Debate Over Medical Marijuana For MS And Other Diseases Heats Up

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The 2012 state ballot approvals of marijuana legalization in Colorado and Washington has been a catalyst for stirring the pot, so to speak, on a wide range of issues and nuances related to the herb — not least marijuana’s clinical use as a therapeutic agent. Medical marijuana remains a hotly-debated topic in the health sciences community, but in addition to the two states that have legalized both medical and recreational marijuana, in another 17 medical pot is legal, and the number is expected to increase to 35 or more in the near future.

Wired’s Matt Honan contends that marijuana is well on its way to general legalization, with a majority of Americans now living in states that have legalized or decriminalized cannabis in some form.

As a public health issue, there are many nuances to the use of marijuana, whether medicinally or recreationally, including its effectiveness — or not — in treating the astonishing range of disorders, including Multiple Sclerosis, for which it is claimed by advocates to be beneficial. However, scientific research, either pro or con, cannot be regarded as conclusive if for no other reason than the there is so relatively little of it for a variety of reasons, particularly bureaucratic and judicial roadblocks to legal acquisition of marijuana for research purposes, and ideological opposition of enforcement agencies and legislators — all of which inhibits approval and funding of marijuana research.

Commenting on what he now considers gratuitous legal and regulatory gatekeeping roadblocks pertaining to medical marijuana access, neurosurgeon and CNN Chief Medical Correspondent Dr. Sanjay Gupta recently issued a public apology for having come out opposing medical marijuana legalization five years ago. Dr. Gupta says he and the general public have been “terribly and systematically misled for nearly 70 years” on marijuana, that he hadn’t previously looked hard enough at the available science, and had been too blindly accepting without evidence that the U.S. Drug Enforcement Agency’s listing of marijuana as a schedule 1 controlled substance was based on sound scientific proof, when it turns out there is no such proof, or even any credible indication.

A report by journalist Paul Armentano originally published on AlterNet and recently re-published by Salon cited University of California at Los Angeles professor and former Washington state ”pot czar” Mark Kleiman telling Los Angeles Times columnist Patt Morrison that as a society, North Americans are largely ignorant when it comes to the subject of weed, contending that “we don’t know nearly as much about cannabis as Pillsbury knows about brownie mix.”

Armentano argues that despite the U.S. government’s nearly century-long prohibition of the plant, cannabis is nonetheless one of the most investigated therapeutically active substances in history, with over 20,000 published studies or reviews in the scientific literature referencing the cannabis plant and its cannabinoids, nearly half of which were published within the last five years according to a keyword search on PubMed Central, the US government repository for peer-reviewed scientific research. He observes that over 1,450 peer-reviewed papers were published in 2013 alone. (By contrast, a keyword search of “hydrocodone,” a commonly prescribed painkiller, yields just over 600 total references in the entire body of available scientific literature.)

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However, Dr. Gupta discovered in doing research for a CNN documentary that much of the science that has been done has been grossly skewed by lopsided emphasis, with only about six percent of current U.S. marijuana studies investigating medical benefits, with the other 94 percent designed to investigate harm, thereby painting “a highly distorted picture.” The imbalance is attributable to a disproportionately anti-marijuana establishment, with any scientific study on medical marijuana needing approval by the National Institute on Drug Abuse, which is strongly biased against cannabis.

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The Case For Marijuana Use In MS

Meanwhile, patients with MS and other serious ailments who have anecdotally determined that marijuana is the only affordable and effective medicine for neuropathic pain are left with a limited range of legal alternatives to Cannabis, which medical marijuana advocates contend are typically dangerous, genuinely addictive, ruinously expensive, and ineffective — or all four combined. Dr. Gupta notes that while someone dies every 19 minutes in the U.S from prescription drug overdose, he could could not find a single documented case of death from marijuana overdose.

Medical Marijuana.ca, an interest group committed to providing the best care and attention for patients by helping them leverage all the benefits of medical marijuana legally, notes that medical marijuana is not for everyone, and is often a last resort for people that have tried a variety of the pharmaceuticals below with little relief or too many side effects. They observe that strong anecdotal evidence exists supporting medical marijuana in treating MS symptoms, but scientific research has been hampered by government legislation.

They observe that drugs commonly prescribed for muscle spasticity and tremors associated with MS include Klonopin, Dantrium, Baclofen (Medtronic), Zanaflex, Klonopin (Clonazepam) and Valium (diazepam), which come with a list of side effects ranging from feeling lightheaded or drowsy, to slurred speech, blurred vision, changes in sexual drive and performance, gastrointestinal changes, muscle spasms and a fast or pounding heartbeat. Benzodiazepines (medicines with names typically ending in “pam”) are also highly addictive and can have nasty withdrawal effects. They also note that benefits of medical marijuana that many MS patients have reported include improvements in muscle spasms, tremors, balance, bladder control, speech, and eyesight, with MS Patients reporting that smoking medical marijuana reduces symptoms such as muscle stiffness and tremors, and allows for greater mobility.

Cannabinoids are bioactive components of the Cannabis plant that display a diverse range of therapeutic qualities. Two forms of cannabidiol (CBD), two forms of cannabigerol (CBG) and two forms of cannabigevarin (CBGV) represent the most common cannabinoids found in the cannabis plant apart from the main psychoactive cannabinlid tetrahydrocannabinol (THC).

Marijuana, MS and Beyond

Cannabinoids (CBs), either produced within the body or taken from an external source (eg: pharmaceutical or medicinal Marijuana), are believed to exert effects that medical marijuana advocates maintain may be of benefit to patients with not only MS, but Irritable Bowel Syndrome (IBS) and certain types of Inflammatory Bowel Disease (IBD), including Crohn’s Disease and Ulcerative Colitis. It is believed that medicinal marijuana affects Cannabinoid Receptors (CB) in the Gastrointestinal Tract and can exert effects that help relieve symptoms. Claimed effects include reduction of pain, inflammation, diarrhea, gastrointestinal hypermotility and secretion. Cannabis can reduce painful Gastrointestinal cramping as it is a smooth muscle relaxant, and can relax the Intestinal spasms. Medical marijuana advocate also believe that Cannabinoids can speed healing of injured Epithelial Tissues. Many of these benefits are attributed to Cannabinoid stimulation of Cannabinoid Receptors (CB) located in many parts of the body.

Read the new report that cautions against the use of marijuana in multiple sclerosis.

The operative premise behind claims for marijuana’s therapeutic efficacy is that the human body produces and utilizes its own cannabinoids, and that marijuana works for neurological pain because phytocannabinoids it contains fit nicely into human cannabinoid receptors, and can thusly be utilized by the human cannabinoid system, substituting for harmful, addictive, costly drugs with many unpleasant side-effects (including death), whole offering benefits they claim no other drug can match in terms of nausea-control and pain-relief.

Whether or not that is an accurate analysis of how medical marijuana allegedly works, many doctors are reluctant to prescribe medical marijuana either because they regard it as “unproven therapy” due to the paucity of research, or because they don’t want to become stigmatized as a “marijuana doctor.” Advocates counter that doubtless there are those would feign illness in order to obtain a medical marijuana prescription for recreational weed, but the same can be said for a vast array of legal, prescribable painkilling pharmaceuticals.

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Nevertheless, Alternet/Salon’s Mr. Armentano contends that thousands of cannabis studies reveal that marijuana and its cannabinoid active constituents are relatively safe and effective therapeutic and/or recreational compounds, and that unlike alcohol and most prescription or over-the-counter medications, cannabinoids are virtually nontoxic to health cells or organs, and they are incapable of causing the user to experience a fatal overdose because unlike opiates or ethanol, cannabinoids are not classified as central nervous depressants and thus cannot cause respiratory failure.

A major 2008 meta-analysis published in the Journal of the Canadian Medical Association (CMAJ June 17, 2008 vol. 178 no. 13 1669-1678) of safety studies on medical cannabinoids over the past 40 years, found marijuana-use associated with virtually no elevated incidences of serious adverse side-effects. The study, “Adverse effects of medical cannabinoids: a systematic review” (CMAJ. Jun 17, 2008; 178(13): 1669–1678. doi: 10.1503/cmaj.071178 PMCID: PMC2413308), co-authored by Tongtong Wang, MSc, Jean-Paul Collet, PhD MD, Stan Shapiro, PhD, and Mark A. Ware, MBBS MSc, who note that “The therapeutic use of cannabis and cannabis-based medicines raises safety concerns for patients, clinicians, policy-makers, insurers, researchers and regulators. Although the efficacy of cannabinoids is being increasingly demonstrated in randomized controlled trials, most safety information comes from studies of recreational use.”

The researchers performed a systematic review of safety studies of medical cannabinoids published over the past 40 years to create an evidence base for cannabis-related adverse events and to facilitate future cannabis research initiatives. They critically evaluated the quality of published studies with a view to identifying ways to improve future studies. A total of 321 articles were deemed eligible for evaluation.

They observe that cannabis is widely used as a recreational drug, with an estimated worldwide annual prevalence (defined as use at least once per year) of 160 million. Moreover, Cannabis preparations have been used medicinally for thousands of years, that the the active ingredients of cannabis termed “cannabinoids” have been identified and characterized, and that it is becoming clear that cannabinoids have considerable therapeutic potential.

The researchers determined that In addition to the use of prescription cannabinoids, medical use of smoked herbal cannabis is “substantial” with an estimated 10%–20% of patients with multiple sclerosis, chronic noncancer pain, HIV/AIDS and epilepsy reporting smoking cannabis for therapeutic purposes.

The coauthors summarize that the efficacy of cannabinoid medicines has been evaluated in various randomized controlled trials. In addition, use of cannabinoids as antiemetics has been systematically reviewed, and potential efficacy has been suggested, with there also having been considerable interest in the use of cannabinoids as adjunctive therapy for pain management, and several small randomized controlled trials have been published recently. Dronabinol and oromucosal A-9-tetrahydrocannabinol–cannabidiol have been proven effective for central neuropathic pain associated with multiple sclerosis. On the other hand, they note that a recent review supported further consideration of cannabinoids for chronic pain but was less encouraging for their use in acute pain conditions.

They conclude that short-term use of existing medical cannabinoids appeared to increase the risk of nonserious adverse events, but risks associated with long-term use were poorly characterized in published clinical trials and observational studies, and that high-quality trials of long-term exposure are required to further characterize safety issues related to the use of medical cannabinoids.

Other examples of research that has been done on medical marijuana, a 2012 study led by Professor of Clinical Neuroscience at the University of Plymouth Centre for Clinical Trials & Health Research John Zajicek found that a standardized dose containing the cannabis extract, tetrahydrocannabinol (or THC), improved muscle stiffness in people with MS.

Researchers in this phase 3 clinical trial tested a pill containing THC in 144 people with MS, against a placebo in 135 people with MS, for up to 12 weeks, and reported that relief from muscle stiffness was nearly twice as high in people taking THC than in people taking a placebo. Cannabis administration was also associated with improvements in body pain, spasms and sleep quality.

The most commonly reported negative side effects associated with the drug included nervous system disorders and gut problems – although none of these were considered severe. Ed Holloway, Head of Care & Services Research at the U.K. MS Society commented that “Muscle spasms and extreme stiffness can be a major problem for people with MS and more treatment options are urgently needed. It’s great to see such promising clinical trial results, and we hope this leads to an effective treatment for people with MS.”

The U. of Plymouth study’s findings were published in the UK Journal of Neurology, Neurosurgery and Psychiatry

On the other hand, a later study on 498 subjects published online in The Lancet Neurology 13 July 2013. also led by Dr. Zajicek and entitled “Effect of dronabinol on progression in progressive Multiple Sclerosis (CUPID): a randomized, placebo-controlled trial” noted that while laboratory evidence had shown that cannabinoids might have a neuroprotective action and slow the course of progressive multiple sclerosis, results showed that the cannabinoid oral dronabinol (A9-tetrahydrocannabinol) had no overall effect on the progression of Multiple Sclerosis in the progressive phase. The researchers note that their findings have implications for the design of future studies of progressive MS, because lower than expected progression rates might have affected their ability to detect clinical change. In the positive column, They noted no serious safety concerns although 114 [35%] of patients in the 329 member dronabinol group had at least one serious adverse event, compared with 46 [28%] among the 164 in the placebo group.

A study at the University of California, San Diego, School of Medicine published in May 2012 in the Canadian Medical Association Journal, found that smoking cannabis can relieve muscle tightness, spasticity (contractions) and pain often experienced by persons with Multiple Sclerosis. The UCSD research was a controlled trial with 30 participants to determine whether inhaled cannabis would help complicated cases for which existing pharmaceuticals are ineffective or trigger adverse side effects. A Canadian Medical Association journal article published in 2010 reported that a single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated.

So the debate continues. Brian Lee of The Telegraph reported last week that a study released in mid-April by researchers from Northwestern University in Chicago and Massachusetts General Hospital/Harvard Medical School in Boston, published in the Journal of Neuroscience found abnormalities in the brains of young adults who regularly smoked marijuana, suggesting that recreational marijuana use may lead to previously unidentified brain changes. The researchers cited a need for more research to understand the long-term effects of low to moderate marijuana use on the brain. However, Mr. Lee also cites Dr. Joseph W. McSherry, a neurologist and University of Vermont professor, referring to the study as more “jibberish from NIDA.”

And so it goes.

Sources:
Journal of the Canadian Medical Association
The Lancet Neurology
Medical Marijuana.ca
U.K. MS Society
CNN
Wired
Salon
The Telegraph