What CBD Brings to Women's Health

Drug Topics®: Why is women's health a good therapeutic target for [cannabidiol] CBD?

Alex Capano: Well, it is actually evidence-based and that, to me, makes a good therapeutic target. We do see CBD products aimed at things that don't really make a whole lot of sense clinically or don't have a lot of evidence to back it up, but when it comes to women's health, the endocannabinoid system has receptors all throughout the body. They're very abundant in the brain and central nervous system but also in the periphery and they're incredibly abundant in female reproductive organs. Those receptors are the main part of the system on which CBD acts. So essentially, these organs are just primed for receiving cannabinoids and the receptors and the endocannabinoid system itself, actually influences or is the primary modulator of really all of the responsibilities of the reproductive system in women. So it is a major player in everything from fertility, follicular genesis, implantation of a fertilized egg into the endometrium, or endometrial lesions for the proliferation and migration of endometriosis, for the HPA [hypothalamus-pituitary-adrenal] axis, the menstrual cycle, for a lot of the changes that occur in the body during menopause. It's also responsible for pleasure and pain and the more fun things that those organs do in female bodies. So, not only are there so many receptors that we can target, but those receptors are responsible for really all of the problems that we are trying to solve in gynecology.

Drug Topics®: How is CBD used in women's health?

Capano: Well, I think that we're still going to find new and novel ways to use it, but currently, it's primarily used for pain and pleasure. Om one hand, we see that women are turning to CBD for pain: all sorts of vulvovaginal pain, dysmenorrhea, period pain and cramps, and they're using it and preferring it over traditional pain medications, certainly over NSAIDs. We see that about 80% to 90% of women experienced some form of pelvic pain. Many of them are using pain medication often or always. It's not, great for you, not great for your GI health. It's severe enough to miss work and school, so there's a serious socioeconomic consequence here, let alone a quality-of-life issue. Some of the respondents in the study said ‘yes, I miss work or school because of the pain,’ but some of them said, ‘look, I show up, but I can't get anything done because this is so debilitating.’ We also see that endometriosis which causes severe pelvic pain, is really common and occurs in about 10% to 15% of women in the US, that's a big number. We don't have good treatment. So, we see that women are turning to CBD for pelvic pain, all sorts of different pelvic pain issues and also for things like vaginal dryness.Tthere seems to be a little bit of use for vaginal atrophy, the evidence there is a little bit further behind pain. And then we also see women using it for pleasure. Women are actually using CBD prior to sexual activity and then reporting increase in libido, increase in satisfactory outcomes, I believe was the term used and a decrease in pain associated with sexual activity. They're using it to improve their lives both by solving a problem and just improving their joy. This is used often. It can be used orally or sublingually, but intervaginal delivery, whether that's through a pellet or a cream, it dose seem to really get through the vaginal mucosa and to the targets quickly, effectively, and you bypass that first pass metabolism. So intervaginal delivery, I think is underutilized by too many people and we're seeing a really nice uptick in the use of CBD intervaginally.

Drug Topics®: Speaking of research, what is there out there that supports the use of CBD and gynecology?

Capano: I did mention a couple of studies about pain and pleasure already. If you take just Australia for example, where CBD is not readily available, the regulatory landscape is entirely different there, but over three-quarters of women with pelvic pain are using CBD. So, accessing it is that much harder and potentially not legal, and they're still going after it. I bring up that study even though it's just as a survey because it compelled one of my colleagues to study this. He is a reproductive researcher and an expert in gynecology, professor Pradeep Tanwar from the University of Newcastle in Australia. He started reading this and he said ‘well, maybe there's something to it.’ We are doing work together in Australia right now and it's fascinating. We're looking not just at symptom relief, but actually stopping the cause of the symptoms in the first place. We first looked at endometriosis, and found that our extract actually killed the endometrial lesions, wiped them away, and was completely nontoxic to other cells, that was unexpected. And he said to his PhD, ‘who did this? How did you do it? What was your method? Do it again. Do it again, do it again. You do it because I don't know if you're doing something wrong, because I don't trust these results. They're too compelling.’ Finally, he's a believer and we found that these women with endometriosis are not just getting improved pain [relief], but it's actually reducing and eliminating these lesions that are causing problems like infertility or chronic pain.

Then we decided to expand the study beyond that and we're actually looking at gynecological malignancies: endometrial cancer, ovarian cancer. It's only been about a year but so far we've had a few dozen women enroll and almost all of them have been responders. These are chemo-resistant patients and chemo-sensitive patients, different stages and grades, so we're really excited about the possibilities there. We filed for patents last October and anticipate filing several more this October. Unfortunately, it's an underfunded and under researched area of health and medicine. That's one thing where it's really exciting to get, a skeptic to convert and say, ‘oh my gosh, I didn't think it was a problem, but I didn't think it actually did anything.’

Beyond that both in animals and humans, there's research in gynecology and cannabinoids, not just about what the system itself does, but also about improving pain, improving pleasure. Even potentially balancing some hormone disruptions, for example, estrogen dominance. There's more out there than I anticipated and I think that a lot of people realize, because it's unexpected, but it is evidence-based.

Drug Topics: What about people who are pregnant breastfeeding or who are trying to conceive?

Capano: Good question. I get this all of the time. The answer is a little bit that we don't know but I can tell you what we do now. If you are pregnant, there's not a lot of studies looking at CBD’s effects on pregnancy and development. There's some THC. Now until recently, the studies done on THC didn't control for confounding variables. So, the women who were using THC and they saw negative outcomes, they were also smoking cigarettes, sometimes using cocaine. or methamphetamine. Was it causal? Was it correlational? We don't know. Recently, last year, there was an article that came out that did a really good job trying to control for those confounders and found that there may be an increase in likelihood of autism spectrum disorders with THC use in pregnancy. That's the only, in my opinion, reliable study that's been done so far to see any sort of negative outcomes. Now we know that CBD works in some ways the opposite way as THC. What we know is a little bit of self-reported data, nothing that's been problematic. When Epidiolex came out, they had to do tests in multiple species, not humans, and saw that there were negative effects at 150, 175, 250 milligrams per kilogram of body weight. That is well beyond the maximum daily dose even recommended at the really high doses that people are taking Epidiolex for severe seizure disorders. That gives me a lot of comfort and reassurance that what people are taking is benign, but, this is what we know and what we don't know. I look at it through a harm reduction lens. Is CBD going to be less harmful than regularly taking benzodiazepines during pregnancy or something like an opiate. That's a discussion to have and to weigh the risks and benefits and understand that we don't know everything yet.

We know that cannabinoids can get into breast milk. These are lipophilic molecules. They like breast milk. They don't get in it very high doses though. The general rule of thumb is we want to have the infant/maternal ratio or maternal/infant ratio, we want it at 10% of what mom is getting when you adjust for weight for baby or less. That's sort of the rule of thumb for what we consider safe when breastfeeding. There was a study done recently out of California and they found that the levels in breast milk of THC and CBD were well below 10%, so that's really reassuring. It's interesting that our endogenous cannabinoids that we make on our own body are actually present in breast milk. There seems to be something advantageous about some cannabinoids at least. Again, we know CBD is much more benign and has a superior safety profile to THC so I feel pretty good about it. Again, it's harm reduction, weighing benefits and risks.

And then lastly, for those trying to conceive. CBD increases your anandamide [the endogenous cannabinoid] levels. It prolongs the half-life by stopping the enzyme that degrades anandamide. High anandamide levels are correlated with successful ovulation. So potentially if you're trying to conceive and you want to ovulate or you're having trouble with ovulation, due to PCOS or something, CBD makes sense. I'm not absolutely certain that you could take enough CBD to increase your anandamide enough for that, but it's not going to hurt. However, anandamide levels that are very low are associated with improved successful implantation of an embryo. If you're trying to conceive, you like CBD and you think ‘I'm having trouble and I want to do everything I can to help because I know it's tricky’ or ‘I use it for x purposes. It's really great and I don't want to stop it the whole time.’ I would use it during ovulation and before that, but once there's potentially an embryo and you're trying for implantation, a few days after ovulation withdraw the CBD [because] we want lower levels of anandamide. Again, not convinced it will truly make any difference with the doses people are using but that's what we know in from a basic science standpoint. So, I'm jumping to conclusions a little bit.

Drug Topics®: What do you see for the future of CBD and gynecology?

Capano: Well, I hope, fingers crossed, that we will see improvements in gynecological cancer treatment. So even using less or lower doses or fewer doses of chemo, but still getting the same response with something that's a lot more tolerable, better outcomes for aggressive cancers. I really hesitate to say that because I think people are sometimes irresponsible [saying things] like ‘cannabis cures cancer’ and we don't know that. We're getting some evidence and we have a long way to go to really figure out how to deliver that effectively across different populations, but I am hopeful. I'm optimistic.

I also see it being something that people use to substitute for NSAIDs and other pain management meds for pelvic pain. Instead of crawling up in a ball in bed all day because you're in such severe pain, actually getting out there and enjoying life. And lastly, to improve sexual pleasure and activity and libido, particularly I think postmenopausal and post-chemo, but I see different deliveries. I want to have a CBD-infused tampon, for example, because sort of two birds, one stone. Regulatory in the US, that's very difficult to achieve. I think we'll see that in Europe much sooner.

I just see more intervaginal delivery and maybe some interesting topicals, if we can really figure out a permeation enhancer for things like symptoms associated with menopause and even some bone density decreases that occur in menopause. They're actually associated with cannabinoid receptor decline on the bones. If you can get more out of those receptors by using plant-derived cannabinoids, it may be a tool to decrease or slow the development of osteoporosis. So yes, I see a lot of opportunity. Can you tell I'm passionate about this area? When I was in the clinic all of the time, I focused on women's health, gynecology. And then when I started studying cannabinoids, it was just really cool to see the combination of two areas. It's advancing faster than what we typically see in healthcare.