Sex-related differences in subjective, but not neural, cue-elicited craving response in heavy cannabis users.

BACKGROUND: Studies indicate that female cannabis users progress through the milestones of cannabis use disorder (CUD) more quickly than male users, likely due to greater subjective craving response in women relative to men. While studies have reported sex-related differences in subjective craving, differences in neural response and the relative contributions of neural and behavioral response remain unclear. METHODS: We examined sex-related differences in neural and behavioral response to cannabis cues and cannabis use measures in 112 heavy cannabis users (54 females). We used principal component analysis to determine the relative contributions of neural and behavioral response and cannabis use measures. RESULTS: We found that principal component (PC) 1, which accounts for the most variance in the dataset, was correlated with neural response to cannabis cues with no differences between male and female users (p = 0.21). PC2, which accounts for the second-most variance, was correlated with subjective craving such that female users exhibited greater subjective craving relative to male users (p = 0.003). We also found that CUD symptoms correlated with both PC1 and PC2, corroborating the relationship between craving and CUD severity. CONCLUSIONS: These results indicate that neural activity primarily underlies response to cannabis cues and that a complex relationship characterizes a convergent neural response and a divergent subjective craving response that differs between the sexes. Accounting for these differences will increase efficacy of treatments through personalized approaches.

Cannabinoid Receptor Type 1 and Its Role as an Analgesic: An Opioid Alternative?

Understanding how the body regulates pain is fundamental to develop rational strategies to combat the growing prevalence of chronic pain states, opioid dependency, and the increased financial burden to the medical care system. Pain is the most prominent reason why Americans seek medical attention and extensive literature has identified the importance of the endocannabinoid pathway in controlling pain. Modulation of the endocannabinoid system offers new therapeutic opportunities for the selective control of excessive neuronal activity in several pain conditions (acute, inflammatory, chronic, and neuropathic). Cannabinoids have a long history of medicinal use and their analgesic properties are well documented; however, there are major impediments to understanding cannabinoid pain modulation. One major issue is the presence of psychotropic side effects associated with D9-tetrahydrocannabinol (THC) or synthetic derivatives, which puts an emphatic brake on their use. This dose-limiting effect prevents the appropriate degree of analgesia . Animal studies have shown that the psychotropic effects are mediated via brain cannabinoid type 1 (CB1) receptors, while analgesic activity in chronic pain states may be mediated via CB1R action in the spinal cord, brainstem, peripheral sensory neurons, or immune cells. The development of appropriate therapies is incumbent on our understanding of the role of peripheral versus central endocannabinoid-driven analgesia. Recent physiological, pharmacological, and anatomical studies provide evidence that one of the main roles of the endocannabinoid system is the regulation of gamma-aminobutyric acid (GABA) and/or glutamate release. This article will review this evidence in the context of its implications for pain. We first provide a brief overview of CB1R's role in the regulation of nociception, followed by a review of the evidence that the peripheral endocannabinoid system modulates nociception. We then look in detail at regulation of central-mediated analgesia, followed up with evidence that cannabinoidmediated modulation of pain involves modulation of GABAergic and glutamatergic neurotransmission in key brain regions. Finally, we discuss cannabinoid action on non-neuronal cells in the context of inflammation and direct modulation of neurons. This work stands to reveal long-standing controversies in the cannabinoid analgesia area that have had an impact on failed clinical trials and implementation of therapeutics targeting this system.

Cross-Cultural Effects of Cannabis Use Disorder: Evidence to Support a Cultural Neuroscience Approach.

PURPOSE OF REVIEW: Cannabis use disorders (CUDs) are prevalent worldwide. Current epidemiological studies underscore differences in behaviors that contribute to cannabis use across cultures that can be leveraged towards prevention and treatment of CUDs. This review proposes a framework for understanding the effects of cross-cultural differences on psychological, neural, and genomic processes underlying CUDs that has the potential to inform global policies and impact global public health. RECENT FINDINGS: We found that cultural factors may influence (1) the willingness to acknowledge CUD-related symptoms among populations of different countries, and (2) neural responses related to the sense of self, perception, emotion, and attention. These findings leverage the potential effects of culture on neural mechanisms underlying CUDs. SUMMARY: As the number of individuals seeking treatment for CUDs increases globally, it is imperative to incorporate cultural considerations to better understand and serve differing populations and develop more targeted treatment strategies and interventions.