The state of Michigan has awarded Wayne State University a $7 million grant to investigate, in military veterans, the potential therapeutic effects of cannabis to improve patients’ quality of life and reduce post-traumatic stress disorder and depressive symptoms that can precede suicide.

The Department of Licensing and Regulatory Affairs’ Marijuana Regulatory Agency awarded the funding as part of its 2021 Veteran Marijuana Research Grant Program.

The School of Medicine’s Associate Professor of Psychiatry and Behavioral Neurosciences Leslie Lundahl, Ph.D., is the lead principal investigator on the five-year project, “Wayne State Warriors Marijuana Clinical Research Program: Investigating the Impact of Cannabinoids on Veteran's Behavioral Health.”

Dr. Lundahl is a research-educator in the Translational Neuroscience Graduate Program and Drug Lab Detroit, a multidisciplinary team at the School of Medicine focused on understanding more about the development and treatment of substance use disorders.

“This project is timely and important because, despite increasing medicalization and legalization of cannabis use across the United States, the safety and effectiveness of therapeutic cannabis/cannabinoids are not yet well established,” Dr. Lundahl said. “Community support of legal cannabis and the perception that cannabis is safe indicates public opinion has outpaced science on cannabis use. There are risks to heavy and chronic use, including impairments in attention, learning and memory, as well as increased risk of mental health problems such as anxiety and depression, and medical issues such as heart attack and lung irritation. At the same time, cannabinoid science is rapidly expanding and it is likely that some of these compounds can help treat common conditions.”

According to the U.S. Department of Veterans Affairs 2020 National Veteran Suicide Prevention Annual Report, more than 6,400 veterans died by suicide in 2018, more than 17 suicides per day. Despite making up only 8% of the population, veterans accounted for 14% of all suicide deaths in U.S. adults. The age- and sex-adjusted suicide rate for veterans increased from 18.5 suicides per 100,000 in 2005 to 27.5 deaths in 2018.

The grant will support a large-scale, randomized, controlled clinical trial over five years and within two studies examining the efficacy of cannabinoids to treat PTSD and suicidality in United States armed forces veterans.

The Michigan Regulation and Taxation of Marijuana Act passed by voters in November 2018 led to the Marijuana Regulation Fund in the state treasury. It requires the Marijuana Regulatory Agency to expend money in the fund until 2022 or for at least two years, to provide $20 million annually to one or more clinical trials approved by the U.S. Food and Drug Administration and sponsored by a non-profit organization or researcher within an academic institution researching the efficacy of marijuana in treating the medical conditions of veterans and preventing veteran suicide.

Results of the work could inform educational efforts and public health policy by providing clinicians with empirical data to guide discussions with their patients about therapeutic cannabinoid use and associated risks; increasing trauma-exposed users’ access to educational resources so they can make informed decisions about cannabinoid use; and improving patients’ health outcomes and lowering health care utilization rates and costs.

The study team includes co-principal investigator and Associate Professor of Psychiatry and Behavioral Neurosciences Seth Norrholm, Ph.D., who will develop and implement a fear-learning paradigm;  co-investigator and Professor of Psychiatry and Behavioral Neurosciences David Ledgerwood, Ph.D., who will oversee the naturalistic observation study; co-investigator and Professor of Psychiatry and Behavioral Neurosciences Tanja Jovanovic, Ph.D. who will oversee the psychophysiology assessments; co-investigator and Professor of Psychiatry and Behavioral Neurosciences Mark Greenwald, Ph.D., who will assist with drug preparation and accountability; and co-investigator and Assistant Professor of Psychiatry and Behavioral Neurosciences Hilary Marusak, Ph.D., who will coordinate with Lipidomics Core Facility Director and Associate Professor of Pathology Krishnarao Maddipati, Ph.D., in the collection, analyses and interpretation of endocannabinoid levels. Professor of Biostatistics Samiran Ghosh, Ph.D., will provide biostatistical input and analyses.

“We have assembled an exceptional and highly accomplished team to explore and develop safe, effective and accessible treatments for combat veterans with suicidality, mood, trauma and related disorders,” Dr. Lundahl said.

The project is a radical change in direction for the lab.

“Over the last 20 years, we’ve been studying the negative effects of cannabis and other drugs of abuse, focusing on understanding mechanisms that underlie the trajectory from initial use to continued use despite significant consequences,” Dr. Lundahl said.

Her goal has been developing and improving treatment options for individuals who want help stopping their substance use. More recently, promising data from both animal and human studies suggest that cannabis and its constituents -- cannabinoids, particularly Tetrahydrocannabinol and Cannabidiol -- have potential for therapeutic benefit.

“This project provides a unique opportunity for us to bring our experience in assessing biobehavioral effects of acute and sustained cannabis use to help identify the potential therapeutic indications of cannabis use, while considering the possible risks of use for these indications,” she said.

Additionally, Dr. Norrholm and his team bring 20 years of experience studying the underlying neurobiology, behavioral features and treatment methods central to the psychological aftermath of traumatic experiences.

“Veterans’ mental health has been central to most programs, both public and private, whose focus is on improving the lives of those who have served our country. The mental and physical scars borne by our service members and veterans are often termed the ‘invisible wounds of war.’ Sadly, whether those wounds appear as depression, addiction, PTSD, relationship problems, or a combination of these outcomes, the end result can be suicidal thoughts, actions and behaviors,” Dr. Norrholm said. “We believe that enhancing our existing treatments as well as exploring novel and innovative interventions is critical to providing better treatment outcomes for veterans, and with that, improved quality of life, increased mood and reduced suicidality.”

In study one, 200 veterans will be randomized into one of four different THC-CBD dose mixtures for a 12-week treatment phase, with one week’s worth of cannabis delivered by a mobile health unit staffed by security as well as research assistants who will secure blood and urine samples on site. In study two, 150 veterans will be randomized into either a naturalistic group that will be followed as they continue to use cannabis as they normally do (observation only), or into a “THC reduction group” in which veterans are asked to switch from their typical cannabis product to using a lower THC/higher CBD product. Adherence to this switch will be incentivized using contingency management.

The overall strategy is to recruit veterans with PTSD who use cannabis to manage mental health symptoms (anxiety, depression, PTSD and/or suicidality). Those who report moderate use will be prioritized for study one, and those who report light or heavy cannabis use will be prioritized to study two.

WSU was awarded the full requested amount of $7,020,950.