Cannabis is rapidly becoming more accepted in American society as a recreational drug. With the ascension of its popularity, comes increased research in how it works, its effects, and its potential utility. Let’s start off with the fundamentals:
Part 1: Localization of the endocannabinoid system:First off let’s talk about about what an Endocannabinoid System is. The ECS is a biological system composed of endocannabinoids, which are endogenous meaning they originate from within an organism, tissue, cell or in this case a lipid. Lipids include many natural oils, and waxes. Since endocannabinoids are endogenous lipids-based retrograde neurotransmitters, they bind to cannabinoid receptors.
So to break it down into non-scientific terms, the endocannabinoid system is what connects to a variety of physiological processes including appetite, pain-sensation, mood, and memory.
THC and CBD are molecules in cannabis that can bind-to and activate neurotransmitters and other cell-receptors via complex chemical mechanisms. When they activate neurotransmitters, they promote chemical reactions within and outside the cell that lead to electrical signal productions by the neuron. They mainly activate cannabinoid 1 receptors (CB1 receptors/CB1R) and cannabinoid 2 receptors (CB2 receptors/CB2R).Now there are at least two types of cannabinoid receptors, CB1 and CB2, both coupled to G-proteins. CB1 receptors are present in the central nervous system and CB1 and CB2 receptors in certain peripheral tissues. Think of it this way, the human body already has receptors waiting to accept cannabis. CB1R and CB2R are mainly responsible for the effects of THC and CBD, and G-protein coupled receptor (GPCR) is a complex type of receptor that will start cascades of chemical activities when activated – ultimately producing widespread systemic effects on your physiology. That’s the “high feeling”.
CB1R is expressed at high levels in certain regions of our forebrain, which is responsible for many of our executive functions. They are additionally found in a very high concentration in various classes of mostly slowing down mediary neurons in our cerebellum, basal ganglia, hippocampus, limbic system, and dorsal afferent spinal cord. They are also expressed in tissues outside of our central nervous system, including adipose, liver, pancreatic, thyroid, uterine/testicular, and skeleto-muscular tissues. Basically, they’re everywhere.
While the roles of CB1 receptors, especially in peripheral tissues, are still unclear, their abundant distribution in regions of our brain above the brain stem explains the psychoactive effects on memory, pain regulation, motor control and more.
Meanwhile, CB2 receptors are primarily found in our GI system, the spleen, and the immune system. They are found in much lower concentrations in sparse regions throughout our central and peripheral nervous system.
Part 2: CB1 and CB2 Receptor ActivationNow that we know that Endocannabinoids are neurotransmitters released natively by our body which react with our very own cannabinoid receptors, we can start learning a little bit about the main receptors CB1 and CB2. They are fairly unique amongst most neurotransmitters in that they are not synthesized, and stored for later use – instead, they are activated when a precursor molecule gets severed in response to some cue.
To help you understand a little betterEndogenous Cannabinoids exist naturally within our bodies whereas Exogenous Cannabinoids come from outside the body or in this case in the cannabis itself.
When exogenous cannabinoids from outside of our body bind to, and activate with cannabinoid receptors, they are less selective than the endogenous cannabinoids (cannabinoids growing from within) our body produces. When we introduce cannabinoids from outside our body (exogenous), there is no clear path/plan for activation of certain regions or receptor densities. Therefore, it can be difficult to predict the effects of exogenous cannabinoids on our endocannabinoid system. This is why certain strains as well as cannabis in general effect people differently. THC and CBD are both examples of this. They effect more receptors than our own natively-made cannabinoid molecules (which is highly regulated by our own bodies), causing either the activation or inhibition of other downstream neurotransmitters. Downstream in this case, refers to neurotransmitter releases that would not have occurred without prior activation. Aka the act of consuming cannabis.
With our CB1 Receptors being localized in our brain as well as the neurotransmitter systems, they are present in primarily affects our motor skills, pain perception, memory, and cognitive abilities. Furthermore, current evidence suggest that both CB1 and CB2 regulate vascular, immune, reproductive, developmental, and metabolic functions in the human body. They interact with each other in complicated ways that vary depending on their relative locations / concentrations in the body and brain. That’s why every consumer may experience different individual effects.Interestingly, due to the relative scarcity of CB2 Receptors in our central nervous system, its stimulation leads to positive peripheral effects such as anti-inflammation and anti-tumor growth, without nearly as much of the psychoactive effects of CB1 receptor activation – thus selective CB2 receptor agonists (a substance that initiates a physiological response when combined with a receptor) are increasingly being researched for their medical use.
