Cannabis Science

Depending upon your industry perspective, when I use the term “cannabis science” you may be thinking of optimal plant growth conditions, the latest extraction techniques, or manufacturing technology. Cannabis science is broadly used and has many applications.

From my perspective, cannabis science relates to the interactions that take place in the body following consumption of a cannabinoid-containing product. By definition, a cannabinoid is a substance that binds to a specific cannabinoid receptor and can be produced in one of three ways: it can be produced in the body, derived from plants, or chemically.

The focus of this article is on the “why and how” that enables cannabis to act in the body.

The Endocannabinoid System

Why cannabis is able to cause biological effects because of the endocannabinoid system (or ECS). Only identified in the last 20 years, The ECS is increasingly recognized as essential to maintaining homeostasis, or balance, in the body. Detected in diverse species ranging from mushrooms to rats to humans, the ECS plays critical roles for regulating mood, sleep, pain and inflammation.

The components of the ECS include the cannabinoid receptors CB1 and CB2, the endocannabinoids that bind to the receptors, including Anandamide, NADA and 2AG, and the enzymes that synthesize and degrade these compounds. It is a “lock and key” system that allows only certain keys to open the locks and initiate a cascade of effects.  Each endocannabinoid binds differently to the receptors to activate or inhibit their responses. The pieces of the ECS work together to synthesize the endocannabinoids “on demand” and transmit chemical messages between cells.

Much research is actively ongoing to fully understand the ways in which the ECS regulates wellness and disease. Conditions such as fibromyalgia, multiple sclerosis, and epilepsy may all relate to impairments of the ECS.  Changes in endocannabinoid levels during menopause may also lead to symptoms including osteoporosis and hot flashes. However, of the U.S. medical schools only 13% currently include the ECS in the curriculum, leaving our medical professionals woefully unaware of the importance of this system.

Phytocannabinoids

How cannabis causes brain and body effects is due to the interaction of phytocannabinoids (plant-based cannabinoids) with the ECS.  Phytocannabinoids are abundant in Cannabis sativa and include tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), cannabichromene (CBC) and the terpene  β-carophyllene. Phytocannabinoids, just like the endocannabinoids, act as “keys” and bind to the CB1 and/or CB2 receptors unlocking downstream effects. This binding of a phytocannabinoid mimics the binding of an endocannabinoid allowing a response in the location of the receptor.

For example, THCA has  demonstrated anti-inflammatory effects in the intestines due to interactions at the local level.  Some phytocannabinoids also interact with receptors in other systems, such as the opiate receptors responsible for pain reduction. This interaction is why the use of cannabis may have medical benefit to patients trying to reduce their opioid drug usage. A recent paper provides a detailed review of the phytocannabinoids interacting with the ECS.

What happens in my brain?

CB1 receptors are plentiful in the brain. Regions rich in CB1 receptors include the cerebral cortex where decision-making takes place, the hippocampus where memory is formed, and the cerebellum that manages coordination. Other brain regions have CB1 receptors as well.  The most prevalent phytocannabinoid, THCA, must be decarboxylated to THC in order for the psychoactive effect to be experienced due to differences in binding affinity of THCA and THC to CB1 receptors.  Different keys can open different doors.  

It is the binding of THC to the CB1 receptor that stimulates neurons in the reward center of the brain. This stimulation leads to dopamine release. Consequently, a flood of dopamine is responsible for the “high” and altered mental state associated with cannabis use. Depending on the amount of cannabis consumed, the response can be mild or dramatic.  As I have previously described, the route of administration also influences the timing and magnitude of effects. Smoking, vaping and nasal administration lead to almost instantaneous effects while edible consumption has a delayed effect.

With frequent cannabis use, CB1 and CB2 receptors can decrease over time.  This is called downregulation requiring more cannabis to achieve the same effect  previously experienced with lower dosages. A strategy worth exploring to refresh the receptors is to take a cannabis holiday. Abstinence for as short as 2 days allows CB1 receptors time to upregulate. Interestingly, microdosing with less than 5 mg of cannabis products does not appear to alter receptor density over time. This may be a long-term option for consumers to enjoy the benefits of cannabis for wellness.