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Females could have better results with CBD for anxiety, but when it comes to pain, some addition of THC might be necessary. Women have more CB1 receptors than men, and they like smoking cannabis rich in THC more than men do, but they are also likely to develop more severe cannabis use disorder. When taking CBD, elderly women should consider smaller doses, and pregnant women should not consume any cannabinoids whatsoever.
These are some of the insights from last month’s scientific conference CBD and Other Cannabinoids: Sex and Gender Differences in Use and Responses, organized by the FDA’s Office for Women’s Health. At the conference, Dr. Cinnamon Bidwell from the University of Colorado presented the results of the Observational Anxiety Study on Inflammation and Stress (OASIS) conducted in the US state of Colorado, which analyzed increased rates of anxiety and differential responses to cannabis in women compared to men.
The study followed three groups of cannabis users – THC, CBD, and 1:1 group. After four weeks of cannabis use, all three groups had shown a significant decrease in anxiety symptoms, but the reduction of anxiety symptoms was strongest in the CBD group, and the CBD group was the only one that reached a normal range of anxiety, while other two groups stayed at the edge of moderate anxiety symptoms.
Also, when the scientists broke the CBD group in two by sex (20 female and 19 male), they found that women reacted much better to CBD than the male with the reduction of anxiety symptoms. Their anxiety level was much higher to start with and CBD consumption brought much stronger relief of anxiety symptoms to the lower levels than those of male consumers. After two weeks of CBD consumption, the level of anxiety in males stayed more or less the same, while in female participants it continued to drop.
Another interesting finding of this study is that CBD led to a much higher reduction of tension comparing to the one found with 1:1 participants. THC group showed an increased level of tension after the trial, while CBD groups’ tension fell almost to the baseline level.
Again, when the scientist broke the CBD group to compare the results of post-use anxiety and tension, they found opposite results for the female and male groups. The female group of CBD consumers had almost none post-use anxiety or tension, while the male group had very high post-use anxiety and tension.
At the same conference, Dr. Daniel J. Clauw from the University of Michigan spoke about sex differences in pain and sensory processing as a reason why cannabinoids may work differently in men and women. What the science learned in the last 20 years is that men and women are different in pain processing. For almost every chronic pain condition, women experience one and a half to two times more pain than men, and the scientific data suggest that the reason for that is because women are more sensitive to pain in their central nervous system. Nociplastic pain, where the pain is coming from the central nervous system demands an entirely different treatment than nociceptive pain because the latter is coming from peripheral structures. Women are more tender and more sensitive to any type of sensory stimuli than men, and as a result, they suffer more pain, especially nociplastic pain. Also, they are more sensitive to pain in the premenstrual phase of their cycle.
Dr. Clauw presented results from a yet unpublished study on the effects of CBD in the treatment of knee pain. Here, using CBD didn’t give results for the female participants as seen in the male. Most pain in men with osteoarthritis may come from the peripheral area, while in women it comes from the central nervous system. That is the first study that led to a conclusion that adding THC to CBD might be necessary for the treatment of osteoarthritic pain when it comes to female patients. That could be the case with conditions like fibromyalgia, headache, or IBS.
From the patient’s perspective, the participant in the conference was Shari Berman, an activist who was diagnosed with Hodgkin’s lymphoma at the age of 25, after returning from her honeymoon. Her doctor suggested six months of chemotherapy and five weeks of radiation, which led to severe nausea, vomiting, and lack of appetite. It was 1989 so when she asked about cannabis treatment, and she was denied to have one.
Eight years later, she was diagnosed with breast cancer, which she most likely sees as a result of the radiation from the previous treatment. After surgery and six months of chemotherapy, she suffered from nausea. This time she got prescribed a new drug that again left her unwell. Again, she asked for marijuana and was denied the drug.
Out of desperation to feel better, she took matters into her own hands and got some marijuana through her friends. She immediately felt better. Just after a couple of puffs, her nausea went away, and she felt like having dinner.
18 years later, her state of Massachusetts approved medical cannabis, and she went through the process of becoming a certified user of medical cannabis. After finding a cannabis doctor, she was disappointed again, because she hasn’t been provided any information. Her experiences at the dispensaries were also not useful as she couldn’t find any information. Doctors in the US are still not informed well enough about the difference between CBD and medical marijuana, she says. Despite the mass consumption, there is still not much knowledge about CBD in the general population, and misconceptions are very often. “Without the regulation, we have a lot of junk out there, and people are wasting money”, she warned.
Dr. Igor Koturbash, the chair of the Department of Environmental and Occupational Health was speaking about the animal models and their correlation with the impact of CBD use on the liver in men and women. There is a lack of animal data on CBD and especially other cannabinoids, as well as a lack of understanding of appropriate dose calculation. The maximum recommended human dose is 20 mg/kg of purified CBD, like the one found in the drug Epidiolex. CBD has the potential to induce drug interaction, which is especially concerning among the elderly. Rates of drug use increase with age and herbal supplements pose a greater risk for liver in women. In mice, the mortality rate from toxicity in females was 40%, much higher than in males (8.5%). Also, murine models have shown that even the vehicle can make a significant difference in toxicity.
Dr. Ryan Vandrey from the John Hopkins University School of Medicine presented his research work on the differences between vaporized and swallowed CBD in healthy adults, and the differences that THC might pose if present. In the study, they used 100mg CBD or/and placebo. Orally, they used capsules, syrup, and Epidiolex. The results show that women tend to rate drug effects as more pleasant and more liking than men. Also, with the addition of THC, an increase in heart rate was higher in men than in women. In blood, they found much higher levels of CBD in women when inhaled comparing to when it orally administrated.
Dr. Vandrey also presented yet unpublished study by Elise Weerts. That study has found a greater density of CB1 receptors in the central nervous system of females than in the central nervous system of males. Also, frequent female cannabis users showed downregulation of CB1 receptors, indicating a neurobiological mechanism for tolerance. In another research, high CBD oils have shown better relief from pain and much better results in the improvement of quality of life in females. On the other hand, in the same research, they found improvement in the ratings of anxiety in both men and women and better magnitude in the relief of depression symptoms in female participants.
The director of the UCLA Cannabis Research Initiative Dr. Ziva D. Cooper underlined the growing rate of female cannabis users in the US, as well as the fact that animal studies show that THC and THC-like drugs are two to three times more potent in female rats. Also, tolerance develops more quickly in female animals than male animals. If these effects translate to humans, the female could express more abuse liability. In a human study where participants were heavy cannabis smokers administrated with cannabis containing 4-6% of THC, male participants showed less sensitivity to pain after cannabis use, and women were much prone to self-administration of cannabis. Again, females reported liking the drug more, and their subjective level of intoxication was higher. The study concluded that cannabis decreases pain response in males, while there is no such effect in females. Females do exhibit greater abuse liability outcomes.
Dr. Yasmin Hurd, the director of the Addiction Institute at Mount Sinai presented her research on sex differences in addiction and related psychiatric disorders. She pointed out that around 30% of cannabis users develop a cannabis use disorder. Men have higher rates of developing cannabis use disorder, but despite that, there is a greater escalation of use and severity of the disease in females. Also, women with cannabis use disorder have higher comorbidity with mood and anxiety disorders and higher externalizing disorders than men. In animal models where CBD was used to treat alcohol addiction, it did help male but not female animals in smaller doses. With higher doses, it worked on females as well. When studying human fetuses, male fetuses showed more negative effects than female fetuses whose mothers were cannabis smokers. Also, children’s social behavior is more impacted by prenatal intake of cannabis in male children.
Dr. Scott E. Parnell from the National Institute on Alcohol Abuse and Alcoholism spoke about preclinical research on the effects of CBD and other cannabinoids on pregnancy. He showed the malformation on the mice embryos exposed to alcohol and very similar embryo malformation when treated with synthetic cannabinoids (CP-55). When studying other cannabinoids, the highest doses of synthetic THC even caused death to some mice embryos. The effects of CBD were more subtle, but there were certainly there, as Dr. Parnell pointed out. When combined with alcohol, synthetic cannabinoids cause cumulative effects, which can be prevented through administrating CB1 receptor antagonists. In conclusion, THC and CBD cause fewer fetal abnormalities than alcohol or synthetic cannabinoids, but they also interact with alcohol and form a synergy dangerous for the early development of the fetus.
Dr. Mark Zakowski, chair of the American Society of Anesthesiologists Committee Obstetric Anesthesia, spoke about the anesthetic consideration of cannabis and CBD use in pregnancy. Underling a 6000-fold difference in the quality of CBD products in the US market, he warned of a rising number of women who use cannabinoids during pregnancy. The endocannabinoid system is present in the placenta, and CBD can affect the fetus. It inhibits fetal liver enzymes, affects the dose of dopamine in the brain, and can cause cognitive impairment. THC is present in breast milk six days after consumption. Today’s marijuana in the US is tenfold or higher on THC content than the one used until the ’80s, so consuming such products can seriously harm fetuses and babies.
The recreational use of marijuana and self-medicating is increasingly common in females, with peak use in the reproductional phase of their lives, as Dr. Nathaniel DeNicola from the American College of Obstetricians and Gynecologists pointed out. It is important to note that the level of CB1 receptors is higher in the fetal brain compared with the adult brain. The endocannabinoid system has a specific role in embryo development. It influences metabolic support, growth of nerve fiber, cell proliferation and migration, and neuroprotection. Cannabis exposure during pregnancy can disrupt endocannabinoid signaling, interfere with the formation of synapses in the central nervous system as well as neuronal interconnections, and cause the impairment of nerve fiber growth and development. There is already moderate evidence that marijuana in pregnancy and breastfeeding can cause decreased growth, decreased IQ score, decreased cognitive functions, and attention problems in the offspring.