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.
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.
WHAT IS TOLERANCE?
CBD, however, is a different beast. Unlike THC, it doesn’t get you high, but can encourage a relaxed feeling. CBD is responsible for many of the health benefits associated with cannabis. It also has different effects on your endocannabinoid system, and a very different tolerance profile to THC.
We all know that taking too much THC produces tolerance—but can the same be said for CBD? CBD has a wide range of medical applications, and it’s important to know whether these become less effective over time. To find out, we’ll dive into the effects of CBD on CB1 receptors, and examine the research in question.
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.
As people have begun looking to cannabidiol (CBD) for its potential benefits, questions have inevitably arisen regarding the implications of introducing a new chemical into your system. Whether you’re using full spectrum CBD oil or isolate CBD, these extracts come from plants and so many consumers may be concerned with what this all means regarding any addictive qualities.
The good news is that the source of a chemical usually doesn’t matter much regarding this property, it all comes down to how the chemical interacts in the body. Cannabis and hemp products, including CBD, interact directly with the endocannabinoid system. Regular cannabis users may be familiar with the compound THC, a psychoactive composite that is predominantly present in the cannabis plant. CBD, however, is the second most potent compound in the plant and the most prevalent chemical in the hemp plant. While THC users may be familiar with the body’s ability to develop a tolerance to the psychoactive nature of this compound, it’s reasonable to wonder if CBD can have a similar effect. Considering both THC and CBD are so closely related, it is easy to assume that they work in similar fashions. In reality, these chemicals work very differently from one another, and an inability to develop tolerance may be another potential reason to consider CBD as a new healthy additive to your lifestyle.
It is easy to surprise yourself in reading about cannabidiols’ potential benefits, especially regarding its ability to avoid the development of tolerance. It turns out that developing tolerance to CBD is a very different process than developing a tolerance for THC, and it’s nearly polar opposite. Instead of developing a chemical tolerance, CBD users experience what’s known as a reverse tolerance. In the case of reverse tolerance, continued use of CBD actually results in a smaller and smaller dose being needed to achieve the same effects as time progresses. As previously mentioned, compounds found in cannabis and hemp plants work closely with the endocannabinoid system by attaching themselves to endocannabinoid receptors. While THC diminishes the effectiveness of these receptors with repeated use, and over a long period of time, CBD promotes increased activity in these receptor cells. More specifically, this means that CBD users don’t face a breakdown of the interaction that cannabidiol has within the endocannabinoid system, so it can stay continually active without diminishing its own effectiveness.
Many CBD users have reported using lower doses as time goes on because lower doses were ultimately needed to achieve the desired effects. Considering this, CBD may prove to be a benefit for anyone interested in using it in their daily lives.
As is the case with most factors related to CBD, further research needs to be done. The growth and development of the industry should prove fruitful for this sort of vital information as companies, and other entities, are able to engage in more research to support these claims. That being said, as is recommended with any new supplemental diet changes, it is advised that you take precautions when approaching your schedule of CBD usage. Additionally, while your CBD dosage may fluctuate over time, it may interact with other medications that you are using to treat certain ailments. Proceed with caution and always consult a physicianl with questions about your own health. Stay soothe!
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.
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.
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.
What about CBD? Can it cause tolerance?
When THC binds to these receptors, it can mimic endocannabinoids and cause the endocannabinoid system to down-regulate in order to avoid becoming overactive. The ECS down-regulates by producing fewer endocannabinoids and fewer endocannabinoid receptors.
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.
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.