The Confusion Over CBD Tolerance
Cannabidiol (CBD) is an excellent herbal remedy and a healing drug that does not lead to drug dependence. In fact, even the Food and Drug Administration had recently approved a CBD-based drug Epidiolex to be used alongside the conventional epilepsy drugs to control seizures in human patients.
However, according to a recent study presented at the annual meeting of the American Epilepsy Society, around a third of patients develop tolerance to CBD [1].
While different people have been seen to respond differently to CBD oil, the science says that CBD use, in itself, does not lead to our bodies building a tolerance towards the substance. This is mostly due to the way this particular cannabinoid reacts with the endocannabinoid system (ECS). [3, 4]
On the contrary, users need fewer doses of CBD with the passage of time. CBD tend to remain in the body for a long time and adds to the effect of the next dosage for daily users – which is true for CBD as well. This is known as Reverse Tolerance.
However, there is evidence of the body developing tolerance towards another cannabinoid contained in the CBD extract – tetrahydrocannabinol (THC) – which acts as a booster of CBD’s effects. With time and prolonged use, the booster’s effects ware off.
This may be the only reason why some individuals have felt a slight lowering in CBD oil’s effectiveness over a period of time.
Naturally, a lot of patients looking for an alternative mode of treatment through CBD oil raise this obvious concern: “Will I grow tolerance towards this substance?”
Here, “tolerance” doesn’t signify drug tolerability, which is a safety issue, i.e., whether the body can tolerate CBD use. Drug tolerance is something entirely different. Let us explain…
What Does Drug Tolerance REALLY Mean?
You may remember from the time you were a kid, how your parents would forbid you to drink caffeinated soda hours before your bedtime. And now that you’re all grown up, it seems their concern was unfounded.
Well, NOT EXACTLY!
As a kid your body was not used to the energy boost that caffeine provides, and would hence, ACTUALLY keep you up at night, bouncing around restlessly, trying to find something to do.
But as you grew up, drinking at least a cup of coffee each morning all through your adult life, your body got adjusted to the nerve stimulant, building up a tolerance to its effects. A caffeinated soda drink will no longer be strong enough to keep you awake and feel restless anymore.
This is sort of a lame-man example of drug tolerance. It applies to anything and everything you eat or drink, especially if they affect your nervous system in any way.
Think about spicy chilies, alcohol in whiskey, bitterness in beer, and sourness in some citric fruits. As a child, you’d never be allowed these things. But, with time, your body got adjusted to them too!
The same applies to medication. Have you wondered why your doctor changes your medication from time to time, increasing the dosage or changing the composition altogether? Drug tolerance — that’s what happens to the body.
In short, it is your body’s reduced reaction to a substance due to repeated, continued or prolonged use.
But how does it happen? Read on to find out…
How DOES Drug Tolerance Develop?
When it comes to developing tolerance to some drug, your brain and liver are real culprits. With time, the receptors in your brain involved in reading your environment and giving you a full experience decreases, and so do their effectiveness.
So for your body to benefit from the medication, your liver must work harder to break them down every time you take them, thus building a tolerance, resistance or immunity towards the drug.
Tolerance could build through any one of these three physiological mechanisms:
- Cellular level: Cellular tolerance or pharmacodynamic tolerance occurs when receptors become desensitized due to repeated binding of that particular substance with the receptors. This is why the body builds a tolerance towards THC. THC binds with the receptors of the endocannabinoid system (ECS) to influence some of the body’s physiological and psychological processes. But, that’s not how CBD interacts with the ECS.
- Metabolic level: Metabolic tolerance or pharmacokinetic tolerance occurs when you orally consume a drug. It depends on your metabolic process. The digestive system takes a longer route for any substance to reach the bloodstream. So, in any case, only a portion of what you consume actually reaches the destination. The substance is broken down by enzymes in your liver, and while a small portion of it is transferred to the bloodstream, the rest is egested from your body. Over time, the portion of the substance that actually reaches its destination organ or bloodstream reduces possibly due to an increase in enzymes that breaks down the substance, thus making the substance less effective by each passing day.
- Behavioral level: Behavioral tolerance generally develops from the use of psychoactive substances – those that cause changes in mood, energy level, or leads to hallucinations or sensations of euphoria. With frequent use of such drugs, a user’s body adjusts itself to function normally while being on the drug. He no longer feels impaired or out of control. It is something that the body does through practice. The same occurs with alcohol and some psychoactive drugs. That’s again why repeated THC use leads to tolerance to the substance.
Interestingly, none of these processes take place in case of CBD.
Does Tolerance Mean Dependence?
But, tolerance does not mean dependence. Just because you can drink a peg more than another person before you have reached your limit doesn’t make you an alcoholic.
Similarly, if you require an extra dose of any substance to have its effect on you, it doesn’t necessarily mean you are dependent on it or addicted to it.
According to the National Institute on Drug Abuse (NIDA) for Teens [2], operating under the aegis of US Department of Health and Human Services, “Tolerance happens when a person no longer responds to a substance the way they did before”.
As the tolerance level increases, the person needs to take a higher dose of the medication to attain the desired effect.
This is exactly why people with substance abusers need to increasingly hike their drug intake to get “high”.
Meanwhile, Dependence has been described by NIDA as the state when a person’s body goes into “withdrawal” when he or she stops using a drug.
Withdrawal manifests with a set of both physiological and psychological disorders, ranging from mild to life-threatening (in cases of alcohol or opioids) symptoms.
It is this withdrawal phase that actually turns a person into an addict. Addiction, unlike tolerance or dependence, is no longer just a condition. It can be categorized as a disorder or disease, for which one needs help to overcome the symptoms and anxiety related to it. The afflicted can’t take control of his or her urges, let alone care of himself or herself.
So, What Does The Science Say About CBD Tolerance?
Past studies on CBD’s effects have not given any indication of the development of tolerance in humans so far.
- According to a 2011 study published in Current Drug Safety, “In human studies, CBD administration did not induce side effects across a wide range of dosages, including acute and chronic dose regimens, and tolerance to CBD did not develop.” [5]
- According to an Expert Peer Review for Cannabidiol (CBD) by the World Health Organisation (Geneva, 6-10 November 2017), “Although tolerance to the effects of THC was observed, no tolerance was observed at any of the doses of CBD administered…No studies assessing the dependence potential (withdrawal and tolerance) of CBD in humans could be identified”.
- Another 2004 study, published in the NeuroReport, in which CBD has been established as a neuroprotectant. In this study, it has been highlighted how CBD does not work by directly binding with the receptors, a reason why it does not lead to the building of tolerance within the body.
- A 2007 study [3], published in the British Journal of Pharmacology, further reinforced the above concept by suggesting that CBD works against those cannabinoids that bind with CB1 and CB2 receptors.
- In a 2018 study, published in the European Journal of Internal Medicine, the researchers had discovered that the level of THC in the CBD should remain under 30mg/day to avoid hallucinations and drug tolerance, indicating that it is THC, and not CBD, that cause tolerance.
- Another 2010 study, published in the Pharmaceuticals (Basel), once again pointed to the fact that CBD does not lead to drug tolerance. However, THC definitely does.
What is Reverse Tolerance?
Unlike THC, to which your body can develop tolerance, CBD has been known to have a “Reverse Tolerance” effect. Intriguing?
Well, it is definitely an exciting thing for those who want to benefit from this cannabinoid.
The reason: Over time, you don’t require to up your CBD intake to have the desired effect; instead you usually have to down your daily intake, as you can achieve the intended effect at much less amount.
In regular CBD users, it has been seen that the cannabinoid does not get completely expelled from the body. Since it does not exactly bind with the receptors and remains intact within the body, it does not run the risk of having reduced effectiveness on the receptors or get metabolized beyond need.
Due to this reason, you would gradually require smaller doses of CBD each day, each week, and so on, until your symptoms would have faded away. This phenomenon is known as Reverse Tolerance!
Isn’t that great!?!
But, it is known for certain how long each person actually needs to reach this point. This usually will vary from person to person and composition to composition, brand to brand. In other words, there is no specific benchmark.
A person with a very weak or imbalanced endocannabinoid system may need more time to reach this stable endocannabinoid function. Others may never reach it, especially if their symptoms are varied and shifting. Still, others may reach it pretty soon, usually because their symptoms were not as severe or were acute (as opposed to chronic).
Nevertheless, it is good news. Since good quality CBD is so expensive, with reverse tolerance, you can hope that you won’t have to depend on it to manage your symptoms forever.
CBD doesn’t just compensate for lack of endocannabinoids…
What’s even better is that CBD boosts the growth and multiplication of endocannabinoids, i.e. the cannabinoids found naturally within the human body. This it does by blocking the enzymes that break them down.
Case in point: Anandamide. This endocannabinoid, also known as a ‘bliss molecule’, is responsible for controlling anxiety, mood, attention, etc. In a CBD user’s body, the enzyme FAAH that breaks anandamide down gets blocked, letting anandamide to remain in the body much longer,
This property of cannabidiol also contributes to the reverse tolerance phenomenon.
Making the most of your CBD
It has already been established that CBD never works the same way on all users. It is always about trial and error to find each user’s CBD sweet spot.
However, it does help to follow a few Easy Guidelines While Using CBD:
- When one brand works, stick to it
- When one method of administration works for you, don’t change it
- Once you’ve found the right CBD product for you, experiment no further
- Start low, go slow policy
- Be consistent with your dosage, reduce it when you feel it’s effects are increasing;
- Initial lack of effect may not mean it isn’t working
- Keep regular records of your physical, mental and emotional changes throughout the tenure of use
- CBD oil has THC, tolerance breaks may be needed
Owing to the way CBD interacts with our ECS, this cannabinoid not only does not lead to tolerance, but it is more likely to cause reverse tolerance. So, it’s no wonder why so many former opioid users are using it to get over their dependence and get well.
Of course, CBD has already been found to have so many therapeutic benefits – all in one product – that no one prescription drug can compete with it. After all, nature usually gives us what’s best for our health!
- CANNABIDIOL-ENRICHED OIL (CBD) EFFECTIVENESS WANES IN A THIRD OF CHILDREN AND ADULTS WITH TREATMENT-RESISTANT EPILEPSY; American Epilepsy Society (AES); Working Towards A World Without Epilepsy; https://www.aesnet.org/about_aes/press_releases/cbd-oil-effectiveness
- Drugs & Health Blog; Tolerance, Dependence, Addiction: What’s the Difference? National Institute of Drug Abuse for Teens; Advancing Addiction Science; https://teens.drugabuse.gov/blog/post/tolerance-dependence-addiction-whats-difference
- Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro; British Journal of Pharmacology; January 22, 2007; Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG; https://www.ncbi.nlm.nih.gov/pubmed/17245363
- Cannabidiol prevents infarction via the non-CB1 cannabinoid receptor mechanism; NeuroReport; October 25, 2004; Hayakawa K1, Mishima K, Abe K, Hasebe N, Takamatsu F, Yasuda H, Ikeda T, Inui K, Egashira N, Iwasaki K, Fujiwara M; https://www.ncbi.nlm.nih.gov/pubmed/15640760
- Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent, Current Drug Safety, 2011; Page 3; Mateus Machado Bergamaschi, Regina Helena Costa Queiroz, José Alexandre S Crippa, and Antonio Waldo Zuardi; https://www.medicinalgenomics.com/wp-content/uploads/2013/01/Bergamaschi_2011.pdf