Study Confirms the Role of the 5-HT2A Receptor in the Psilocybin Psychedelic Experience

Researchers used PET scans and blood psilocin levels to verify that the subjective experiences brought on by psilocybin come from stimulation of the serotonin 5-HT2A receptor.

February 28, 2019 -

As interest in the therapeutic uses of psilocybin continues to grow, scientists are making discoveries about how this compound works in the body. Through various experimental work, scientists have come to understand that the serotonin receptor in the brain called 5-HT2A is where psilocin (the active metabolite of psilocybin) binds to cause the psychedelic experience.1-6 A new study presents data that confirms this mechanism.

In January 2019, researchers at Copenhagen University Hospital and Imperial College London published new findings confirming the role of the 5-HT2A receptor in the psychedelic experience produced by psilocybin.7 The unique and important thing about this study is they monitored two physiological aspects of the test subjects while they were under the influence of psilocybin—the levels of psilocin in their blood plasma and the amount of psilocin bound to the 5-HT2A receptors in their brains.

The study used eight healthy volunteers who received baseline blood testing and PET (positron emission tomography) scans. They also completed a questionnaire to evaluate their subjective experiences before, during, after taking psilocybin.  While they were still in the PET scanner, the volunteers received a single oral dose of 3 – 30 mg of pure psilocybin. The researchers monitored the receptor occupancy in the brains of the volunteers throughout the study. Blood draws were also done to check their amount of psilocin in their blood.

The Results Point to the 5-HT2A Receptor

When the data were analyzed, three significant findings emerged:

  • The higher the psilocybin dose, the more 5-HT2A receptors were occupied in the brain. Receptor occupancy hit 72% at the highest dose (30 mg).
  • The amount of psilocin in the blood plasma and the calculated receptor occupancy in the brain were strongly related. The authors stated they “…conformed to a single-site binding model.”
  • The intensity of the subjective effects had strong correlations to receptor occupancy in the brain, levels of psilocin in the blood, and questionnaire scores.

These results showing concurrent blood psilocin levels, psilocin binding in the brain, and subjective effects confirm that stimulation of 5-HT2A receptors in the brain is a key determinant for the psilocybin psychedelic experience.

Magic Mushrooms Contain Several Compounds

It’s important to remember that psilocybin and psilocin are only two compounds in magic mushrooms. Scientists don’t understand (and are not currently studying) how these other compounds interact or how they work with different types of serotonin receptors in the brain. The psychedelic experience brought on by magic mushrooms comes from a combination of all these variables, as well as the dose, set, and setting.

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