Can You Build Up A Tolerance To CBD?
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.
Understanding cannabinoid tolerance
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.
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.
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.
What about CBD? Can it cause tolerance?
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.
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.
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 is reverse 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.
Unfortunately, our understanding of CBD and the endocannabinoid system is far from complete. There’s still a lot more research needed before we can begin making concrete statements about CBD and how it works inside the body. However, current research shows that CBD doesn’t cause tolerance like other cannabinoids might.
It's possible to build up a tolerance to some cannabinoids, but what about CBD? In this article, we explore whether cannabidiol can cause tolerance.
Can You Develop a Tolerance to CBD?
The question of cannabidiol (CBD) tolerance comes up frequently. Considering CBD is a cannabinoid from the same plant as tetrahydrocannabinol (THC), it is natural to assume CBD shares many of THC’s characteristics. It is well known that both CBD and THC have many therapeutic applications. But the similarities between these two cannabinoids tend to end there.
Apart from some primary differences between hemp-CBD and THC (more about this later), they share another difference—the risk of tolerance. This is a huge problem with THC when used for medicinal or recreational purposes. An initial dose eventually will become ineffective when taken on a regular basis, and the dosage has to be increased in order to achieve the same effect.
Fortunately, CBD does not seem to trigger the same buildup of tolerance. In fact, it is reported to have the opposite effect, a phenomenon called reverse tolerance.
How Does Tolerance Develop in the First Place?
Tolerance most commonly develops with drugs, illicit or otherwise, that bind directly to endocannabinoid receptors in the body. When the drug molecules continue binding to the same receptors, the same dose becomes less and less effective over time. Our bodies adapt to the continual presence of the new compound so that eventually, more medicine is required to achieve the same effect. 
With THC, research clearly links long-term use to increased tolerance. Unlike CBD, THC binds quite strongly to the CB1 receptor in the brain. This strong connection is the reason THC triggers a mind-altering experience. Through continued use, THC eventually reduces the number of available cannabinoid receptors.
CBD is a different story. So far, animal and clinical studies show that it’s generally safe and well-tolerated, with an excellent side-effect profile and no toxicity. 
A 2012 study determined that chronic THC users had fewer cannabinoid receptors than non-users. After a four-week break from THC usage, the same users could return to lower dosages. Their cannabinoid levels also returned to normal. 
How Does Reverse Tolerance Work?
As the name suggests, reverse tolerance is the exact opposite of tolerance. It is also referred to as “drug sensitivity.” When reverse tolerance occurs, continued use of a substance actually brings down tolerance levels, and a smaller dose is needed to achieve the same effect.
For most substances—including pharmaceuticals, nicotine, alcohol, and illicit drugs such as cocaine and methamphetamines—most people experience increased tolerance levels. However, in rare circumstances, some people have reported the opposite effect. For example, alcoholics actually may develop a reverse tolerance to alcohol due to severe liver damage.
Although only limited studies have explored the development of tolerance to CBD, the consensus is that there is little to no risk of developing it. The hypothesis states that because CBD technically does not bind to any one endocannabinoid receptor, it avoids the problem of tolerance altogether. 
Unlike THC, which reduces cannabinoid receptors over time, CBD promotes increased receptor activity. Whatever is responsible for CBD’s reverse tolerance, more often than not, patients find they can slowly decrease their dosage over time.
However, forum participants report differently.
Personal Anecdotes about CBD Oil Tolerance
In a Reddit thread now archived under the CBD community, some users reported signs of CBD tolerance. Users mostly seemed to report a tolerance when taking CBD for anxiety. But upon closer inspection, many complaints came from people struggling to find a high-quality source of CBD oil. 
Clearly, more research is needed to understand the root cause of their experience. Yet did these Redditors experienced an increased tolerance to CBD, or was something else going on?
Writing for Marijuana.com, Dr. Bonni Goldstein, a physician based in California who specializes in medicinal cannabis, discusses her patients’ experience with CBD tolerance. According to her, it’s not as straightforward as one would assume based only on clinical research. She postulates that CBD tolerance may develop due to:
1. A Product Change
Since the market is still largely unregulated, products are not standardized and can vary greatly in quality. Also, good-quality CBD oil costs more in general, and this sometimes prompts a product change. Yet this logic seldom makes sense. What does it help to take cheaper CBD oil, but then you develop a tolerance and have to take more—which costs you more anyway? So, it would make sense to spend on a more expensive, high-quality product that you know will be efficacious.
2. CBD Saturation
CBD saturation, which sometimes develops especially in children using CBD for epilepsy. According to Goldstein, parents report breakthrough seizure activity after long-term CBD use. To counter this, she prescribes reduced dosages and sometimes even a multi-day break from CBD. In most cases, this resolves the issue, and a lower CBD dose does the trick. This phenomenon, however, is yet to be formally studied.
3. CBD Isolate vs Whole-Plant CBD
Goldstein also found in her practice that children using whole-plant CBD products don’t seem to develop any tolerance problems. This is most probably due to the so-called “entourage effect,” which demonstrates that the compounds in cannabis work better together than as isolates. 
Again, more research is required to understand the nuances of adjusting a CBD dosage. At the moment, people usually rely on self-experimentation.
Three Other Differences Between CBD and THC
So, one clear difference between the two cannabinoids is tolerance development. There are three more. Cannabidiol owes its rise in popularity—at least in part—to the fundamental differences between the two.
- Cannabidiol doesn’t trigger psychoactivity, but it’s another story altogether for THC.
- Also, CBD can soothe anxieties, while THC is known to trigger them.
- There is, furthermore, the legal quagmire that THC currently finds itself in, especially in the United States. Hemp-derived CBD products are all exempt from that dilemma, thankfully.
The current body of research on CBD oil tolerance mainly highlights the differences between THC and CBD. If you believe you could be developing a tolerance to CBD, it’s worth seeking out the advice of a medical practitioner well-versed in cannabinoid therapy.
Is CBD tolerance a real thing? SOL*CBD has all you need to know about CBD oil tolerance and whether or not developing a tolerance to it is a possibility.