Human Reproductive System
The reproductive system is comprised of internal and external organs that operate together and serve several functions. These organs serve the purpose of pro-creating and facilitate sexual pleasure.
The female reproductive system consists of external parts that include the clitoris, labia majora, labia minora, and Bartholin’s glands. Internally the major organs are the vagina, uterus, and ovaries that produce the female’s ova. The vagina is appended to the uterus through the cervix, and the womb is connected to the ovaries via fallopian tubes. Hormonal changes trigger the release of one ovum or egg. The egg is released through the fallopian tube; this process is ovulation. If the ovum is not fertilized, it is discharged through menstruation.
There are two major parts in the male reproductive system, the testes, and penis. The testes, produce sperm and are located in an external pouch called the scrotum. The testes are placed here to be kept slightly cooler than the body, in case they become too cold, they are drawn closer to the body for warmth, or further in case of cooling is required.1, 2
Genetic influences, environmental factors and stressful lifestyles all affect sexual behavior and health. Disorders affecting the reproductive health are directly related to CB1 and CB2 receptors located throughout the system.3 – 5
Role of CBD in Reproductive Disorders and Diseases
Since the discovery of the endocannabinoid system, research and studies have shed light on the significant role of endocannabinoid signaling in several reproductive-related issues. These issues amongst others include Sertoli cell survival, spermatogenesis, fertilization, preimplantation embryonic development, implantation placentation, and postimplantation early growth. This has created new perspectives in clinical applications that point towards the likely effect of cannabinoid in improving infertility and promoting the overall reproductive health.3, 6
Endometriosis
Endometriosis is when the tissue that forms the uterine wall (the lining of the womb) is present on other organs in the body, Endometriosis is a painful, inflammatory disease that usually transpires in the inferior abdomen, or pelvis, but can also appear anywhere in the body. Women with endometriosis often have lower abdominal pains, pain during periods, or even during intercourse, and may even report a difficulty getting pregnant. Endometrial tissue can increase due to hormonal changes resulting in intra-abdominal bleeding and adhesion development.7
There is no single reason for developing endometriosis but is commonly associated with retrograde menstruation. Endometriosis is an idiopathic autoimmune clinical endocannabinoid deficiency (CECD), where CB2 receptor receptivity is affected. The endocannabinoid system adjusts hormonal imbalance in the reproductive system.
Surgical and hormonal intervention are both used against endometriosis, yet it can still cause chronic pain and disability. Cannabidiol administration has shown the ability to modulate bloating and pain associated with endometriosis. CBD oil has anti-inflammatory and analgesic properties as well as the ability to improve CB2 anandamide binding.8
Endometrial Cancer
Endometrial adenocarcinoma is a common intra-abdominal malignancy in women. Early detection is often associated with improved prognosis; however, treatment is still limited to radiation and chemotherapy; their aggressive side-effects are well documented. Clinical endocannabinoid deficiency (CECD) associated with endometrial adenocarcinoma is idiopathic autoimmune that affects CB2 receptors. The endocannabinoid system has a protective role against several types of cancers. Research has shown the effectiveness of cannabidiol (CBD) in inhibiting the metastasis in both in vitro and in vivo studies, Despite the limited human studies, CBD has analgesic benefits and is warranted as an adjunctive malignancy therapy.9-11
Prostate Cancer
Prostate cancer is a malignancy that transpires in the prostate; a small gland in men that originates the seminal fluid that nourishes and transports sperm. Millions of men are affected by prostate cancer, and if detected early, it is usually curable. The tumor commonly grows slowly and is confined within the gland, here it is unlikely to cause harm. However, due to the low number of men receiving prostate examination and PSA screenings the detection is delayed, risking a poor prognosis.
At early stages of prostate cancer, there might be no signs or symptoms, but as it advances symptoms that appear include, trouble urinating, blood in semen, discomfort in the pelvic area and even erectile dysfunction. It is not clear what causes prostate cancer, and the clinical endocannabinoid deficiency (CECD) associated with it is idiopathic autoimmune. The CECD in prostate cancer affects mostly CB2 receptors.
Cannabidiol promotes apoptosis in cancerous cells and inhibits the development and metastasis of the tumor as shown by clinical studies. The therapeutic administration of CBD in the early stages of prostate cancer has shown a promising effect, and also as a preventative therapy to maintain a healthy prostate.8, 12-24
Testicular Cancer
Cancer of the testicle is one of the least common forms of cancer that usually affects men between the ages of 15 and 49. Typically the symptoms are painless and appear in as swelling or lump in one of the testicles, or even as a change in form or texture of the testicles.
Testicular cancer is life-threatening, and due to its closeness to the lymph system, it makes it harder to manage unless detected early. It is associated with an idiopathic immune CECD, where cannabidiol has previously demonstrated effectiveness in inhibiting metastasis and spread of malignant cells.12-14
References:
- Johnstone C, Hendry C, Farley A, McLafferty E. Endocrine system: part 1. Nurs Stand. 2014 May 27;28(38):42-9 Available at https://www.ncbi.nlm.nih.gov/pubmed/24844520
- Uberto Pagotto, Giovanni Marsicano, Daniela Cota, Beat Lutz, Renato Pasquali; The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance, Endocrine Reviews, Volume 27, Issue 1, 1 February 2006, Pages 73–100, available at https://doi.org/10.1210/er.2005-0009
- Gertsch, J. (2017) Cannabimimetic phytochemicals in the diet – an evolutionary link to food selection and metabolic stress adaptation?. British Journal of Pharmacology, 174: 1464–1483, available at https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.13676
- Lipina, C., & Hundal, H. S. (2017). The endocannabinoid system: no longer anonymous in the control of nitrergic signalling? Journal of Molecular Cell Biology, 9(2), 91-103, available at https://discovery.dundee.ac.uk/en/publications/the-endocannabinoid-system-no-longer-anonymous-in-the-control-of-
- George W. Booz, Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress, Free Radical Biology and Medicine, Volume 51, Issue 5, 2011, Pages 1054-1061, ISSN 0891-5849, available at: http://www.sciencedirect.com/science/article/pii/S0891584911000116
- El-Remessy, Azza B. et al. Neuroprotective Effect of(−)Δ9-Tetrahydrocannabinol and Cannabidiol in N-Methyl-d-Aspartate-Induced Retinal Neurotoxicity. The American Journal of Pathology , Volume 163 , Issue 5 , 1997 – 2008, available at https://ajp.amjpathol.org/article/S0002-9440(10)63558-4/fulltext
- Liou G, El-Remessy A, Ibrahim A, et al. Cannabidiol As a Putative Novel Therapy for Diabetic Retinopathy: A Postulated Mechanism of Action as an Entry Point for Biomarker-Guided Clinical Development. Current pharmacogenomics and personalized medicine. 2009;7(3):215-222. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955420/
- Hayakawa, K. , Mishima, K. , Nozako, M. , Hazekawa, M. , Irie, K. , Fujioka, M. , Orito, K. , Abe, K. , Hasebe, N. , Egashira, N. , Iwasaki, K. and Fujiwara, M. (2007), Delayed treatment with cannabidiol has a cerebroprotective action via a cannabinoid receptor‐independent myeloperoxidase‐inhibiting mechanism. Journal of Neurochemistry, 102: 1488-1496. Available at https://doi.org/10.1111/j.1471-4159.2007.04565.x
- Hind, W. H., England, T. J., and O’Sullivan, S. E. (2016) Cannabidiol protects an in vitro model of the blood–brain barrier from oxygen‐glucose deprivation via PPARγ and 5‐HT1A receptors. British Journal of Pharmacology, 173: 815–825. Available at https://doi.org/10.1111/bph.13368
- Parray, H.A. & Yun, J.W. Cannabidiol promotes browning in 3T3-L1 adipocytes. Mol Cell Biochem (2016) 416: 131. https://doi.org/10.1007/s11010-016-2702-5
- Gregory I. Liou, John A. Auchampach, Cecilia J. Hillard, Gu Zhu, Bilal Yousufzai, Salman Mian, Sohail Khan, Yousuf Khalifa; Mediation of Cannabidiol Anti-inflammation in the Retina by Equilibrative Nucleoside Transporter and A2A Adenosine Receptor. Invest. Ophthalmol. Vis. Sci. 2008;49(12):5526-5531. Available at http://iovs.arvojournals.org/article.aspx?articleid=2164704
- El-Remessy, Azza B. et al. Neuroprotective and Blood-Retinal Barrier-Preserving Effects of Cannabidiol in Experimental Diabetes The American Journal of Pathology, Volume 168, Issue 1, 235 – 244 (2006) available at https://ajp.amjpathol.org/article/S0002-9440(10)62086-X/fulltext
- Zuardi, Antonio Waldo. (2008). Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Revista Brasileira de Psiquiatria, 30(3), 271-280. Available at https://dx.doi.org/10.1590/S1516-44462008000300015
- Fernández-Ruiz, J., Sagredo, O., Pazos, M. R., García, C., Pertwee, R., Mechoulam, R., & Martínez-Orgado, J. (2013). Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? British Journal of Clinical Pharmacology, 75(2), 323–333. Available at http://doi.org/10.1111/j.1365-2125.2012.04341.x
- Ashleigh L. Osborne, Nadia Solowij, Katrina Weston-Green, A systematic review of the effect of cannabidiol on cognitive function: Relevance to schizophrenia, Neuroscience & Biobehavioral Reviews, Volume 72, 2017, Pages 310-324, ISSN 0149-7634, available at https://doi.org/10.1016/j.neubiorev.2016.11.012.
- Szaflarski, Jerzy P. et al. Cannabis, cannabidiol, and epilepsy — From receptors to clinical response, Epilepsy & Behavior , Volume 41 , 277 – 282 (2014), availble at https://doi.org/10.1016/j.yebeh.2014.08.135
- Jan Malte Bumb, Frank Enning & F Markus Leweke (2015) Drug repurposing and emerging adjunctive treatments for schizophrenia, Expert Opinion on Pharmacotherapy, 16:7, 1049-1067, available at https://doi.org/10.1517/14656566.2015.1032248
- Baron, E. P. (2015), Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It’s Been …. Headache: The Journal of Head and Face Pain, 55: 885-916. Available at https://doi.org/10.1111/head.12570
- Yu, Y., Chen, H., & Su, S. B. (2015). Neuroinflammatory responses in diabetic retinopathy. Journal of Neuroinflammation, 12, 141. Available at http://doi.org/10.1186/s12974-015-0368-7
- Tam, J., Liu, J., Mukhopadhyay, B., Cinar, R., Godlewski, G., & Kunos, G. (2011). Endocannabinoids in Liver Disease. Hepatology (Baltimore, Md.), 53(1), 346–355. Available at http://doi.org/10.1002/hep.24077
- Silveira, J. W., Issy, A. C., Castania, V. A., Salmon, C. E. G., Nogueira-Barbosa, M. H., Guimarães, F. S., … Bel, E. D. (2014). Protective Effects of Cannabidiol on Lesion-Induced Intervertebral Disc Degeneration. PLoS ONE, 9(12), e113161. Available at http://doi.org/10.1371/journal.pone.0113161
- Marcelo H. Napimoga, Bruno B. Benatti, Flavia O. Lima, Polyanna M. Alves, Alline C. Campos, Diego R. Pena-dos-Santos, Fernando P. Severino, Fernando Q. Cunha, Francisco S. Guimarães, Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats, International Immunopharmacology, Volume 9, Issue 2, 2009, Pages 216-222, ISSN 1567-5769, available at https://doi.org/10.1016/j.intimp.2008.11.010
- Robson, P. J. (2014), Therapeutic potential of cannabinoid medicines. Drug Test. Analysis, 6: 24-30. Available at https://doi.org/10.1002/dta.1529
- Stanley, C. P., Hind, W. H., & O’Sullivan, S. E. (2013). Is the cardiovascular system a therapeutic target for cannabidiol? British Journal of Clinical Pharmacology, 75(2), 313–322. Available at http://doi.org/10.1111/j.1365-2125.2012.04351.x
- Rajesh, M., Mukhopadhyay, P., Bátkai, S., Patel, V., Saito, K., Matsumoto, S., … Pacher, P. (2010). Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory and cell death signaling pathways in diabetic cardiomyopathy. Journal of the American College of Cardiology, 56(25), 2115–2125. Available at http://doi.org/10.1016/j.jacc.2010.07.033
- Ronen Durst, Haim Danenberg, Ruth Gallily, Raphael Mechoulam, Keren Meir, Etty Grad, Ronen Beeri, Thea Pugatsch, Elizabet Tarsish, and Chaim Lotan, Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury. American Journal of Physiology-Heart and Circulatory Physiology 2007 293:6, H3602-H3607 available at https://doi.org/10.1152/ajpheart.00098.2007
- Walsh, S. K., Hepburn, C. Y., Kane, K. A. and Wainwright, C. L. (2010), Acute administration of cannabidiol in vivo suppresses ischaemia‐induced cardiac arrhythmias and reduces infarct size when given at reperfusion. British Journal of Pharmacology, 160: 1234-1242. Available at https://doi.org/10.1111/j.1476-5381.2010.00755.x
- Rajesh, M., Mukhopadhyay, P., Bátkai, S., Haskó, G., Liaudet, L., Drel, V. R., … Pacher, P. (2007). Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption. American Journal of Physiology. Heart and Circulatory Physiology, 293(1), H610–H619. Available at http://doi.org/10.1152/ajpheart.00236.2007
- Natalia Battista, Monica Bari, Cinzia Rapino, Federica Trasatti, Antonella D’Agostino & Mauro Maccarrone (2009) Regulation of female fertility by the endocannabinoid system, Human Fertility, 10:4, 207-216, available at https://doi.org/10.1080/14647270701429879
- T. Karasu, T.H. Marczylo, M. Maccarrone, J.C. Konje; The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility, Human Reproduction Update, Volume 17, Issue 3, 1 May 2011, Pages 347–361, available at https://doi.org/10.1093/humupd/dmq058
- Gruden, G., Barutta, F., Kunos, G., & Pacher, P. (2016). Role of the endocannabinoid system in diabetes and diabetic complications. British Journal of Pharmacology, 173(7), 1116–1127. Available at http://doi.org/10.1111/bph.13226
- Weiss, L., Zeira, M., Reich, S., Slavin, S., Raz, I., Mechoulam, R., & Gallily, R. (2008). Cannabidiol Arrests Onset of Autoimmune Diabetes in NOD Mice. Neuropharmacology, 54(1), 244–249. Available at http://doi.org/10.1016/j.neuropharm.2007.06.029
- Malhotra S, Heptulla RA, Homel P, Motaghedi R. (2017). Effects of Marijuana Use on Thyroid Function and Autoimmunity, Pages 167-173, Available at https://www.ncbi.nlm.nih.gov/pubmed/27799014
- Bifulco M, Malfitano AM, Pisanti S, Laezza C. (2008). Endocannabinoids in endocrine and related tumours. Pages 391-408. Available at https://www.ncbi.nlm.nih.gov/pubmed/18508995