How THC and CBD Interact

By Seshata

How THC and CBD Interact

Tetrahydrocannabinol (THC) and cannabidiol (CBD) are perhaps the best known of the many compounds found within cannabis, and as a result, there is abundant research into their properties, both in isolation and in combination with each other.

Cannabinoids and the EC System

As our understanding of the endocannabinoid system (ECS) has expanded in recent decades, we have begun to comprehend the extent to which THC and CBD work together to exert an array of biological effects inside the human body. In simplistic terms, an agonist chemical binds to a receptor and produces a certain biological action, while an antagonist blocks such actions from taking place. THC is a partial agonist at the CB₁ and CB₂ receptors, and a study published by the Neuropharmacology journal in 2010 suggests that THC might also act as a full agonist at certain CB₁ receptors found on the GABAergic neurons. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that reduces neuronal excitability in the central nervous system, among other roles.

CBD, on the other hand, is an antagonist—which, due to the rarity of such compounds (to date, no naturally-occurring endogenous antagonists of the cannabinoid receptors have been found), goes some way towards explaining its potential importance in medicine. To date, only one other phytocannabinoid antagonist has been found—Δ9-tetrahydrocannabivarin (THCV). According to The British Journal of Pharmacology in 2005, the trace compound appears to antagonize both the CB₁ and CB₂ receptors.

How CBD Mediates the Effect of THC

As THC is an agonist, it activates the cannabinoid receptors and stimulates further downstream activity in the body. As CBD is an antagonist, it will bind to the receptor but leave it inactive, meaning that no further downstream activity is generated.

If THC and CBD are ingested simultaneously by an individual, the agonising effect of THC will be mediated by the antagonising effect of CBD. In practice, what essentially occurs is that a receptor will be encountered by either a THC or a CBD molecule, and will readily bind to either. If the first molecule it encounters is THC, downstream activity can occur; if the first molecule is CBD, no downstream activity will occur.

In a system with multiple cannabinoid receptors in the presence of multiple THC and CBD molecules, one can expect the overall agonising effect of THC to be mediated by the CBD molecules that have managed to encounter a receptor first. Depending on the ratio of receptors that have bound to THC compared to CBD, the agonising effect of THC will be more or less inhibited.

What Does this Mean for Clinical Practice?

While THC and CBD each have numerous medicinal benefits when used in isolation, there is mounting evidence that for some conditions, using THC and CBD together in specific ratios can have an enhanced effect. Perhaps most significantly, research conducted by Dr Ethan Russo and Dr Geoffrey Guy of GW Pharmaceuticals into the oromucosal spray Sativex (the world’s first pharmaceutical cannabis preparation to win market approval) that it published in Medical Hypotheses in 2006. Their findings yielded substantial evidence that THC and CBD produce an augmented effect when used in a 1:1 ratio. This ratio has proven successful in treating the symptoms of muscle spasticity, chronic pain and urinary tract symptoms in multiple sclerosis. THC and CBD in combination have also proven successful at treating sleep disturbances, peripheral neuropathic pain, rheumatoid arthritis and cancer pain.

Current research merely scratches the surface of a vast and practically unexplored area of medical science, and as we learn more, we discover just how complex the activity of the endocannabinoid system truly is. For example, recent studies demonstrated that the endocannabinoid system is heavily involved in modulation of dopaminergic and vanilloid signalling, and that the activity of the cannabinoid receptors can vary wildly according to the area of the body, the genetic makeup of the individual and the individual’s current state of health.

Seshata is a full-time cannabis journalist and researcher currently based in Italy. Find Seshata over at Facebook, Twitter, Instagram, Google+ or her own personal site

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