Study Provides Insights into Effects of Cannabis Tolerance Breaks

Tolerance refers to your body’s process of getting used to cannabis, which can result in weaker effects.

In other words, you need to ingest more to get the same effects you once did. This can be particularly problematic if you’re using cannabis for medical reasons.

New research has found that cannabis tolerance is linked to neurometabolic alterations in the brain’s reward circuitry. The findings, published in the journal Addiction Biology, help explain why the effects of cannabis are less prominent in frequent cannabis users.

A growing body of evidence suggests that regular cannabis users develop tolerance to the impairing, as well as the rewarding effects. The finding that cannabis altered circuitry and distorted behavior in occasional, but not chronic users, suggests reduced responsiveness of the reward circuitry to cannabis intoxication in chronic users.

“These neurobiological mechanisms are important to elucidate, both in the context of therapeutic use of cannabis-based medications (e.g. deciding on dose in long-term treatment), as well as in the context of public health and safety of cannabis use when performing day-to-day operations (e.g. developing traffic laws),” said Natasha L. Mason, a PhD candidate at Maastricht University and the corresponding author of the new study

In the double‐blind study, 12 occasional and 12 frequent cannabis users consumed the drug or a placebo before undergoing brain imaging scans. The participants also completed a measure of their reaction times and attentional lapses, along with an assessment of their subjective high.

The researchers observed significant differences between the occasional users, who consumed cannabis 1 time a month to 3 times a week, and the frequent users, who consumed the drug at least 4 times a week. In particular, cannabis resulted in alterations in the brain’s reward circuitry, including decreases in functional connectivity, in occasional users. But these changes were absent in chronic users.

The finding that cannabis altered reward circuitry and distorted behavior in occasional, but not chronic users, suggests the development of neural-adaptations in the brain’s reward system after excessive use of cannabis that reduces the circuitry and behavioral response to acute cannabis impairment. Chronic users just don’t get as high as occasional users, meaning they are not nearly as impaired as less chronic users with the same consumption.

“However, little is known about cannabis use patterns and motives underlying such patterns among medical and recreational users, and the impact of changes in cannabis use patterns have not been studied in the lab. Thus knowledge on frequency, dose and duration of cannabis use that is needed to achieve, maintain or lessen tolerance however is very limited, but will be of importance in the context of cannabis therapeutics and in legal settings when evaluating the impact of cannabis exposure on human function.”

How do I manage my tolerance?


From a practical perspective, having a general knowledge of your tolerance can help you dose safely, more effectively, and even save you some money.

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If you’re planning a day with multiple doses, consider “backloading” your THC content. You’ll always be most sensitive to the effects of THC during your first dose, so keep your first dose small, and allocate larger doses later. Use cannabis products with a higher CBD-to-THC ratio. CBD won’t give you a “high,” but it does seem to have several potential health benefits, such as reducing pain and inflammation. Rotating between high-CBD, low-THC and high-THC, low-CBD strains may also prevent tolerance. Unlike THC, CBD use does not lead to tolerance since it increases the body’s natural endocannabinoids. Because CBD can only interact with CB1R at reasonably low concentrations, the effects of CBD are not subject to a tolerance build-up.

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