Medial prefrontal cortex mechanisms of cannabidiol-induced aversive memory reconsolidation impairments

THC and CBD: Similarities and differences between siblings

Cannabidiol attenuates fear memory expression in female rats via hippocampal 5-HT1A but not CB1 or CB2 receptors

Cannabinoids: Revealing their complexity and role in central networks of fear and anxiety.

Cannabidiol (CBD) is a non-intoxicating cannabinoid compound with diverse molecular targets and potential therapeutic effects, including effects relevant to the treatment of psychiatric disorders. In this scoping review, we sought to determine the extent to which sex and gender have been considered as potential moderators of the neuropsychiatric effects and pharmacokinetics of CBD. In this case, 300 articles were screened, retrieved from searches in PubMed/Medline, Scopus, Google Scholar, PsycInfo and CINAHL, though only 12 met our eligibility criteria: eight studies in preclinical models and four studies in humans. Among the preclinical studies, three suggested that sex may influence long-term effects of gestational or adolescent exposure to CBD; two found no impact of sex on CBD modulation of addiction-relevant effects of Δ⁹-tetrahydrocannabinol (THC); two found antidepressant-like effects of CBD in males only; and one found greater plasma and liver CBD concentrations in females compared to males. Among the human studies, two found no sex difference in CBD pharmacokinetics in patient samples, one found greater plasma CBD concentrations in healthy females compared to males, and one found no evidence of sex differences in the effects of CBD on responses to trauma recall in patients with post-traumatic stress disorder (PTSD). No studies were identified that considered the role of gender in CBD treatment effects. We discuss potential implications and current limitations of the existing literature.

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Sex Differences in the Neuropsychiatric Effects and Pharmacokinetics of Cannabidiol: A Scoping Review

Female but not male rats show biphasic effects of low doses of Δ9-tetrahydrocannabinol on anxiety: can cannabidiol interfere with these effects?

Background: Sex differences in the response to the anxiety-related effects of cannabinoid drugs have been reported, with females being more sensitive than males. Evidence suggests that, according to sex and estrous cycle phase (ECP), the content of the endocannabinoids (eCBs) N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) varies in brain areas involved in the anxiety-like behavior. Methods: Considering the lack of studies evaluating sex and ECP differences in the eCB system in anxiety, using URB597, a fatty acid amide hydrolase inhibitor, or MJN110, a monoacylglycerol lipase inhibitor, we explored the effects of increasing AEA or 2-AG levels, respectively, in cycling and ovariectomized (OVX) female adult Wistar rats, as well as males, subjected to the elevated plus maze. Results: The administration of URB597 (0.1 or 0.3mg/kg; intraperitoneally) either increased or reduced the percentage of open arms time (%OAT) and open arms entries (%OAE), being anxiolytic in diestrus and anxiogenic in estrus. No effects were observed in proestrus or when all ECPs were analyzed together. Both doses produced anxiolytic-like effects in males. In OVX females, the anxiolytic-like effect of URB597 0.1 was associated with low levels of estradiol, whereas the anxiogenic-like effect of URB597 0.3 was spared by estradiol pretreatment. The systemic administration of MJN110 3.0 mg/kg reduced the risk assessment behavior (RAB), suggesting an anxiolytic-like effect independent of the ECP. When considering the ECP, MJN110 3.0 increased the %OAT and reduced the RAB, being anxiolytic in estrus and diestrus. No effects were observed in proestrus. Both doses of MJN110 were anxiogenic in males. In OVX females, the anxiolytic-like effect of MJN110 was dependent on low estradiol levels. Conclusion: Together, our findings support the evidence that females react differently to the effects of cannabinoids in the anxiety-like behavior; in addition, AEA and 2-AG modulation elicits anxiety-like responses that are closely influenced by hormone levels, mainly estradiol.

The Estrous Cycle Influences the Effects of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase Inhibition in the Anxiety-Like Behavior in Rats.

Effects of delta-9 tetrahydrocannabinol on fear memory labilization and reconsolidation: A putative role of GluN2B-NMDA receptor within the dorsal hippocampus

Bruna Wuilleumier Salemme

Papers

Female but not male rats show biphasic effects of low doses of Δ9-tetrahydrocannabinol on anxiety: can cannabidiol interfere with these effects?

The Estrous Cycle Influences the Effects of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase Inhibition in the Anxiety-Like Behavior in Rats.

Effects of delta-9 tetrahydrocannabinol on fear memory labilization and reconsolidation: A putative role of GluN2B-NMDA receptor within the dorsal hippocampus