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Know Your Medicine: Tolerance and Reverse Tolerance
Author: Bonni Goldstein, M.D. 11/08/2017 - 16:27:00

The concept of cannabis tolerance is quite interesting. Now that patients are using preparations that contain different prominent cannabinoids, including delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), and cannabinol (CBN), the question of tolerance no longer relates to THC only. 

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. Animal research in the 1990s suggested that tolerance developed due to a reduction of cannabinoid receptors in the brain after they were exposed to chronic THC. 

A 2012 study in humans found the same results, namely 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. Interestingly, the researchers in this study also reported that different parts of the brain became tolerant at different rates. For instance, one may be using THC to treat pain and anxiety and may find with chronic, heavy use that the anxiety is lessened but the effects on pain relief are lost. 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.

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