“How does tolerance work?”—This is a common question that even advanced cannabis users might wonder about. If you are a habitual cannabis user you will likely have noticed that after a while your favorite ganja does not hit the spot quite in the same way it used to and so you might try and seek out another more potent strain or delivery method in hopes of regaining the desired “high”. To say it bluntly, pun intended, the reason you are experiencing numbness to the effects of cannabis and THC is because your body is trying to compensate and re-calibrate its normal operation functions to the chronic presence of the phytocannabinoids in its systems. Your body does this by physically adjusting how the cells respond to continuous intoxication with cannabis. The result of tolerance can be both good or bad. It can be good in a sense that tolerance can blunt undesired side-effects of cannabis. But it can be bad, when it forces you into a cycle of taking more frequent and higher doses in order to chase the euphoria of a progressively harder to achieve high. - The good news is: Tolerance is reversible. If you are mindful about your cannabis consumption then tolerance can be managed, and if you are already experiencing tolerance, then you can get rid of it by taking a 2–4 week break from cannabis.
Regular cannabis use causes the body to build tolerance, resulting in less potency.
The base concept
Before we get to the subject of tolerance you need to first appreciate that your body is an intricately balanced ecosystem of interconnected and interdependent biochemical systems. What this means is that for everything to run smoothly all the biochemical systems in your body need to run with precision in timing, concentrations, temperature and location. To account for inevitable variability, our bodies are quite good at “buffering” changes in order to maintain optimal conditions for our cells to operate in. Every biological system in your body has an optimal range.
For example, in order for your body’s essential enzymes to function your body temperature needs to be maintained within just the right range. While 37C is optimal we can accept a reasonable spread between 36C and 38C without too much trouble. But go beyond 42C or below 34C for too long and you will end up damaging your cells. Another example would be maintaining just the right acidity of your blood, which must not be too acidic nor alkaline. The body achieves this via metabolic pathways involving the kidneys, a respiratory path through the lungs and a weak carbonic acid / bicarbonate ion based buffer system.
So, if you have a metabolic imbalance that lowers your blood pH, then your brain can tell your lungs to release more carbon dioxide (CO2). Carbon dioxide is a waste product your cells release as a result of processing nutrients with oxygen. Eliminating CO2 through the lungs will increase your blood pH. Alternatively, your kidneys can excrete excess bases or acids.
Tolerance is a mechanism the body uses to compensate for biochemical imbalances
But humans are imperfect and diverse, so while we know what the optimal pH range of human blood is, the amount of work each of those buffering mechanisms needs to put in to achieve balance is individually different for everyone’s genetic background and overall physical status. Every human requires a unique calibration. Maybe you are a heavy smoker and your lungs are not quite as effective as they used to be, well then your metabolic pH compensation will have to work extra hard. Conversely, you may have healthy lungs but your acid-base balance is disturbed via metabolic mechanisms. Perhaps as a result of the wrong diet. In that case your respiratory system will need to compensate more. The outcome is the same, your blood is maintained at pH 7.4 but which pathway gets you there is different. It also means that if you end up in the hospital with abnormal blood pH then you know you are in trouble, because that means your buffering systems have already failed. Body temperature and blood pH are important variables that all of us will have consciously dealt with at one point or another, but they are far from the only systems that need to be balanced. There are many thousands more that are equally as important but far more complicated. You can get a taste of this when you visit the doctor and get a blood test. They’ll always return a chart that shows where your blood lands along various important axes that need to be balanced.
How does this all relate to cannabis tolerance?
Well the core idea is the same. Tolerance is a mechanism the body uses to recalibrate and compensate for biochemical imbalances. What your base calibration looks like largely depends on your genetic background. So for example, if you inherit a defective gene from a parent then some metabolic pathways could be impacted. But, if the diminished function lands within the compensatory range of your various buffer systems then your body can adapt and recalibrate and you may never know that there is a problem. It is a lifelong process and your body will continuously re-evaluate its environment. The same is true for the compounds and receptors involved in the endocannabinoid system (ECS). The human body expects a certain amount of “endo”-cannabinoids and cannabinoid receptors to be present at certain times and in specific tissues. As with everything else, the release and metabolism of cannabinoids is tightly regulated. So when you frequently flood the body with external cannabinoids in high dosage for a long duration, then your body will eventually try and compensate in order to re-establish its preordained balance.
The good news! Tolerance is reversible, just take a break.
In particular for cannabis the current scientific consensus is that tolerance is a result of adaptation in the CR1 cannabinoid receptor system. Specifically, when the CR1 receptor is continually overstimulated then the cells react by down-regulating the receptor throughout the central nervous system. This means that even when there is an excess of cannabinoids available that could interact with the receptor, overall signaling will be reduced because there are overall less receptors available. From euphoria to analgesia tolerance can affect all of the neurobiological activity of cannabis and dull its effects. Whether or not you consider that a boon or bane depends on your use case. If you are a medical user you may not enjoy some of the cognitive impairment of cannabis use. In that case you might consider tolerance a boon as it will provide you with a milder experience. On the other hand it is clear that by and large the cannabis community is trying to counteract the effects of tolerance. Chief strategy to achieve this is the pursuit of products with ever increasing concentrations of THC. But, as with all things cannabis, there isn’t a huge amount of systematic research available so far. So there is a risk that increasing THC concentrations could bring about tolerance sooner.
How can I avoid tolerance? Can I get rid of it?
If you are experiencing tolerance, then I have good news for you. It is totally reversible. Studies have shown that even 48h of abstinence can reduce the amount of tolerance you are experiencing and total reversal can be achieved within a few weeks.
Breaking a habit like this can be hard and so you’ll find yourself wanting to replace the habit with other things. Smokable herbs are often replacements people like to go for. However, keep in mind that many of the terpenes found in smokable herbs also bind to the CR1 receptor. So it is possible that you could actually trigger the tolerance response by smoking replacement herbs. The best approach is moderation through mindful consumption of cannabis. The sparse data that does exist supports the idea that you can avoid tolerance in the first place, if you only occasionally or in-frequently use cannabis. If you can avoid daily use, you are going to be much less likely to develop tolerance in the first place.