Science & tech

The most impactful cannabis studies of all time

Published on November 5, 2018 · Last updated July 28, 2020

The following compendium of landmark cannabis studies is exclusively focused on top-level research that either fundamentally advanced our understanding of the plant’s therapeutic properties, or thoroughly debunked some pernicious piece of official misinformation—such as “smoking weed gives you lung cancer.”

But that’s only half the story when it comes to the intersection of science and cannabis. So before we get to the good stuff, let’s start with an unfortunately typical example of the kind of spurious evidence that has been consistently used over the last hundred years to support the government’s all-out war on cannabis.

Find Legal Cannabis NearbyOur story begins in 1974, when Dr. Robert Galbraith Heath published research conducted at Tulane University, where he chaired the Department of Psychiatry and Neurology. Today, the late Dr. Heath is a controversial figure in the world of neuroscience, largely due to his pioneering efforts to study deep brain stimulation (a.k.a. electro-shock) as a “conversion therapy” for homosexuals, and his willing participation in illegal, CIA-led human experiments of a “brainwashing” drug called bulbocapnine. But at the time, his credentials remained impeccable.

And so, when Heath produced findings supposedly showing that “the active ingredient in marijuana [THC] impairs the brain’s circuitry,” the press dutifully ran headlines claiming “Pot Causes Brain Damage” without a trace of skepticism. While anti-cannabis politicians like then California Governor Ronald Reagan immediately seized on the study as evidence that cannabis was far too dangerous to even consider legalizing.

Like many federally funded studies of the era, Heath’s research was deeply flawed. InSmoke Signals: A Social History of Marijuana, author Martin Lee calls out his exceedingly small study of rhesus monkeys as “a textbook case of scientific fraud.”

“Shackled in air tight gas masks, Heath’s monkeys were [regularly] forced to inhale the equivalent of 63 high-potency marijuana cigarettes in five minutes. Lo and behold, the primates suffered brain damage from suffocation and carbon monoxide poisoning, but Heath attributed the results to marijuana toxicity”

Heath’s findings were never replicated, and several prominent follow up studies—including one at the National Center for Toxicology Research—directly repudiated his conclusions.

Then in 2003, the US Department of Health and Human Services was granted a patent on “cannabinoids as neuroprotectants,” based on evidence that compounds found in the cannabis plant not only don’t cause brain damage, they’re actually effective in “limiting neurological damage following…stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and HIV dementia.”

To this day, cannabis remains a Schedule 1 narcotic—a categorization that flies in the face of not just the latest cutting-edge research into the plant’s incredible medicinal potential, but also some of the oldest medical texts in existence. For example, The Divine Farmer’s Herb Root Classic (2727 BC)—widely considered the world’s oldest pharmacopeia—lists cannabis among the “supreme elixirs of immortality,” and recommends it as a superior treatment for “constipation, ‘female weakness,’ gout, malaria, and rheumatism.”

And as our list of landmark cannabis studies makes clear, that’s just for starters.

Indian Hemp Drugs Commission (1894)

In 1893, India was under British rule, and the colonial government became concerned about the amount of cannabis (i.e., “hemp drugs”) being consumed by the locals. So teams of British and Indian medical professionals were dispatched throughout the country to collect information on not just the health effects of cannabis, but also the social and moral impact.  

The result was a massive research paper (over 3,000 pages), with recorded testimony from almost 1,200 “doctors, coolies, yogis, fakirs, heads of lunatic asylums, bhang peasants, tax gatherers, smugglers, army officers, hemp dealers, ganja palace operators, and the clergy.”  Nearly all of the data in the seven volume report bolstered two key conclusions: moderate cannabis consumption is either relatively harmless or beneficial, and cannabis prohibition would be supremely unjust.

“To forbid or even seriously to restrict the use of so gracious an herb as hemp would cause widespread suffering and annoyance,” the report concluded. For the next 50 years, this research would stand as the most thorough and scientifically rigorous available.

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The Laguardia Report (1944)

Most impactful marijuana research studies of all time: Reefer madness

(Gillian Levine for Leafly)

In direct response to the Reefer Madness-era misinformation campaigns of Harry J. Anslinger (head of the Federal Bureau of Narcotics), New York City mayor Fiorello La Guardia commissioned a blue ribbon panel of leading doctors, psychiatrists, psychologists, pharmacologists, chemists and sociologists, and tasked them with making a thorough investigation of cannabis based on a comprehensive review of all available scientific literature, plus primary research.

Released as The La Guardia Report, the landmark study earned the endorsement of the prestigious New York Academy of Medicine, while unambiguously declaring that the prohibition of cannabis fails the smell test.

“Marijuana, like alcohol, does not alter the basic personality,” the report’s authors concluded. “Marijuana does not of itself give rise to antisocial behavior. There is no evidence to suggest that the continued use of marihuana is a steppingstone to the use of opiates. Prolonged use of the drug does not lead to physical, mental, or moral degeneration, nor have we observed any permanent deleterious effects from its continued use. Quite the contrary, marihuana and its derivatives and allied synthetics have potentially valuable therapeutic applications which merit future investigation.”

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The Discovery of THC (1964)

When a team of Israeli researchers led by Dr. Raphael Mechoulam first discovered THC in 1964 and identified it as the primary psychoactive compound found in the cannabis plant, that was not just a breakthrough in our collective understanding of cannabis—it also led to a series of breakthroughs in our understanding of how the human body functions.

By the late 1980s, this would include the discovery of an entirely new system in the body—the endocannabinoid system—which can be thought of as your “root-level operating system,” a kind of central processing unit that regulates and alters the functioning of many other important systems and keeps them in balance.

Leafly’s comprehensive explainer on the endocannabinoid system breaks down exactly how it works, and why its discovery was groundbreaking not just for medicinal cannabis, but for medicine in general.

The Shafer Commission Report (1972)

After studying cannabis for more than two years, a team of experts hand-picked by President Richard M. Nixon returned with a set of recommendations that started with immediately removing all criminal penalties for cannabis, including “casual distributions of small amounts,” since “neither the marijuana user nor the drug itself can be said to constitute a danger to public safety.”

“Criminal law is too harsh a tool to apply to personal possession even in the effort to discourage use…It implies an overwhelming indictment of the behavior which we believe is not appropriate. The actual and potential harm of use of the drug is not great enough to justify intrusion by the criminal law into private behavior, a step which our society takes only with the greatest reluctance.”

Known collectively as the Shafer Commission, the eminent researchers that compiled the report knew all-too-well that their findings flew in the face of the government’s official position on legalization, but hoped nonetheless their comprehensive research would spark a fact-based debate of the evidence that would in turn lead to significant reform.

Instead, Nixon attacked the commission and ignored its recommendations, before pushing the whole thing down the memory hole. The very next year, he created the Drug Enforcement Administration (DEA) and charged them with waging “all out war” on cannabis.

The first study to show that cannabis exhibits anti-tumor properties was originally designed to demonstrate the plant’s dangers.
The first study to show that cannabis exhibits anti-tumor properties was originally designed to demonstrate the plant’s dangers.

Cannabis Shrinks Tumors (1974)

The first ever study to show that cannabis exhibits anti-tumor properties was originally designed to demonstrate the plant’s dangers, specifically harm to the immune system. Funded by NIDA and a grant from the American Cancer Society, researchers at the Medical College of Virginia implanted tumors into mice, which were then “treated for 10 consecutive days with delta-9-THC, beginning the day after tumor implantation.” Presumably to show that THC makes cancer grow faster.

Instead, when the research was published in The Journal of the National Cancer Institute, it showed that ”mice treated for 20 consecutive days with THC and CBN had reduced primary tumor size.”

Great news, right?

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The study’s authors were certainly ready to investigate this exciting development further, but instead, NIDA cut off all of their funding and made every effort possible to suppress their research. As a result, only a single newspaper article, published August 18, 1974 in the local section of the Washington Post, covered this breakthrough discovery.

It would take nearly three decades before Dr. Manuel Guzman, professor of biochemistry at the University of Madrid, managed to follow up on the original 1974 experiments, with similar results. In the March 2000 issue of the journal Nature Medicine, Guzman reported that cannabinoids (like THC) not only shrink cancerous tumors in mice, they do so without damaging surrounding tissues.

Cannabis Treats Nausea Caused by Chemotherapy (1975)

Harvard Medical School Associate Professor Dr. Lester Grinspoon first started researching cannabis back the 1960s, in an effort to convince his best friend, famed astronomer Carl Sagan, to stop smoking so darn much of the stuff. Quickly, however, Grinspoon realized the case against cannabis was all based on government propaganda—an insight he explored in depth in a bestselling book called Marihuana Reconsidered (1971).

Ever since, the good doctor has been a leading voice for medical cannabis. He also witnessed the plant’s therapeutic power firsthand when his son Danny was diagnosed with leukemia at age 15, as he explained in a personal essay on his life’s journey with the plant.

“On a normal day of chemotherapy, I hoped we could make it home from the hospital before Danny’s vomiting would start, and we always had to put a big bucket next to his bed. But the first time he tried taking a few puffs prior to a round of treatments, he got off the gurney and said, ‘Mom, there’s a sub shop in Brookline. Could we stop for a sub-sandwich on the way home?’ And all I thought was, ‘Wow.’”

Dr. Grinspoon eventually convinced the head of Boston Children’s Hospital’s oncology department to undertake a 1975 study (published in the New England Journal of Medicine) that for the first time demonstrated the efficacy of THC for nausea and vomiting associated with chemotherapy.

Cannabis Helps AIDS Patients Without Serious Side Effects (1997)

Most impactful marijuana research studies of all time: Cannabis helps AIDs patient

(Gillian Levine for Leafly)

Throughout the AIDS crisis, Mary Jane Rathburn volunteered as a nurse’s assistant. While making the rounds in local hospital wards, she would discreetly provide home-baked cannabis-infused “magically delicious” brownies for free to those in need.

Eventually, “Brownie Mary’s” tireless public service caught the eye of Dr. Donald Abrams, now the head of oncology at San Francisco General Hospital. Inspired by her example, Abrams set out to prove via science what he’d already seen with his own eyes. Namely, that cannabis is a uniquely effective medicine for those suffering with AIDS-related nausea.

In 1997, after a long and bitter battle with the federal government, Abrams at last secured almost one million dollars from NIDA to conduct clinical trials of the short-term safety of cannabinoids in HIV infection. In time, he would publish a string of studies showing that cannabis given to HIV patients “did not hurt the immune system, did not increase viral load, did not negatively interact with the protease inhibitors, and actually did facilitate increased caloric intake as well as weight gain.”

Cannabis Doesn’t Cause Lung Cancer (2006)

The largest case-control study ever done on the subject unexpectedly concluded that smoking cannabis—even frequently and in large amounts—does not lead to lung cancer.

Dr.Donald Tashkin, a prominent pulmonologist at the University of California at Los Angeles, has spent over forty years studying the effects of cannabis on the lungs. When some of his earliest research established that the plant’s tar contains cancer-causing chemicals as potentially harmful as tobacco, Tahskin perhaps understandably jumped to the conclusion that smoking cannabis regularly must significantly damage the lungs.

But in 2006, with funding from the National Institute on Drug Abuse, he led the largest case-control study ever done on the subject, and rather unexpectedly concluded that smoking cannabis—even frequently and in large amounts—does not lead to lung cancer.

Those findings were “against our expectations,” according to Tashkin:

“We hypothesized that there would be a positive association between marijuana use and lung cancer, and that the association would be more positive with heavier use. What we found instead was no association at all, and even a suggestion of some protective effect.”

The study not only debunked a powerful anti-cannabis talking point, it strongly indicated that the plant has powerful medicinal properties.

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Cannabis Reduces Opioid Overdoses (2014)

When it comes to cannabis and the opioid epidemic currently wreaking havoc in America, there’s basically two schools of diametrically opposed thought: Either cannabis fuels the current crisis via the gateway drug effect, or cannabis has the potential to help immensely by providing a far safer alternative for pain relief as well as a potential pathway out of addiction.

For starters, the so-called “gateway theory” has been so roundly debunked that even the DEA gave up on it.

Between 1999 and 2010, states with legal medical cannabis averaged almost 25% fewer opioid overdose deaths.

And more importantly, studies have consistently shown that opioid abuse goes down significantly in places with access to legal cannabis. Much of this drop is attributable to those suffering with chronic pain or other conditions treatable with opioids who choose to use cannabis instead. A 2011 study headed by Dr. Donald Abrams also found that cannabis makes opioid drugs more effective, allowing smaller opioid doses to provide the same level of pain relief, with correspondingly lowered side effects and danger of dependence..

Marcus Bachhuber, assistant professor of medicine at the Montefiore Medical Center in New York City, first started hearing about this phenomenon from patients more than fifteen years ago. In 2014, he published research in the journal JAMA Internal Medicine that showed between 1999 and 2010, states with legal medical cannabis averaged almost 25% fewer opioid overdose deaths. Since that landmark study, many other papers have bolstered the argument that cannabis can play an important role in terms of harm reduction when it comes to prescription drug abuse—including two new studies (both published in the May 2018 issue of JAMA Internal Medicine) showing that when states legalize cannabis there’s a marked drop in opioid prescriptions.

According to W. David Bradford, an economist at the University of Georgia and an author of one of the studies.

“In this time when we are so concerned—rightly so—about opiate misuse and abuse and the mortality that’s occurring, we need to be clear-eyed and use evidence to drive our policies. If you’re interested in giving people options for pain management that don’t bring the particular risks that opiates do, states should contemplate turning on dispensary-based cannabis policies.”

Cannabis vs. PTSD (Ongoing)

Dr. Sue Sisley says she was abruptly fired in 2014 from a faculty position at the University of Arizona when her long planned study of cannabis as a treatment for PTSD became a political hot button among local politicians. Sisley ultimately prevailed, and now serves as one of two principal investigators in a multi-site study sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS) and funded by a $2.1 million grant from the Colorado Department of Public Health and Environment.

The world’s first controlled clinical trial evaluating smoked medical cannabis as a treatment for PTSD is a triple-blind, outpatient, randomized, placebo-controlled study of 76 combat veterans randomly assigned either a high-THC strain, a high-CBD strain, a 1:1 THC/CBD ratio strain, or a placebo. Currently in its third year, the study has proceeded well, but in the meantime, PTSD-related suicides remain at epidemic levels among US combat veterans.

CBD Stops Seizures (Ongoing)

In direct response to a flood of inquiries from parents of epileptic children, the US federal government in 2014 quietly fast-tracked a trial of cannabidiol (CBD) as a treatment for seizure disorders, proving that political pressure can indeed push them to approve studies into the potential benefits of cannabinoids. But while many advocates sought to test whole-plant or full-spectrum medicines, the study has been strictly limited to a single compound found in cannabis—not coincidentally one supplied in “purified” form by GW Pharmaceuticals, which also funded the study, and is currently seeking FDA approval to sell the a prescription CBD medicine called Epidiolex.

In May 2018, the New England Journal of Medicine published an update on this ongoing research showing that patients taking just 20mg of CBD per kilogram of body weight had 42% fewer seizures, on average, compared with a 17% reduction in the placebo group.

According to a comprehensive report on the study from Leafly’s Ryan Basen, these extremely promising results have GW Pharmaceutical’s CBD drug on track for imminent FDA approval.

“If approved, Epidiolex would become the first medication derived from the cannabis plant allowed in the US. The FDA has previously approved synthetic cannabis medications, which more closely resemble tetrahydrocannabinol (THC), but nothing plant-derived nor anything featuring CBD.

Sativex, a GW Pharma product that incorporates both THC and CBD, has been approved for medical use outside the U.S. Epidiolex features a solution of 100 mg/ml of CBD dissolved in sesame oil, ethanol, sweetener, and a flavoring agent, according to the FDA review. The medication is harvested from cannabis plants specifically bred for medical purposes, with high CBD concentration, according to a GW Pharmaceuticals report.”

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David Bienenstock
David Bienenstock
Veteran cannabis journalist David Bienenstock is the author of "How to Smoke Pot (Properly): A Highbrow Guide to Getting High" (2016 - Penguin/Random House), and the co-host and co-creator of the podcast "Great Moments in Weed History with Abdullah and Bean." Follow him on Twitter @pot_handbook.
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