The 5-HT2C receptor belongs to the same 5-HT2 subfamily as 5-HT2A, the receptor most linked to psychedelic effects. Many psychedelics touch both. A review quotes a screen in which DMT bound nine serotonin receptor subtypes, 5-HT2C among them (Barker, 2018), and a pharmacology review attributes mescaline’s effects mainly to 5-HT2A to 2C receptors (Dinis-Oliveira et al., 2019).
Blocking studies separate the two. A 2016 review describes rodent work in which a selective 5-HT2A blocker fully blocked DMT’s head twitch and its discriminative-stimulus effects, while a 5-HT2C blocker had little or no effect (Carbonaro and Gatch, 2016). A 2000 review grouped bufotenine with LSD, psilocin and 5-MeO-DMT as acting at both receptors (McBride, 2000).
What 5-HT2C contributes in people is unresolved. A 2011 review notes that phenylalkylamines such as mescaline are selective for 5-HT2 receptors, while indoleamines are relatively non-selective across serotonin receptors (Halberstadt and Geyer, 2011). Binding a receptor is not proof that it drives an effect.
Sources
- Barker, 2018, Frontiers in Neuroscience
- Carbonaro and Gatch, 2016, Brain Research Bulletin: DMT neuropharmacology
- Dinis-Oliveira et al., 2019, Current Molecular Pharmacology: mescaline
- Halberstadt and Geyer, 2011, Neuropharmacology
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