What does cannabis have to do with women’s health? We talked to the doctor and cannabis expert of Kalapa Clinic, Mery Peña, about this interesting topic. Mery Peña has been working with the use of cannabinoids to treat various women’s conditions for many years.
Kalapa: The term “women’s health” is not universally defined. Women have different needs depending on their age, physical and mental health, sexual orientation and cultural experience. What do you associate with women’s health?
Mery Peña: In humans as in animals, males and females are different: we process information differently, perceive experience and emotions in different ways, we have a diverse language and social skills, we have differences in genetic and hormonal expression. In modern societies women are usually the ones that take care of health management in the family, women are the ones that sort out medical appointments and the ones that get medicines from the pharmacy.
Yet there’s a clear sex-gap in pharmaceutical research from preclinical studies, clinical trials to post-marketing surveillance, with a bias towards males. Only after the ‘90s women started participating in clinical trials, consequently, there’s still a lot we don’t know regarding pharmacokinetic and pharmacodynamic differences amongst the sexes, and therefore women experience adverse drug reactions from approved drug products more often than men. We still need to understand pathophysiologic mechanisms and why some conditions are more frequent on males or females.
This is starting to get tackled on current research specially in cannabinoids investigation, in contrast with the past, when females were excluded or underrepresented in both clinical and preclinical studies, attention and interest in possible sex differences is now developing in many fields of biomedical research.
There are several groups in the world investigating the differences between men and women in their response to the abuse-related and pain-relieving effects of cannabinoids, and the role that circulating hormones and endocannabinoids contribute to these differences. Both animal and human studies reveal while females are more sensitive to the pain-relieving benefits of delta-9-tetrahydrocannabinol (THC), the primary psychotropic component of cannabis, they are also more sensitive to the negative effects.
Now that we know that in some regions of the brain, the endocannabinoid levels and the CB1 receptor density and affinity fluctuate as a function of sex and hormonal cycle, supporting the hypothesis of possible sex hormone-dependent differences in the sensitivity of certain neuronal processes triggered by cannabinoid treatment.
Also, there´s the possibility that sex differences in the behavioural effects of cannabinoids are related to sex differences in drug disposition and body fat distribution. Cannabinoids are lipophilic, women have a higher percentage of body fat than men, so is possible that women may experience weaker effects with the same dosage compared to men because more delta9-THC is retained by fat cells. Also, cannabinoids may be differentially metabolized to active and inactive metabolites in men and women.
Although research regarding gender and the endocannabinoid system has continued to expand, to date, there has been limited clinical impact of this new knowledge. Hopefully as research advances this will translate in better and more individualized approaches regarding medical cannabis and women´s health. Personally, I always try to adapt the treatment to the different moments of the menstrual and ovarian cycle my female patients might be experiencing, adjusting dosages, even using different cannabinoids in different moments is crucial, yet not always easy, as not many women are aware of the changes they experience through their hormonal cycle, so by inviting them to pay more attention to these changes, they get more connected to their cyclic nature and that is always positive, I think.
Kalapa: Today we know that our body’s endocannabinoid system influences the female reproductive system. For example, it is involved in the maturation of eggs and the implantation of an embryo in the uterus. Endocannabinoids are therefore involved in the menstrual cycle and pregnancy. But not only that: studies also show the ability of cannabinoids to fight cancer cells. So research is also discussing the role of cannabinoids or the endocannabinoid system and ovarian cancer. Can you explain this connection for us?
Mery Peña: Beyond the palliative effects of cannabinoids, helping with chemotherapy induced nausea, improving sleep and pain in oncological patients, these molecules are gaining recognition for their role in the pathophysiology of cancer.
Cannabinoids show a variety of anticancer effects by disturbing the signalling pathways involved in malignant transformation and tumour progression. The endocannabinoid system can initiate apoptosis and autophagy, mount inflammatory responses against malignant cells, and block angiogenic and metastatic processes trough different mechanisms: stimulation of TRPV1 or PPARγ, along with inhibition of COX2. Taking this into account we must mention other molecular ways including MAPK, cAMP, and others, all activated by ligand-receptor interactions at the cannabinoid receptors.
In the ovary we have both CB1 and CB2 receptors. And there are studies that revealed a tumour grade-dependent expression of CB1 receptors in ovarian cancer.
It has been reported that cannabinoid receptors and their endogenous ligands are generally upregulated in the cancer cells and tissue when compared to non-cancerous. The expression of the various components of the endocannabinoid system is not homogenous across all cancers and the mechanisms are complex, there is still a lot of research to do and it is very tricky to interpret the results as plasma and local tissue levels of various components of the endocannabinoid system do not necessarily correlate.
To complicate things even more, the system fluctuates alongside the menstrual and ovarian cycle, but all these said, I am sure that in the not-so-distant future cannabinoids will be key tools in the treatment of ovarian cancer, among other ovarian diseases as polycystic ovarian syndrome, and for sure in the future, elements of the endocannabinoid system will be used as biomarkers for oocyte maturity.
Kalapa: The most common abdominal disease in women is endometriosis. The disease can be accompanied by immense pain, menstrual cramps, pain during intercourse and infertility. Mery, have you had any positive experiences with cannabinoids in treating endometriosis?
Mery Peña: Endometriosis is one of my favourite subjects for so many reasons: The pathological mechanisms remain unclear, the diagnosis is difficult often including surgery, its often related to painful intercourse and fertility concerns, overall bringing great suffering for patients and their families and huge costs for society.
Let’s start by considering pain. The endometriosis-associated pain mechanisms are complex and interconnected and can be divided into three main categories of pain: the nociceptive, the inflammatory, and the neuropathic pain. All three categories are closely related to the endocannabinoid system function. Cannabinoids can help with their anxiolytic and anti-inflammatory effect and normalize the altered signalling.
Some authors have described endometriosis as an ‘‘endocannabinoid deficiency’’ condition, women with endometriosis have lower levels of CB1 receptors in endometrial tissue. Reduced endocannabinoid system function has been suggested to lead to growth of endometriosis tissue and a more severe pain experience.
Pain management for patients with endometriosis needs to be more effective, target the hormonal and immunologic environment, downregulate proliferation while enhancing apoptosis, and normalize the invasive mechanisms. All these aspects could be tackled by modulating the endocannabinoid system and tone. I have had mixed results working with women with endometriosis, as it depends on so many different aspects: the products available for them are different in different countries, some of them experience moderate analgesia, but some patients experiment incredibly good results with very low dosages. So, I think is a resource that is worth to try.
Kalapa: Another important topic in women’s health is menopause. At some point it happens to all of us – only with which physical and/or mental complaints the menopause comes along, is very different from woman to woman. What are your experiences with cannabis treatment in this phase of a woman’s life?
Mery Peña: Tell me about it! As I am becoming older, I can understand better the great discomfort the vasomotor symptoms of menopause can bring to many of my patients, with the heat wave we are experiencing in Europe currently we all have discovered that is very hard to function with hot flashes and poor sleep.
As Canada and some states in North America release data, we realise that more women are turning to cannabis and cannabis derived medicines to relieve these symptoms, so we have several published articles where the frequency of self-reported cannabis use was significantly correlated to the number and severity of menopausal symptoms. Women report large beneficial effects for treating joint and muscle discomfort, irritability, sleep problems, depression, anxiety, and hot flashes, but a lesser benefit for other symptoms such as heart discomfort, exhaustion, vaginal dryness, and bladder problems.
Again, as with endometriosis, I think that if we put on a balance the possible benefits against the secondary effects and we compare the pharmaceutical options we have for these conditions: hormonal therapy, pain killers, antidepressants, medical cannabis should be an option that every woman in every part of the world should have the right to consider and get affordable access to. Doctor Mery Peña is a member of the Kalapa Clinic medical team. She graduated in General Medicine from the National University of Colombia and is a registered physician in Barcelona. She has specialized in Traditional Chinese Medicine through several postgraduate courses. Mery Peña has worked as a physician in Barcelona at the clinical level in the Centre Integral de Serveis en Salut Mental (CIS) and in elderly care. Today she offers consultation on the use of cannabinoids.