Cannabinoids

Cannabinoids are molecules that are chemically related to tetrahydrocannabinol (THC), the euphoric ingredient found in marijuana. These are pharmacological and physiological drugs that interact with body receptors. There are three types of cannabinoids: synthetic, endogenous, and plant. Chemical manufacture produces synthetic cannabinoids, while the body produces endogenous cannabinoids, and plant cannabinoids are biological—mostly plant-derived. They can also be applied therapeutically to pain, anxiety, and seizure conditions. In more recent times, the medical uses of cannabinoids have come into greater plain sight. But addiction is still a huge issue with their clinical use – especially misuse of THC with all manner of side-effects.

Chemical Properties and Classification

They are made up of a polycyclic aromatic hydrocarbon molecule with oxygen functional groups. Cannabinoids – THC, CBD, etc. – are plant constituents, plant ingredients. It's not like there's much between THC and CBD (21 carbon, 30 hydrogen, 2 oxygen). But they are different in the location of chemical bonds, which is how they latch onto receptors and get hitched on to drugs. It's the most potent psychoactive compound in marijuana, and interacts with CB1 receptors to create psychoactive effects in the central nervous system like euphoria and perception. Rather CBD is anxiolytic, painkiller, anti-inflammatory and contains less THC.

The endogenous cannabinoids are chemicals your body produces in the same manner as the plant cannabinoids. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are natural cannabinoids that govern the neurological system, immunological system, and other metabolic pathways in the body via physiological mechanisms.

They even mimic the effects or behavior of chemically manufactured cannabinoids derived from plants. HU-210 and JWH-018, the two most widely used synthetic cannabinoids, are mostly utilized in laboratory clinical studies and drug discovery. Synthetic cannabinoids are more frequently employed in neurotherapeutic applications when they are more physiologically powerful and receptor-driven.

Pharmacokinetics of Plant Cannabinoids

The science of pharmacokinetics is concerned with how molecules are taken up, scattered, metabolized and removed. Two of the most commonly found plant cannabinoids – THC and CBD – have pharmacologically divergent functions, whether inhaled or smoked, bursts through the bloodstream and out into the brain and beyond.  In smoking or vaping marijuana, the more that THC is dissolving, the quicker the effects will kick in. When swallowed, THC is less bioavailable due to digestion, but it stays in the body longer. THC has a rather short half-life – its effects tend to begin within two hours.

CBD differs from THC in its pharmacokinetics. The half-life of CBD is generally longer in the body and its metabolism is more complicated. It's mainly metabolized in the liver via the cytochrome P450 enzyme complex, and its metabolites typically carry multiple drug effects. Although CBD takes longer to take effect, it remains in the body for longer.

Figure 2. Biosynthetic Pathway of Plant-derived Cannabinoids
(Source: Rosenberg EC, et al. 2015)

Challenges of Addiction

The misuse of cannabinoids, specifically THC misuse, is a huge problem in the clinical context. THC Activates the brain reward system via CB1 receptors and produces pleasure and euphoria. Consequently, long-term consumption can result in dependence and addiction, which could affect memory, cognition and learning. THC can develop cannabis dependence when used long term, with studies revealing its effects on memory, learning, and attention.

Despite its lack of potent psychoactive effects and non-drug dependency, misuse of cannabinoids remains problematic, especially as it involves the tension between therapeutic value and abuse potential. Therefore, it is important to be diligent and administer them properly to gain therapeutic benefits from cannabinoids and avoid abuse and addiction.

These multiple pharmacological effects make cannabinoids potentially promising for clinical applications in neurological disorders, cancers and pain. But addiction and abuse are a potentially huge concern that needs to be addressed. We'll need more research and regulation to ensure cannabinoids are properly and safely utilized in clinical settings.

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