After years of delays, researchers are set to move forward on a landmark clinical trial meant to evaluate the efficacy of smoked medical marijuana to treat post-traumatic stress disorder (PTSD) in military veterans. The study is being funded with tax revenue from legal cannabis sales in Michigan.

The Multidisciplinary Association for Psychedelic Studies, or MAPS, announced this week that the U.S. Food and Drug Administration (FDA) granted approval for Phase 2 of the research, what MAPS described in a press release as “a randomized, placebo-controlled study of 320 Veterans suffering from moderate to severe PTSD who have previously used cannabis.”

The group said the study “is designed to investigate the inhalation of high THC dried cannabis flower, versus placebo cannabis, with the daily dose being self-titrated by participants.” It’s meant to reflect consumption patterns already happening across the country and study “the ‘real-world’ use of inhaled cannabis to understand its potential benefits and risks in treating PTSD.”

The project is years in the making, MAPS said, noting that it encountered numerous issues in clearing the research with FDA that only recently were resolved.

“After 3 years of negotiations with the FDA, this decision opens the door to future research into cannabis as a medical treatment, offering hope to millions,” the organization said.

“These data are critical to inform patients, medical providers, and adult-use consumers when considering cannabis in treatment plans for the management of PTSD, pain, and other serious health conditions,” the group’s press release said, “yet regulatory obstacles have historically made it difficult or impossible to conduct meaningful research on the safety and effectiveness of cannabis products typically consumed in regulated markets.”

MAPS said that over the years, it responded to five partial clinical hold letters from FDA that halted the study’s progress.

“On August 23, 2024, MAPS responded to the FDA’s fifth clinical hold letter by submitting a Formal Dispute Resolution Request (FDRR) to resolve the continued scientific and regulatory disagreement with the Division on four key issues,” according to the organization: “1) the proposed THC dose of the cannabis flower product, 2) smoking as a delivery method, 3) vaping as a delivery method, and 4) the enrollment of cannabis naïve participants.”

Sue Sisley, a psychiatrist and the principal investigator for the study, said the trial will help shed more light on the scientific legitimacy of using smoked marijuana to treat PTSD. Despite growing use of cannabis among patients with PTSD and the condition’s inclusion in many state medical marijuana programs, she said there’s a lack of rigorous data evaluating the treatment’s efficacy.

“Within the United States, millions of Americans are smoking or vaporizing cannabis to manage or treat their symptoms,” Sisley said in a statement. “In the absence of high-quality data related to cannabis, much of the information available to patients and regulators is rooted in prohibition and focused only on potential risks, without consideration of potential benefits.”

“In my own practice, Veteran patients have shared how smoking cannabis helped them manage their PTSD symptoms more than traditional pharmaceuticals,” she continued. “Suicide among Veterans is an urgent public health crisis, but it’s solvable if we invest in researching new treatments for life-threatening health conditions like PTSD.”

Phase 2 of the research, Sisley said, “will generate data that doctors, like myself, can use to develop treatment plans to help people manage their PTSD symptoms.”

Allison Coker, director of cannabis research at MAPS, said the resolution with FDA came when the agency said it would allow Phase 2 to proceed with smoked cannabis at commercially available THC levels. Vaporization remains on hold, however, until FDA can assess the safety of any particular delivery device.

In response to FDA’s separate concern around enrolling cannabis-naive participants in the study, MAPS updated the protocol to require that participants must have “prior experience inhaling (smoking or vaporizing) cannabis.”

FDA had also taken issue with the study’s design of allowing self-titration—meaning participants can consume as much cannabis as they choose, up to a certain amount—but MAPS refused relent on that point.

An FDA spokesperson told the New York Times, which first reported the Phase 2 approval, that she was unable to provide details about what led to the decision but said that the agency “recognizes that there is great need for additional treatment options for mental health conditions such as PTSD.”

The study is being funded by Michigan’s Veteran Marijuana Research Grant Program, which uses state revenue from legal cannabis taxes to fund FDA-approved, nonprofit-sponsored clinical trials “researching the efficacy of marijuana in treating the medical conditions of United States armed services veterans and preventing veteran suicide.”

State officials announced $13 million in funding for the research back in 2021, part of a total $20 million grant funding round. Another $7 million that year went to Wayne State University’s Bureau of Community Action and Economic Opportunity, partnered with researchers to study how cannabis might treat a variety of mental health disorders, including PTSD, anxiety, sleep disorders, depression and suicidality.

In 2022, meanwhile, the Michigan Cannabis Regulatory Agency recommended that year’s $20 million go toward two universities: the University of Michigan, where researchers proposed looking at the use of CBD in pain management, and Wayne State University, which was awarded grants for two separate studies: one that billed itself as the “first randomized, controlled, large-scale clinical trial” to examine whether the use of cannabinoids could improve outcomes for veterans with PTSD who are undergoing prolonged exposure (PE) therapy and another into the effects of marijuana on “neuroinflammation and neurobiological underpinnings of suicide ideation in veterans with PTSD.”

The founder and president of MAPS, Rick Doblin, said in the group’s announcement of the newly FDA-approved trial that veterans “are in dire need of treatments that can ease their challenging symptoms of PTSD.”

“MAPS takes pride in leading the way to open new research pathways by challenging the FDA to think differently,” he said. “Our cannabis work challenges FDA’s typical approach to scheduled dosing and administration of drugs. MAPS refused to compromise the study design in order to fit into the standard box of FDA thinking in order to ensure that cannabis research reflects cannabis use.”

MAPS’s past research has included not just cannabis but also, as the group’s name suggests, psychedelics. It created a spinoff drug development company, Lykos Therapeutics (formerly MAPS Public Benefit Corporation), that sought FDA approval earlier this year of MDMA to treat PTSD.

But in August, FDA declined to approve the MDMA-assisted therapy. Separate research, published in the Journal of Psychedelic Studies, found that while results of clinical trials have been “encouraging,” more robust research is needed before MDMA-assisted therapy (MDMA-AT) sees widespread adoption over currently available forms of treatment

Some health officials said afterward that the effort nevertheless reflected progress at the federal level.

“We all feel some type of way about the decision that came out some time ago, and that’s OK,” said Leith J. States, chief medical officer at the Office of the Assistant Secretary for Health. “It’s indicative of a fact that we’re moving forward…and we’re doing things in a way that marches us forward in an incremental way.”

Separately this month, a Drug Enforcement Administration (DEA) judge rejected a veterans group’s petition to participate in an upcoming hearing on the Biden administration’s marijuana rescheduling proposal, which the organization, the Veterans Action Council (VAC), called a “travesty of justice” that excludes key voices that would be affected by the potential policy change.

While DEA “devised a reasonably inclusive stakeholder assortment” of witnesses, VAC said it still “failed” to fulfill its mandate to allow testimony from interested parties. And the veterans organization said that’s evidenced by the fact that Mulrooney has since delayed the formal hearing proceedings until early 2025 because DEA provided insufficient information about their selected witnesses’ position on rescheduling or why they should be considered interested parties.

Meanwhile in Congress, a new U.S. Senate bill introduced this month aims to ensure benefits for veterans exposed to potentially hazardous chemicals during the Cold War era—including psychedelics like LSD, nerve agents and mustard gas. The secret testing program, which ran from 1948 to 1975 at an Army base in Maryland, involved former Nazi scientists administering the substances to American military members.

More recently, the U.S. military has also invested millions in an effort to develop a new class of drugs that offers the same fast-acting mental health benefits as traditional psychedelics but without a psychedelic trip.

Veterans have taken a lead role in both medical marijuana legalization and the psychedelics reform movement currently unfolding at the state and federal levels. Earlier this year, for example, veterans service organizations (VSOs) pressed members of Congress to more urgently pursue the potential benefits of psychedelic-assisted therapy and medical marijuana.

The requests from groups like the Iraq and Afghanistan Veterans of America, Veterans of Foreign Wars of the United States, Disabled American Veterans and the Wounded Warrior Project came on the heels of organizations at last year’s set of annual VSO hearings criticizing the Department of Veterans Affairs (VA) for “dragging their feet” on medical marijuana research.

Led largely by Republican politicians, efforts at reform have included a GOP-sponsored psychedelics bill in Congress that focused on veterans’ access, various state-level changes and a bevy of hearings on expanded access.

Rep. Derrick Van Orden (R-WI), who filed one congressional psychedelics bill that advanced through a committee, is also a co-sponsor of a bipartisan measure to provide funding to the Department of Defense (DOD) to conduct clinical trials into the therapeutic potential of certain psychedelics for active duty military members. That reform was signed into law by President Joe Biden under an amendment attached to the 2024 National Defense Authorization Act (NDAA).

In March, congressional appropriations leaders also unveiled a spending package that contains language providing $10 million to facilitate the psychedelics studies.

In January, VA separately issued a request for applications to conduct in-depth research on the use of psychedelics to treat PTSD and depression. And last October, the department launched a new podcast about the future of veteran health care, with the first episode of the series focused on the healing potential of psychedelics.

At the state level, the governor of Massachusetts in August signed a military veterans-focused bill that includes provisions to create a psychedelics working group to study and make recommendations about the potential therapeutic benefits of substances like psilocybin and MDMA.

Meanwhile in California, lawmakers in June pulled from consideration a bipartisan bill that would have authorized a pilot program to provide psilocybin treatment to military veterans and former first responders.

Correction: As the result of an editing error, an earlier version of this story attributed quotes to incorrect members of the MAPS team. Those attributions have been corrected.

Ben Adlin via (https://www.marijuanamoment.net/fda-approves-long-awaited-clinical-trial-of-smoked-marijuana-to-treat-ptsd-in-veterans/)

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