Advances in Cannabinoid Research for Veteran Health

For Veterans: Understanding the Endocannabinoid System and Key Cannabinoids

Veterans are using cannabis products, but many have questions. Cannabinoids are compounds that interact with the body’s endocannabinoid system (ECS), a network of receptors and signaling molecules that help regulate mood, pain sensation, immune function, and other processes. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most well-known cannabinoids. THC is the primary psychoactive component of cannabis; it binds to cannabinoid receptors (especially CB₁ in the brain) to produce euphoria and analgesia, but can also cause side effects like anxiety in some cases. THC’s effects include pain relief, reduction of nightmares, appetite stimulation, and aiding the extinction of fear memories. CBD, in contrast, is non-intoxicating. It interacts more subtly with cannabinoid receptors and other targets (like serotonin 5-HT₁A receptors and enzymes such as FAAH). CBD can counteract some of THC’s side effects and has anxiolytic, anti-inflammatory, analgesic, and neuroprotective properties. Preclinical studies show that both THC and CBD may modulate fear and stress responses – for example, animal models have found that administering these cannabinoids can reduce fear conditioning, block the reconsolidation of traumatic memories, and accelerate the extinction of fear responses. These effects align with the ECS’s role in emotional memory processing and suggest a biological rationale for cannabinoid-based therapies in post-traumatic stress disorder (PTSD).

Other phytocannabinoids are also under investigation. Cannabigerol (CBG), often called the “mother cannabinoid” because it is a chemical precursor to THC and CBD, is non-intoxicating and is being explored for its potential anti-inflammatory and neuroprotective effects. Cannabinol (CBN), a mildly psychoactive breakdown product of THC, is believed to have sedative properties and is being tested for improving sleep quality. In fact, a recent controlled trial found that 20 mg of CBN nightly reduced nighttime awakenings and overall sleep disturbance without next-day fatigue. Cannabichromene (CBC) and tetrahydrocannabivarin (THCV) are yet other cannabinoids of interest – early research suggests CBC may have anti-inflammatory and analgesic effects, while THCV has a more complex profile (in low doses it can act as a CB₁ receptor antagonist, potentially suppressing appetite or anxiety). Although these minor cannabinoids have not yet featured prominently in veteran-specific studies, they represent the broader landscape of cannabinoid science. Overall, by acting on the ECS’s receptors throughout the nervous and immune systems, cannabinoids like THC, CBD, CBG, and others hold therapeutic promise across a range of conditions relevant to veterans – from chronic pain and insomnia to anxiety, depression, and neurodegenerative disorders.

From Battlefield to Recovery: A Veteran’s Journey with Cannabis

Real-world veteran experiences put a human face on the science. Currently, The University of Northern Colorado, in conjunction with NC AmVets and CBD manufacturer Vantage Hemp, are conducting a nationwide survey of Veterans’ and CBD.  They hope to gain deeper insight into the use of cannabinoids among veterans. Take the story of Sarah Rudder, a U.S. Marine veteran who endured profound trauma and injury. On September 11, 2001, then-17-year-old Rudder was at the Pentagon for a ceremony when the building was attacked. In the aftermath, she helped evacuate survivors and in doing so suffered a severe ankle injury that eventually led to an amputation. Returning to civilian life, Sarah grappled with chronic pain from her injury and psychological scars from the tragedy. She was prescribed a cocktail of medications – at one point 16 different pills a day – including opioids and mood stabilizers to manage pain, nightmares, and anxiety. The side effects were debilitating. “I was in a zombie state… I know it’s going to end up killing me if I continue,” she recalled, describing the toll of these medications.

Desperate for an alternative, she turned to something previously unthinkable for a Marine: medical cannabis. On her doctor’s suggestion, Sarah researched other patients’ stories and decided to give cannabinoids a try. The results were transformative. As she incorporated cannabis (in carefully dosed, legal medical formulations) into her regimen, she was able to wean off the majority of her pills, including heavy painkillers. Her pain became manageable, her sleep and mood improved, and the intrusive nightmares waned. In her words, “It literally saved my life, and now I am healthier and fitter than I have ever been”. Sarah Rudder’s journey from injury and PTSD to advocacy is not an isolated case. Many of her fellow veterans have reported similar benefits – using cannabis to ease anxiety, relieve chronic pain, and reduce reliance on opioids and other medications. In a 2023 anonymous survey of over 500 U.S. veterans who use medical cannabis, 91% reported improved quality of life and nearly half said cannabis helped them cut down on prescription drugs (especially opioids, antidepressants, and sleep aids). These voices underscore a critical point: veterans are increasingly turning to cannabinoids as a tool for coping with the lasting wounds of war. Their lived experiences are driving demand for rigorous research – to validate benefits, understand risks, and guide safe use.

Clinical Trials Targeting PTSD and Suicide in Veterans

The debilitating psychological impact of combat has pushed PTSD to the forefront of veteran health research. Traditional treatments (therapy and SSRIs) help many, yet a significant number of veterans continue to experience severe symptoms. In recent years, attention has turned to cannabinoids as a novel therapeutic avenue. A major effort underway is the Wayne State University Warrior C.A.R.E. (Cannabis and Behavioral Health) program, which is conducting a large clinical trial focused on veterans with PTSD and suicidal ideation. Known by its registry ID NCT06381180, the Warrior CARE trial is a Phase 1/2 study planning to enroll 500 U.S. veterans – one of the largest of its kind. The trial is randomized and controlled, meaning participants will be assigned to receive a cannabinoid-based treatment or placebo. Importantly, it is designed to parse out the effects of different cannabinoids: one group will receive THC, another CBD, another a combination of THC+CBD, and a control group a placebo. The goal is to examine the therapeutic potential of these cannabinoids for PTSD symptoms and suicidality. By including veterans who have a history of cannabis use or interest in using cannabis for relief, the study also aims to reflect real-world conditions. Principal Investigator Dr. Leslie Lundahl, PhD, and her colleagues (including Dr. Hilary Marusak, who helped establish the Warrior CARE program) lead the multidisciplinary team. While not veterans themselves, the researchers have decades of experience in substance use and PTSD research. Funded by the State of Michigan’s Veteran Marijuana Research grant program, this ambitious trial launched in late 2024 and is slated to run through 2030. The hope is that it will provide high-quality evidence on whether cannabis can safely reduce PTSD severity or suicidal thoughts in veterans – potentially pointing toward new interventions for those who haven’t found sufficient relief in existing treatments.

Another notable study addressing PTSD is taking place within the U.S. Department of Veterans Affairs (VA) system. At the VA San Diego Healthcare System, Dr. Mallory Loflin (a research scientist with VA and UC San Diego) is leading a Phase 2 trial (NCT03518801) investigating CBD as an adjunct to prolonged exposure therapy for PTSD. Prolonged Exposure (PE) therapy is a gold-standard psychotherapy for PTSD, but it can be emotionally challenging, and not all who undergo it achieve remission. Preclinical research suggests that CBD may enhance “extinction learning” – the process of unlearning fear associations – and reduce hyperarousal. In this VA trial, 136 veterans of all service eras with diagnosed PTSD will receive capsules containing either pharmaceutical-grade CBD or a placebo, in addition to undergoing an intensive 3-week course of PE therapy. The study’s objective is to see if CBD can boost the effectiveness of psychotherapy, perhaps by accelerating the emotional processing of trauma memories or by alleviating insomnia and anxiety that often impede therapy. This trial, funded by a $1.3 million VA grant, began recruiting in 2019. As of now, no results are published, but the scientific rationale is strong – CBD’s anxiolytic and sleep-stabilizing effects could meaningfully support PTSD patients through therapy. Dr. Loflin notes that engagement in treatment is critical: if CBD can improve sleep and reduce anxiety, veterans might be more likely to stick with therapy and see it through. The outcome of this study is eagerly anticipated, as it merges a biological treatment with a psychological one, aiming for a complementary approach to PTSD care.

It’s worth noting that these modern trials build upon earlier research which hinted at cannabinoids’ PTSD benefits. Over a decade ago, Canadian military psychiatrist Col. (Ret.) Rakesh Jetly conducted a pioneering randomized trial using nabilone – a synthetic THC analog – to treat PTSD-related nightmares. In that small crossover study with treatment-resistant patients, nabilone significantly outperformed placebo in reducing nightmare frequency and intensity. Half the subjects had major improvement in nightmare symptoms on nabilone, versus only 11% on placebo. They also reported better overall well-being, and the drug was reasonably well-tolerated. While that trial (10 patients in the final analysis) was preliminary, it provided a proof of concept that targeting the ECS could alleviate specific PTSD symptoms. More recently, observational studies have observed similar trends: For instance, a 2019–2020 longitudinal study followed 150 individuals (veterans and non-veterans) with PTSD over a year. Those who **used cannabis regularly showed a greater decrease in PTSD symptom severity over time and were 2.5 times more likely to no longer meet PTSD criteria at one-year follow-up compared to non-users. They especially saw reductions in hyperarousal symptoms among the cannabis-using group. Such findings, though not from randomized trials, added impetus for controlled research like the Warrior CARE and VA CBD trials. On the other hand, experts caution that self-medicating with cannabis can carry risks (dependence, variable dosing, etc.), and not all studies see a long-term benefit. A recent systematic review concluded that evidence for cannabis in PTSD is still limited and mixed, calling for more rigorous trials. This is exactly what the current wave of VA- and university-led studies seeks to provide.

One milestone was reached in 2021, when the first FDA-regulated, randomized controlled trial of whole-plant cannabis for PTSD in veterans was completed. Sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS) and led by Dr. Sue Sisley, MD (a physician renowned for advocating veteran cannabis research), this Phase 2 trial (NCT02759185) tested four different potencies of smoked cannabis in 76 veterans with chronic, treatment-resistant PTSD. The study was a triple-blind, placebo-controlled crossover design – meaning each participant tried multiple conditions (high-THC cannabis, high-CBD cannabis, THC/CBD mix, and placebo) in different phases. The results, published in PLOS ONE in 2021, were intriguing if initially sobering: no cannabis formulation produced a statistically significant improvement in PTSD symptoms above placebo by the primary endpoint. Over three weeks of treatment, all groups – including placebo – saw some improvement in symptoms, and the cannabis was well-tolerated with no serious adverse events. Essentially, while veterans did experience relief while using cannabis, the placebo group did nearly as well. These findings highlight the importance of expectancy and the need for larger, longer trials. The investigators noted that the study was relatively brief and possibly underpowered to detect small differences. They also pointed out that all participants, even those on placebo, had access to some form of cannabis after the trial, which may have influenced outcomes in crossover phases. Despite the lack of a clear drug-vs-placebo effect, the trial provided critical safety data and feasibility insights. Notably, it demonstrated that veterans with PTSD can participate in a rigorous cannabis trial (navigating regulatory hurdles that had stalled such research for years) and that cannabinoid therapies merit further exploration. MAPS and other groups have called for phase 3 trials with improved cannabis products (the 2021 study was limited to government-provided cannabis of middling potency and quality). The silver lining is that this research legitimized the topic: it raised new questions rather than closing the door. For veterans like Sarah who swear by cannabis’s effects, the fact that all groups improved might suggest that even the ritual of treatment and support of a trial can help, or that cannabis’s benefits vary greatly by individual. Ongoing studies with larger samples and refined methods will help clarify these nuances.

Tackling Chronic Pain: Cannabinoids for Veterans’ Aches and Injuries

Chronic pain is another scourge disproportionately affecting veterans – whether from combat injuries, musculoskeletal wear-and-tear, or conditions like neuropathy. Opioid painkillers, long a mainstay for serious pain, carry risks of dependence and overdose, leading to an urgent search for safer alternatives. Cannabis-based therapies have emerged as a promising option for pain management, and research is now catching up to veteran patients’ enthusiasm. The U.S. VA is currently sponsoring a landmark Phase 2 trial to evaluate cannabinoids for chronic neuropathic pain in veterans. Sometimes simply called the “Chronic Neuropathic Pain Study,” this proof-of-concept trial (VA Study #I01CX002378, NCT05351801) is led by Dr. Deepak D’Souza at the VA Connecticut Healthcare System (West Haven). The trial will recruit 320 veterans who suffer from high-impact neuropathic pain – a type of nerve pain often described as burning or tingling, which can result from nerve damage, diabetes, or injuries. Veterans have shown significant interest in cannabis for neuropathic pain, yet as the investigators note, no large controlled trials had been done in this population. This study is designed to fill that gap. It uses a randomized, double-blind, four-arm design to rigorously test whether THC, CBD, or a combination of THC+CBD is superior to placebo in reducing pain over an 8-week treatment period. All participants will be those not currently using cannabis (to ensure a clean baseline and avoid confounding by tolerance or withdrawal). Outcome measures include pain intensity scales and functional improvements, as well as tracking any side effects. By comparing pure THC vs pure CBD vs their combination, researchers hope to learn which component (or synergy of components) provides analgesia with minimal downside. This trial is the first large, FDA-regulated cannabis trial focused on pain in the VA system, and it will yield important data on efficacy and safety specifically in veterans.

While results from the VA neuropathic pain trial won’t be available until its completion (projected around 2025–2027), its initiation reflects existing evidence that pushed the field forward. Previous clinical studies on cannabinoids for chronic pain – mostly in non-veteran populations – have indicated that cannabinoids can offer modest relief in certain pain conditions. For example, neuropathic pain (nerve pain) is one area where cannabis-based medicines have shown benefit. A systematic review by the National Academies in 2017 found conclusive or substantial evidence that cannabis is effective for chronic pain in adults, though much of that was based on trials of mixed THC/CBD formulations in illnesses like multiple sclerosis. More recent meta-analyses, including a VA Evidence Synthesis Program report, characterize the evidence as “low-strength” but suggest cannabis may improve neuropathic pain in some patients. There have also been small trials of cannabis extracts for pain – for instance, an open-label study in 2020 reported that a legal hemp-derived oil (high in CBD) led to significant pain reductions in a group of patients with neuropathy (this was not specific to veterans, but it demonstrated feasibility and safety). Beyond pain intensity, an important consideration is quality of life and opioid sparing. Many veterans on long-term opioids have sought to reduce their doses. As noted earlier, survey data show a sizeable fraction of veterans feel cannabis helps them use fewer opioids and other pain meds. The ongoing VA trial will objectively assess whether cannabinoids can fulfill this harm-reduction promise in a controlled setting.

Another angle being explored is how cannabinoids might alleviate the emotional component of chronic pain. Chronic pain and conditions like PTSD often feed into each other in veterans – pain can worsen insomnia and depression, which in turn amplify pain perception. Interestingly, CBD’s anxiolytic and sleep-improving effects could indirectly help pain sufferers by improving overall mental health. Some preclinical research even hints that cannabinoids induce pain relief through novel pathways: for example, by activating CB₁ receptors on pain-processing neurons, THC can dampen pain signals; CBD, while not binding strongly to CB₁, can influence inflammatory pain through immune modulation (via CB₂ receptors and other mechanisms). All of this paints a picture of cannabinoids as multi-modal agents – potentially addressing not only the sensation of pain but also the distress and insomnia that accompany it.

Evolving Research and the Road Ahead for Veterans

The body of research on cannabinoids and veterans’ health is rapidly evolving. What started as anecdotal reports and small studies has now led to large-scale clinical trials backed by government and academic institutions. This momentum is driven by a recognition that veteran issues like PTSD, suicidal ideation, chronic pain, and depression demand innovative solutions. Cannabinoid-based therapies, once on the fringes, are now being examined with the same rigor as conventional pharmaceuticals. As we’ve seen, early results are mixed but generally encouraging: PTSD-oriented studies have shown that cannabinoids can be safe for veterans and possibly helpful as adjuncts, though definitive proof of efficacy awaits larger trials. Pain studies are anticipated to clarify whether THC, CBD, or their combination best alleviates neuropathic pain – and at what doses and schedules.

Beyond formal trials, complementary lines of research will continue to enrich our understanding. Neuroscientists are mapping out how the endocannabinoid system in the brain changes after trauma, and why boosting this system might restore balance in stress circuits. For instance, lower levels of the endocannabinoid 2-AG have been found in individuals with PTSD, suggesting a potential biological target for treatment. Preclinical studies in labs are testing new cannabinoids (and related molecules) in cell and animal models of trauma, pain, and even traumatic brain injury – conditions prevalent in veteran populations. And as researchers publish findings, open-access knowledge sharing is being emphasized: many of the references in this discussion are freely available, reflecting a push to ensure that both scientists and veterans can learn from the emerging data without barriers.

Crucially, the evolving research maintains a veteran-centric perspective. Real-life stories like Sarah’s highlight both the potential and the pitfalls: cannabis was a salvation for her, but not everyone’s journey is the same. By grounding studies in veteran experiences – for example, including veterans in trial design and focusing on conditions they prioritize – the research stays aligned with actual needs. It’s also prompting changes (albeit slowly) in institutional attitudes. The VA, while still officially cautious about endorsing cannabis, is at least facilitating studies and allowing patients to discuss cannabis use without stigma. Organizations run by veterans are advocating for greater access to medical cannabis and calling for policy reform, armed with data from these new studies that they indeed “save lives, and veterans deserve full legal access”.

In summary, cannabinoid research for veteran health has moved from hope to hypothesis to active investigation. We now understand the pharmacology better – THC and CBD acting on an endogenous system that regulates fear, pain, and mood – and this guides thoughtful clinical trials. Veterans suffering PTSD flashbacks or chronic pain are no longer relegated to either standard meds or unvetted self-medication; instead, they are helping test scientifically-grounded cannabinoid therapies. The coming years will tell us which cannabinoids, at what doses and in what combinations, truly make a difference. Even as we await definitive answers, the process itself is impactful: it validates veterans’ voices and opens up new conversations between patients and providers about integrative care. For veterans like Sarah Rudder, who have given so much in service, these advancements represent more than academic progress – they represent promise. The ultimate vision is a future where a veteran can access effective, evidence-based cannabinoid options to ease physical and psychological wounds, as a proud and informed participant in their own journey of healing. Each study, each published result, brings us one step closer to that goal – a new hope steadily emerging from the intersection of science and the lived experience of our veteran community.

Sources:

1. Guernsey, E. Cannabinoid Receptors With THC (illustration of THC’s mechanism) – Wikimedia Commons (2019).
2. Loflin, M., VA San Diego – CBD + Prolonged Exposure Therapy trial interview, VA Research Currents (Feb 2019).
3. Smart, R. et al. – Warrior CARE: Cannabis Behavioral Health trial description, Wayne State Univ. (2025).
4. TrialX/VA – Proof of Concept Trial of Cannabis Derivatives in Neuropathic Pain (VA) (2025).
5. Bonn-Miller, M. et al. – Long-term impact of cannabis on PTSD symptoms: a prospective study, Cannabis Cannabinoid Res. (2020).
6. Sisley, S. et al. – First RCT of smoked cannabis for PTSD (MAPS study), PLOS ONE 16(3):e0246990 (2021).
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