By Mark Moyad, MD // University of Michigan

Come on Moyad Man, what is the truth here? Part I (which means there will be a sequel or part II-yeah where we will reveal that Darth Vader is Luke Skywalker’s father or something like that!!!)

Over the past several years, as I traveled, I always knew that at least one person in the audience would ask THE QUESTION. And, if I gave a lecture in Colorado I would get THE QUESTION many, many times! THE QUESTION was not whether or not I want to get married (I am happily married and no one would ever ask me that except in a dream I had in high school, where all 3 detectives from the Charlie’s Angels TV show asked me to get married on the same day). THE Question is whether or not “Marijuana is beneficial or is a treatment for _________________” and in the blank fill in every possible disease that has impacted humankind since the beginning of time! So, excuse me for using the words “dude” or “man” a lot in this column but, since we are talking about marijuana, I thought it was appropriate since Ann Arbor, Michigan (where I grew up and still live) was the site of the first annual “hash bash” (still held once a year), which is supposed to bring attention to improving legalization of marijuana. In reality I think it was a conspiracy by one of the major pizza companies to increase sales that day. I mean, Domino’s first store in the world was only a short distance from the hash bash gathering. Coincidence? I think not. But a non-proven Moyad conspiracy? I think so.

Bottom Line

One of the best reviews and meta-analysis of marijuana (aka “cannabinoids”-some of its active ingredients) for medicinal use concluding with the following after examining 79 clinical trials (with over 6450 participants) [1]:

“There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term adverse events (AE’s, aka side effects)”

The AE’s that were more common in these clinical trials were the following: Dizziness, dry mouth, nausea, fatigue, sleepiness, sedation, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. OUCH!!! It sounds like a pharmaceutical TV commercial where the person comes on and lists all the potential side effects really fast like they are studying for a career in auctioneering.

Next, an expert from HAAAARVARD (I love to say that) looked at 28 randomized trials and stated the following [2]: “Use of marijuana for chronic pain, neuropathic pain, and spasticity due to multiple sclerosis is supported-by high-quality-evidence.” YEAH!!

However, this author expressed some of the side effects or concerns with marijuana use such as: …”addiction and worsening of psychiatric illnesses such as some anxiety disorders, mood disorders, psychotic disorders, and substance use disorders…” OUCH!

Also [2]: “Regular marijuana use results in physical problems as well. It is associated with increased incidence of symptoms of chronic bronchitis and increased rates of respiratory tract infections and pneumonia. Preliminary research points to an association between marijuana use and myocardial infarction, stroke, and peripheral vascular disease.” OUCH! OUCH!

Then, in one of the most recent respiratory reviews of marijuana, the following concerns were expressed after looking at 48 articles [3]: “The research indicates that there is a risk of lung cancer from inhalational marijuana as well as an association between inhalational marijuana and spontaneous pneumothorax, bullous emphysema, or COPD. A variety of symptoms have been reported by inhalational marijuana smokers, including wheezing, shortness of breath, altered pulmonary function tests, cough, phlegm production, bronchodilation, and other symptoms.” OUCH x 3!

Look, I am excited about marijuana and some of its medically active ingredients (aka “cannabinoids”) to help patients with a variety of conditions, including cancer pain, to reduce nausea and vomiting, to perhaps improve appetite, and for kids and adults with seizures that do not respond to other options. It is interesting. HOWEVER, it is also overhyped in some areas of medicine (“fights cancer”?). And can it come with numerous concerning side effects and high costs for some patients? OH YEAH BABY! Medical marijuana has now become a massive area of profit for many state governments and owners of those groovy medical marijuana facilities, so always seeking the real truth, apart from the hype and cash flow, will be critical! So, please read on ladies and germs!

Please Tell Me More Dude Man!

Let’s just review a few facts about marijuana [1-3] simply because people no longer have the attention spans to read long paragraphs without being distracted, and I am too lazy to write long paragraphs.

-Marijuana has many; names: “Pot” , “weed," “grass," “ganja," “joint," “reefer," “dope," “Scholz” (okay, I made that last one up)”…

-Before the Marijuana Tax Act of 1937, cannabis was actually used medicinally, and in 1970, it was officially classified as a Schedule 1 drug because of its potential for abuse, lack of safety, and other reasons. Other schedule 1 drugs include ecstasy, heroin, and LSD.

-Over half of the states in the U.S. currently have laws legalizing marijuana in some form! Wow! Wow spelled backwards! Marijuana itself is not FDA approved to treat any medical condition (Ahhhhh, the irony).

-Marijuana=Cannabis=from the Cannabis sativa plant. And, over 60+ cannabinoids and 400 compounds have been found in marijuana. Cannabinoids are some of the active ingredients in marijuana that could treat some diseases.

-The most well-known cannabinoid is THC (tetrahydrocannabinol), which is the primary ingredient thought to cause the “high” or “buzz” (this is what I am told-I have no experience with it, except in college when someone FORCED me to smoke and inhale it, or else they would not let me leave the fraternity house.

-Interestingly, two cannabinoid (THC-like) drugs known as “dronabinol” (THC in sesame seed oil) and “nabilone” (another THC copycat) have been available in the U.S. for some time as FDA-approved oral prescription drugs! These drugs were approved for nausea and vomiting caused by cancer chemotherapy and also for appetite stimulation in medical situations that could cause unhealthy, excessive weight loss (“wasting” or “cachexia”). Some “experts” think these drugs should be tried first before moving on to the other options mentioned in this article.

-Another cannabinoid that is getting a lot of interest is Cannabidiol (CBD), WHICH DOES NOT CAUSE INTOXICATION or the HIGH of THC. And, this CBD is being tested now in countless medical situations, including as a topical oil to rub on the skin of an area impacted by cancer pain or because of other types of pain (arthritis, etc). In fact, I have known many patients in the past 5 years that tell me they get good relief from their pain when using this topical CBD oil and apply it directly on the site of their pain. I have parents tell me that CBD, when ingested, might impact the number of seizures their child is experiencing. Of course, this is not definitive proof, but it is interesting based on what we know from some studies. The future of research for cancer and the treatment of side effects will be the impact of CBD in many clinical trials.

Medical form which can be purchased from some state-approved medical marijuana locations | COMMENTS FROM Mark “The Dude” Moyad

Hashish | Concentrated resin cake which is ingested or smoked

Hashish Oil | Cannabis oil plant extraction which is usually smoked or inhaled

Infusion | Plant material mixed with a medium that is not volatile such as a cooking oil or butter and ingested.

Marijuana | Dried plant consists of flowers, leaves, and stems and usually smoked or vaporized.

Tincture | Liquid extract of cannabinoids and is consumed sublingually (under tongue)

*Note: CBD oil and marijuana extracts can be placed in food, brewed as tea, smoked, swallowed in other forms, are in clinical trials as a straight ingestible liquid, spray etc. If you are willing to look around or travel you can find it in all these forms and many others (Gummi marijuana? Yup!).

Hey Moyad Dude Man-Tell Me Even More!

Cannabis comes in all shapes, sizes, and delivery systems or ways to get some of the active ingredients. The table below are some of the most common [1-3].

Let’s just face the facts as they exist right now: Human evidence currently suggests that marijuana could be a treatment for chronic pain, nerve (aka “neuropathic”) pain, and muscle spasms due to multiple sclerosis or from other neurologic issues. There is also some evidence that it could help with seizures, posttraumatic stress disorder, and very questionable or limited evidence on glaucoma. In fact, in 2014 the American Academy of Ophthalmology once again stated that marijuana is NOT a proven treatment for glaucoma [4,5].

So, where can I look to learn even more about oral (or topical) CBD for example? In my opinion, you need to look at some of the clinical trials that have just been completed in other areas of medicine to get some idea of what might happen to you when you ingest CBD. For example, it is interesting that recently published data from the first large-scale prospective study using CBD in patients with treatment-resistant epilepsy was promising [6]. A total of 162 children and young adults aged 1 to 30 years were given a 99% purified oil-based form of an oral (although some received it through a gastric tube) cannabidiol (“Epidiolex” from GW Pharmaceuticals, London, UK) as an additional treatment to their current anti-seizure drugs. Mild to moderate side effects were common and included sleepiness in 25%, reduced appetite in 19%, diarrhea in 19%, fatigue in 13%, convulsion in 11% but only 3% stopped treatment because of a side effect. The study was 12 weeks but it shows a fairly good short-term safety record for a drug. It also shows that there are notable side effects just like a drug. In terms of effectiveness, there was a median reduction in monthly motor seizures of 36.5%, which is similar to the impact of some commonly used antiepileptic drugs in this population. What is also interesting is that in these kinds of studies (and others) the potential for a major placebo effect is strong. For example, data from Colorado shows that patients of families who moved to this state to help treat their loved ones were two times as likely to have a larger than 50% seizure reduction (47% responder rate) compared with the patients who already had been living in Colorado (22% response) [7]. Regardless, this CBD (Epidiolex) study showed enough success to remain optimistic.

One concern in future studies is the potential for drug interactions, because cannabidiol can block liver enzymes of metabolism and could increase the concentration of some drugs to dangerous levels [8]. All of the drugs it clinically impacts are not known as of yet, so, if using it for cancer side effects, just keep this in mind and check with the doctor or medical team you trust for the latest information on this and other issues. Still, do not use CBD or marijuana until you have read the dramatic final part of this column!

THE MOYAD OVERALL HIP & GROOVY SUMMARY-BUCKLE UP FOR 12 GNARLY THINGS!

So, let’s review what I have learned thus far about marijuana or some of its derivatives from my 25+ years of experience and reviewing much of the literature:

1. Personally, if you are healthy I think the risks of marijuana outweigh the benefits unless, of course, you win the lottery and just want to try it one time to celebrate the fact that you no longer have to ever listen to your boss or some of your annoying coworkers ever again . Marijuana is NOT proven to be heart healthy and in fact could be heart unhealthy, and the smoke does not make the lung tissue happy even though you could feel temporarily happy. Both cigarette smoke and marijuana can contain cancer-causing compounds such as “nitrosamines,” “phenol,” “polycyclic aromatic hydrocarbons,” “vinyl chlorides,” blah blah blah. Thus, both types of smoke can contain particulate matter and carcinogens.

2. The two 1985 FDA approved THC-like drugs (dronabinol aka Marinol, and nabilone aka Cesamet-both mostly THC copycats) should be discussed more often as an option for nausea and vomiting prevention in cancer chemotherapy treatment, and to help encourage weight gain and appetite stimulation in cancer patients. Interestingly, there is even some evidence of dronabinol improving “dysgeusia” the taste of food and appetite in one small study (see the final reference-number 12). Interestingly, zinc supplements (50 mg 3 times a day) are arguably first line evidence for dysgeusia (see reference 12) and have their own potential for side effects (that is a different Moyad article dudes and dudettes). Taste changes are not uncommon with chemotherapy and other drugs.

3. A variety of forms of medical marijuana should also be considered for nausea and vomiting and to stimulate appetite and weight gain in some cancer patients.

4. A variety of forms of medical marijuana (from topical, edible, and inhalable) should also be considered for different types of cancer pain because they may have less toxicity than using narcotics and could be just as effective in some cases. There are also some types of pain that simply do not respond to major medications, and in these cases medical marijuana should be discussed or investigated.

5. A variety of forms of medical marijuana make a lot of people (including state governments) a lot of moola-it has become a major cash cow (get it…”moola”). Graze on that joke for a second. I know I milked that joke for all its worth)! So, the sheer profitability of marijuana now causes many people to highlight all the potential benefits and fail to mention the reality or evidence. This is also known as a conflict of interest!

6. Marijuana is “natural” so should I get excited about it? Just because it is natural is not the reason I get excited about diddly squat (aka anything)...I mean, poison ivy and arsenic are natural folks but I usually do not recommend those things, except to my big brother when he pushed my face in the snow when we were kids. I get excited when patients have more and more effective options and the benefit outweighs the risk, and this is why I am currently excited (and because Oreo cookies have a new limited-time-only strawberry and chocolate flavor out and it is also exciting. And this could be useful to know if you try any of the things discussed and get hungry...).

6. Do I think marijuana or one of its compounds can fight cancer or encourage the growth of cancer? Yes! Since we have no idea at the moment and some laboratory studies suggest both possibilities, we have to be honest. We have no idea except it could reduce some symptoms/side effects of cancer and the treatment of cancer. It is really irresponsible to use a laboratory study as definitive proof that marijuana fights cancer? For example, there was a drug that impacts one cannabinoid receptor in the brain that so many “experts” were convinced would be a great weight loss drug. It was marketed in Europe briefly (known as Acomplia-google that bad boy) but was removed from the market because of serious side effects such as anxiety, suicidal ideation, nausea, and some new cases of multiple sclerosis that may have been drug related [9]. The gluteus maximus/bottom line is for every cannabidiol study that suggests it fights cancer in the laboratory there are other studies that suggest the opposite, or simply the potential for toxicity of normal cells [10,11]. Interestingly, the expression of cannabinoid receptors on a tumor could actually be there for improved survival and could be a correlation of tumor grade. For example, THC has been shown to promote tumor growth in some immunocompetent animals. So, when or if receiving immune stimulating drugs this could be an issue [12]. Look, if you are a mouse or a rat we can cure you of almost anything today, but until we get more human studies we have no idea if it fights, accelerates, or does nothing to the growth of cancer.

7. Hemp milk does not contain THC but in some cases is fortified with 450-500 mg of calcium per cup, so you could drink one cup a day instead of taking a calcium supplement. Hemp seeds are also a groovy source of protein.

8. I believe President Clinton did inhale the marijuana he tried. And, I believe other presidents also smoked and fully inhaled marijuana at least once. I have no proof but anyone going into politics today has got to be somewhat “high” to get involved in this reality TV show cage match!

9. Stress, anxiety, depression, pain, nausea and vomiting, and appetite stimulation are some of the areas where affected cancer patients in a desperate situation could theoretically (what a politically correct word for “just go ahead and look into it”) determine if it is an option. Always remember that there are also many other good options in these situations that should ALSO ALWAYS get some attention. For example, megesterol is a drug used in prostate cancer to reduce hot flashes, and it also can stimulate appetite at a different dosage if needed. In other words, researching all of the side effect treatment options, and not just the impact of marijuana, is critical.

10. I find it embarrassing and ridiculous that in some cases of advanced cancer or other situations where a person needs to feel comfortable, they are not offered the option of marijuana, CBD or another alternative option to at least try, and instead have to “live with it” or get hooked on narcotics (and some of the ugly nasty side effects that come with these approved drugs). Objectively speaking, a discussion of the positives and negatives of marijuana to prevent or treat some side effects should be given to cancer patients just like any other conventional or alternative option.

11. There is a potential bright future for some types of marijuana delivery drugs for patients dealing with cancer and other issues. For example, nerve pain or nerve issues from chemotherapy are an ugly side effect and “Nabiximols” (trade name=”Sativex” from GW pharmaceuticals, which also has the drug “Epidiolex," which is a CBD product for epilepsy mentioned earlier) is an oromucosal spray containing cannabinoids (THC and CBD in a 1:1 ratio=wow dual threat!) that has shown some promise for pain in small clinical trials [13,14]. Epidiolex has a good chance of FDA approval for certain seizures and, since it does not make you “high,” it and other CBD products will continue to get research for cancer side effects and other medical conditions [15].

12. Oh, and by the way, Darth Vader was Luke’s father and when in doubt in any murder mystery you should be suspicious of the butler. And I do believe that BigFoot is alive and well in the Upper Peninsula of Michigan and goes bowling with Elvis and Jimmy Hoffa every Friday night. Later Dudes & Dudettes!

 


Moyad Dude Man Gnarly & Awesome Medical References

  1. Whitling PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 2015;313:2456-2473.
  2. Hill KP. Medical marijuana for treatment of chronic pain and other medical and psychiatric problems: a clinical review. JAMA 2015;313:2474-2483.
  3. Martinasek MP, McGrogan JB, Maysonet A. A systematic review of the respiratory effects of inhalational marijuana. Respir Care 2016;61:1543-1551.
  4. Anonymous. American Academy of Ophthalmology reiterates position that marijuana is not proven treatment for glaucoma. 2015. http://www.aao.org/newsroom/news-releases/detail/american-academy-of-ophthalmology-reiterates-posit Accessed 27 January 2017.
  5. Novack GD. Cannabinoids for treatment of glaucoma. Curr Opin Ophthalmol 2016;27:146-150.
  6. Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional study. Lancet Neurol 2015
  7. Press CA, Knupp KG, Chapman KE. Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy. Epilepsy Behav 2015;45:49-52.
  8. Detyniecki K, Hirsch LJ. Cannabidiol for epilepsy: trying to see through the haze. 2016;15:235-237.
  9. Russo EB. Cannabidiol claims and misconceptions. Trends Pharmacol Sci 2017, epub ahead of print.
  10. Bagavandoss P, Crawford B, Kramer C. Inhibition of cervical cancer cell proliferation by cannabidiol. Planta Med 2016;81(S01): S1-S381.
  11. Deng L, Ng L, Ozawa T, Stella N. Quantitative analyses of synergistic responses between cannabidiol and DNA-damaging agents on the proliferation and viability of glioblastoma and neural progenitor cells in culture. J Pharmacol Exp Ther 2017;360:215-224.
  12. Davis MP. Cannabinoids for symptom management and cancer therapy: the evidence. J Natl Compr Canc Netw 2016;14:915-922.
  13. Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-blind, placebo-controlled, pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage 2014;47:166-173.
  14. Johnson JR, Lossingol D, Burnell-Nugent M, Fallon MT. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. J Pain Symptom Manage 2013;46:207-218.
  15. McCall C. Momentum grows for medical use of cannabis. Lancet 2015;386:1615-1616.

Mark A. Moyad, MD, MPH, currently occupies an endowed position created and funded entirely by the patients he has helped over the past 20+ years.  He is the Jenkins/Pokempner Director of Complementary and Alternative Medicine at the University of Michigan Medical Center-Department of Urology.  Mark received his medical education from the University of South Florida College of Public Health and the Wayne State University School of Medicine.





 

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