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Cannabis Tolerance: What Does the Evidence Say?

Nov 20, 2018 | By Alexander Beadle

Cannabis Tolerance: What Does the Evidence Say?
Alexander Beadle

Science Writer

Most conversations about cannabis tolerance revolve around the experiences of recreational cannabis users. Often this revolves around the need for higher doses of the drug to experience their desired intoxication level; on the other hand, after prolonged usage of the same dose they may feel they no longer experience some of the common side effects of cannabis use, such as poor attention, anxiety, or confusion.

However, for those who use cannabis for medicinal purposes, tolerance can be a big problem. While recreational users have reported that taking short breaks from cannabis use, known as “t-breaks”, has helped combat some of their tolerance symptoms, this is rarely an option for people who are using cannabis to manage pain or extreme discomfort. The more moderate critics of medicinal cannabis often cite this build-up of tolerance in debating whether the long-term effectiveness of the drug is satisfactory enough to permit its widespread use.

There has been a wealth of previous research into specific aspects of cannabis tolerance: from the more subjective reported effects on mood and intoxication, to the more easily quantifiable effect on heart rate and EEG signals. Many of these studies have reported conflicting results, most likely due to differing extents of cannabis use history, the potency of cannabis used in the studies, and individual sensitivity. Researchers at King’s College London have conducted the first systematic literature review of cannabis tolerance studies involving the comparison of regular cannabis users (RU, daily to weekly cannabis use) to occasional or non-regular cannabis users (NRU, weekly or less cannabis use). The aim of this study was to identify pockets of evidence for the development of cannabis tolerance against a specific effect of cannabis use.

Tolerance and perceived intoxication

Perhaps unsurprisingly, studies into intoxication and other subjective effects were the most commonly investigated by researchers, with 22 unique studies involving a total of 629 participants being conducted in the past 50 years. Of these 22 studies, 15 found some positive evidence of cannabis tolerance affecting intoxication.

Where studies focussed on the effects following a single administration of cannabis, there was mixed results. Four studies found no significant difference in reported intoxication between RU and NRU populations; but three larger-scale studies concluding that there was less pronounced and shorter spells of intoxication in RU versus NRU group.

In studies that examined repeated cannabis administration, the development of tolerance was more clearly observed. Lower levels of intoxication were consistently reported by RU in comparison to NRU, with some studies also observing corresponding decreases in reports of “good feelings” and “stimulation” in RU, and higher numbers of NRU reporting feelings of tiredness at high cannabis dosages.

Additionally, one study reported that in users who had built up a cannabis tolerance, a one week period of abstinence from cannabis use did result in a measurable partial recovery from the effects of cannabis tolerance.

Other domains showing degrees of tolerance

Cognitive function showed the highest degree of tolerance among the various domains examined by cannabis tolerance studies.

In studies concerning acute cannabis use, finding showed that memory and learning, attention, and psychomotor ability were all less impaired in RU compared to NRU and non-users (NU) when completing the Critical Tracking Test (CTT), a common cognitive function assessment. However, when given a different test to assess sustained attention, no evidence for tolerance was observed in RU in comparison to NRU, indicating that the effect of tolerance on attention may be limited to just damping the tendency for divided attention. Other cognitive functions, such as impulsivity and time perception have been the subject of only a few studies, but it appears that no tolerance is built up to cannabis’ effect on impulsivity in RU, but that RU were more accurate in judging the passing of time than NRU.

Studies of repeated cannabis administration have also demonstrated the development of tolerance to the effects on cognitive function, with the vast majority of these studies demonstrating tolerance in the areas of learning, memory, vigilance, and psychomotor ability.

In addition to intoxication and cognitive function, the literature review also found pockets of evidence for the building up of partial tolerance in regular cannabis users against other behavioral and physiological effects. Resting heart rate, anxiety, and confusion were all found to be lessened to some extent in RU versus NRU. From a physiological perspective, RU also experienced smaller changes in EEG signals, cortisol release, and prolactin levels than NRU.

The bigger picture

The researchers who conducted the literature review acknowledge that these pockets of conclusive results are merely the highlights in a messy and confusing landscape of cannabis tolerance studies. Currently, many areas of study only have a very limited number of studies covering them, or a very limited number of participants across multiple studies. Other areas have been heavily researched, but due to differing study methods the results from these studies can be conflicting. This makes it hard to say conclusively whether cannabis tolerance can affect these certain domains of behavior.

Still, there is enough evidence available from the wealth of cannabis tolerance studies to safely conclude that with sustained long-term use at a set dosage, it is indeed possible to develop a tolerance to some of the effects of cannabis. It has also been shown that cannabis tolerance in frequent cannabis users can decrease following a relatively short break from cannabis use.

Further research is definitely needed in the field of cannabis tolerance study. Behavioral and physiological effects were identified as particularly important areas which require additional research.

Further investigation of the neurobiological mechanisms that underpin the development of cannabis tolerance has been identified as key to improving our understanding of the field. By increasing our knowledge of how cannabis tolerance works, it may be possible to better model the outcomes of long-term regular cannabis usage, as well as improve the long-term effectiveness of cannabis as a medicinal treatment for those who rely on it.

 

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