Cannabis doesn’t kill brain cells like methamphetamine, nor does it cause the connections between brain cells to wither away like alcohol. However, repeated cannabis consumption does lead to a phenomenon known as “tolerance.”
If you stop using cannabis, the brain can recover impressively quickly, generally within weeks.
What is Tolerance?
Tolerance to THC can be explained by the cannabinoid type I (CB1) receptors in the brain, which decrease with continued cannabis use. Essentially, you need to consume more THC to achieve the same high. Over time and with continued use, it may seem impossible to get high at all. However, if you stop, the brain can recover quickly.
How Tolerance Develops
THC activates CB1 receptors to make you feel stoned. The high results from an abnormal increase in CB1 receptor activity. Once THC is gone, this activity usually returns to normal. However, repeated exposure to THC over days or weeks causes the brain to minimize the increase in CB1 receptor activity, fighting back to preserve normal activation patterns. This is achieved by reducing the number of CB1 receptors, weakening their effects, or altering genetic expression.
Mechanisms of Tolerance
Repeated activation of CB1 receptors by THC leads to desensitization (a weakening of the response to THC) and internalization (removal of CB1 receptors from the cell’s surface). When these processes occur, you’ll need to consume more THC to get high.
Desensitized receptors are still available for THC to bind, but their impact is lower than it once was. Internalized receptors are no longer available for THC to bind, as they are removed from the cell’s surface and either stay inside or are broken down.
As CB1 receptors are frequently activated, they become less associated with the components that carry out the receptors' effects. Proteins in the cell act like a coach to detect weak receptors and pull them from the game. Desensitized CB1 receptors are tagged with a phosphate group, signaling their removal from the cell’s surface.
The Timeline of Tolerance
The speed at which tolerance to THC develops depends on the dose and frequency of consumption, use history, and individual DNA. Studies in mice show that tolerance to THC’s effects can develop within 36 hours of twice-daily injections. After a week of THC exposure, behavior normalizes in less than two weeks of abstinence, with tolerance to THC’s sedative effect recovering quicker than its effect on pain.
Recovery from Tolerance
Compared to other recreational drugs, cannabis is unique in the speed at which the brain recovers following abstinence. A study of daily cannabis users reported that CB1 receptor levels increased to near-normal levels after just two weeks of abstinence.
Since internalization of CB1 receptors is the predominant consequence of excessive THC consumption, this explains why the brain recovers faster with cannabis abstinence than with many other drugs. CB1 receptors can be reproduced and sent back to the cell’s surface to recover normal brain function.
Cannabis vs. Other Substances
Excessive alcohol consumption can be toxic to the brain, causing injury or death to brain cells. Abstaining from alcohol can lead to some recovery, but it is often slower and less complete than with cannabis. Methamphetamine, on the other hand, offers little recovery of brain functioning even after a year of abstinence and can kill brain cells.
Given these comparisons, sticking with cannabis seems to be a safer choice.
