Sex-Dependent Vulnerability to Cannabis Abuse in Adolescence

Rubino, Tiziana; Parolaro, Daniela

doi:10.3389/fpsyt.2015.00056

Cited by 48 publications

(34 citation statements)

References 51 publications

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“…Cannabinoid use in adolescence has profound effects on cannabis use and related changes in biology and behavior in adulthood [56, 57], in a sex-dependent manner [58–60]. The majority of the literature examining these effects at the neurobiological level is in animal models, with some investigation in humans.…”

Section: Adolescent Cannabinoid Exposure Impacts Adulthood: Preclinicmentioning

confidence: 99%

Mechanisms Underlying Sex Differences in Cannabis Use

et al. 2017

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Purpose of the Review Cannabis is the most commonly used illicit substance worldwide. In recent decades, highly concentrated products have flooded the market, and prevalence rates have increased. Gender differences exist in cannabis use, as men have higher prevalence of both cannabis use and cannabis use disorder (CUD), while women progress more rapidly from first use to CUD. This paper reviews findings from preclinical and human studies examining the sex-specific neurobiological underpinnings of cannabis use and CUD, and associations with psychiatric symptoms. Recent Findings Sex differences exist in the endocannabinoid system, in cannabis exposure effects on brain structure and function, and in the co-occurrence of cannabis use with symptoms of anxiety, depression and schizophrenia. In female cannabis users, anxiety symptoms correlate with larger amygdala volume and social anxiety disorder symptoms correlate with CUD symptoms. Female cannabis users are reported to be especially vulnerable to earlier onset of schizophrenia, and mixed trends emerge in the correlation of depressive symptoms with cannabis exposure in females and males. Summary As prevalence of cannabis use may continue to increase given the shifting policy landscape regarding marijuana laws, understanding the neurobiological mechanisms of cannabis exposure in females and males is key. Examining these mechanisms may help inform future research on sex-specific pharmacological and behavioral interventions for women and men with high-risk cannabis use, comorbid psychiatric disease, and CUD.

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Section: Adolescent Cannabinoid Exposure Impacts Adulthood: Preclinicmentioning

confidence: 99%

Mechanisms Underlying Sex Differences in Cannabis Use

et al. 2017

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“…Further, given that recent reviews have suggested that greater female vulnerability to cannabis use disorder may be linked to important biological differences such as neuronal maturation over adolescence, sex-specific responses to cannabinoid compounds, and hormone and cannabinoid receptor interactions (Kuhn, 2015;Rubino & Parolaro, 2015), increased cannabis use among adolescent females is of particular concern.…”

Section: Discussionmentioning

confidence: 99%

Evidence for Sex Convergence in Prevalence of Cannabis Use: A Systematic Review and Meta-Regression

Chapman

Slade

Swift

et al. 2017

J. Stud. Alcohol Drugs

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ABSTRACT. Objective: Generally, cannabis use has been more prevalent in men than in women. However, emerging evidence suggests that the prevalence of cannabis use is converging among males and females from recent cohorts. This study aimed to systematically summarize published literature on birth cohort changes in male-to-female ratios in prevalence of cannabis use. Method: Twenty-two studies with a median sample size of 85,052 were identified for inclusion. Data were collected between 1979 and 2010, representing birth cohorts from 1936 to 1999. For quantitative synthesis, male-to-female ratios in prevalence of any cannabis use were calculated for all 5-year birth cohorts available, generating 348 separate ratios among birth cohorts from 1941 to 1995 in 30 countries. Random-effects meta-analyses generated pooled sex ratios, stratified by 5-year birth cohorts. Results: Of the 22 included studies, 10 reported some evidence of sex convergence in cannabis use among more recent cohorts. Quantitative synthesis found that the ratio of cannabis use prevalence in males and females decreased significantly from 2.0 among cohorts born in 1941 to 1.3 among those born in 1995. Conclusions: Findings support the narrowing sex gap in the prevalence of cannabis use. Results are concordant with a broader literature demonstrating sex convergence in prevalence of other substance use, particularly alcohol use and related harms. Both young women and men should be the target of prevention and early intervention efforts. Future research in more diverse global settings, especially in low-and middle-income countries, would enhance the international scope of the findings. (J. Stud. Alcohol Drugs, 78, 344-352, 2017) RECENT REPORTS INDICATE that about 3.5% of the population worldwide has used cannabis in the past year, making it one of the most widely used psychoactive substances (Gowing et al., 2015). Although studies from some countries have shown declines in prevalence of cannabis use among more recent birth cohorts (ter Bogt et al., 2014), others have reported significant increases over the past decade, with recent estimates of past-year prevalence in the United States as high as 9.5% (Hasin et al., 2015). In other countries, patterns of use over time have been more complex, particularly among young people (Copeland et al., 2013). In Australia, for example, although overall prevalence of cannabis use among those aged 12-17 has been declining, those who are using cannabis are doing so in greater quantities (Roxburgh et al., 2010). Similarly, a recent analysis of data from France, Germany, and the United States determined that despite some variations in patterns of use across these three countries, cannabis use was beginning at an earlier age among more recent cohorts (Legleye et al., 2014). These findings are particularly concerning given mounting evidence that chronic or prolonged cannabis use at young ages is associated with adverse psychiatric and other sequelae (Copeland et al., 2013;Hall & Degenhardt, 2009;Silins et al., 2014;Vo...

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“…Behavioral and other studies suggest considerable sexual dimorphism in the brain endocannabinoid (EC) system of both humans and rodents [18][19][20][21][22][23]. However, little is known concerning the molecular details on which these differences are based-especially with regards to factors outside the brain that influence brain endocannabinoid levels.…”

Section: Discussionmentioning

confidence: 99%

“…Although most animal studies of the EC system have been performed with male rodents, increasing evidence indicates that the EC system of female humans and rodents differs significantly from that of their male counterparts [18][19][20][21][22]. For example, females have a higher pain sensitivity threshold and are more susceptible to cannabinoid antinociception [18,21,23,24].…”

Section: Introductionmentioning

confidence: 99%

Female Mice are Resistant to Fabp1 Gene Ablation‐Induced Alterations in Brain Endocannabinoid Levels

Martin

Chung

Landrock

et al. 2016

Lipids

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Although liver fatty acid binding protein (FABP1, L-FABP) is not detectable in brain, Fabp1 gene ablation (LKO) markedly increases endocannabinoids (EC) in brains of male mice. Since the brain EC system of females differs significantly from that of males, it was important to determine if LKO differently impacted the brain EC system. LKO did not alter brain levels of arachidonic acid (ARA)-containing ECs, i.e arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), but decreased non-ARA-containing N-acylethanolamides (OEA, PEA) and 2-oleoylglycerol (2-OG) that potentiate the actions of AEA and 2-AG. These changes in brain potentiating EC levels were not associated with: i) a net decrease in levels of brain membrane proteins associated with fatty acid uptake and EC synthesis; ii) a net increase in brain protein levels of cytosolic EC chaperones and enzymes in EC degradation; or iii) increased brain protein levels of EC receptors (CB1, TRVP1). Instead, the reduced or opposite responsiveness of female brain EC levels to loss of FABP1 (LKO) correlated with intrinsically lower FABP1 level in livers of WT females than males. These data show that female mouse brain endocannabinoid levels were unchanged (AEA, 2-AG) or decreased (OEA, PEA, 2-OG) by complete loss of FABP1 (LKO).

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Sex-Dependent Vulnerability to Cannabis Abuse in Adolescence

Cited by 48 publications

References 51 publications

Mechanisms Underlying Sex Differences in Cannabis Use

Mechanisms Underlying Sex Differences in Cannabis Use

Evidence for Sex Convergence in Prevalence of Cannabis Use: A Systematic Review and Meta-Regression

Female Mice are Resistant to Fabp1 Gene Ablation‐Induced Alterations in Brain Endocannabinoid Levels

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