A classic psychedelic is one that works mainly through the serotonin 5-HT2A receptor. A 2016 review reports a consensus that psychedelics are agonists or partial agonists at brain 5-HT2A receptors (Nichols, 2016). For two of them the human test has been done: the 5-HT2A blocker ketanserin blocked psilocybin’s effects in 1998 (Vollenweider et al., 1998) and fully blocked LSD’s general subjective effects in 2017 (Preller et al., 2017).
The group splits into two chemical families. A 2011 review places LSD, psilocybin, psilocin and DMT among the indoleamines and mescaline among the phenylalkylamines (Halberstadt and Geyer, 2011). “Classic” separates them from drugs that act differently, such as ketamine or MDMA.
The members are not interchangeable. A 2016 lab comparison found that LSD bound 5-HT2A more tightly than psilocin or DMT and also hit adrenergic and dopamine receptors (Rickli et al., 2016). Time course differs too: in one trial of 32 healthy people, mescaline lasted a mean 11.1 hours, LSD 8.2 and psilocybin 4.9 (Ley et al., 2023). In Canada, psilocybin, psilocin, LSD, DMT and mescaline are all in Schedule III (CDSA).
Sources
- Nichols, 2016, Pharmacological Reviews: Psychedelics
- Halberstadt and Geyer, 2011, Neuropharmacology: receptors and hallucinogens
- Rickli et al., 2016, European Neuropsychopharmacology: receptor profiles
- Ley et al., 2023, Neuropsychopharmacology: mescaline, LSD and psilocybin compared
Last checked .