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The dis-LIST

Glaucoma

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Promising results hint that THC might one day treat glaucoma.

Glaucoma is an umbrella term for a group of diseases that damage the optic nerve—the signalling pathway bringing color and image information from the retina to the brain.1 Damaged nerve cells in the eye can narrow a person’s field of vision and even lead to complete blindness. According to the World Health Organization, about 4.5 million people are blind as a result of glaucoma in the world—that’s slightly more than 12 percent of all human blindness.2 About three million people who suffer from glaucoma are in the United States, according to the American Glaucoma Society.3 Unfortunately it’s a bit sneaky in that patients often only notice the decrease in their peripheral vision after a large swath of cells is already dead and the disease is in the advanced stages.3,4 Currently, there is no known cure, and patients typically manage the condition for the rest of their lives with medicine, surgery, or both. 

Although the exact ways in which the diseases work are poorly understood, two aspects are well known: damage to the cells of the optic nerve, and in most cases, there is an increase in pressure within the eye. The most effective medicines used to treat glaucoma aim to lower the pressure within the eye.1,5 Researchers published a study in 1971, in the prestigious “Journal of the American Medical Association” showing that smoking marijuana decreased intraocular pressure.7 We know today that THC is at least one of the components responsible for this effect. 

Keeping intraocular pressure low seems to work to hold off the worst glaucoma has to offer. Even so, for a minority of patients who are successfully keeping eye pressure low, the disease still progresses. That is why some researchers are looking beyond pressure-lowering medicines and taking a closer look into medications that can also protect the nerve cells from damage4—something THC has also been shown to do.5

THC seems like a good candidate to treat glaucoma because of the combination of its ability to protect neurons as well as lower intraocular pressure. THC affects change in the body by connecting to at least two cannabinoid receptors.7 One of these is the well-known cannabinoid CB1 receptors. They are found throughout the brain and eyes and can affect pain, mood, movement and memory.5,8,9 As it turns out, CBD is actually not well-suited to the job according to results we’ll get to below.

Smoking cannabis as a way to treat glaucoma has drawbacks. It lasts a short duration (three to four hours according to the American Glaucoma Society),10 has potentially undesirable psychoactive and other side-effects, as well as the possibility of building up resistance. The society issued a position statement in 2009 saying it does not recommend cannabis for glaucoma treatment. However, the statement hints that the position might change if more promising research becomes available.

In the 11 years since the statement came out, there have been more studies. Recent research in animal models highlights the possibility that some form of THC might one day be available to treat glaucoma.

Since smoking has its challenges, researchers have tried delivering THC and CBD under the tongue (THC lowered eye pressure for four hours and CBD had no effect or raised the pressure) and via eye drops.11 The eye drops failed at first, because the THC didn’t get very far into the eye, due to its love of lipids or lipophilic nature. A team of pharmaceutical researchers from the University of Mississippi has been tackling this problem. They published a study last year in the journal “Translational Vision Science and Technology” pointing to early success in developing a new eye drop.12,13 It allowed the THC to penetrate more deeply into rabbits’ eyes and decreased intraocular pressure for six hours. They were able to override THC’s hydrophobic nature by attaching it to molecules that made the whole nano-sized medicine able to sink all the way into the rabbit’s eye. In their paper, the researchers also point out that, if recent findings are correct, THC can protect the cells in the optic nerve from damage and deeper penetration may help increase this positive effect.

In a 2018 study published by the online journal “Investigative Ophthalmology & Visual Science,” Indiana University researchers investigated on which receptors THC and CBD were working in mice.7 They found the two compounds were working with different receptors. THC lowered eye pressure. CBD, though it may have neuroprotective effects, worked against THC and kept the pressure from decreasing and, in some cases, could even have the unwanted effect of increasing eye pressure. 

In one surprise result, they found a marked difference in how the cannabinoids affected male and female mice. Males had a much more pronounced decrease in eye pressure from THC. When they looked into this, they found the males had more of the relevant receptors.7

In short, before THC could be a good long-term solution to this life-long condition, there are some hurdles to overcome. In their position statement, the American Glaucoma society states: “Unless a well tolerated formulation of a marijuana-related compound with a much longer duration of action is shown in rigorous clinical testing to reduce damage to the optic nerve and preserve vision, there is no scientific basis for use of these agents in the treatment of glaucoma.”10 Rigorous clinical testing is the gold standard for choosing a safe and effective treatment. Such research will continue to be difficult to conduct as long as cannabis is still listed as “Schedule 1” under the Controlled Substances Act, meaning it is considered to be a substance with no medical use and a high potential for abuse. If Congress or the federal administration changes the classification, researchers will likely have more opportunities to conduct relevant research in humans.


References:

1.https://higherlogicdownload.s3.amazonaws.com/AMERICANGLAUCOMASOCIETY/4ca07187-fb0f-4dc3-a19c-33093862484d/UploadedImages/Documents/559_cyclophoto4_final.pdf

2. https://www.who.int/blindness/causes/priority/en/index6.html

3. https://www.americanglaucomasociety.net/patients/glaucoma-faqs

4. Bucolo, C., Plantania, C.B.M., Drago, F., Bonfiglio, V., Reibaldi, M., Avitabile, T., Uva, M. (2018). Novel Therapeutics in Glaucoma Management. doi: 10.2174/1570159X15666170915142727.

5. Rapinoa, C., Tortolania, D., Scipionib, L. & Maccarroneb, M. (2018). Neuroprotection by (Endo)Cannabinoids in Glaucoma and Retinal Neurodegenerative Diseases. Current Neuropharmacology (16), 959-970.

6. Hepler R.S., Frank I.R. (1971) Marihuana smoking and intraocular pressure. JAMA (217),1392.

7. Miller S., Daily L., Leishman E., Bradshaw H., Straiker A. (2018). D9-tetrahydrocannabinoland cannabidiol differentially regulate intraocular pressure. Invest Ophthalmol Vis Sci (59), 5904–5911.

8. Piomelli D. (2003). The molecular logic of endocannabinoid signalling. Nat Rev Neurosci (4), 873–884.

9. Straiker, A.J., Maguire, G., Mackie, K., Lindsey, J. (1999). Localization of cannabinoid CB1 receptors in the human anterior eye and retina. Invest Ophthalmol Vis Sci. Sep (40:10), 2442-2448. 

10. https://www.americanglaucomasociety.net/about/statements

11.  Tomida, I., Azuara-Blanco, A., House, H., Flint, M., Pertwee, R.G., Robson, P.J. (2006). Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. Journal of Glaucoma: Oct15(5), 349-53.

12. 2019: Taskar, P.S., Patil, A., Lakhani, P., Ashour, E., Gul, W., El Sohly, M.A., Murphy, B., Majumdar, S. (2019) D9-Tetrahydrocannabinol derivative-loaded nanoformulation lowers intraocular pressure in normotensive rabbits. Trans Vis Sci Tech: 8(5),15.https://doi.org/10.1167/tvst.8.5.15

13. Adelli, G.R., Bhagav, P., Taskar, P., et al. (2017). Development of a D9-tetrahydrocannabinol amino acid-dicarboxylate prodrug with improved ocular bioavailability. Invest Ophthalmol Vis Sci. (58), 2167–2179. doi: 10.1167/iovs.16-20757

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The dis-LIST

Weight Loss

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Like many other stigmas attached to cannabis, the commonly painted picture of cannabis users as overweight individuals has proven to be nothing more than a fable. 

Though cannabis is known for its appetite-stimulating properties, research has shown that cannabis users are less likely to be obese than their non-cannabis using counterparts.1 A study from the International Journal of Epidemiology concludes that cannabis may create cellular changes in the human body that affect weight gain. 

Omayma Alshaarawy, an assistant professor of family medicine says, “It could be something that’s more behavioral like someone becoming more conscious of their food intake as they worry about the munchies after cannabis use and gaining weight.” “Or it could be the cannabis use itself, which can modify how certain cells, or receptors, respond in the body and can ultimately affect weight gain. More research needs to be done.”

The American Journal of Medicine expanded on this research and published a study exploring the effect of cannabis use on glucose, insulin, and insulin resistance among adults in the U.S. The study followed 4,657 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010.2

Though cannabis is known for its appetite-stimulating properties, research has shown that cannabis users are less likely to be obese than their non-cannabis using counterparts.

Their results show lower insulin levels among cannabis users; however, a surprising finding was cannabis use showing significant correlations to smaller waist circumferences. According to the study, “The mechanisms underlying this paradox have not been determined, and the impact of regular marijuana use on insulin resistance and cardiometabolic risk factors remains unknown.”2 

What is fascinating is the results from these studies have proven to be true regardless of sample size, or even factors like gender and age. Dr. Sunil Aggarwal is a cannabis researcher and physician. He says, “There is a correlation between cannabis use and reduction in the BMI. This association holds even after controlling for other variables.” 

Though this study did not produce definitive results, other plausible explanations include the cannabinoid tetrahydrocannabivarin (THCV) as an appetite reducer and cannabis contributing to the restoration of a healthy gut microbiome. 

The thought process behind cannabinoid’s role in suppressing appetite is that of THCV blocking the CB1 receptor.3 The CB1 receptor has been shown, through research, to play a role in the regulation of ghrelin, aka the “hunger hormone.”4 When THCV blocks it, appetite is reduced. THCV has also been linked to blood sugar regulation. While solid research has yet to be published, preliminary and anecdotal findings are yielding promising results. 

Many cannabis companies are realizing the potential THCV holds, and are cashing in. Doug’s Varin is a line of high-THCV products, produced by California Cannabinoids. The product line was founded by Doug who set out to find a way to treat his wife’s medical condition. Doug’s Varin was born, and appetite suppression as a benefit is touted on the company’s website. Even Flow Kana launched a high-THCV cultivar to add to their respected product line. 

It is pretty well-known that cannabinoids can manipulate endocannabinoid receptors in the digestive tract, resolving symptoms like nausea and vomiting.5 There is, however, also preparatory buzz attributing cannabis’s antimicrobial effects with weight loss when it enters the digestive system. The thought is that the antimicrobial compounds kill off bad bacteria, promoting a healthy gut flora and thus, weight loss.

From 2015 to 2016, 39.8% of Americans were considered obese.6 Cardiovascular disease, stroke, type 2 diabetes, and certain cancers have been linked back to obesity. The obesity epidemic is prevalent, and oftentimes, those who have lived a certain lifestyle for so many years need extra help in changing their habits. While research on cannabis and weight loss is new, its findings may be worth looking into in order to potentially put a dent in the obesity epidemic.


REFERENCES:

1. Alshaarawy, O., & Anthony, J.  International Journal of Epidemiology, 48(5) 2019. doi: 10.1093/ije/dyz044

2. Penner, E. A., et al. The American Journal of Medicine, 126(7). 2013. doi: 10.1016/j.amjmed.2013.03.002

3. Thomas, A. et al.  Lesley A Stevenson, Kerrie N Wease, Martin R Price, Gemma Baillie, Ruth A Ross, and Roger G Pertwee. British Journal of Pharmacology, 146(7). 2005. doi: 10.1038/sj.bjp.0706414

4. Pradhan, G. et al. Current Opinion in Clinical Nutrition and Metabolic Care, 16(6). 2013. doi: 10.1097/MCO.0b013e328365b9be 

5. Parker, L.A., et al. British Journal of Pharmacology, 163(7) 2011. doi: 10.1111/j.1476-5381.2010.01176.x

6. “Adult Obesity Facts.” Centers for Disease Control and Prevention. www.cdc.gov

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The dis-LIST

Tremors

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Shaky legs and trembling hands or facial muscles are among the afflictions patients with Parkinson’s disease commonly contend. Tremors such as these commonly persist when people are at rest and are often made worse by stress or strong emotions. In addition to these resting tremors, more than 25% of patients with Parkinson’s also have a tremor when they are active. Tremors may first appear in only one side of the body before moving to both sides. And though not life-threatening, tremors can make activities of daily life more challenging, possibly even threatening a patient’s ability to live independently.

More research needs to be done on the effects of cannabis on tremors, because as is often the case, the research that has been done is often small scale and the results are not verified by further studies. The research has yet to detail the extent of benefits, risks, and clinical uses of cannabis. What has been done suggests that tremors in patients with Parkinson’s may be helped with cannabis while evidence for patients with multiple sclerosis is either non conclusive or shows no response. 

This year, a small, yet well-constructed study of 24 patients with Parkinson’s found that CBD significantly decreased the size of their tremors. Patients were placed in a public speaking situation—a scenario designed to increase their stress and therefore the size of their tremors.1 Some were given CBD and others were given a placebo and neither the researchers nor the patients knew who received what. Later the groups were swapped. When the results were decoded and analyzed, patients who received CBD had a significant decrease in the severity of their tremors.

In a study from 2004, researchers were able to study a larger pool of patients with Parkinson’s disease.2 In this study smoking cannabis significantly improved the tremors for 31% of the 339 Parkinson’s patients in the study. Another smaller study with 22 participants done in 20143 once again found smoking cannabis significantly improved tremors for patients.

This year, a small, yet well-constructed study of 24 patients with Parkinson’s found that CBD significantly decreased the size of their tremors.

Researchers have attempted to shed light on tremors in those suffering from MS as well. Initial work on rats in 20004 and 20165, suggested that CB1 was somehow related to this symptom, however later studies in humans did not support this finding. In 2003, a 15-week randomized and placebo-controlled trial, used oral THC (Marinol) versus oral cannabis extract (each with 12.5 mg) versus a placebo and saw no difference in patient ratings of their tremors.6 Later in 2010, another large double-blind, randomized placebo-controlled study with 337 patients with multiple sclerosis lasted for 8 weeks.7 In this study, participants received up to 24 doses of either a placebo or an oral nabiximols spray with 65 mg THC and 60 mg CBD. Again, patients evaluating their own tremors found no effect. It’s important to note that tremors were not the main focus of either of these studies.

A significant number of patients suffer from a third kind of tremor called essential tremor. This type of tremor is brought on with movement or activity and affects eight times the number of people who suffer from tremors from Parkinson’s disease. Even less research has been done on the effects of cannabis on this type of tremor than on Parkinson’s or multiple sclerosis. However, research results should be released soon from a small pilot safety and efficacy trial out of the University of California San Diego that looks at oral capsules of THC/CBD in patients with essential tremor.8


REFERENCES:

1 De Faria, S.M, et al. Journal of Pyschopharmacology, 7:269881119895536. 2020 doi: 10.1177/0269881119895536.

2 Venderova K, et al. Movement Disorders, 19(9):1102–1106. 2004.

3 Lotan, I. et al. Clinical Neuropharmacology, 37(2). 2014. doi: 10.1097/WNF.0000000000000016.

4 Baker D, et al. Nature, 404(6773):84–87. 2000.

5 Abbassian, H. et al. British Journal of Pharmacology, 173(22). 2016. doi: 10.1111/bph.13581. 

6 Zajicek J., et al. Lancet, 362(9395):1517–1526. 2003.

7 Collin C., et al. Neurological Research, 32(5):451–459. 2010.

8 International Essential Tremor Foundation https://www.essentialtremor.org/

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The dis-LIST

Melanoma

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Each month we study a specific topic or disease. As you read the title of this article, you may be asking yourself, “What does melanoma have to do with Parkinson’s disease?” Well, there is actually a surprising link between the two.1 A study done a decade ago showed that melanoma prevalence appears to be higher in patients with PD than in the general population. Another study stated that there was an increased risk for melanoma for PD patients using the drug levodopa.2 Levodopa, is a drug commonly prescribed to PD patients, and it impacts the body’s creation of melanin and melanocytes. The association between PD and melanoma may be explained by pigmentation changes in melanin and/or melanin synthesis.

Melanoma is the most serious type of skin cancer and is the most common type of cancer worldwide.3 In the U.S., 10,000 new cases are diagnosed every day, and two patients die every hour. Melanoma is a type of skin cancer that develops when the cells that give the skin its tan or brown color, known as melanocytes, start to grow out of control.4 Melanoma has the potential to metastasize anywhere in the body.  

Standard treatment for melanoma includes surgical removal of the area in question. Depending on the size of the lesion, radiation and chemotherapy are often used in conjunction with surgery. Various intravenous treatments and injections are used when needed as well. These invasive treatments can be exhausting, especially if the patient has any other conditions or is immunocompromised. Thanks to current studies and the advancements in alternative medicine, we are beginning to see the promising effects of other plant medicines when it comes to the prevention and treatment of melanoma. 

We are what we eat, and according to the Skin Cancer Foundation, there are certain phytonutrients (plant based nutrients) that we can eat to help prevent skin cancer. Those nutrients include, “vitamins C, E, and A, zinc, selenium, beta carotene (carotenoids), omega-3 fatty acids, lycopene and polyphenols.”5  Many dermatologists recommend high amounts of these antioxidants in your diet to help prevent skin cancer. There are many plants and herbs that contain these nutrients. Herbs, spices, and composite herbal medicines are among the categories that contain the most antioxidants, and there have been over 3,500 identified.6

One of those herbal medicines is cannabis. The cannabinoid receptors in our ECS are located in every cell in our bodies.7 CB1 receptors are present in the nervous system and CB2 receptors are located in the peripheral nervous system. Interestingly, human melanomas and melanoma cell lines express both CB1 and CB2 cannabinoid receptors. In a study published by the Federation of American Societies for Experimental Biology (FASEB), “Activation of these receptors decreased growth, proliferation, angiogenesis and metastasis, and increased apoptosis, of melanomas in mice.”8 This is promising research for using phytocannabinoids for the treatment of melanoma. 

In another study published in 2019 in the Journal of Surgical Research,9 cannabinoid therapy was introduced to malignant melanoma tumors in mice. The cannabinoid CBD was injected into melanoma tumors in mice, and the tumors shrunk significantly in size. 9 Cannabinoids are proving to be a unique source of treatment based on their targeted action on cancer cells and their ability to spare normal cells.10 These findings should guide research and assist scientists to better understand the mechanisms by which cannabinoids could be utilized as an adjunctive treatment of cancer. 

In closing, skin cancer is nothing to ignore. It can be 100% effectively treated if caught in time. There is a simple way to keep track of any moles, birthmarks, freckles, or any area on your body that has more pigmentation than other parts, we can call it the skin cancer alphabet. If you pay attention to the letters in this mnemonic device you can put your mind at ease by knowing what to look for and making note of any changes. If you feel like something is different, schedule an appointment with your primary doctor or dermatologist. You can never be too safe when it comes to the prevention and treatment of melanoma.


REFERENCES:

1. Bertoni, J.M. et al. JAMA Neurology. 2010. doi:10.1001/archneurol.2010.1

2. Huang, P. et al. Translational Neurodegeneration, 4 (21). 2015. doi: 10.1186/s40035-015-0044-y

3.Skin Cancer Foundation. “Skin Cancer Facts and Statistics.” www.skincancer.org. 

4. American Cancer Society. “What is Melanoma Skin Cancer?” www.cancer.org

5. Skin Cancer Foundation. “Can your diet help prevent skin cancer?” June 8, 2017. www.skincancer.org 

 6. Paur, I. et al. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. 2011.

7. Pertwee, R. Pharmacology and Therapeutics, Volume 74, Issue 2. 1997. doi: 10.1016/S0163-7258(97)82001-3

8. Blazquez, C. et al. Federation of American Societies for Experimental Biologies. 2006. doi: 10.1096/fj.06-6638fje

9. Simmerman, E. et al. Journal of Surgical Research, Volume 235. March 2019. doi:  10.1016/j.jss.2018.08.055

10. Safaraz, S. et al. American Association for Cancer Research. January 2008. doi: 10.1158/0008-5472.CAN-07-2785

11. “Mayo Clinic Minute: The A, B, C, D, E’s of Skin Cancer.” Ian Roth. May 1, 2018. mayoclinic.org.

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