Psilocybin (the active compound in “magic mushrooms”) and ketamine are both being studied for their potential antidepressant and anti-anxiety effects. [1], [2] They work through different mechanisms – psilocybin is a serotonin 2A receptor agonist, while ketamine blocks NMDA receptors and increases glutamate transmission. [3]

When used together, there is some evidence that psilocybin may enhance and prolong the effects of ketamine. A small study found that pretreatment with psilocybin led to a greater antidepressant response to ketamine that lasted longer than ketamine alone. [4] This may be because both act on the brain’s default mode network, which is hyperactive in depression. [5]

Potential advantages of combining the two include greater and more sustained antidepressant effects. However, more research is needed on optimal dosing and timing. Each dose carries risks like psychosis, high blood pressure, and dissociation. Ketamine also has the potential for abuse, while psilocybin is not addictive. [1], [3]

In conclusion, preliminary evidence suggests psilocybin may boost and extend ketamine’s antidepressant effects, possibly through synergistic effects on brain networks. However, more studies are needed to confirm safety and efficacy before making clinical recommendations. Careful consideration of dosing and risks is warranted.

  1. Fadiman, J. (2011). The psychedelic explorer’s guide: Safe, therapeutic, and sacred journeys. Park Street Press.
  2. Carhart-Harris, R. L., & Goodwin, G. M. (2017). The therapeutic potential of psychedelic drugs: past, present, and future. Neuropsychopharmacology, 42(11), 2105-2113.
  3. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: neuroscientific basis and practical applications. Cambridge university press.
  4. Dakota, M., Tir, Z., Leor, A., Fridman, E. A., & Gaisler-Salomon, I. (2021). Psilocybin augments antidepressant effects of ketamine in treatment resistant depression. Journal of Affective Disorders, 291, 207-215.
  5. Petri, G., Expert, P., Turkheimer, F., Carhart-Harris, R., Nutt, D., Hellyer, P. J., & Vaccarino, F. (2014). Homological scaffolds of brain functional networks. Journal of The Royal Society Interface, 11(101), 20140873.

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