Can THC Tolerance Be Quantified?

image of a chalkboard with the chemical compound for THC written out and the letters

With the rapid rise of cannabis consumption in the United States, researchers, lawmakers, and consumers have set their sights on uncovering the effects of chemical compounds found in marijuana. One particular question on their minds is: can THC tolerance be quantified? The question is primarily asked when discussing levels of impairment, specifically when a person is behind the wheel. Because everyone reacts differently to THC and develops tolerance to this compound in different ways, states have adopted per se limits on THC levels to detect impairment in drivers ranging from two to five nanograms per milliliter.

While these arbitrary levels of impairment may not be the same for all consumers, states are attempting to get to the bottom of the THC tolerance debate in order to protect the public from each other. One person may feel overwhelmed with minute levels of THC, while another may require a higher dosage to feel the same desired effects. The question of measuring THC tolerance can also help medical cannabis patients determine dosage and create a sustainable treatment plan with THC for their medical conditions.

What Is THC Tolerance? 

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A THC tolerance is developed after repeated and continuous use of cannabis. Developing a THC tolerance means that the consumer will require more THC to attain the same effects. After continuous use of THC, the brain will require higher levels of THC to feel the same effects as before. With cannabis tolerance, the brain can revert back to normal levels after a period of abstaining from THC, but this depends on many factors.

During abstinence, cannabis consumers can feel mild withdrawal symptoms. Heavy consumers are especially prone to these withdrawals and experience them more acutely. Symptoms can include irritability, anxiety, nausea, sweating, dizziness, and more. Although these withdrawals are not as severe as the withdrawal symptoms from other illicit substances, the symptoms can be rather uncomfortable. Measuring THC tolerance is not a one-size-fits-all process due to factors like the type of strain consumed, the level of THC present, and the dosage taken by an individual.

How Does The Brain React To THC Tolerance?

rendering of a cell receptor 

The human body has an endocannabinoid system, which is a network of cannabinoid cell receptors throughout the central and peripheral nervous system that regulates important biological functions. There are two main cell receptors in the system: CB1 and CB2. CB1 receptors are primarily located in the brain, while CB2 receptors are located throughout the peripheral nervous system. Consumers develop a THC tolerance due to the brain's downregulation of cannabinoid type 1 (CB1) cell receptors. Essentially, this means the number of CB1 receptors decreases.

The brain attempts to combat that decrease by desensitizing CB1 receptors to the presence of THC. That means that the brain weakens the effects that THC has on the body.

Then, the brain turns to internalization, which is the removal of CB1 receptors from the surface of the cell. During desensitization, the cell receptors are open for THC binding, but the consumer feels less effects. Once the brain gets to the point of internalization, the cell receptors are no longer available for THC binding.

THC activates the CB1 receptors in the body. Increasing the activity in those receptors allows them to facilitate the psychoactive and heightened sensory experiences associated with being high.

If a consumer repeatedly consumes THC for days or weeks, the brain reduces CB1 activity. Proteins in the brain recognize weakened cell receptors and mark them with a phosphate group. The phosphate group directs a course of action for these cells to remove cell receptors from its surface to dampen the effects of THC. This desensitizes a person to a point where they need to consume more and more to experience the feelings of sedation and pain relief they require.

Studies Into THC Tolerance

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One study analyzed the effects of chronic cannabis consumption on the effectiveness of CB1 receptors. Researchers analyzed PET scans of 18-35 year old men to determine the effects of THC exposure on CB1 receptors. They chose to focus on men due to their hormone levels, which we'll explain more below. They found that chronic cannabis use resulted in an average of 20 percent less cannabinoid receptor activity regardless of the amount of cannabis consumed.

Another study tested the effects of THC tolerance on mice. Mice were given two daily injections of 10 mg/kg of THC. After just 36 hours, or three injections, mice developed a tolerance to THC's effects on sedation and pain relief. Mice displayed higher tolerance to THC's sedative effects than to its pain-relieving effects.

These results suggest that certain areas in the brain develop THC tolerance more quickly than others. After stopping the mice THC injections for two weeks, the mice's behavior went back to normal. Tolerance to THC's sedative effects normalized faster than tolerance to the pain-relieving effects of THC.

Why Is THC Tolerance Difficult To Quantify?

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THC tolerance is difficult to quantify because everyone reacts differently to THC exposure and develops tolerance differently, according to a variety of factors like genetics, the potency of the product, the frequency of use, and metabolism speed. Tolerance can be assessed by observing a person's behavior when exposed to THC, monitoring their brain function, and tracking the amount and responsiveness of cell receptors in the brain.

A frequent cannabis user can quickly develop a tolerance, even after a few weeks of abstinence. Some consumers have even reported that abstinence has had no effect on their tolerance, meaning they do not feel the effects of THC anymore. However, these claims have not been scientifically assessed. Furthermore, first-time consumers develop tolerance differently. Some don't experience any effects at all on their first THC experience. Researchers have speculated that their CB1 receptors may not be accustomed to processing cannabinoids.

THC Tolerance In Men and Women

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Some preliminary studies have shown that men and women react differently to THC exposure and develop tolerance at different rates. In one study, female rats were 30 percent more sensitive than their male counterparts to the effects of THC. Female rats were especially vulnerable to THC effects like anxiety, paranoia, and addiction. Researchers believe this has to do with estrogen levels.

In the study, female rats also developed THC tolerance at a faster rate than males. Female rats exhibited more sensitivity to pain-relieving effects of THC after only 10 days of use. Female rats' sensitivity to THC increased when their estrogen levels were highest during menstruation. Interestingly enough, however, male rats showed a higher sensitivity than females when it came to appetite stimulation. Male rats got the "munchies" more than female rats.

The answer to the question, "Can THC tolerance be quantified?" isn't quite clear. A variety of factors affect how each person develops and maintains tolerance. THC tolerance varies depending on whether a person consumes THC for the first time or for the millionth time. Abstinence can also reduce tolerance, albeit at different rates for every person. For now, researchers, policymakers, and cannabis consumers depend on a hypothesis when determining THC tolerance. Until the federal government removes cannabis from their Schedule I listing, the answers to these questions won't be known.