Cannabis derivatives have proved to exert highly specific DS effects, which are not substituted by other classes of drugs (i.e., opioids or more direct dopaminergic compounds) nor are they reversed by antagonists of various neurotransmission systems (Järbe and Ohlin, 1977), supporting the idea that the DS effects only involve the cannabinoid system (Yamamoto and Takada, 2000).
The ever-expanding world of the endocannabinoids: A concise introduction
Fabiana Piscitelli, Vincenzo Di Marzo, in Cannabinoids in Neurologic and Mental Disease, 2015
One year before the molecular characterization of THC, another abundant cannabis component, cannabidiol (CBD), had already been identified (Michoulam and Shvo, 1963), whereas other chemically related terpene phenolic compounds, including cannabichromene (CBC) and cannabigerol (CBG), were isolated from Cannabis sativa soon thereafter (Gaoni and Mechoulam, 1964b; Gaoni and Mechoulam, 1966). When it became clear that these natural products are nearly unique to the cannabis plant, or maybe simply because they were first identified from this source, these compounds were collectively named “cannabinoids
” Thus, the name “cannabinoid” indicates any secondary metabolite from various strains of cannabis with biogenetic origin from a terpene, normally geranyl pyrophosphate, and a phenol, i.e., olivetol or olivetolic acid
It is now established that cannabinoids are produced by the plant flowers as their corresponding carboxylic acids, which are then decarboxylated following heating or desiccation. Interestingly, a compound similar to CBG acid, but clearly not directly derived from olivetol, was recently isolated from South African plants of the Helichrysum genus (Lourens et al., 2008).
Thus, cannabinoids might not be unique to the cannabis plant, although their biosynthesis in other plants might follow different routes. Furthermore, of all the natural cannabinoids that were initially tested, THC was shown to be the only one responsible for the “recreational” properties induced by the smoking of marijuana in humans.
These properties can be described as general mood and sensory altering effects leading to, among others, euphoria and sedation (Panagis et al., 2008). Later, a definition of THC-like activity was given as the ensemble of “central” pharmacological effects that THC induces in non-human primates, dogs (ataxia), and rodents.
In mice, it was proposed that the concomitant induction of (1) immobility in a square box, (2) catalepsy on a ring, (3) analgesia in the hot plate or tail-flick tests, and (4) hypothermia, known as the “tetrad” of tests for “cannabimimetic” activity, would be a good predictor of THC-like pharmacological activity (Martin et al., 1991).
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