How does medicinal cannabis work?
Medicinal cannabis works via the endocannabinoid system (ECS)
The ECS is a complex and essential signalling network that plays a role in maintaining many physiological balance across numerous body functions.
The ECS is primarily composed of three main components:
Endocannabinoids
These are endogenous (naturally produced within the body) lipid-based retrograde neurotransmitters. The two primary endocannabinoids are anandamide (AEA) and 2-arachidonoylglycerol (2-AG).
Receptors
Located on cell surfaces, these receptors bind to endocannabinoids. The two main types are CB1 receptors (mostly found in the central nervous system) and CB2 receptors (primarily in peripheral organs, especially cells related to the immune system).
Enzymes
These are responsible for producing and breaking down endocannabinoids. The main enzymes are fatty acid amide hydrolase (FAAH), which breaks down AEA, and monoacylglycerol acid lipase (MAGL), which degrades 2-AG.
Every animal, from mammals to birds and even some invertebrates, possesses an endocannabinoid system (ECS).
How the ECS works
The ECS is triggered when there is a homeostatic shift or deviation from normal conditions (or if you can bear the term ‘imbalance’), such as inflammation or heightened pain perception.
When the shift is detected, the ECS synthesises endocannabinoids from lipid-based precursors within cellular membranes.
Unlike traditional neurotransmitters that flow from pre- to post-synaptic neurons, endocannabinoids signal in reverse. They move from post- to pre-synaptic sites, a phenomenon termed 'retrograde signaling’.
These endocannabinoids interact with specific cannabinoid receptors, primarily CB1 and CB2, which are found on various cells. Through these interactions, they modulate cellular activities, like reducing the release of inflammatory agents or altering neurotransmitter secretion, thereby driving the system back toward equilibrium.
To ensure that these endocannabinoids don't overstay their regulatory role, specific enzymes rapidly degrade them post-action.
Medicinal cannabis and the ECS
Setting aside the myriad components of medicinal cannabis, we’re going to focus on the two most recognised cannabinoids: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
Despite structural variances between the endocannabinoids and the phytocannabinoids, similar actions have been observed within the ECS.
THC
This cannabinoid chiefly binds to CB1 receptors predominantly located in the brain. This binding underlies the psychoactive 'high' traditionally associated with cannabis consumption.
It's vital to approach THC with caution in animals. This is due to its potential to induce toxic reactions, ranging from mild disorientation to severe distress. Moreover, legal implications surround its prescription.
The medicinal cannabis products vets are currently allowed to prescribe contain ≤3% THC. This is not enough to induce psychoactive effects. We’re mentioning THC because higher levels are in products registered for human use: you need to be careful when writing prescriptions for these products. It is also important for when a client asks you if they can just use their own CBD for their pet – it always helps to have a reason rather than just saying no!
CBD
CBD's mechanism of action is multifaceted. While it doesn't bind directly to CB1 or CB2 receptors in the same manner as THC, it modulates the ECS in indirect ways.
One such mechanism is the inhibition of the enzyme FAAH, which results in an increased availability of the endocannabinoid anandamide. Additionally, CBD can act as an antagonist at certain cannabinoid receptors, attenuating the effects of cannabinoids that activate these receptors.
CBD's influence extends beyond the ECS. It interacts with a multitude of receptors, like the serotonin 5-HT1A receptor and the transient receptor potential vanilloid (TRPV) channels. These interactions play a role in pain modulation, inflammation reduction, and other physiological processes.
Receptors
CB1 receptors are predominantly found in the central nervous system, especially in the brain. They also exist in peripheral organs and tissues, albeit in lower densities. The binding of certain cannabinoids to these receptors can modulate neurotransmission, affecting mood, memory, appetite, and pain perception.
CB2 receptors are mainly located in the peripheral nervous system, especially on immune cells. They play a role in modulating immune responses and inflammation.
The widespread distribution of cannabinoid receptors means cannabinoids can potentially influence a wide range of physiological processes in animals, from cognition to immune responses.
