How CB1 Receptor Activity and Distribution Contribute to Make the Male and Female Brain Different Toward Cannabinoid-Induced Effects



Sex-dependent differences have been consistently reported in the prevalence and frequency of use of Cannabis, with patterns of use, subjective effects, and progression to dependence being different in male and female smokers. As confirmed by animal studies, cannabinoids exert sex-dependent effects in many physiological and behavioral aspects, including food intake and energy balance (stronger in males) and emotional regulation (stronger in females). Following chronic THC exposure during adolescence, cannabinoid receptors undergo desensitization, which is greater in adolescent female animals than in male animals. Preclinical research is greatly contributing to elucidate the neurobiological bases for sex differences in cannabinoid effects, among which different cannabinoid pharmacodynamic and pharmacokinetic and gonadal hormones play crucial roles. The sexual dimorphism of the brain in cannabinoid subtype 1 receptor (CB1R) distribution and function massively contributes to the variety of differences reported in cannabinoid-induced effects between the two sexes. The distribution and activity of neuronal CB1Rs in the male and female brains and how they can be differently affected by stress and drugs of abuse have been investigated in many brain areas. In this chapter, we will first provide an overview on the brain sexual dimorphism and the sex-dependent effects of cannabinoids. Then we will review both clinical and laboratory-based research evidence revealing important sex-related differences in CB1 receptor level and function in different brain areas. Finally, the influence of gonadal hormones in determining such differences will be discussed.


Ventral Tegmental Area Cannabis User Early Life Stress Chronic Unpredictable Mild Stress Maternal Deprivation 
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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Biomedical Sciences, Division of Neuroscience and Clinical PharmacologyUniversity of CagliariMonserratoItaly
  2. 2.Institute of Neuroscience-Cagliari, National Research CouncilCagliariItaly

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