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Sex-dependent Effects of Cannabis & Cannabinoids

Updated: May 27, 2023

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Welcome to Cannabis Conclusions, a unique educational series from Higher Learning LV that is targeted at hemp and cannabis industry professionals. This series provides readers with the conclusion section from important modern peer-reviewed research studies.

A July 2017 study entitled "Sex-Dependent Effects of Cannabis and Cannabinoids: A Translational Perspective" that was published in the journal Neuropsychopharmacology explored "the sex-dependent effects of cannabis and cannabinoids by synthesizing findings from preclinical and clinical studies focused on sex comparisons of their therapeutic potential and abuse liability, two specific areas that are of significant public health relevance."

The study reported that, due to "the demonstrated pain-relieving effects of cannabinoids in clinical trials and the commonly reported use of cannabis to reduce chronic pain, most preclinical sex difference studies published to date have focused on determining whether cannabinoids are equi-potent and -efficacious analgesics in females versus males."

Study Conclusions

"Sex differences in any phenomenon can be categorized as quantitative—phenomena that are essentially the same but differ in magnitude between the sexes, or qualitative—phenomena that occur only in one sex, or that differ in underlying mechanism.

"At this point, primarily quantitative sex differences in cannabinoid effects have been demonstrated in animal and, to a lesser degree, in human studies. That is, cannabinoid drugs have been found to be more or less potent, and in a few cases more or less efficacious, in one sex compared to the other, on a variety of End points.

"Small sex differences in therapeutic drug potency are unlikely to be important clinically, because drug dose can be readily adjusted up or down to compensate for any individual difference in drug effect. In contrast, large sex differences in therapeutic drug potency, or sex differences in therapeutic drug efficacy are more likely to be clinically significant, since escalating drug dose to compensate for relative lack of effect results in no gain in effect (when efficacy is low), and/or overwhelming adverse effects. Increasing dose to compensate for a lack of potency or efficacy can also lead to greater development of tolerance and dependence.

"Small sex differences in therapeutic drug potency are unlikely to be important clinically, because drug dose can be readily adjusted up or down to compensate for any individual difference in drug effect."

"These consequences of increasing drug dose have significant implications when considering the potential utility of cannabis and cannabinoids as a viable therapeutic option. Considering that cannabis is widely used recreationally, sex differences in initial potency and efficacy may also affect the likelihood of developing CUD, and achieving and maintaining abstinence in people who seek treatment for this disorder.

"Findings from preclinical studies demonstrate that females are particularly sensitive to the reinforcing effects of a CB1 receptor agonist. These findings coupled with epidemiological and smaller observational studies reporting that women accelerate to problematic cannabis use at a faster rate than males and exhibit more severe withdrawal symptoms when abstinent underscore the importance of addressing sex-dependent effects of cannabis and cannabinoids for both therapeutic and abuse-liability perspectives."

View the original study.

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