• According to research on the effects of CBD on users, there appears to be no indication that repeated and continual CBD use may lead to tolerance(1).
  • Studies show that the body can tolerate up to 200mg of CBD daily for the improvement of psychological conditions(2)
  • Research suggests that CBD may be linked to decreasing the onset of THC tolerance when treating pain(3)
  • CBD use is still under medical trials and research, so individuals under medical supervision should consult their doctor before taking CBD for their medical condition. 

Understanding CBD Tolerance

Tolerance is the adaptive capacity of the body to endure or become unresponsive to medication or treatment(4). 

Substance tolerance is a common concern in patients after being subject to long-term medication use for their health conditions. Drugs, after repeated use, may lose their effectiveness resulting in increased dosages or additional medication(5). 

In the case of CBD and THC tolerance, study findings about these two cannabinoid constituents, though still inconclusive, showed a potential symbiotic and beneficial partnership between the two. 

Understanding Cannabinoids and the Endocannabinoid System

Cannabis sativa is a herbaceous plant that contains cannabinoids that interact with the body through the endocannabinoid system (ECS)(6)

The ECS is a network of chemicals and cannabinoid receptors that maintain the body’s vital functions such as memory, learning, sleep, pain control, temperature, eating, and immune response(7).

The ECS has two receptors, namely, CB1 and CB2.  CB1 receptors are present in the brain’s reward centers(8). Studies now suggest that the endocannabinoid system may have a role in delivering signals that trigger the brain’s reward areas.  

The reward system is a collection of receptors that, when stimulated, releases hormones that reinforce motivation and may affect behavior(9).

Given this understanding of the body’s reward system, researchers have hypothesized that the ECS may be affected by cannabis constituents and may modify the body’s reward mechanisms(10).

Cannabidiol (CBD) and tetrahydrocannabinol (THC) are two cannabinoid components that have caught the interest of numerous research, specifically on cannabis products, drugs, and supplements.

This interest may be due to the compounds’ interaction with ECS receptors

However, cannabis tolerance is an issue that continues to push researchers into understanding how the body reacts to this type of drug. 

Moreover, the cannabis plant is sparking legal controversy because of its notoriety as an addictive plant. However, due to research on the positive effects of cannabinoids, its negative image is slowly being changed.

How Tolerance Works

Tolerance is the body’s reaction when subjected to long-term use or exposure to drugs. Tolerance diminishes the effect of a substance, which may result in a weakened bodily response to drug exposure(11). 

How tolerance exactly works in the human body is still not concretely known. However, research on how the ECS and endocannabinoid receptors are continually moving forward. 

Tolerance may have different effects on various individuals who are using different kinds of drugs. In cases involving opioids, tolerance happens when cellular change occurs due to the constant presence of opioid molecules that bind to receptors in the body(12). 

Repeated overstimulation of the brain and its receptors forces the system to rebalance itself. However, once the body restores its balance, it will have a new normal ceiling, which in turn, lessens the effectiveness of a particular drug(13). 

A drug’s full effects are felt by the user when they take the substance for the first time. However, if the user continues to take the drug, their body adapts, and to get the same effect, they need to take more medication(14). 

This phenomenon is referred to as tolerance. After only two to three doses, tolerance can start to develop with opioids.    

The same body function happens when cannabinoids, primarily THC, are repeatedly used by the body. The system adapts to the constant levels of CBD or THC, which forces its system to recalibrate and end up with a new threshold. 

CBD Tolerance vs. CBD Dependence

It is vital to differentiate tolerance from dependence. Drug dependence is when a person suffers from mental impairment due to chronic use of psychoactive substances(15)

It is common for a drug dependent individual to experience withdrawal symptoms after diminished substance use. People experiencing withdrawal may feel physically ill when substance cravings are unmet(16)

Studies show that cannabinoids work similarly to alcohol and other opioids in accessing the body’s reward system(17). Research suggests that cannabinoids such as THC may result in users experiencing THC tolerance and dependency.  

CBD and THC are among the most accessed cannabinoid constituents in the cannabis plant exact. THC is a psychoactive substance that gives cannabis users a “high” and euphoria(18). 

On the other hand, CBD is a nonpsychoactive substance predominantly used for treating conditions such as seizures linked to Dravet and Lennox-Gestaut syndrome(19). 

Why Do People Develop CBD Tolerance?

According to research on the effects of CBD in patients, there appears to be no indication that constant CBD use may lead to tolerance(20). 

CBD is a cannabinoid constituent and is at the forefront of research and studies targeting the benefits of Cannabis sativa or marijuana. 

However, it is highly recommended that individuals use CBD products under medical supervision.   

Managing CBD Tolerance

Research show CBD use may not produce the desired effect and cause complications mainly due to drug-to-drug interactions(21).  

CBD is one substance extracted from the cannabinoid-rich extract of the cannabis plant. Research on CBD showed potential anti-psychoactive properties and may also help reduce THC‘s adverse effects(22).

One of the methods to manage tolerance is a tolerance break. A tolerance break allows ample time for substances like THC(23) to be removed or expelled by the body. 

The average time frame for a tolerance break to work is at least 21 days long, which is the time it takes for the body to remove substances like THC(24)

How Fast Does CBD Tolerance Build?

Studies continue to mount, showing the positive effects of CBD on the body. High CBD dosage, especially in treating chronic pain, may result in adverse effects. However, in most cases, CBD is well accepted by the body(25).

CBD is also linked to possible ways of treating decreasing tolerance to substances like THC(26). The study further showed that CBD may affect the metabolic process of THC, which may result in lowering tolerance. 

CBD Tolerance vs. THC Tolerance

THC tolerance is far different from CBD tolerance. However, research suggests that dependency cases in CBD users may not happen because of its limited abuse liability and safety profile that is accepted well by the body(27).

A study showed that one primary use of THC may help treat anorexia linked to AIDS. However, continued doses in patients showed a decrease in their well-being(28)

However, observations show that THC tolerance will not only reduce the effects of the substance in the body but also produce unwanted side effects such as:

Furthermore, research suggests that a combination of CBD and THC may result in the decreased development of tolerance(29)

Defining Substance Tolerance

Substance tolerance is the reduced effect of a drug or medication due to continual use(30). Meanwhile, withdrawal is the adverse effect of reducing dosages after repeated use. 

Dependence and building tolerance may be linked incidentally to addiction when it is the result of a constant presence of a particular drug in the body(31)

Defining Substance Dependence and Withdrawal

Drug dependence, sometimes called substance dependence, is a chronic disease that stems from and is directly linked to continual, persistent, and excessive use of psychoactive substances(32)

The definition continues that the result may involve impairment and social and mental dysfunction.

Meanwhile, substance abuse is a possibly life-threatening condition where a person is actively engaged in a dangerous pattern of drug or substance use(33)

Withdrawal is a condition that results when a person stops the use of a substance where they become dependent(34). Withdrawal symptoms differ in severity depending on the drug or substance dependency length. 

What Is CBD Reverse Tolerance?

Reverse tolerance is when repeated use of a drug or substance increases the body’s sensitivity to the medication, which enhances the initial desired effect(35). The term reverse tolerance is also referred to as sensitization. 

However, despite the current research on reverse tolerance, studies are still not conclusive on how the body produces these heightened effects after repeated drug or substance use. 

Further research on the benefits and adverse effects of Cannabis sativa and its products are still at the forefront of discovery. 

What Happens Inside the Body After Taking CBD?

CBD engages the ECS differently compared to THC and other opioids. Research suggests that CBD has a low affinity or less interaction with the CB1 and CB2 receptors(36).

Added to this study, researchers show that CBD products, particularly CBD oil products, may offer a solution to opioid addiction(37)

Research shows that CBD is a nonpsychoactive substance that may neutralize the potential side effects associated with THC use(38). A 20:1 CBD: THC ratio may offer a better chance of preventing psychoactive effects and may inhibit dependence and tolerance.

Studies have also hypothesized that CBD may have the potential for treating conditions such as inflammations, seizures, and anxiety. However, side effects of CBD use may include diarrhea, appetite changes, and in some cases, tiredness(39)

There are many delivery methods for administering CBD into the body. There are products such as gummies, edibles, topicals, full-spectrum CBD oils, and high-quality tinctures

Though, positive results are slowly being observed. 

However, many of these products are still under clinical trial. Although researchers may suggest that CBD tolerance is highly improbable, the effects of the compound are still inconclusive. 

Is There a Limit to How Much CBD One Should Take?

According to a 2011 study, the highest amount of CBD used to treat chronic pain is 1,500mg daily(40). The investigation shows CBD use has health benefits and is well tolerated by the body, though research on this is still limited and not yet conclusive. 

However, in studies on CBD amounts, there are cases where side effects may occur after regular use, mainly due to interactions with other drugs(41). Some of the side effects observed are diarrhea, vomiting, liver-related conditions, and somnolence or drowsiness(42).

What Happens if One Takes CBD Every Day?

Studies have shown that the body can tolerate 200mg of CBD daily for treating psychological conditions(43). The study also shows no after effects and may help lessen cannabis dependence and addiction.  

The Food and Drug Administration (FDA) approved the CBD-based drug, Epidiolex, for the treatment of seizures associated with epilepsy (Dravet and Lennox-Gestaut syndrome) in children(44)

However, CBD products may trigger side effects due to impurities in the solution, drug interactions, and other complications(45)

It is noteworthy that the FDA approved only Epidiolex, Syndros, Marinol, and Cesamet as cannabis-based and related prescription medications(46)

  1. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies
  2. Cannabidiol Adverse Effects and Toxicity
  3. Cannabidiol Modulation of Antinociceptive Tolerance to Δ9-Tetrahydrocannabinol
  4. Definition of tolerance
  5. drug tolerance
  6. The endocannabinoid system: Essential and mysterious
  7. Ibid.
  8. The endocannabinoid system in brain reward processes
  9. Cannabinoid regulation of brain reward processing with an emphasis on the role of CB1 receptors: a step back into the future
  10. Ibid.
  11. The Molecular Basis of Tolerance
  12. Opioids and the Physiology of Tolerance
  13. Ibid.
  14. Ibid.
  15. [The definition of drug dependence]
  16. Drug addiction (substance use disorder)
  17. Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications
  18. What are cannabinoids?
  19. Cannabidiol for epilepsy (Lennox-Gastaut syndrome, Dravet syndrome)
  20. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies
  21. Cannabidiol Adverse Effects and Toxicity
  22. Does Cannabidiol Protect Against Adverse Psychological Effects of THC?
  23. T-Break: Take a Cannabis Tolerance Break
  24. Ibid.
  25. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies
  26. Cannabidiol Modulation of Antinociceptive Tolerance to Δ9-Tetrahydrocannabinol
  27. The Endocannabinoid System and Cannabidiol’s Promise for the Treatment of Substance Use Disorder
  28. Tolerance to Chronic Delta-9-Tetrahydrocannabinol (Δ9-THC) in Rhesus Macaques Infected With Simian Immunodeficiency Virus
  29. Cannabidiol Modulation of Antinociceptive Tolerance to Δ9-Tetrahydrocannabinol
  31. The relationship of addiction, tolerance, and dependence to alcohol and drugs: a neurochemical approach
  32. [The definition of drug dependence]
  33. Withdrawal
  34. Ibid.
  35. Reverse tolerance definition
  36. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin
  37. Clinicians’ Guide to Cannabidiol and Hemp Oils
  38. Does Cannabidiol Protect Against Adverse Psychological Effects of THC?
  39. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies
  40. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies
  41. Cannabidiol Adverse Effects and Toxicity
  42. Ibid.
  43. Ibid.
  44. FDA Approves First Drug Comprised of an Active Ingredient Derived from Marijuana to Treat Rare, Severe Forms of Epilepsy
  45. What are the benefits of CBD — and is it safe to use?
  46. FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)
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