Many notice that after regularly smoking cannabis, it takes more and more to feel its effects- if any at all. While abstinence for some time- be it a few weeks or months- often seems to reset the cycle, to understand why we build a tolerance to cannabis, we have to delve into the role it plays in our brains.
Tetrahydrocannabinol (THC) is the primary psychoactive compound in cannabis and is responsible for the euphoric ‘high’ feelings of cannabis. In particular, it works by activating the cannabinoid receptor CB1 located on the body’s neurons, as a part of the endocannabinoid system. This system is known to play a crucial role in regulating functions, including sleep, pain, mood, and appetite.
A 2016 study investigating how THC works in the brain found that heavy smokers of cannabis tended to have reduced CB1 receptor availability in most brain regions. To see how this could be modulated, the researchers split the study participants into two groups- one was asked to not smoke cannabis for two days, and the other for 28 days.
In the end, they found that the receptor availability began to replenish after just two days of abstinence, and continued for over four weeks. While after four weeks, receptor availability still didn’t match that of the control group who did not smoke cannabis, it appears that from as little as two days of abstinence, tolerance to THC, and indeed cannabis, starts to decrease.
While interesting findings, the researchers note that their results may not be conclusive due to their small sample size- 11 heavy cannabis users and 19 users. Furthermore, they note that they only looked at the number of joints consumed by each participant as opposed to specific levels of THC. They also do not know how CB1 upregulation continues beyond four weeks of abstinence.