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The dis-LIST

Nighttime Pain

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With chronic pain, getting a good night’s sleep can be a constant battle. Pain assaults sleep on two fronts, the first being easier to guess: nighttime pain. Just moving in the night can jar you awake with pain disrupting your sleep cycle, causing health problems that worsen over time.1,2 Adults over the age of 65 who experience nighttime pain at least 3 times a week are 6 times more likely to feel excessively sleepy the next day,3 and persistent insomnia can cause depression, anxiety, and an increased risk for accidents and being absent at work or school.1

Before you jump in and say pain medications might help, the second thing disrupting sleep is more subtle: side effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin can cause gastroesophageal reflux disease.1 People often use proton pump inhibitors to manage side effects, but at night, stomach pH can get out of control and disrupt sleep with heartburn and acid indigestion.1,4 Opioids are more potent for pain relief, but they are even worse for sleep.

Researchers monitored patients taking opioids for advanced cancer, and they found opioids limited deep sleep, the time when your muscles relax and your brainwaves finally slow down. If you miss out on deep sleep in the first few hours of a night, you might just wake up and go right back to bed.5 These sleep disruptions can worsen pain levels over time, subverting the whole point of opioids, and contribute to mental health problems such as depression.1

As the national opioid epidemic has generated more honest discussion about the addictiveness and side effects of opioids, many patients have turned to medical cannabis for chronic pain relief and help sleeping. This is not the first time in history either. Cannabis was used as an herbal sleep remedy in ancient Indian Ayurveda tradition, and when cannabis was brought to Western medicine in the 1850s, doctors widely prescribed cannabis for sleep when conditions such as pain interfered.1 Now we have a wide range of cannabis cultivars, so it’s no longer as simple as saying cannabis is good for sleep. We must consider how different cannabinoids affect our ECS and work to relieve conditions such as pain and disrupted sleep.

THC is the primary psychoactive cannabinoid and can ease the pain pathway of the central nervous system.1 THC can be effective in relieving chronic pain, and in the short-term, THC can help you fall asleep faster and make you feel like you’re sleeping better. For example, patients with fibromyalgia found THC to be more effective than the prescription sleep drug amitriptyline. 

In the 1850s, doctors widely prescribed cannabis for sleep when conditions such as pain interfered…

The other most abundant cannabinoid, CBD, can relieve pain, reduce inflammation, and scavenge oxidants without any psychoactive effects.1 At low doses, CBD can be stimulating and increase wakefulness, but as dosage increases, CBD can be sedating. For example, a high dose of 160 mg CBD per day can increase sleep time and decrease sleep disruptions.2 When treating nighttime pain specifically, most research has combined the sedating effects of CBD with pain-relief from THC.

The leader in nighttime pain research has been GW Pharmaceuticals, the company that achieved FDA approval for using CBD to treat drug-resistant epilepsy. GW has another product for treating chronic pain in multiple sclerosis, Sativex, which is a whole plant extract with an equal ratio of THC and CBD.1 In clinical trials, GW amassed reports from more than 2,000 people with a total of 1,000 patient years of Sativex exposure, and they demonstrated extracts with 1:1 THC to CBD consistently improved sleep for patients with chronic pain.1,2 Over 80% of patients reported their sleep was satisfactory, good, or very good through 124 weeks of use, without any evidence of tolerance build-up or dysregulated sleep–wake cycles.1

While Sativex is not yet approved by the FDA, we can borrow the cumulative evidence to suggest which cannabis cultivars and/or products to try for nighttime pain. THC can help manage pain symptoms and initiate sleep, but CBD is an important component to maintain long-term sleep rhythms. So, you could first try extracts with a 1:1 THC to CBD ratio. You might also find some benefit using cannabis high in CBD and low in THC with terpenoids that are sedative, such as terpineol.1 When it comes to how much you should take, when you should take it, and if you should take a low dose of CBD in the morning, that’s up to you.

Insomnia from chronic nighttime pain can drain daytime energy, so it’s easy to finally get a few nights of pain relief with cannabis but not notice imbalanced sleep rhythms when sleep has been disrupted for so long. I would strongly suggest anyone using cannabis for nighttime pain should take careful notes on what they tried, for how long, and how they felt. Note how long it took to get to sleep, if you woke up in the middle of the night, how long you slept, if you felt rested in the morning, and how your energy levels were the next day. Were you alert and ready to go, or did you feel drowsy in the middle of the day? If so, that could be a sign you’re taking too much THC, or the balance of CBD to THC is too low. Sativex clearly showed us patients with chronic pain can manage nighttime pain and sleep with cannabis products, but it might take a little experimentation to figure out how cannabis can work best for you.


REFERENCES

1. https://doi.org/10.1002/cbdv.200790150
2. https://doi.org/10.1007/s11920-017-0775-9
3. https://doi.org/10.1002/ana.20863
4. https://doi.org/10.1111/j.1365-2036.2006.02944.x
5. https://doi.org/10.1200/JCO.2007.12.2135

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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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