Receptor occupancy is the proportion of a receptor type that a drug is sitting on. In people it is measured with positron emission tomography (PET): a radioactive tracer that binds the receptor is scanned before and after the drug, and the drop in tracer signal shows how much the drug has taken up.
The key psychedelic study was published in 2019. Eight healthy volunteers were scanned before and after psilocybin. Psilocybin occupied 5-HT2A receptors in the brain, and both occupancy and psilocin levels in blood tracked the volunteers’ ratings of subjective intensity; the authors concluded that 5-HT2A stimulation is a key determinant of the psychedelic experience (Madsen et al., 2019).
Occupancy maps are also used indirectly. A 2023 study of intravenous DMT compared its brain connectivity changes with an average PET map of 5-HT2A density from other people and found they correlated (Timmermann et al., 2023). Matching maps across groups is a correlation, not proof. The 2019 study is small, and occupancy does not by itself explain the content of an experience.
Sources
- Madsen et al., 2019, Neuropsychopharmacology: 5-HT2A occupancy and psilocin
- Timmermann et al., 2023, PNAS: DMT EEG-fMRI
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