Recent Research on Medical Marijuana

Emerging Clinical Applications For Cannabis & Cannabinoids
A Review of the Recent Scientific Literature, 2000 — 2015

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Humans have cultivated and consumed the flowering tops of the female cannabis plant, colloquially known as marijuana, since virtually the beginning of recorded history. Cannabis-based textiles dating to 7,000 B.C.E have been recovered in northern China, and the plant’s use as a medicinal and mood altering agent date back nearly as far. In 2008, archeologists in Central Asia discovered over two-pounds of cannabis in the 2,700-year-old grave of an ancient shaman. After scientists conducted extensive testing on the material’s potency, they affirmed, “[T]he most probable conclusion … is that [ancient] culture[s] cultivated cannabis for pharmaceutical, psychoactive, and divinatory purposes.”

Modern cultures continue to indulge in the consumption of cannabis for these same purposes, despite a present-day, virtual worldwide ban on the plant’s cultivation and use. In the United States, federal prohibitions outlawing cannabis’ recreational, industrial, and therapeutic use were first imposed by Congress under the Marihuana Tax Act of 1937 and then later reaffirmed by federal lawmakers’ decision to classify marijuana — as well as all of the plant’s organic compounds (known as cannabinoids) — as a Schedule I substance under the Controlled Substances Act of 1970. This classification, which categorizes the plant by statute along side heroin, defines cannabis and its dozens of distinct cannabinoids as possessing ‘a high potential for abuse, … no currently accepted medical use, … [and] a lack of accepted safety for the use of the drug … under medical supervision.’ By contrast, cocaine and methamphetamine — which remain illicit for recreational use but may be consumed under a doctor’s supervision — are classified as Schedule II drugs; examples of Schedule III and IV substances include anabolic steroids and Valium respectively, while codeine-containing analgesics are defined by a law as Schedule V drugs, the federal government’s most lenient classification. Both alcohol and tobacco remain unscheduled.

In July 2011, the Obama Administration rebuffed an administrative inquiry seeking to reassess cannabis’ Schedule I status, and federal lawmakers continue to cite the drug’s dubious categorization as the primary rationale for the government’s ongoing criminalization of the plant and those who use it. A three-judge panel for the US Court of Appeals for the District of Columbia affirmed the Administration’s position in 2013, arguing that a judicial review of cannabis’ federally prohibited status was not warranted at the time.

Most recently, in April 2015, a federal judge in Sacramento upheld the constitutionality of cannabis’ Schedule I classification in a case argued by members of the NORML Legal Committee. The judge’s ruling opined that the federal law ought to remain in place as long as there remains any dispute among experts as to cannabis’ safety and efficacy.

Nevertheless, there exists little if any scientific basis to justify the federal government’s present prohibitive stance and there is ample scientific and empirical evidence to rebut it. Despite the US government’s nearly century-long prohibition of the plant, cannabis is nonetheless one of the most investigated therapeutically active substances in history. To date, there are approximately 22,000 published studies or reviews in the scientific literature referencing the cannabis plant and its cannabinoids, nearly half of which were published within the ten years according to a key word search on the search engine PubMed Central, the US government repository for peer-reviewed scientific research. While much of the renewed interest in cannabinoid therapeutics is a result of the discovery of the endocannabinoid regulatory system (which is described in detail later in this booklet), some of this increased attention is also due to the growing body of testimonials from medical cannabis patients and their physicians.

The scientific conclusions of the overwhelmingly majority of modern research directly conflicts with the federal government’s stance that cannabis is a highly dangerous substance worthy of absolute criminalization.

For example, in February 2010 investigators at the University of California Center for Medicinal Cannabis Research publicly announced the findings of a series of randomized, placebo-controlled clinical trials on the medical utility of inhaled cannabis. The studies, which utilized the so-called ‘gold standard’ FDA clinical trial design, concluded that marijuana ought to be a “first line treatment” for patients with neuropathy and other serious illnesses.

Several of studies conducted by the Center assessed smoked marijuana’s ability to alleviate neuropathic pain, a notoriously difficult to treat type of nerve pain associated with cancer, diabetes, HIV/AIDS, spinal cord injury and many other debilitating conditions. Each of the trials found that cannabis consistently reduced patients’ pain levels to a degree that was as good or better than currently available medications.

Another study conducted by the Center’s investigators assessed the use of marijuana as a treatment for patients suffering from multiple sclerosis. That study determined that “smoked cannabis was superior to placebo in reducing spasticity and pain in patients with MS, and provided some benefit beyond currently prescribed treatments.”

A summary of the Center’s clinical trials, published in 2012 in the Open Neurology Journal, concluded: “Evidence is accumulating that cannabinoids may be useful medicine for certain indications. … The classification of marijuana as a Schedule I drug as well as the continuing controversy as to whether or not cannabis is of medical value are obstacles to medical progress in this area. Based on evidence currently available the Schedule I classification is not tenable; it is not accurate that cannabis has no medical value, or that information on safety is lacking.”

Around the globe, similarly controlled trials are also taking place. A 2010 review by researchers in Germany reports that since 2005 there have been 37 controlled studies assessing the safety and efficacy of marijuana and its naturally occurring compounds in a total of 2,563 subjects. By contrast, many FDA-approved drugs go through far fewer trials involving far fewer subjects. In fact, according a 2014 review paper published in the Journal of the American Medical Association, the median number of pivotal trials performed prior to FDA drug approval is no more than two and over one-third of newly approved pharmaceuticals are brought to market on the basis of only a single pivotal trial.

As clinical research into the therapeutic value of cannabinoids has proliferated so too has investigators’ understanding of cannabis’ remarkable capability to combat disease. Whereas researchers in the 1970s, 80s, and 90s primarily assessed cannabis’ ability to temporarily alleviate various disease symptoms — such as the nausea associated with cancer chemotherapy — scientists today are exploring the potential role of cannabinoids to modify disease.

Of particular interest, scientists are investigating cannabinoids’ capacity to moderate autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease, as well as their role in the treatment of neurological disorders such as Alzheimer’s disease and amyotrophic lateral sclerosis (a.k.a. Lou Gehrig’s disease.) In 2009, the American Medical Association (AMA) resolved “that marijuana’s status as a federal Schedule I controlled substance be reviewed with the goal of facilitating the conduct of clinical research and development of cannabinoid-based medicines.”

Investigators are also studying the anti-cancer activities of cannabis, as a growing body of preclinical and clinical data concludes that cannabinoids can reduce the spread of specific cancer cells via apoptosis (programmed cell death) and by the inhibition of angiogenesis (the formation of new blood vessels).

Researchers are also exploring the use of cannabis as a harm reduction alternative for chronic pain patients. According to the findings of a 2015 study published by the National Bureau of Economic Research, a non-partisan think-tank, “[S]tates permitting medical marijuana dispensaries experience a relative decrease in both opioid addictions and opioid overdose deaths compared to states that do not.” The NBER findings are similar to those published in 2014 in the Journal of the American Medical Association (JAMA) Internal Medicine which also reported that the enactment of statewide medicinal marijuana laws is associated with significantly lower state-level opioid overdose mortality rates. “States with medical cannabis laws had a 24.8 percent lower mean annual opioid overdose mortality rate compared with states without medical cannabis laws,” researchers concluded. Specifically, they determined that overdose deaths from opioids decreased by an average of 20 percent one year after the law’s implementation, 25 percent by two years, and up to 33 percent by years five and six.

Arguably, these recent discoveries represent far broader and more significant applications for cannabinoid therapeutics than many researchers could have imagined some thirty or even twenty years ago.

THE SAFETY PROFILE OF MEDICAL CANNABIS

Cannabinoids possess a remarkable safety record, particularly when compared to other therapeutically active substances, particularly prescription drugs. Most significantly, the consumption of marijuana — regardless of quantity or potency — cannot induce a fatal overdose. According to a 1995 review prepared for the World Health Organization, “There are no recorded cases of overdose fatalities attributed to cannabis, and the estimated lethal dose for humans extrapolated from animal studies is so high that it cannot be achieved by … users.”

In 2008, investigators at McGill University Health Centre and McGill University in Montreal and the University of British Columbia in Vancouver reviewed 23 clinical investigations of medical cannabinoid drugs (typically oral THC or liquid cannabis extracts) and eight observational studies conducted between 1966 and 2007. Investigators “did not find a higher incidence rate of serious adverse events associated with medical cannabinoid use” compared to non-using controls over these four decades.

That said, cannabis should not necessarily be viewed as a ‘harmless’ substance. Its active constituents may produce a variety of physiological and euphoric effects. As a result, there may be some populations that are susceptible to increased risks from the use of cannabis, such as adolescents, pregnant or nursing mothers, and patients who have a family history of psychiatric illness. Patients with a history of heart disease or stroke may also be at a greater risk of experiencing adverse side effects from marijuana. As with any medication, patients should consult thoroughly with their physician before deciding whether the medical use of cannabis is safe and appropriate.

HOW TO USE THIS REPORT

As states continue to approve legislation enabling the physician-supervised use of medical marijuana, more patients with varying disease types are exploring the use of therapeutic cannabis. Many of these patients and their physicians are now discussing this issue for the first time and are seeking guidance on whether the therapeutic use of cannabis may or may not be advisable. This report seeks to provide this guidance by summarizing the most recently published scientific research (2000-2015) on the therapeutic use of cannabis and cannabinoids for a variety of clinical indications.

In some of these cases, modern science is now affirming longtime anecdotal reports of medical cannabis users (e.g., the use of cannabis to alleviate GI disorders). In other cases, this research is highlighting entirely new potential clinical utilities for cannabinoids (e.g., the use of cannabinoids to modify the progression of diabetes.)

The conditions profiled in this report were chosen because patients frequently inquire about the therapeutic use of cannabis to treat these disorders. In addition, many of the indications included in this report may be moderated by cannabis therapy. In several cases, preclinical data and clinical data indicate that cannabinoids may halt the advancement of these diseases in a more efficacious manner than available pharmaceuticals.

For patients and their physicians, this report can serve as a primer for those who are considering using or recommending medical cannabis. For others, this report can serve as an introduction to the broad range of emerging clinical applications for cannabis and its various compounds.

Paul Armentano
Deputy Director
NORML | NORML Foundation
Washington, DC
August 28, 2015

* The author would like to acknowledge Drs. Dale Gieringer, Estelle Goldstein, Dustin Sulak, Gregory Carter, Steven Karch, and Mitch Earleywine, as well as Bernard Ellis, MPH, former NORML interns John Lucy, Christopher Rasmussen, and Rita Bowles, for providing research assistance for this report. The NORML Foundation would also like to acknowledge Dale Gieringer, Paul Kuhn, and Richard Wolfe for their financial contributions toward the publication of this report.

** Important and timely publications such as this are only made possible when concerned citizens become involved with NORML. For more information on joining NORML or making a donation, please visit: http://www.norml.org/support. Tax-deductible donations in support of NORML’s public education campaigns should be made payable to the NORML Foundation.

A Second Look at Ohio: Why It’s Worth Supporting | NORML Blog, Marijuana Law Reform

by Keith Stroup, NORML Legal Counsel
October 19, 2015

With the 2015 election day only two weeks away, and prodded by our friend Russ Belville at 420 Radio for failing to more enthusiastically embrace Issue 3 in Ohio, this seemed like a good time to take a second look at the measure on the ballot in Ohio to both legalize marijuana for medical purposes and fully legalize marijuana for all adults.

First, one might justifiably ask the authors of this measure why they would bother with medical marijuana at all. If marijuana is legal for all adults, that includes patients as well as recreational users, and it removes the need for patients to pay a physician to confirm their need for marijuana. With the exception of a small medical use program that would cover those minors who have a legitimate medical need, there is no need for two separate legalization distribution systems.

But having somewhat duplicative legalization systems, while it may not be efficient, is not a reason to oppose Initiative 3.

Provisions Limiting Access to the New Market Are Not New

The reason given by most who claim to support legalization, but who oppose the Ohio proposal, is the reality that the investors who have put up millions of dollars to qualify the initiative for the November ballot also stand to profit handsomely from their investment, by controlling the 10 commercial cultivation centers allowed under this plan. It strikes many of us as inappropriate to build such an economic advantage by a few rich investors into the state’s constitution.

But as Belville and others (including this author) have noted, several other states that have legalized marijuana (for medical use) have limited entry into the legal industry by placing severe limits on the numbers of licenses that will be permitted, or by requiring such enormous financial investments that ordinary citizens are effectively shut out of the industry. So limiting access to the commercial cultivation centers in the newly legal market would be nothing new, nor should it justify opposing this opportunity to end marijuana prohibition in Ohio. We should focus on ending prohibition, and not get distracted by who will profit from the legal market.

Why NORML Supported I-502

In his latest rant, Belville questions why NORML and other pro-legalization organizations would endorse I-502 in Washington state in 2012, which failed to legalize personal cultivation, and included a 5 nanogram per se DUID provision that would leave many smokers unfairly subject to a DUID charge, but would either remain neutral on Issue 3 in Ohio (MPP, ASA and DPA) or tepidly endorse the proposal (NORML).

The answer to this question is simple: In 2012 marijuana for personal use was illegal in all 50 states, and had been for more than 75 years. It was crucial that some state – any state – show the courage to break the mold and openly defy federal law, as New York and a handful of other states did near the end of alcohol prohibition. For the legalization movement to gain credibility and force our way onto the mainstream political agenda, we had to take legalization out of the theoretical realm and demonstrate that it actually works.

Our opponents had always claimed that if we legalize marijuana, the sky would fall. Everyone would sit home and get stoned all day; no one would go to work or live an ordinary life; and western civilization as we know it would come to an end (perhaps that’s a slight exaggeration, but you get the point).

Of course, we would counter that legalization would stop the senseless arrest and prosecution of otherwise law-abiding citizens who smoke marijuana responsibly, and save enormous amounts of law enforcement resources that could be redirected to fighting serious and violent crime.

But until we had at least one state with the fortitude to declare itself out of the prohibition game, we had no actual data to validate either position. It was an endless theoretical argument, with no clear winner.

The approval of legalization in Washington and Colorado in 2012, by giving us these two state laboratories where we could measure the actual impact of legalization, was the game changer that catapulted full legalization into the mainstream political debate, and gave us the measurable evidence that legalization is indeed the solution that most Americans are looking for. And the fears that were stoked by our opponents – of a spike in adolescent marijuana smoking, or carnage on the roads caused by stoned drivers – simply did not materialize. In fact, just the opposite. Adolescent use is slightly down in the legalization states, and there has been no increase in DUID cases.

We gave our strong support to I-502 in Washington (as well as A-64 in Colorado) even with its limitations, because of the crucial need to demonstrate that a majority of the voters in a state would support full legalization, and that legalization actually works on the ground, with few, if any, unintended consequences. Those first two victories made it possible for our subsequent victories in Alaska and Oregon in 2014, and hopefully many more to follow.

ballot_box_leaf

There. Now I have said it, clearly and unequivocally. Issue 3 in Ohio should be endorsed by all who favor legalization, even with its imperfections. As the NORML board of directors concluded when we endorsed the Ohio proposal, unless the current proposal in Ohio is approved, it will likely be five years or more (perhaps far longer) before marijuana will be legalized in Ohio. Under their current laws, roughly 12,000 Ohioans are arrested on marijuana charges each year. Does anyone really believe we should sit by waiting for a more acceptable version of legalization to magically appear, while another 60,000 to 100,000 smokers are arrested in Ohio?

In addition, just as the victories in Washington and Colorado were especially significant because they were the first, and opened the door for serious consideration in additional states, it would be an enormous step forward politically to adopt full legalization in Ohio — a large, conservative midwestern state. And it would suddenly put full legalization on the table for serious consideration by many other similarly situated states.

Its time to legalize in Ohio.

A Second Look at Ohio: Why It’s Worth Supporting | NORML Blog, Marijuana Law Reform.

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National NORML is starting a membership drive today to help with their efforts to bring cannabis reform to the nation!

If you are not already a member of Pittsburgh NORML please consider joining NORML’s team with a donation or a membership. Your donation will help NORML’s efforts across the country.

NORML possesses is our members. They are our lifeblood and the driving force behind the multitude of statewide and local reform efforts taking place around the country. That’s why NORML is pushing to build our ranks in advance of the 2016 election by launching the weeklong NORML Nation Membership Drive. As many of you know, presidential elections tend to attract a larger pool of younger and more politically progressive voters. We hope to tap into this expected voting block to achieve unprecedented successes in 2016.

2016 will be a watershed year for ending marijuana prohibition at the local, state and federal level. NORML and NORML chapters are engaging in multistate strategy to assist with marijuana-related ballot initiatives and legislative reform efforts, and we and the NORML PAC are pushing for federal reform by lobbying members of Congress in support of The CARERS Act, The Marijuana Businesses Access to Banking Act, and The Regulate Marijuana Like Alcohol Act, as well as additional budgetary amendments and regulatory reforms.

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If you’re already NORML Chapter Leader or Member, you can earn money for your local NORML Chapter through the NORML Nation Chapter Contest! The top three chapters with the most referrals to the NORML Nation will earn $1,000, $500, and $250! I’ll be sending around an email to Chapter Leaders with more information about the NORML Nation Chapter Contest.

Thank you in advance for helping us make this a successful membership drive. You can help us reach our goal by encouraging others to become members of NORML and to donate to our work. You can also join the NORML Nation Membership Drive Facebook event, and invite your friends!

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