An assessment of sex differences in Δ 9 -tetrahydrocannabinol (THC) taste and place conditioning

Hempel, Briana; Wakeford, Alison G.P.; Nelson, Katharine H.; Clasen, Matthew M.; Woloshchuk, Claudia J.; Riley, Anthony L.

doi:10.1016/j.pbb.2016.11.006

Cited by 16 publications

(19 citation statements)

References 77 publications

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“…Only one group has explored cannabinoid self-administration in females, and significantly faster acquisition, as well as more robust maintenance, was observed in female rats compared to male rats [108]. Sex-dependent differences do emerge irrespective of self-administration, such as enhanced sensitivity to THC-induced taste avoidance [109] and THC discrimination [110] in female rats, but further investigation must be done to systematically examine preclinical sex differences in cannabinoid reinforcement.…”

Section: Sex Differences In the Rewarding Properties Of Cannabinoidsmentioning

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: Sex Differences In the Rewarding Properties Of Cannabinoidsmentioning

confidence: 99%

Mechanisms Underlying Sex Differences in Cannabis Use

et al. 2017

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“…In regard to cannabinoid-elicited nausea, Hempel et al (2017) showed that THC was more potent and efficacious in female rats compared to males in decreasing saccharin consumption in a conditioned taste aversion procedure, suggesting that females are more sensitive than males to the aversive effects of THC, or females were better than males at learning the drug-taste association (which the authors concluded may be the case). Interestingly, considerable animal research suggests that cannabinoid treatment could be useful for alleviating chemotherapy-induced nausea and vomiting (Rock and Parker, 2016).…”

Section: Potential Therapeutic Effects Of Cannabis and Cannabinoidsmentioning

confidence: 99%

Sex-Dependent Effects of Cannabis and Cannabinoids: A Translational Perspective

Cooper

Craft

2017

Neuropsychopharmacol.

246

162

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Recent policy changes have led to significant increases in the use of cannabis for both medical and recreational purposes. Although men are more likely to endorse past month cannabis use and are more frequently diagnosed with Cannabis Use Disorder relative to women, a growing proportion of medical cannabis users are reported to be women. The increased popularity of cannabis for medical purposes and the narrowing gap in prevalence of use between men and women raises questions regarding sex-dependent effects related to therapeutic efficacy and negative health effects of cannabis and cannabinoids. The objective of this review is to provide a translational perspective on 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. Hormonal and pharmacological mechanisms that may underlie sex differences in the effects of cannabis and cannabinoids are highlighted.

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“…Specific knowledge about the sex-dependence of the rewarding effects of Δ 9 -THC is sketchy, given that PC studies with Δ 9 -THC have been conducted almost exclusively with male rodents (Hempel et al 2017). This rather ungrounded negligence of sex differentiation is an issue that needs to be addressed in future PC studies.…”

Section: Sex and Agementioning

confidence: 99%

“…Preclinical studies have yielded sex-dependent differences in CB1R density and G-protein activation (Rubino and Parolaro 2011;Cooper and Craft 2018). Furthermore, it has been specified that female animals self-administer synthetic cannabinoids faster and at higher rates than males and are more susceptible to drug and cue-induced reinstatement (Fattore et al 2007(Fattore et al , 2010bHempel et al 2017). The implications of these findings are not yet entirely clear.…”

Section: Sex and Agementioning

confidence: 99%

“…The implications of these findings are not yet entirely clear. Albeit, sex might be an important factor involved in the increased sensitivity to the rewarding as well as reinforcing properties of cannabinoids (Fattore et al 2007(Fattore et al , 2010bHempel et al 2017) and the development of stronger withdrawal symptoms in females (Harte-Hargrove and Dow-Edwards 2012). However, more studies investigating the putative sexual dimorphism of cannabinoid reward and reinforcement are needed on both physiological and behavioral levels, in order to uncover the underlying mechanisms.…”

Section: Sex and Agementioning

confidence: 99%

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Highway to hell or magic smoke? The dose-dependence of Δ⁹-THC in place conditioning paradigms

2018

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The prerequisites for responsible cannabis use are at the heart of current inquiries into cannabis decriminalization by policy makers as well as academic and nonacademic stakeholders at a global scale. Δ-tetrahydrocannabinol (Δ-THC), the prime psychoactive compound of the , as well as cannabimimetics that resemble the pharmacological properties and psychological effects of Δ-THC, lend themselves handsomely to the preclinical scrutiny of reward-related behavior because they carry marked translational value. Although a functional dichotomy of the psychological effects of Δ-THC (rewarding versus aversive) has been abundantly reported in place conditioning (PC) paradigms, and might be best attributed to a dose-dependence of Δ-THC, most PC studies with Δ-THC feature no significant effects at all. Therefore, after decades of rigorous research, it still remains undetermined whether Δ-THC generally exerts rewarding or aversive effects in rodents. Here, we set out to extrapolate the commonly alleged dose-dependence of the rewarding and aversive effects of Δ-THC from the existing literature, at the behavioral pharmacological level of analysis. Specifically, our meta-analysis investigated: (i) the alleged bidirectional effects and dose-dependence of Δ-THC in the PC test; (ii) methodological inconsistencies between PC studies; and (iii) other pharmacological studies on cannabinoids (i.e., dopamine release, anxiety, stress, conditioned taste aversion, catalepsy) to substantiate the validity of PC findings. Our findings suggest that: (i) Δ-THC dose-dependently generates rewarding (1 mg/kg) and aversive (5 mg/kg) effects in PC; (ii) an inconsistent use of priming injections hampers a clear establishment of the rewarding effects of Δ-THC in PC tests and might explain the seemingly contradictory plethora of nonsignificant THC studies in the PC test; and (iii) other pharmacological studies on Δ-THC substantiate the dose-dependent biphasic effects of Δ-THC in PC. A standardized experimental design would advance evidence-based practice in future PC studies with Δ-THC and facilitate the pointed establishment of rewarding and aversive effects of the substance.

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An assessment of sex differences in Δ 9 -tetrahydrocannabinol (THC) taste and place conditioning

Cited by 16 publications

References 77 publications

Mechanisms Underlying Sex Differences in Cannabis Use

Mechanisms Underlying Sex Differences in Cannabis Use

Sex-Dependent Effects of Cannabis and Cannabinoids: A Translational Perspective

Highway to hell or magic smoke? The dose-dependence of Δ⁹-THC in place conditioning paradigms

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An assessment of sex differences in Δ 9 -tetrahydrocannabinol (THC) taste and place conditioning

Cited by 16 publications

References 77 publications

Mechanisms Underlying Sex Differences in Cannabis Use

Mechanisms Underlying Sex Differences in Cannabis Use

Sex-Dependent Effects of Cannabis and Cannabinoids: A Translational Perspective

Highway to hell or magic smoke? The dose-dependence of Δ9-THC in place conditioning paradigms

Contact Info

Product

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Highway to hell or magic smoke? The dose-dependence of Δ⁹-THC in place conditioning paradigms