Recent Medical Marijuana Research

Clinical Applications For Cannabis & Cannabinoids
A Review of the Recent Scientific Literature, 2000 — 2021

Table of Contents

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 BCE 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 decades-long, 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 the cannabis plant — as well as all of its organic chemical compounds (known as cannabinoids) — as a Schedule I substance under the Controlled Substances Act of 1970. This classification, which categorizes the plant alongside 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. Both alcohol and tobacco are unscheduled.

CHALLENGING CANNABIS’ SCHEDULE I STATUS

The ongoing classification of the cannabis plant as a Schedule I controlled substance is inconsistent with scientific opinionpublic attitudes, and the overwhelming majority of state laws. Furthermore, there now exists ample scientific and empirical evidence to rebut the federal government’s contention. Despite the nearly century-long prohibition of the plant, cannabis is nonetheless one of the most investigated therapeutically active substances in history. To date, there are over 36,000 peer-reviewed papers in the scientific literature referencing the cannabis plant and its cannabinoids, according to a keyword search on the search engine PubMed Central, the US government repository for peer-reviewed scientific research. In recent years, this volume of research has grown exponentially, with more than 20,000 papers published just in the past decade. Much of this more recent research has been dedicated to exploring and verifying cannabis’ therapeutic activities in various patient populations – including in FDA-approved gold-standard clinical trials. A summary of this clinical trial data 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.”

THE SHIFTING FOCUS OF CANNABIS RESEARCH

As clinical research into the therapeutic value of cannabinoids has proliferated so too has investigators’ understanding of cannabis’ remarkable capacity to combat disease. Whereas researchers in the 1970s, 80s, and 90s primarily assessed marijuana’s 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 modulate disease.

For example, 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 (aka Lou Gehrig’s disease).

Investigators are also studying the anti-cancer activities of cannabis, as a growing body of preclinical 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 many patients. To date, dozens of studies document patients’ use of cannabis as an alternative to various prescription drugs, specifically opioids.

Arguably, these recent discoveries represent far broader and more significant applications for cannabinoid therapeutics than many researchers could have imagined some 30 or even 20 years ago.

THE SAFETY PROFILE OF MEDICAL CANNABIS

Cannabinoids possess a remarkable safety record, particularly when compared to conventional prescription drugs. Most significantly, the consumption of marijuana — regardless of quantity or potency — cannot induce a fatal overdose. States a World Health Organization review paper, “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.”

The use of cannabis for therapeutic purposes is also rarely associated with significant adverse side effects. A prominent review of clinical trial data “did not find a higher incidence rate of serious adverse events associated with medical cannabinoid use” compared to nonusing controls over a four decade period. A more recent review of the relevant literature concludes that among the average adult user, the health risks associated with marijuana “are no more likely to be dangerous” than many other behaviors or activities, including the consumption of acetaminophen (the pain relieving ingredient in Tylenol).

That said, cannabis should not be viewed as a “harmless” substance. Its active constituents may produce a variety of physiological and mood-altering effects. As a result, there may be some populations that may be vulnerable 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 or who possess a clinical high risk for developing a psychotic disorder. Patients with a history of cardiovascular disorders, heart disease, or stroke may also be at an elevated risk of experiencing adverse side effects from marijuana, particularly smoked cannabis. 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 PUBLICATION

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 highlighting hundreds of relevant, recently published scientific research (2000-2021) on the therapeutic potential of cannabis and cannabinoids for a variety of indications. This summary of the available peer-reviewed research is among the most comprehensive reviews available in the modern literature and is the result of hundreds of hours of research and writing.

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). In all cases, science has sufficiently made the case that cannabis is safe and effective for certain patient populations. This fact should no longer be the subject of any serious debate.

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

Paul Armentano
Deputy Director
NORML | NORML Foundation
Washington, DC
July 9, 2021

* 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. Oaksterdam University alumna Vanessa Garcia deserves special recognition for her significant contributions to the 2021 edition of this publication. 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 and make financial contributions. For more information, please visit: norml.org/support. Tax-deductible donations in support of NORML’s public education campaigns should be made payable to the NORML Foundation.