CBD is very different from other cannabinoids, and we’re still a ways away from completely understanding this compound and its actions throughout the body. What we do know, however, is that it doesn’t bind to cannabinoid receptors in the same way as THC. Instead, it acts via numerous other chemical pathways. Some resources suggest that CBD can activate over 60 different molecular pathways in the body.
While CBD doesn’t bind to endocannabinoid receptors, it can still interact with them indirectly. For example, studies have shown that it can work as an inverse agonist of CB1 receptors. Nonetheless, there is no current research claiming that CBD causes users to develop tolerance. Instead, it’s widely regarded as a safe, non-toxic compound that’s very well-tolerated. A 2011 study published in the journal Current Drug Safety stated that human trials testing various dosages of CBD didn’t cause side effects or tolerance.
So far, studies indicate that CBD can affect serotonin receptors, vanilloid receptors, GABA receptors, gamma receptors, and more. Other studies show that CBD can inhibit a process known as reuptake, and thereby temporarily increase the amount of certain chemicals in the brain, such as serotonin and anandamide.
What about CBD? Can it cause tolerance?
In fact, some research suggests that CBD may cause reverse tolerance. Unlike THC, which occupies the role of endocannabinoids and can down-regulate the endocannabinoid system, CBD can increase endocannabinoid levels (e.g. by inhibiting reuptake). Hence, over time, users may find that they need lower doses of CBD to get the same results. Though this is currently just theory.
It is possible to build up a tolerance to some cannabinoids, like THC. THC is the main psychotropic compound in cannabis and delivers its effects by binding to CB1 receptors. These receptors work like little locks that are designed to be opened by endocannabinoids like anandamide and 2-AG, but some plant-derived cannabinoids with a similar structure (like THC) can also bind directly to them.
Most people taking cannabidiol are told that taking a regular, repeated dose is the key to getting the right results. But could taking CBD so regularly cause people to build up a tolerance and therefore constantly require a stronger dose? In this article, we take a closer look at whether it’s possible to build up a tolerance to CBD.
As a result, people who regularly consume these cannabinoids may find that they need increasingly larger doses in order to feel the same effects. This can also affect the endocannabinoid system’s ability to learn and adapt to factors like stress as it has become over-dependent on THC.
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.
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 has a different relationship to CB1 than other cannabinoids, acting as an antagonist. Through a form of activity called negative allosteric modulation  , 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.
A LOOK AT THC
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.
To answer these questions, we’ll begin with a brief overview of tolerance formation.
These days, CBD is more and more being seen as a wonder drug, and has shown effectiveness at treating epilepsy, alleviating anxiety, improving symptoms of arthritis, and reducing the risk of diabetes  . Whether you take it in a tincture, smoke it in flower form, or swallow it in pills, CBD is a wonderful addition to any health-conscious person’s repertoire. But is there such thing as too much CBD? Can ingesting this cannabinoid too often build tolerance to its positive effects?
Studies  seem to suggest  that CBD is not tolerance-forming, and may in fact have reverse-tolerance effects; in other words, taking CBD regularly may result in users needing less of the cannabinoid to achieve the same results. 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.
After long-term CBD use, the users may begin to experience seizures again.
Most substances cause people to experience increased tolerance levels. Everything from pharmaceuticals, nicotine, alcohol, and hard drugs like cocaine and methamphetamines.
There is, however, something to be aware of, called CBD saturation. This is often found in users taking CBD oil for epilepsy.
How Does Reverse Tolerance Work?
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There are only limited studies into the tolerance of CBD, but the general consensus is that there is little to no risk of developing a tolerance.
Another significant difference between the two is the risk of tolerance. The main issue with THC is that when used for medicinal or recreational purposes, there is a slow increase in levels of tolerance.
The truth is that CBD and THC share a few traits (they both affect the endocannabinoid system, for example), but they are, in fact, very different.