We found a decrease in CB1 receptor binding in subjects who had smoked large amounts of cannabis on a daily basis for years. Even in these heavy smokers, the union returned to normal levels in most regions after about 4 weeks of abstinence. Once THC has been metabolized and eliminated, CB1 receptors begin to be upregulated and return to their normal level of availability. Upregulation after a single or occasional dose of cannabis occurs quickly.
Most people don't feel affected the next day. Experts recommend taking longer tolerance breaks of approximately 21 days. This is because it takes about three weeks (sometimes even longer) for THC to be completely eliminated from the system. This is because THC binds to fat, making it much more difficult to get rid of it quickly.
Imaging studies have given us more information about how long it takes for our brain's CB1 receptors to be replenished. These studies have suggested that a minimum of 28 days are required for CB1 receptor expression to be fully restored. As a result, neurons react immediately to THC overstimulation by reducing the number of CB1 receptors. Because THC acts directly on those receptors, too much THC can overload the receptors and reduce their functioning.
Tolerance develops when you oversensitize your cannabinoid (CB) receptors with an excess of THC, which reduces the number of receptors. In fact, a very recent study with male participants between 18 and 35 years old focusing on CB1 receptors confirmed that regular (but moderate) daily cannabis users had 20% fewer CB1 receptors than control group participants who did not use cannabis. With the persistent downregulation of the CB1 receptor 24 hours after smoking a joint, the pilots were still in a state of slight reduction in cannabinoid tone. When neurons containing CB1 receptors are overstimulated by the stronger and more prolonged activation of THC, a homeostatic response occurs in an effort to rebalance the brain.
Laboratory animals that receive a daily dose of THC for two weeks have 20 to 60% fewer CB1 receptors, depending on the area of the brain being measured. The right amount can also change over time because the body develops a tolerance to certain cannabinoids. A single exposure to cannabis begins with a single exposure to marijuana through various mechanisms, including extracting receptors from inside the cell so that they are no longer available for stimulation. Omega-3 fatty acids (found in fish, nuts and seeds, as well as in supplements) help the endocannabinoid system to work properly.
The number of CB1 receptors in the brain that react with THC decreases over time, as they become desensitized with frequent use. Reducing the tone of cannabinoids has the opposite effect on the perception of novelty than the increase in cannabinoid tone. Because of the way THC interacts with the body and the receptors, at a given stage, increasing THC can have negative effects on the body and its ability to function. Research shows that, although continued use of THC depletes CB1 receptors, it is possible to recover them over time and return them to their previous levels.