The Food and Drug Administration blocked one Michigan study into post-traumatic stress disorder, contending it’s too dangerous to have participants inhale marijuana, even though that’s how most veterans use the drug. In another series of proposed studies, it took researchers nearly two years to secure a federally approved marijuana supply for study — by law, they can’t use pot widely available at dispensaries. Those studies are still months from beginning.
The delays in Michigan underscore the challenges of studying potential health benefits and consequences of marijuana in the United States, where it remains federally illegal even as it is lawful in most states. Scientists hope that research will accelerate if the federal government soon loosens restrictions on the drug. But they fear that federal regulators’ deep-rooted skepticism of marijuana and legal barriers will continue to hamper studies that must balance safety and scientific rigor with the immutable reality that millions already smoke joints, inhale vapes and eat edibles to medicate themselves.
“It’s very important to have empirically sound data and real-world investigations of the products that patients are actually using and the ways they are using them,” said Staci Gruber, director of the Marijuana Investigations for Neuroscientific Discovery initiative at McLean Hospital near Boston, who is not involved in the Michigan studies.
The FDA has declined to comment on proposed clinical studies involving marijuana and has said it continues to support “robust scientific research needed to develop new drugs from cannabis and is committed to encouraging the research and development of these new drugs” through its regulatory process.
For decades, marijuana has been classified as a Schedule I controlled substance, the same category occupied by heroin and LSD. That means it is deemed to have no accepted medical use and is associated with a high risk of abuse. Thirty-eight states and D.C. have legalized medical marijuana. Twenty-four states and D.C. have approved recreational marijuana. President Biden directed the Department of Health and Human Services in 2022 to review whether marijuana should remain Schedule I.
The health agency notified the Drug Enforcement Administration in August that it was recommending marijuana be placed into Schedule III, which includes prescription medications ketamine and testosterone. The DEA is expected to decide on marijuana’s classification in coming months. HHS’s recommendation was based on a scientific analysis from the FDA that was made public in January.
Researchers have long complained about red tape strangling their ability to study marijuana.
To conduct studies, they must submit a research protocol, get approved by the DEA to research Schedule I drugs and then follow strict security rules.
“I have to account for every milligram that I’ve used and what I have left over, and I have to keep it in a gun safe in a locked room I only get into with my thumb,” said Meg Haney, a professor of neurobiology and director of the Cannabis Research Laboratory at Columbia University, who is not involved in the PTSD studies but has received FDA approval to study inhaled marijuana and its effect on pain.
For nearly five decades, the University of Mississippi was the only institution authorized by the federal government to grow marijuana for research, although its supply was criticized for being weaker than the pot most people consume. The university now produces higher-potency marijuana and extracts. The DEA authorized more cultivators to provide marijuana for study in recent years.
In 2022, Biden signed the Medical Marijuana and Cannabidiol Research Expansion Act, meant to speed approval of permits. Regardless of whether the drug is reclassified, legal experts argue restrictions on marijuana research remain under the 2022 act. “Not only does it make cannabis research harder than ever, but it cements its backward, anti-science regime in place for good,” Shane Pennington, a D.C. attorney who specializes in regulatory issues involving controlled substances, wrote in an analysis.
Even if marijuana is reclassified, the FDA must approve investigational new drug applications for marijuana research. The FDA approved one cannabis-related drug, Epidiolex, made from CBD, a cannabis extract that does not cause a high. The drug is used to treat rare forms of epilepsy. The FDA has approved three other nausea drugs made from synthetic versions of THC, the compound in marijuana that causes a high.
The FDA has not approved any cannabis plant products, highlighting what researchers say is the agency’s disdain for botanical products. The agency has seen an explosion in requests for research; in November, the FDA said it was reviewing more than 150 applications for studies into cannabis and related products.
Legal experts say that under federal law, if the drug is moved to Schedule III, that will allow doctors or state-authorized dispensaries to provide medical marijuana to patients without a prescription, as long as it does not involve interstate commerce — and with no FDA drug approval needed.
Universities often lead the way on marijuana research. Companies are unwilling to invest in gold-standard clinical trials that the FDA requires to bring a marijuana product to market, said Paul Armentano, deputy director of NORML, a more than five-decade-old organization that battles restrictions on marijuana use.
Marijuana, after all, can be obtained legally in most states, he said. “Why on earth in a practical sense would a pharmaceutical company spend the tens of millions, if not billions, to try to bring a botanical cannabis product to market to treat a specific symptom?” Armentano said.
The FDA analysis of existing scientific research of cannabis as medicine found mixed results. It concluded there is “some credible scientific support” for using marijuana to treat conditions such as nausea and vomiting. The agency said it did not find support for the drug providing benefits for epilepsy, anxiety and PTSD. One study cited by the FDA examined medical records of 2,000-plus veterans with PTSD and concluded pot may worsen symptoms or nullify other treatments.
“The overwhelming impression is that marijuana and mental health do not mix,” said the study’s author, Samuel T. Wilkinson, an associate professor of psychiatry at Yale University School of Medicine. “Those of us who see patients are continuously fighting an almost information war from patients who say I hear it helps with this, it helps with that.”
In Michigan, veterans like Anton Harb said they believe marijuana holds promise for PTSD treatment and staves off suicidal impulses. He’s a former Army artilleryman who served in Iraq and says marijuana helped ease nightmares, anxiety and depression caused by PTSD. “Cannabis set me on a path of healing,” said Harb, 41. “I want other veterans to be able to at least make an informed decision.”
Harb has criticized the glacial pace of research. When Michigan legalized recreational marijuana in 2018, the initiative mandated that tax dollars generated from sales be spent on research approved by the FDA.
Since 2021, Michigan’s Cannabis Regulatory Agency has awarded $40 million in grants to the University of Michigan, Wayne State University and the Multidisciplinary Association for Psychedelic Studies, a nonprofit known as MAPS.
The FDA had approved the nonprofit’s first study of inhaled marijuana for vets with PTSD. The results, published in 2021 and paid for by a Colorado state grant, looked at inhalation in 76 veterans. Researchers found no safety concerns, and the veterans showed “significant improvements” in symptoms for smoked marijuana — but no significant difference over a placebo.
Researchers say the larger trial in Michigan, paid for by a $12.9 million state grant, will study 320 veterans. Scientists at the Scottsdale Research Institute in Phoenix, which is leading the MAPS study, plan to use stronger marijuana supplied by a Canadian company.
The FDA held up the second trial over concerns about inhalation and danger to the lungs in smoking pre-rolled marijuana cigarettes and vaping, as well as THC dosing. In a Dec. 28 letter, an FDA official said the hold would be lifted if the “drug delivery method” changes. MAPS founder Rick Doblin said the agency approved many past smoking studies — including his group’s first.
“What has changed in the science between the first one and the second one? Nothing. They’ve just gotten more conservative,” Doblin said.
MAPS plans to appeal the ruling. The FDA declined to comment, saying the agency’s “ability to discuss pending [applications] is strictly limited by federal law.”
Some experts, including a prominent pulmonologist who has studied the effects of marijuana smoking, say there is no evidence marijuana smokers are at significant risk of developing lung cancer or pulmonary disease like tobacco smokers. But a study published Wednesday found that frequent cannabis smoking may significantly increase a person’s risk for heart attack and stroke. The observational study, funded by the National Institutes of Health, examined health records of nearly 435,000 Americans.
The Wayne State research also involves veterans inhaling vaporized marijuana, although researchers have not yet applied for FDA approval of the trial. Researchers first needed to secure certification of enough high-THC marijuana from the University of Mississippi for 550 veterans. That was completed only in recent weeks, after nearly two years of trying to find the supply.
The FDA has approved the University of Michigan clinical trial — which is studying CBD — illustrating the smoother path to research when not studying marijuana. Researchers are recruiting 468 veterans who will take Epidiolex or a placebo to test whether it alleviates chronic pain.
Harb said he believes that CBD study is a waste. “I deal with thousands of veterans,” Harb said. “We don’t use CBD, man.”
The study’s lead investigator, Kevin Boehnke of the University of Michigan, acknowledged researching CBD is easier because it is not a controlled substance. He rejected Harb’s criticisms, saying the study is appropriate because some veterans don’t want to get high.
“I respect him and respect what he’s trying to do,” Boehnke said of Harb. “I think we just have different opinions on how we’re going to approach this same question of trying to develop science that helps.”
Daniel Gilbert contributed to this report.
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