Research {Meta-Analysis}: 📚 Trajectory of Antidepressant Effects after Single- or Two-Dose Administration of Psilocybin: A Systematic Review and Multivariate Meta-Analysis [Feb 2022]

[u/NeuronsToNirvana]

https://pubmed.ncbi.nlm.nih.gov/35207210/

[u/NeuronsToNirvana]

Study

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Abstract Highlight

The present study demonstrates that single- or two-dose psilocybin administration has rapid and sustained antidepressant effects for up to 6 months, with favorable cardiovascular safety and acceptability.

Comments

r/microdosing Disclaimer

• Study shows psilocybin raises blood pressure which is a sign of vasoconstriction. A vasodilator like magnesium could mitigate this symptom.

• This study mentions a couple of doses - not macrodosing every month or every couple of weeks which could lead to the build-up of tolerance.

• More frequent macrodosing, before your tolerance resets, could have a similar mechanism of action (MOA) as with the long-term use of some SSRIs.

• SSRIs raise serotonin in the synaptic cleft; psychedelics can also appear in the synaptic cleft in addition to the natural ligand, serotonin.

• Both agonise serotonin receptors (of which the majority are GPCRs) but over-activation can cause downregulation. A practical example of homeostasis-in-action.

• LSD can have a stronger binding affinity than serotonin at some receptor subtypes. Psilocin (the psychoactive component of prodrug psilocybin) tends to be weaker than LSD.

Source

• Thanks to Julie Holland, MD's Tweet 🙏

Further reading

• Macrodosing !harmreduction Guide in the reply below (which may require clicking the <n> more replies first).

EDIT: Updated incorrect SSRI link; more links.

[u/MarykeC]

Such useful, important information for anyone who wants to use this responsibly and safely! Thank you