Sex differences, endocannabinoids, and pain

    December 01, 2022 2 min read

    Sex differences, endocannabinoids, and pain

    Sex differences in pain perception and analgesia is a burgeoning research field. For clinical and pharmaceutical applications this is a reasonable and useful thing to want to understand. Are there such sex differences? And are they evident in cannabinoid analgesia specifically? 

    The answer to the first question is Probably. Male and female mammalian pain perception does appear to differ slightly. For the second question, nothing definitive can be said yet, either about efficacy or mechanisms that might mediate differences in efficacy. The reason for that lies in the nature of the studies that have been conducted so far. 

    Interestingly, in rat studies, females have displayed greater sensitivity to Δ9-THC than males. This appears to be a function of metabolism, hormones, and receptor expression. The same has not been observed in mice, however, so this effect may be species-specific. Something that is known about human females is that estrous stage, ovariectomy, and hormone replacement can all influence the expression of cannabinoid receptors and ligands, and the affinity and efficacy of these ligands and receptors, in various brain regions. It should therefore be that cannabinoid anti-nociception studies should evaluate variables like menstrual stage or hormone factors. So far they have not. Estrous cycle itself has only been evaluated in a third of cannabinoid pain studies so far. 

    Not that pain studies themselves are lacking. They exist in abundance, and we have written about them extensively in other blog posts. They have already revealed important insights into the variable nature of pain itself. (Pharmacologically speaking, inflammatory pain in arthritis is not the same as chemotherapy-induced neuropathic pain, for example.) But studies to date have tended to pool men and women together, and omit statistical analyses between the two groups that might begin to illuminate important sex differences that may exist. 

    The way ahead is quite clear, and there is much to warrant it. A fine review article of the state of research thus far exists inBlanton HL, et al., Pharmacol Biochem Behav. 2021 Mar;202:173107. doi: 10.1016/j.pbb.2021.173107. 

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