Cannabis tolerance sucks.
Sure, taking a massive blunt to the face without melting into the upholstery might impress your friends, but it makes you an expensive date. More seriously, if you’re taking cannabis for medical problems like irritable bowel syndrome or insomnia, developing a tolerance can interfere with your treatment.
Luckily, even a short break from smoking, or a T break, can reduce your tolerance back to before you were such a heavy toker.
Oddly, across all tolerance studies, the concentration levels of tetrahydrocannabinol (THC) and its metabolites measured in the bloodstream of heavy smokers didn’t seem to correlate at all with how high the test subjects said they were on questionnaires, or how well they performed on cognitive and memory tests.
In fact, some stoner volunteers recruited in cannabis tolerance research efforts showed full tolerance to the cognitive effects of marijuana, but not the euphoric aspect of the marijuana high. Their physiological responses were still similar, but “blunted” according to the 2018 research from Neuroscience and Behavioral Reviews, a scientific journal that apparently doesn’t shy away from unintentional puns.
“Cognitive function is the domain showing the highest degree of tolerance, with some evidence of complete absence of acute effect (full tolerance),” according to the research, which was a meta-analysis reviewing results of a lot of different cannabis tolerance studies to-date. “The acute intoxicating, psychotomimetic, and cardiac effects are also blunted upon regular exposure, but to a lesser extent (partial tolerance). Limited research also suggests the development of cannabis tolerance to other behavioral, physiological, and neural effects of cannabis.
Is cannabis tolerance permanent?
Luckily, though chronic use of the chronic has profound effects on the brain, brains of heavy smokers become indistinguishable from non-smoker brains on an MRI after as little as a month of abstinence, according to one landmark study.
In this experiment, heavy users showed a marked reduction of CB1 receptors, the workhorse of the body’s endocannabinoid nerve signaling system, but those CB1 receptors re-appeared after quitting smoking. The same disappearance and reappearance of function are seen in cannabis-induced memory loss following three days of abstinence.
The human endocannabinoid system is a series of receptors and specific neurotransmitters concentrated in the brain, gut and throughout the body, to a lesser degree. This system governs mood, perception, sleep, hunger, stress response and a host of other physiological and emotional processes. It is the endocannabinoid system that THC and its counterpart cannabidiol (CBD) hijacks to produce both the marijuana high and the plant’s therapeutic effects.
The study in Biological Psychiatry, Cognitive Neuroscience, and Neuroimaging showed that the heavy toking volunteers had about 15 percent fewer CB1 receptors in their brains. After making that baseline measurement, researchers had the volunteers quit and monitored their brains.
Some were back to being indistinguishable from the non-smoking control group’s brains in as little as two days, while all the tokers’ brains were back to normal CB1 receptor levels within 28 days.
“Cannabis dependence is associated with CB1R downregulation, which begins to reverse surprisingly rapidly upon termination of cannabis use and may continue to increase over time,” the study states.
Why do you lose CB1 receptors when you smoke lots of weed?
CB1 receptors are part of a huge family of neuroreceptors called G-protein-coupled receptors (GPCRs). They’re all made of the same basic substrate of molecules arranged in a ring, providing a basic opening in the cell membrane. On this basic building block, your DNA codes for all kinds of molecular accessories, customizing that opening to receive only specific neurotransmitter molecules.
Think of a Lego block set. Almost every set comes with a flat, green baseplate you build up from. You can build a castle or a spaceship or a dollhouse, but in each instance, you start with the same baseplate. The human body has thousands of different types of GPCRs, so named because they are built on the same base ring of G proteins, and scientists have no clue about the function of most of them.
When you consume marijuana, you flood those CB1 receptors with cannabinoids far above what they evolved to process, day-to-day. As a result, the molecules that accept the cannabinoid transmitters get heavy wear-and-tear.
Luckily, all the body’s systems exist to be used, and they all have mechanisms for repairing themselves to various degrees. When your CB1 receptors get worn out from overuse, your cells suck them away from the cell wall to institute repairs in a process called internalization. This causes the receptor to “uncouple” from the signaling process.
“Two cellular correlates implicated in the development and maintenance of tolerance are CB1 cannabinoid receptor internalization and uncoupling of receptor signal transduction,” states a 2008 study in the journal Neuropharmacology. “Both processes have been proposed as mediators of tolerance because of observations that chronic THC treatment causes both region-specific decreases in CB1 receptors and G-protein coupling in the brain.”
With continued daily cannabis use, these uncoupled receptors tend to stay uncoupled longer. The remaining receptors are able to do the work of the approximately 15 percent of receptors that fall out-of-order in daily smokers because the brain continues to be flooded with cannabinoids from the weed, according to current thinking.
But with just a couple days of abstinence, your body is able to fend off that cannabis tolerance and catch up with repairs and send the offline CB1 receptors back to work. So, according to the study mentioned above, even heavy tokers’ brains return to a normal amount of CB1 receptors after a monthlong T break.