Cannabinoids

Defined by the receptor rather than by the plant: everything here binds CB1 or CB2, whether it grew in cannabis, is made by the body, or was designed in a laboratory. CB1 is dense in the brain and CB2 largely peripheral and immune, and a compound's split across the two — and whether it is a partial agonist, a full agonist or an inverse agonist — matters more than its origin. CBD is a phytocannabinoid with little CB1 affinity; JWH-018 and MDMB-4en-PINACA are full agonists with no ceiling.

CB1 is sparse in the brainstem centres driving respiration, which is why acute respiratory depression is not the characteristic cannabis harm. That belongs to partial agonists at cannabis-like doses and does not carry to the synthetics, where seizures, tachyarrhythmia and hyperthermia are reported. Heavy sustained use has its own pattern: cyclical vomiting, dependence, and psychosis in those predisposed.