The Basics of Cannabis & CBD – (Part 2)

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In the last blog, we talked about the historical use of cannabis and its more recent uses as a medicinal plant. We also introduced the topic of cannabinoids and, more specifically, cannabidiol (CBD). Now, let’s dive into some more details on cannabinoids, the endocannabinoid system (ECS) and CBD.

Understanding Cannabinoids and the Endocannabinoid System

Cannabinoids are a set of diverse chemical compounds that can act on cannabinoid receptors and interact with the endocannabinoid system in your body. There are phytocannabinoids and endocannabinoids. Phytocannabinoids, such as CBD, are bioactive secondary metabolites produced by the cannabis plant. They are synthesized and accumulate in the trichomes on the surfaces of both cannabis leaves and flowers. Endocannabinoids are endogenous and created within the body. The human endocannabinoid system is composed of two primary endocannabinoid messengers, anandamide and 2-arachidonoylglycerol (2-AG), and at least 30 to 50 receptors expressed throughout the body on various cell types that function together to maintain homeostasis. Anandamide and 2-AG levels increase on demand in response to a given stimuli (e.g., pain). Anandamide and 2-AG are synthesized in a localized stimulus-dependent manner from membrane phospholipid precursors. In contrast, when cannabis is used for recreational or medicinal purposes, all susceptible receptors in your body are bathed in phytocannabinoids, resulting in myriad outcomes. (MJBizCon, Science Symposium, Orser C., 2018)

The endocannabinoid system is involved in regulating various physiological and cognitive processes including fertility, pregnancy, pre- and post-natal development, appetite, pain sensation, mood and memory, and mediating the pharmacological effects of cannabis. The ECS is also involved in mediating some of the physiological and cognitive effects of voluntary physical exercise in humans and other animals, such as contributing to exercise-induced euphoria as well as modulating locomotor activity and motivational salience for rewards. The ECS is arguably the most complex and dynamic system in the human body. We’re just at the tip of the iceberg with what we know and understand from a scientific standpoint.

Cannabinoid Extraction from Cannabis

For cannabinoids, such as CBD, to be delivered to humans in an isolated or semi-isolated form, they must be extracted from cannabis plants. Cannabinoids can be separated from the cannabis plant through extraction processes. The extraction process that is used is very important and can affect the quality and safety of the end product that is extracted. Organic solvents such as hydrocarbons and alcohol are often used as solvents, and so is butane. Extraction using carbon dioxide (CO2) is a popular option and also one of the cleanest options. After the cannabinoids are extracted, the isolated compounds can be separated using various distillation techniques.

Pharmacology of Cannabinoids

Cannabinoids can be delivered to the body in many ways, including smoking, vaporizing, oral ingestion, sublingual absorption, transdermal patches, intravenous injection and even rectal suppository. Since cannabinoids such as CBD are metabolized in the liver, bioavailability can be an issue. Vaping and smoking appear to have the greatest bioavailability, but many people are concerned with the risks of smoking and vaping. Oral bioavailability of CBD is relatively low but can be improved by using a full-spectrum extract and through sublingual and buccal absorption. The introduction of more bioavailable forms of CBD will be at the forefront of research and product development over the coming years.

Cannabinoid Receptors

Two primary endocannabinoid receptors have been identified: CB1 (first cloned in 1990) and CB2 (cloned in 1993). The intoxicating effects of cannabis are principally mediated by CB1, which is widely distributed throughout the brain, but mainly in the frontal cortex, basal ganglia and cerebellum. CB1 is also present in several tissues and organs, including adipose tissue, the gastrointestinal tract, the spinal cord, the adrenal and thyroid glands, liver, reproductive organs and immune cells. CB1 is the main molecular target of the endocannabinoid, anandamide, as well as its mimetic phytocannabinoid, THC. CB2 is principally expressed in immune cells but can also be found in various other cell types, including chondrocytes, osteocytes and fibroblasts, meaning that it can be considered the peripheral cannabinoid receptor. It is also present in some nervous tissues, such as dorsal root ganglia and microglial cells.

CBD doesn’t actually bind to either CB1 or CB2 receptors. In fact, CBD has little to no affinity for these receptors, and acts as a partial antagonist to CB1 and as a weak inverse CB2 agonist. It still is not exactly known how CBD interacts and delivers its effects within the endocannabinoid system, but the body of research is already extremely promising and shows that CBD can have beneficial effects for various forms of cancers, social anxiety disorder, psychosis and other mental conditions and pain management. Cannabinoids and the endocannabinoid system will be at the forefront of scientific community for decades to come, and the world is about be taken over by a cannabis-evolution.

Bruni, N., et al. (2018) Molecules, 23, 2478. 

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