Cannabinoid
[5] At least 100 distinct phytocannabinoids have been isolated from cannabis, although only four (i.e., THCA, CBDA, CBCA and their common precursor CBGA) have been demonstrated to have a biogenetic origin.
The ECS plays an important role in multiple aspects of neural functions, including the control of movement and motor coordination, learning and memory, emotion and motivation, addictive-like behavior and pain modulation, among others.
[14] CB1 receptors are found primarily in the brain, more specifically in the basal ganglia and in the limbic system, including the hippocampus[11] and the striatum.
CB1 receptors are absent in the medulla oblongata, the part of the brain stem responsible for respiratory and cardiovascular functions.
[21] The classical cannabinoids are derived from their respective 2-carboxylic acids (2-COOH) by decarboxylation (catalyzed by heat, light, or alkaline conditions).
Delta-9-tetrahydrocannabinol (Δ9-THC, THC) and delta-8-tetrahydrocannabinol (Δ8-THC), through intracellular CB1 activation, induce anandamide and 2-arachidonoylglycerol synthesis produced naturally in the body and brain[citation needed][dubious – discuss].
[31][32][33] Through its mechanism of partial agonism at the CB1R, CBN is thought to interact with other kinds of neurotransmission (e.g., dopaminergic, serotonergic, cholinergic, and noradrenergic).
Its structure and chemical synthesis were achieved by 1940[34], followed by some of the first pre-clinical research studies to determine the effects of individual cannabis-derived compounds in vivo.
[36][35] Although scientific reports are conflicting, the majority of findings suggest that CBN has a slightly higher affinity for CB2 as compared to CB1.
Although CBN has been marketed as a sleep aid in recent years, there is a lack of scientific evidence to support these claims, warranting skepticism on the part of consumers.
Next, CBGA is independently converted to either CBG, THCA, CBDA or CBCA by four separate synthase, FAD-dependent dehydrogenase enzymes.
[43] A widespread dietary terpene, beta-caryophyllene, a component from the essential oil of cannabis and other medicinal plants, has also been identified as a selective agonist of peripheral CB2-receptors, in vivo.
Liquid chromatography (LC) techniques are also possible and, unlike GC methods, can differentiate between the acid and neutral forms of the cannabinoids.
There have been systematic attempts to monitor the cannabinoid profile of cannabis over time, but their accuracy is impeded by the illegal status of the plant in many countries.
Cannabinoids can be administered by smoking, vaporizing, oral ingestion, transdermal patch, intravenous injection, sublingual absorption, or rectal suppository.
[50] Research shows the effect of cannabinoids might be modulated by aromatic compounds produced by the cannabis plant, called terpenes.
However, an integrated hypothesis of cannabinoids' actions on these processes has yet to be formulated due to conflicting data and the complexity of the pathways involved.
[54] The drug, made by GW Pharmaceuticals, was first approved by Canadian authorities in 2005 to alleviate pain associated with multiple sclerosis, making it the first cannabis-based medicine.
[63] The first discovery of an individual cannabinoid was made, when British chemist Robert S. Cahn reported the partial structure of Cannabinol (CBN), which he later identified as fully formed in 1940.
[citation needed] Due to molecular similarity and ease of synthetic conversion, CBD was originally believed to be a natural precursor to THC.
[citation needed] The Agriculture Improvement Act of 2018 has been interpreted as allowing any hemp-derived product not exceeding 0.3% Δ9-THC to be sold legally in the US.
Because the law limited only Δ9-THC levels, many other cannabinoids are generally considered legal to sell and are widely available in stores and online, including Δ8-THC, Δ10-THC, HHC, and THCP,[68][69] but have not had the same in-depth research that the Δ9 isomer has on the human body; carrying potential risks in the short- or long-term.
[72] Many substances are scheduled at the state level under various synonyms owing to the different dibenzopyran and monoterpenoid naming conventions.
All of these compounds are members of a family of signalling lipids called N-acylethanolamines, which also includes the noncannabimimetic palmitoylethanolamide and oleoylethanolamide, which possess anti-inflammatory and anorexigenic effects, respectively.
[11] In particular, one in vitro study suggests that 2-AG is capable of stimulating higher G-protein activation than anandamide, although the physiological implications of this finding are not yet known.
[83] Prior to this discovery, it had been synthesized as a stable analog of 2-AG; indeed, some controversy remains over its classification as an endocannabinoid, as another group failed to detect the substance at "any appreciable amount" in the brains of several different mammalian species.
Although in this intercellular signaling role they are similar to the well-known monoamine neurotransmitters such as dopamine, endocannabinoids differ in numerous ways from them.
For instance, when the release of the inhibitory transmitter GABA is reduced, the net effect is an increase in the excitability of the endocannabinoid-releasing cell.
On the converse, when release of the excitatory neurotransmitter glutamate is reduced, the net effect is a decrease in the excitability of the endocannabinoid-releasing cell.
[95] [citation needed] The runner's high, the feeling of euphoria that sometimes accompanies aerobic exercise, has often been attributed to the release of endorphins, but newer research suggests that it might be due to endocannabinoids instead.
