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ALS

Amyotrophic Lateral Sclerosis

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Neurodegenerative diseases like ALS have a significant impact upon quality of life for those diagnosed with the condition. As the body’s neural network is damaged, our minds lose control of their ability to control voluntary, everyday movements like walking, eating, and speaking.1 New studies on cannabis as a promising treatment option show that cannabis could potentially help in the management of the disease and symptoms like spasticity and cramps—as well as helping to delay disease progression.2-8 As more research is done on cannabis and conditions like ALS, researchers are hopeful that the endocannabinoid system (ECS) may prove to be a promising route for providing effective treatment.7,9  

What is ALS?

Also known as Lou Gehrig’s disease, ALS is “A progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord.” Discovered in 1869, “ALS usually strikes people between the ages of 40 and 70, and it is estimated there are at least 16,000 Americans who have the disease at any given time.”1 In the same neurodegenerative diseases family as multiple sclerosis, the damage caused by inflammation and a lack of muscle nourishment leads to scarring and hardening along the spine, which blocks motor neurons, resulting in the brain’s diminished ability to initiate and control muscle movement. This can cause patients to lose the ability to control most voluntary movements. Patients lose the ability to eat, speak, move, and even breathe in some cases.  

There is no cure for motor neuron disease, so improved symptom control and quality of life are important for patients.

There are two types of ALS that are most common: sporadic and familial. Familial ALS (FALS) is responsible for less than 10% of all cases in the U.S. and, as the name suggests, is an inherited condition. Sporadic ALS is responsible for the remaining 90-95% of cases and can affect anyone, anywhere—though men are more likely to be diagnosed with disease, and military veterans are twice as likely to be diagnosed with ALS than non-military adults.1

ALS & Cannabis: What does the science say?

As more research comes out surrounding cannabis and its effectiveness as a treatment option, we are learning more specifically about how cannabis can be helpful for patients living with ALS. “There is no cure for motor neuron disease, so improved symptom control and quality of life are important for patients,” Dr. Nilo Riva explained. This particular phase II study looked at the efficacy of orally administered cannabinoids in reducing spasticity in 60 adult ALS patients. The study found that, when taken in conjunction with first-line antispasticity drugs, a 1:1 THC:CBD oral solution reduced spasticity in patients when compared to placebo administration.2,3

Additional studies that have examined the many properties of cannabis as they relate to symptom management for individuals with ALS have proposed that cannabis “Should be considered in the pharmacological management of ALS” due to its applications for “Analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction.”7 While some studies have found no noticeable change in symptoms such as cramps when managing symptoms with THC, other studies suggest that cannabinoids are effective “symptom control agents.”4,9 Reviews of the existing literature on the ECS as it relates to neurodegenerative diseases like ALS as well as the therapeutic benefits and potential of cannabinoid-therapy suggest that cannabinoids might be effective at managing symptoms as well as having the potential to slow disease progression.9 

Further, cannabinoids are being found to not only help with symptom management but also the underlying causes of ALS. “Two of the primary hypotheses underlying motor neuron vulnerability are susceptibility to excitotoxicity and oxidative damage,” Dr. Chandrasekaran Raman, lead researcher of one such study, explains. “There is rapidly emerging evidence that the cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage.”6 Dr. Raman’s study involved mice and investigated the efficacy of THC administration before and after symptom onset. It found THC was able to delay motor impairment and prolong survival when administered at the onset of tremors. Additionally, the study noted THC was anti-excitotoxic when administered in vitro, and in vitro administration was “Extremely effective at reducing oxidative damage in spinal cord cultures.”6 Further studies have found that cannabinoids like THC that bind with CB1 receptors help with the inflammation that causes neurodegeneration, and cannabinoids like CBD that bind with CB2 receptors actually help to delay the progression of the disease itself.8 

If you’re one of the more than 16,000 people in the U.S. living with ALS, or know someone who is, consider the available information on cannabis’ efficacy at both managing symptoms as well as delaying disease progression. Oral and IV administration are among the most studied administration routes, and current findings suggest that administration involving equal parts THC and CBD might prove beneficial over THC-only administration.1-4,6-8 Before beginning any cannabis treatment, talk with your doctor about current research and ask about how cannabis could be incorporated into your current treatment plan.


REFERENCES:

1. ALS Association. “What is ALS?” www.als.org

2. The Lancet.. ScienceDaily, 13 December 2018. https://www.sciencedaily.com/releases/2018/12/181213190606.htm

3.  Riva, N. et al. Lancet Neurology, 2018. doi: 10.1016/S1474-4422(18)30406-X

4. Weber M., et al.  Journal of Neurology, Neurosurgery & Psychiatry, 81. 2010. doi: 10.1136/jnnp.2009.200642

5. Carter, G.T., & Rosen, B.S. American Journal of Hospice and Palliative Medicine, 18, no. 4. July 2001. doi: 10.1177/104990910101800411

6. Raman, C. et al. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, 5:1. 2004. doi: 10.1080/14660820310016813

7. Giacoppo, S., & Mazzon, E. Neural regeneration research, 11(12). 2016. doi: 10.4103/1673-5374.197125

8. Shoemaker, J.L., et al. Journal of Neurochemistry, 101. 2007. doi: 10.1111/j.1471-4159.2006.04346.x

9. Pryce G., & Baker D. Endocannabinoids in Multiple Sclerosis and Amyotrophic Lateral Sclerosis. In: Pertwee R. (eds) Endocannabinoids. Handbook of Experimental Pharmacology, vol 231. 2015.

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The dis-LIST

Anxiety

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This article hits close to home. I have an anxiety disorder. I work hard at it, and I’ve been pretty successful coping. But there are still days when I just can’t control it. Sometimes I wake up, and without a conscious thought to it, my nervous system is on fire. My muscles feel permanently constricted. My mind races frantically from one point to the next. What I need most is to relax, but even thinking about trying to relax intensifies my anxiety. I’m not alone—40 million adults in the United States experience an anxiety disorder every year1—and about half of all people use medicinal cannabis to manage anxiety.1,2 Count me in.

It’s normal to worry about things big and small: about work, a presentation, paying the bills, where the world is heading. But when worries interfere with day-to-day functions, anxiety becomes a disorder. Past trauma, specific phobias, or just daily life can trigger panic—the quintessential anxiety disorder is post-traumatic stress disorder (PTSD)3—and what gets triggered is a neurological response centered in fear. For example, people with PTSD have a hyperactive amygdala, an evolutionarily ancient part of our brain that stores fear-related memories and responds to threats with fear, aggression, and defensive behavior.3 The effects aren’t just psychological, though. Anxiety can cause physical symptoms such as headaches, nausea, and gastrointestinal problems.

Treating anxiety disorders is generally a two-part process. The first part is medication, primarily with selective serotonin reuptake inhibitors (SSRIs) for long-term anxiety management and benzodiazepines such as Valium—which can be addictive—for acute attacks. As with any medication, there can be side effects: nausea, drowsiness, headaches, and sexual problems. The second part, cognitive behavioral therapy (CBT), is just as important. CBT is a type of professional counseling that helps people recognize thought patterns and change behaviors that lead to anxiety. Both medication and CBT are equally effective, and their effects combine for the best chance at long-term anxiety management.4

Millions of people are using cannabis as an alternative medication for anxiety disorders, and in several surveys, most people reported exceptional anxiety relief.2,5,6 But there’s also a bit of a paradox, because 10–20% of users consistently report anxiety as a negative side effect of cannabis.2,6

Honestly, at this point in time, we have more questions than answers. We know our ECS plays a role in anxiety. Patients with PTSD have more type I cannabinoid (CB1) receptors in their nervous systems and lower concentrations of natural endocannabinoids that activate those receptors. We also know that anxiety is a major negative side effect of pure THC, but pure CBD can reduce anxiety by decreasing neural activity in the amygdala, similar to benzodiazepines.2 However, when we look at how people respond to the whole cannabis plant, these trends don’t really hold.

We often focus on THC and CBD as the main components of cannabis, but they alone can’t explain the differences between cannabis cultivars. A cannabis plant has over 150 different terpenes; different combinations give each cultivar its unique smell and taste.2 It’ll take a long time before we understand how all these components work in concert—a synergistic action called the “entourage effect”—but meanwhile, scientists have asked the experts: cannabis users!

One thing is clear, not all cultivars of cannabis are equally effective for relieving anxiety. In one survey, 84% of users in Canada reported that medical cannabis helped relieve their anxiety. About 40–50% of people reported anxiety relief using C. indica and hybrid cultivars, compared to 7-10% reporting increased anxiety. The results for C. sativa cultivars were far more mixed; 30% reported increased anxiety, the same percentage of people reporting relief.5

Another study went even deeper and examined the total cannabinoid and terpene content in cannabis cultivars that were reported as best for anxiety (Bubba Kush, Skywalker OG Kush, Kosher Kush) and least effective (Chocolope, CBD Shark, Tangerine Dream). Interestingly, one slightly C. sativa-dominant hybrid (Blueberry Lambsbread) made the list as both most effective and least effective,1 meaning people had vastly different experiences with the same cultivar.

So, how can you find the cultivar of medical cannabis uniquely suited for your anxiety? Try focusing on cultivars that are pure C. indica or C. indica-dominant hybrids and have low CBD. Try a few cultivars at different doses and keep notes on which is most effective for you. 

But what about long-term anxiety management? Well, here’s where it gets a little tricky. If you find that medical cannabis helps with sudden anxiety attacks but doesn’t reduce how often the attacks occur, then there are concerns about dependency, even if cannabis itself isn’t considered addictive. After all, long-term management is the main reason why SSRIs are prescribed first, instead of benzodiazepines. But if you want to avoid pharmaceuticals altogether, you should consider integrating medical cannabis with professional therapy—CBT counseling in particular.

Unfortunately, easy access to medical cannabis appears to be leaving therapy out of the equation for some. In one study, 80% of Californians who used medical cannabis for anxiety or depression were not prescribed cannabis for that reason,1 so they wouldn’t have received professional recommendations for therapy. In another study, only 20% of Canadians using medical cannabis for anxiety disorders had ever received CBT counseling. Some of these people were also using considerable amounts of cannabis—23% used ≥3 grams cannabis per day.5 Another study hinted that stronger doses of cannabis may not provide better symptom relief but could cause more side effects, both positive and negative6—you can read more about that study in the Research Corner on page 14.

Overall, medical cannabis could prove extremely effective for relieving anxiety symptoms. Each person is unique though, so finding the cultivar and dosage that works for your anxiety will require some experimentation. But even with that, conventional medication or cannabis is only half the battle. If you face persistent anxiety attacks, talk to your doctor; professional CBT counseling may be the missing piece for long-term anxiety management.


References:

1. Kosiba, J., Maisto, S., and Ditre, J. “Patient-reported use of medical cannabis for pain, anxiety, and depression symptoms: Systematic review and meta-analysis.” Social Science & Medicine 233 (2019): 181-92. https://doi.org/https://doi.org/10.1016/j.socscimed.2019.06.005.
2. Kamal, B., Kamal, F., and Lantela, D. “Cannabis and the anxiety of fragmentation—a systems approach for finding an anxiolytic cannabis chemotype.” Frontiers in Neuroscience 12 (2018): 730. https://doi.org/10.3389/fnins.2018.00730.
3. Zoellner, L., Rothbaum, B., and Feeny, N. “PTSD not an anxiety disorder? DSM committee proposal turns back the hands of time.” Depression and Anxiety 28, no. 10 (2011): 853-6. https://doi.org/10.1002/da.20899.
4. Cuijpers, P., Sijbrandij, M., Koole, S., Andersson, G., Beekman, A., and Reynolds, C. “Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta-analysis.” World Psychiatry 13, no. 1 (2014): 56-67. https://doi.org/10.1002/wps.20089.
5. Turna, J., Simpson, W., Patterson, B., Lucas, P., and Van Ameringen, M. “Cannabis use behaviors and prevalence of anxiety and depressive symptoms in a cohort of Canadian medicinal cannabis users.” Journal of Psychiatric Research 111 (2019): 134-39. https://doi.org/https://doi.org/10.1016/j.jpsychires.2019.01.024.
6. Stith, S., Vigil, J., Brockelman, F., Keeling, K., and Hall, B. “The association between cannabis product characteristics and symptom relief.” Nature Scientific Reports 9, no. 1 (2019): 2712. https://doi.org/10.1038/s41598-019-39462-1.

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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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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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