. Tolerance is believed to be because of a down-regulation of the serotonin (5HT2A) receptors in the brain (Isbell, 1961). If a client has consumed LSD, they will not only have a tolerance to LSD but also psilocybin.
To give you an idea of how psilocybin and LSD tolerance changes over time, please consult this calculator.
Note: this calculator is for demonstration purposes only and is not designed to be an effective dosing tool as there may be various factors that can affect tolerance. It also lists the amount of mushrooms in grams of dried mushrooms which is a different value of measurement used in psilocybin-assisted therapy.
Oral doses exceeding 25 mg are considered to be high but not dangerous (Johnson et al., 2008). Brown et al. (2017) found that psilocybin at doses of 0.6mg/kg (42mg in a 70kg adult) is well tolerated.
Aronson, J. K. (Ed.) (2016). Meyler's Adverse effects of Drugs (16th Ed.). Elsevier. https://doi.org/10.1016/B978-0-444-53717-1.00158-X.
Brown, Randall T.; Nicholas, Christopher R.; Cozzi, Nicholas V.; Gassman, Michele C.; Cooper, Karen M.; Muller, Daniel; Thomas, Chantelle D.; Hetzel, Scott J.; Henriquez, Kelsey M.; Ribaudo, Alexandra S.; Hutson, Paul R. (2017). Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Clinical Pharmacokinetics, (), –. doi:10.1007/s40262-017-0540-6
Hasler, F., Bourquin, D., Brenneisen, R., Bär, T., & Vollenweider, F. X. (1997). Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. Pharm Acta Helv, 72(3), 175-184. https://doi.org/10.1016/s0031-6865(97)00014-9
Hasler, F., Bourquin, D., Brenneisen, R., & Vollenweider, F. X. (2002). Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man. J Pharm Biomed Anal, 30(2), 331-339. https://doi.org/10.1016/s0731-7085(02)00278-9
Holzmann, P. P. (1995). Bestimmung von Psilocybin-metaboliten im Human plasma und urin. University of Tübingen]. Tübingen, Germany.
Isbell, H., Wolbach, A. B., Wikler, A., and Miner, E. J. (1961). Cross-tolerance between LSD and psilocybin. Psychopharmacologia, 2.
Johnson, M., Richards, W., & Griffiths, R. (2008). Human hallucinogen research: guidelines for safety. J Psychopharmacol, 22(6), 603-620. https://doi.org/10.1177/0269881108093587
Kamata, T., Nishikawa, M., Katagi, M., & Tsuchihashi, H. (2006). Direct detection of serum psilocin glucuronide by LC/MS and LC/MS/MS: time-courses of total and free (unconjugated) psilocin concentrations in serum specimens of a “magic mushroom” user. Forensic Toxicology, 24, 36-40.
Kuypers, K. P. C, Ng, L., Erritzoe, D., Knudsen, G. M., Nichols, C. D., Nichols, D. E., Pani, L., Soula, A., and Nutt, D. (2019). Microdosing psychedelics: More questions than answers? An overview and suggestions for future research. Journal of psychopharmacology, 33(9), 1039-1057.
Lindenblatt, H., Krämer, E., Holzmann-Erens, P., Gouzoulis-Mayfrank, E., & Kovar, K. A. (1998). Quantitation of psilocin in human plasma by high-performance liquid chromatography and electrochemical detection: comparison of liquid-liquid extraction with automated on-line solid- phase extraction. J Chromatogr B Biomed Sci Appl, 709(2), 255-263. https://doi.org/10.1016/s0378-4347(98)00067-x
Passie, T., Seifert, J., Schneider, U., & Emrich, H. M. (2002). The pharmacology of psilocybin. Addict Biol, 7(4), 357-364. https://doi.org/10.1080/1355621021000005937
Rush, B., Marcus, O., Shore, R., Cunningham, L., Thomson, N., and Rideout, K. (2022). Psychedelic Medicine: A Rapid Review of Therapeutic Applications and Implications for Future Research. Homewood Research Institute. https://hriresearch.com/research/exploratory- research/research-reports/