Blunted highs: Cannabis tolerance behavioral models and pharmacodynamics

Chronic daily cannabis use builds tolerance to some but not all of the effects of cannabis

With the increase of cannabis legalization, chronic cannabis use is expected to rise in the coming years. How might this chronic cannabis use affect us differently from intermittent use?

Here, researchers examine the neurobiological and behavioral mechanisms of cannabis tolerance in chronic cannabis users compared to intermittent users.

THC and brain activity
During acute cannabis use, tetrahydrocannabinol (THC) binds to endogenous cannabinoid type 1 (CB1) receptors in our brains, which increases activity in brain areas including the prefrontal cortex, which controls attention and memory, and the mesolimbic dopamine system, which controls reward. This results in the well known effects of cannabis including decreased decision making, attention, and motor control, and increased euphoria and analgesia.

In chronic cannabis users, these effects are blunted because CB1 receptors are downregulated to balance out the increased presence of cannabinoids binding to these receptors. This creates tolerance to the effects of cannabis: fewer CB1receptors mean less activation of the prefrontal cortex and mesolimbic dopamine system and therefore a less potent response to cannabis.

How quickly does one build tolerance to the effects of cannabis?
Research shows that tolerance builds quickly with continuous daily use of cannabis at high doses, but not with intermittent cannabis use. Additionally, tolerance is quickly reversed with abstinence from cannabis.

With these blunted effects, many chronic cannabis users believe that they have volitional control over their actions when under the influence. This is shown to be somewhat, although not completely true.

For example, chronic users can choose to improve their performance on repetitive tasks when under the influence of cannabis, but have poorer performance on tasks requiring high attention and motor skills.

Avoid high tolerance to cannabis
CED Clinic recommends avoiding building a high tolerance. Frequent users should consider taking a cannabis break of one to two days, at least every two weeks. Daily cannabis use can lead to increased dosage requirements, which is not harmful but can be costly.

Need an expert opinion on your cannabis tolerance level?
To learn how chronic cannabis use could affect you, book an appointment with our medical cannabis doctors at your convenience through our virtual booking link or by giving us a call (617–500–3595).

Dr. Caplan and his team at The CED Clinic in Needham, MA are available to guide and support you!

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