If there’s an area where men outperform women, it’s in how much cannabis they consume. The available data suggests that three-quarters of weed smokers are men and—though marijuana addiction is fairly rare—they are much more likely to develop dependence than women.
For years, health professionals have grappled with this reality, leaving the question of how women respond to the drug and how they might differ from men in that aspect. This matters because the culture of weed is slowly beginning to change. More flexible cannabis policies around the globe that have happened in the last two decades have led to a greater acceptance of the drug, both for medical and recreational purposes. In the US, the number of people who use cannabis is therefore rising steadily and women appear to make up a large part of these new consumers. The gap between women’s use of weed and men’s is shrinking, especially when looking medical cannabis.
These changes comes at a time when, across all realms of science, researchers are starting to realize that a range of drugs may work differently in males and in females, and to investigate the mechanisms involved. Medical cannabis may just be one of those therapeutics that triggers a different response according to sex. Given the growing number of women using it, scientists believe it’s time we start paying attention.
“It’s important that we investigate how the effects of cannabis differ for males and females because a growing number of people are using it for therapeutic purposes,” says researcher Chandni Hindocha, who studies cannabinoids (chemical compounds in cannabis like THC and CBD) at University College London. “Preclinical data suggests that women may experience more adverse effects than men. We need to clarify this to allow women to balance out the pros and cons of taking medical cannabis—as they would do with any other medicine.”
Most of the quality research in humans regarding the therapeutic effects of cannabis have focused on pain relief, and to date this is the area where the evidence is the strongest. Other indications are beginning to emerge, ranging from chemotherapy-induced nausea, to anxiety, PTSD or PMS. However, very few of these studies have investigated sex differences.
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While going through the scientific literature on the subject, Ziva Cooper, an associate professor of clinical neurobiology at Columbia University, decided it was time to do something about this. “When it comes to cannabis and cannabinoids, there has been a lot of evidence from animal studies showing that there are profound differences between males and females, especially in the area of pain relief. These findings piqued my interest in studying this in humans,” she explains.
Focusing on pain relief, she tested how differences in pain sensitivity and tolerance differ among male and female cannabis smokers. In a 2016 placebo-controlled study, Cooper and a colleague had participants who were already regular weed smokers immerse their hand in cold water to report how much pain they felt, and to see how long they could tolerate it, after smoking a cannabis cigarette. Men appeared to experience greater pain relief than women.
Animal studies can partly guide us to understand these findings. Experiments have indicated that females rats are more sensitive to the pain relieving effects of THC, the main psychoactive constituent of cannabis. However, when given this compound everyday, they also develop tolerance much faster than males. This means that on the long run, they may need higher doses of THC to get the same pain-relieving effect.
“We have looked at the effects of cannabis in heavy recreational cannabis users. It’s possible that the women were not getting pain relief because they developed tolerance to this effect, requiring a higher strength or dose,” Cooper points out. “We need to study both higher strengths in women as well as measure the effects of cannabis and cannabinoids in patient population who are lighter users, to determine how cannabis and cannabinoids can help ease pain.”
In a review published a few months back in Nature Neuropsychopharmacology, the researcher put these conclusions in perspective with other findings on the subject. Beyond the sex-differentiated effects in the management of pain, the research gleaned that females might also experience stronger adverse effects than males when using medical marijuana.
While the data is clear that men are more likely to be cannabis users, this is at odds with the results of studies conducted in both animals and humans. Females indeed appear to be more sensitive to cannabinoids and to escalate more rapidly from trying cannabis to the point of addiction. When they stop taking the drug, withdrawal symptoms also appear to be stronger—and they’re more likely to experience anxiety and nausea.
What remains unclear is what biological mechanisms are driving all these differences in the first place. "What is mediating these differences? Is it because there are differences in the brain's cannabinoid receptors?” Cooper wonders. “Is it because the drug is metabolized differently? Or perhaps differences are driven by hormones.”
Although it’s too early to say, her review makes a compelling case that the metabolic breakdown of cannabis in the body may differ between males and females. This may have an impact at the molecular level, regulating long term sex differences, in particular the increased tolerance seen in females relative to males.
Men and women also seem to have different preferences when it comes to the way they consume cannabis too, with women more likely to turn to edibles. Exploring how the route of administration may change the effects of the drug will then also prove crucial in the future. Studies will also have to move on from looking at the effects on pain to studying other conditions, as the evidence suggests women are more likely to take medical cannabis to help treat mental health issues such as anxiety and depression.
Answering all these questions will be difficult, in particular because cannabis research receives little funding and is still strictly regulated, so designing rigorous studies is no easy feat. A lot of variables have to been controlled, from the doses given to participants to the method of consumption, the type of pain patients may be feeling, or other relevant social factors.
“If you compare male and female pain patients or cannabis-dependent users, any sex differences you find may be confounded by environmental factors such as social influences on medical or recreational drug use,” says Tom Freeman, senior academic fellow at King's College London. These challenges explain why so little medical cannabis research is still taking place despite the recent policy shifts, and more specifically, why investigating women’s responses has only just started to be seen as a priority.
For researchers in the field, the situation cannot change soon enough. "Things have to move. We need to do quality research and to include female's response from the get-go. Otherwise, we will always conclude that there is limited evidence for the medical use of cannabis,” Hindocha says. “How can we use cannabis more safely, who’s likely to benefit and who is not? Seeing the growing number of medical cannabis users, including women, these are pressing questions we cannot ignore anymore.”
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