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By Arielle Friedman

These days, CBD products are a common feature in health food shops and even supermarkets. Most people have heard of the cannabinoid, and millions of people take it for one reason or another. Even the World Health Organization has reported on its good safety profile[1]. But is there such thing as too much CBD? Can ingesting this cannabinoid too often build tolerance to its positive effects?

To answer these questions, we’ll begin with a brief overview of tolerance formation.


Tolerance is the process by which one has to increase one’s use of a drug to get the same effects one had to begin with. Tolerance is distinct from addiction or dependence, which is the compulsive use of a drug, or the need to keep taking a drug to feel “normal”. Tolerance can form through multiple mechanisms: cellular, where the cell becomes less responsive to the substance; metabolic, where less of the substance reaches the site of interaction; behavioural, where the user becomes accustomed to the substance's effects.

THC Tolerance


As pot smokers will attest, regular use of THC builds tolerance—seasoned smokers will find themselves consuming many times as much as new users. Further, tolerance develops unevenly and also varies depending on individual physiology. As such, the full experience of getting high will be different the more one smokes. Many regular users take “T-breaks” or switch strains to recharge their tolerance after heavy use.

THC tolerance happens mainly through the cells. THC works by binding with CB1 receptors in the brain. When this happens repeatedly, the cells try to reverse the effect and maintain normal CB1 activity. They accomplish this through two main methods: the first is called desensitisation, where CB1 receptors start binding to cannabinoids less easily. The second method is called internalisation, and it’s the process by which CB1 receptors are pulled from the surface of the cell into its interior; unlike desensitised receptors, which can still be activated by THC, albeit to a lesser degree, internalised cells become entirely unresponsive.

Because the cannabinoid doesn’t bind to the CB1 receptor, it doesn’t produce the psychotropic effects tied to THC. However, it influences the endocannabinoid system in different ways; it binds to “expanded ECS” receptors and disrupts enzymatic processes.


CBD has a different relationship to CB1 than other cannabinoids, acting as an antagonist. Through a form of activity called negative allosteric modulation[3], CBD reduces the binding affinity of the CB1 receptors, making them less responsive to other cannabinoids. As such, the effects of CBD work in the opposite direction of THC—instead of over-activating your endocannabinoid system, it gives it a break. And in fact, many issues with the endocannabinoid system may stem from it being overactive—causing issues like anxiety and overeating.

CBD also increases the body’s natural endocannabinoids, since it competes with them for binding proteins which break them both down. CBD can be thought of as a kind of endocannabinoid-reuptake inhibitor.

This combination of antagonising CB1 receptors and increasing natural endocannabinoids produces CBD’s characteristic relaxed, focussed, and “flow state” effects. But can this effects profile be tolerance-forming?

CBD Tolerance


Studies[4] seem to suggest[5] that CBD is not tolerance-forming, and may in fact have reverse-tolerance effects; this finding could have important implications as researchers ascertain the full potential of the cannabinoid. It would seem CB1 cells don’t resist negative allosteric modulation in the same way they resist direct intense stimulation. Further, given CBD’s specific relationship to CB1 receptors, it likely helps modulate the tolerance-forming pattern of THC. Pot smokers concerned about tolerance would be wise to add some CBD to their cannabinoid diet.

More research is needed to confirm the “reverse tolerance” hypothesis, but the evidence suggests that CBD users probably don’t need to worry about tolerance. This really is remarkable, especially given CBD’s wide range of medicinal effects; many of the issues it addresses are currently being treated with heavy pharmaceuticals that are themselves tolerance-forming. CBD’s lack of tolerance-building is yet another compelling point in favour of this miracle cannabinoid.

This content is for educational purposes only. The information provided is derived from research gathered from external sources.

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