Reverse Tolerance To Cannabis

Tolerance is defined as the need to use more of a drug to get the desired effect. Stated another way, less of an effect is achieved with a previously effective amount. It is clear that tolerance to THC develops following repeated exposure. How much exposure is needed to develop tolerance appears to be different for each person. A 2012 study in humans found that chronic, heavy users of THC-rich cannabis had a decreased number of cannabinoid receptors when compared to non-users. The same study also showed that a 4-week abstinence from THC resulted in an increased number of receptors, revealing that tolerance to THC is reversible. Tolerance to the effects of THC is easy to reverse with either abstinence or significant reduction of dosing for a few days. The vast majority of THC users do not experience withdrawal symptoms, however, if this does occur, CBD-rich cannabis can counteract most discomfort. Cannabidiol (CBD) does not cause tolerance as it does not work by binding to the cannabinoid receptor the same way that THC does.

What is Reverse Tolerance?

Reverse tolerance, also called drug sensitization, describes a condition in which some habitual users of a drug will, over time, require less of the drug (instead of more) to achieve the same effect. It’s most often discussed with reference to marijuana, but sometimes alcohol also. One theory is that marijuana accumulates in the body for a long time and that’s what produces the effect — i.e. you think you may be having just a little, but you’ve already got a lot in you. Another theory is that it’s just a psychological illusion. As users become more familiar with how to smoke it, they do so more efficiently and learn to identify the effects earlier. Therefore, they think they need less to achieve the same effect.

In a 1981 study that looked at cannabinoids as potential antiepileptics, animals developed tolerance to THC in all of the seizure models tested. In contrast, CBD showed evidence of reverse tolerance, meaning the seizures were effectively treated with lower doses over the three weeks of treatment. Quite interestingly, there are dozens of reports of reverse tolerance by parents of children with epilepsy who have been using CBD successfully to reduce seizures.

Research looking at the mechanisms of action for reverse tolerance for substances other than CBD suggests that various non-cannabinoid receptors, including GABA receptors and NMDA receptors, are likely involved. CBD is also known to interact with these receptors. Another hypothesis of the mechanism of action for CBD reverse tolerance is that CBD enhances endocannabinoid function leading to less CBD needed over time. Likely multiple and overlapping mechanisms of action are contributing to this phenomenon.

When people develop a reverse tolerance to alcohol, it’s usually because of liver damage. They lose the ability to break down alcohol, so a little bit produces a big effect.

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