Summary: A new review examines biological sex differences in responses to cannabis. Researchers report that women may develop problematic cannabis use faster than men and that females show distinct endocannabinoid levels and more sensitive receptors in brain regions tied to social behavior.
Source: Frontiers.
Cannabis use has increased alongside decriminalization, legalization and the rise of synthetic alternatives. As use expands, researchers are finding that risks and effects differ between females and males.
A recent review published in Frontiers in Behavioral Neuroscience evaluates animal studies that probe how sex hormones—such as testosterone, estradiol (a form of estrogen) and progesterone—interact with the endocannabinoid system. The endocannabinoid system is a network of brain circuits that uses the same family of signaling molecules targeted by cannabis, and this review highlights biological mechanisms that may underlie observed sex differences in cannabis sensitivity and addiction vulnerability.
Animal studies
“It has been difficult to get laboratory animals to self-administer cannabinoids in ways that precisely mirror human patterns of use,” says study co-author Dr. Liana Fattore, Senior Researcher at the National Research Council of Italy. “Nevertheless, animal work examining how natural sex hormones and synthetic anabolic-androgenic steroids influence cannabinoid self-administration has provided important insights into sex-dependent differences in cannabis response.”
Beyond social and cultural factors, the review identifies several biological differences between males and females that shape cannabis-related behaviors and risks.
Population data show men are up to four times more likely to try cannabis and, on average, consume higher doses and use more frequently.
“Male sex steroids can increase risk-taking and alter the brain’s reward circuits, which may contribute to higher initiation rates of drug use among males,” explains Fattore. “This applies to endogenous male hormones like testosterone and to synthetic anabolic steroids as well.”
However, despite lower average use, females often transition more rapidly from initial cannabis exposure to habitual use. The review emphasizes that men and women differ not only in prevalence, frequency and motives for cannabis use, but also in vulnerability to develop cannabis use disorder.
“At a neurochemical level, females appear more prone to developing cannabis addiction,” Fattore notes.
Animal experiments point to estradiol as a key modulator. In female rats, estradiol influences movement control, social behavior and sensory filtering—functions that overlap with drug-seeking and reward processing—by modulating the endocannabinoid system. That modulation feeds back to influence estradiol production, creating a bidirectional relationship between sex hormones and cannabinoid signaling.
Female rats display different baseline levels of endocannabinoids and possess more sensitive cannabinoid receptors in brain areas involved in movement, social interaction and sensory processing. These molecular and receptor-level differences also change across the reproductive cycle, further altering sensitivity to cannabinoids.
“Consequently, interactions between the endocannabinoid system and dopamine—the neurotransmitter central to pleasure and reward—are sex-dependent,” the authors write, suggesting that reward-system dynamics differ by sex and may influence addiction risk.
Human impact
Interpreting these findings for humans is complicated by variability across studies. Differences in the specific cannabinoids tested, animal strains, timing and duration of hormone exposure all affected outcomes in the reviewed literature.
Still, human evidence aligns with key themes from animal work. Estradiol appears to regulate female responses to cannabinoids, and genetic and hormonal differences lead males and females to process information, perceive emotions and respond to addictive substances differently.
Clinical and laboratory observations show that blood levels of enzymes that metabolize endocannabinoids fluctuate during the menstrual cycle, and imaging studies indicate that cannabinoid receptor levels in the brain change with aging in females—patterns that parallel shifts in estradiol.
Given growing cannabis availability and evolving patterns of use, the authors argue that a better understanding of how sex steroids and the endocannabinoid system interact is critical for public health planning.
“There is a growing need for gender-informed approaches to detoxification and relapse prevention for people with cannabis addiction,” Fattore says. “Developing personalized, evidence-based prevention and treatment strategies requires further research into the biological sources of sex differences in cannabis response.”
Source: Matt Prior – Frontiers
Publisher: Organized by NeuroscienceNews.com.
Image Source: Image in the public domain.
Original Research: Open access research titled “The Modulating Role of Sex and Anabolic-Androgenic Steroid Hormones in Cannabinoid Sensitivity” by Dicky Struik, Fabrizio Sanna and Liana Fattore in Frontiers in Behavioral Neuroscience. Published October 26, 2018.
doi: 10.3389/fnbeh.2018.00249
Suggested citation formats were provided by the original publisher. Please cite the original Frontiers article for academic use.
Abstract
The Modulating Role of Sex and Anabolic-Androgenic Steroid Hormones in Cannabinoid Sensitivity
Cannabis is the most commonly used illicit drug worldwide. Although its use is associated with multiple adverse health effects, including the risk of developing addiction, recreational and medical cannabis use is increasingly legalized. Synthetic cannabinoid drugs have also become more popular and are linked to mass poisonings and occasional fatalities. Identifying factors that influence cannabis use and addiction is therefore important. As with other drugs of abuse, the prevalence of cannabis use and addiction varies between males and females, suggesting sex influences cannabinoid sensitivity. While the exact role of sex in initiation and maintenance of cannabis use in humans remains unclear, animal studies strongly indicate that endogenous sex hormones modulate cannabinoid sensitivity. Synthetic anabolic-androgenic steroids further modify substance use, supporting the role of sex steroids in drug sensitivity. The discovery that pregnenolone, the precursor of all steroid hormones, can control cannabinoid receptor activation reinforces the connection between steroid hormones and the endocannabinoid system. This review summarizes literature on how endogenous and synthetic steroid hormones influence the endocannabinoid system and cannabinoid effects.