Overview of the Research on Cannabis for PTSD

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) characterizes post-traumatic stress disorder (PTSD) as a disorder related to trauma or stress, associated with “exposure to actual or threatened death, serious injury or sexual violation.” There are four proposed diagnostic clusters of symptoms from which PTSD victims suffer (1):

Re-experiencing . . . spontaneous memories of the traumatic event, recurrent dreams related to it, flashbacks or other intense or prolonged psychological distress.

Avoidance . . . [of] distressing memories, thoughts, feelings or external reminders of the event.

Negative cognitions and mood represents myriad feelings, from a persistent and distorted sense of blame of self or others, to estrangement from others or markedly diminished interest in activities, to an inability to remember key aspects of the event.

Finally, arousal is marked by aggressive, reckless, or self-destructive behavior, sleep disturbances, hyper-vigilance, or related problems.

PTSD researcher George Fraser notes that while PTSD is generally associated with experiences by those in the military, “the majority” of those who actually suffer from PTSD experienced trauma related to physical or sexual abuse, traffic accidents, natural disasters, or interpersonal violence (2).

Prevalence

Estimates of the lifetime prevalence of PTSD cluster between 8% to 10%, where prevalence is estimated to be higher in women than in men (2–5). Furthermore, PTSD is estimated to be more prevalent than other anxiety disorders such as panic disorder, obsessive compulsive disorder, and generalized anxiety disorder (2).

Comorbidities

PTSD is associated with several comorbid conditions, including depression, anxiety, psychosis, and substance use disorders (4,6).

Current Treatments

PTSD is currently treated with a combination of any of a variety of psychotherapies (for example, prolonged exposure therapy, cognitive processing therapy, and extinction learning) and medications (for example, selective serotonin reuptake inhibitors [SSRIs], serotonin/norepinephrine reuptake inhibitors [SNRIs], antiadrenergic agents, and second-generation antipsychotics) (4,6–8). Unfortunately, however, current treatments are not very effective and adherence is low, generally leading victims to suffer significant impairments in long-term quality of life (2,3,6,9).

Origin

In a nutshell, “PTSD is a psychiatric condition that develops as an aberrant adaptation to a traumatic event” (10). Moreover, “the diversity of the symptoms such as flashbacks, nightmares, hyperarousal, avoidance, numbing, anxiety, anger, impulsivity, or aggression suggests the involvement of multiple neurotransmitter systems” (3). Indeed, a group of Johns Hopkins and NYU researchers described the origins of PTSD as involving many neurotransmitter systems, including: the noradrenergic, serotonergic, endogenous cannabinoid, opioid, hypothalamic-pituitary adrenal (HPA) axis, and glutamate systems (9).

Researchers have thus established that PTSD involves the endocannabinoid system (ECS) directly, and it involves many other neurotransmitter systems that, in turn, are moderated by the ECS. Given the centrality of the ECS in the emergence of PTSD, it makes sense that people who suffer from PTSD have been found to have low levels of ECS activity; that is, their ECSs are malfunctioning. Taken together, these two findings, the centrality of the ECS in modulating symptoms of PTSD and the diminished levels of ECS activity, suggest that enhancing ECS tone—such as by using cannabis—may very well help address symptoms of PTSD (4,8,11,12).

Cannabis Mechanisms of Action for Addressing Symptoms of PTSD

The major symptoms of PTSD include fear and hypervigilance, flashbacks, sleep disorders, stress and anxiety, and depression. Let’s consider each of these major symptoms of PTSD, each symptom’s emergence in the body, the role the ECS plays in this origin, and thus how cannabis may be expected to address that symptom.

Fear and Hypervigilance

Individuals who develop PTSD generally experience a traumatic event within a certain context—that is, in the presence of certain sights, sounds, or smells—and then they develop an association between the event and that context. In other words, the PTSD is “anchored” to that context, and, thereafter, whenever those same sights, sounds, or smells reappear, they trigger flashbacks of the event, together with the associated fear. This phenomenon is called fear conditioning. Most people who are conditioned by a certain trigger will eventually become deconditioned, that is, experience fear extinction. Extinction generally occurs when the trigger appears often enough in the absence of the event that initially caused the fear conditioning. Unfortunately, many people who suffer from PTSD are unable to achieve fear extinction.

Forms of behavioral therapy may help decondition fear in those who suffer from PTSD, but these therapies are often not fully effective in bringing long-term relief (5).

Experiencing fear, fear conditioning, and fear extinction all take place in a region of the brain called the amygdala, which is responsible for acquiring, storing, and forgetting memories. People who suffer from PTSD develop “hyperactivity of the amygdala.” Researchers have also shown that the amygdala contains ECS receptors and that those ECS receptors are less active in people who sufferer from PTSD (5,8–10,13,14). This underactivity of the ECS in the amygdala of people with PTSD suggests that cannabis should be effective in helping victims extinguish fear associated with traumatic memories.

In sum, PTSD victims have been conditioned to associate a particular trigger with the memory of an event, together with the fear experienced during that event. This activity takes place in the brain’s amygdala, where ECS activity has been shown to occur, but is lacking in PTSD victims. As such, cannabis may help enhance ECS activity in the amygdala and extinguish the fear associated with the trigger.

Flashbacks

Even if cannabis can help people who suffer from PTSD to extinguish the fear associated with a trigger, the memory of the traumatic event often still remains to haunt the victim.

Researchers have identified a specific region of the brain, the hippocampus, as being involved in memory learning, storage, and retrieval, and also as being overactive in sufferers of PTSD (8,10,13). Another function of the hippocampus is to actively manage memory extinction, that is, the active pruning by the brain of “unnecessary” memories (15). So the region of the brain responsible for storing and retrieving memories is not only overactive in people with PTSD, but it is also unable to forget undesirable memories.

At the same time, researchers have found ECS receptors in the hippocampus and have concluded that cannabis may help with the extinction of aversive memories in people who suffer from PTSD (7,8,11,14,16).

Noteworthy is the fact that PTSD has been “persistent and resistant to pharmacological interventions,” due to the lack of therapeutics to help with memory extinction (15). This suggests that cannabis may be a valuable new therapeutic that may very well bring new-found relief to PTSD patients.

Sleep Disorders

It is well-known that people with PTSD suffer from sleep problems, in particular delayed onset of sleep and greater numbers of awakenings during the night (8). It has been shown that cannabis (specifically, THC) can help decrease REM sleep, the stage in which nightmares occur, while enhancing deep sleep, the regenerative and restorative stage of sleep (8,11). Cannabis should thus be able to help address sleep problems in people with PTSD.

Stress and Anxiety

Any threat to our physical or emotional well-being creates stress, which then triggers our primal fight-or-flight response. Our body’s response to threats is moderated by the hypothalamic-pituitary-adrenal (HPA) axis located in our central and peripheral nervous systems (17). When we experience stress, the HPA secretes hormones that prepare our bodies to deal with those threats; for example, our heart rate and blood pressure both increase, while our digestive, reproductive, and immune system functioning decrease. Normally, hormones secreted by the HPA axis also serve as feedback mechanisms to shut down the stress response after the threat has passed. However, PTSD impairs the feedback mechanism, leading to constant states of arousal (18).

Animal studies have shown that chronic stress is associated with low levels of a certain endocannabinoid that is produced within our bodies, called AEA. Among other functions, AEA helps to alleviate stress (9). Studies have also shown that increasing the levels of cannabinoids in our bodies leads to reduction in levels of anxiety-promoting hormones, which then reduces anxiety (8,9). There is thus a clear mechanism for cannabis to reduce stress and anxiety in patients with PTSD.

Depression

Depression is a common comorbidity associated with PTSD (6,8,10). Low levels of ECS activity have been associated with depression (10), and as mentioned, victims of PTSD tend to exhibit low levels of ECS activity. Next, researchers have also linked depression to low levels of serotonin, a neurotransmitter in the body (9); indeed, primary treatments for depression, SSRIs, serve to increase levels of serotonin. Finally, researchers have shown that cannabinoids enhance serotonin levels in the body, thereby reducing symptoms of depressions (8,10). Taken together, the research thus suggests that cannabis can help address depression in PTSD suffers both directly, by increasing ECS activity in the body generally, as well as indirectly, by increasing serotonin activity.

Clinical Studies on Cannabis for PTSD

There have been a number of clinical studies of cannabis use for PTSD. One systematic review of clinical studies of cannabis for PTSD conducted in 2019 included 12 studies (10). I found an additional five studies to add to this review (19–23). As emphasized by the systematic reviewers, these dozen and a half studies are quite varied in methodology and generally low-powered. That being said, these studies generally show that cannabis improves symptoms associated with PTSD, including stress, anxiety, depression, nightmares, sleep, and fear extinction.

Concerns Regarding Cannabis and PTSD

Researchers of cannabis use for PTSD expressed a couple of concerns: First, higher doses of THC may provoke anxiety or psychosis in cannabis users. And second, high coincidences of cannabis use disorder are found in people who suffer from PTSD.

Anxiogenic and Propsychotic Potential of THC

It is well-known that low doses of THC generally reduce anxiety, while higher doses may very well promote either anxiety or psychosis (6,10). For a population of individuals who already suffer from anxiety, any risk of exacerbating this sensation is not welcome. Researchers do point out, however, that CBD has garnered interest as potentially reducing anxiety, where CBD may be used either on its own or in tandem with THC to mitigate any anxiety-promoting risks of THC (6).

PTSD and Addiction

There’s a high prevalence of cannabis use in people who suffer from PTSD. There is also a high prevalence of substance use disorders (SUD) in PTSD sufferers, involving either cannabis, alcohol, or other drugs. Orsolini and colleagues note, “It has been estimated that individuals with PTSD are 2–4 times more likely to have a SUD compared to individuals without PTSD” (10,13).

Researchers recognize that people who suffer from PTSD are likely to use cannabis or other substances to self-medicate. In fact, surveys of PTSD sufferers who use cannabis specifically indicate they do so because it helps relieve their symptoms (10,22,23).

At the same time, Orsolini and colleagues make the interesting observation that the malfunctions in circuitry that cause PTSD are the same malfunctions involved with development of addiction. In other words, rather than SUDs being the result of PTSD victims’ attempts to self-medicate, victims may be predisposed to addiction for the very same reasons they were vulnerable to PTSD (10).

In Sum

PTSD is a disorder in which an individual’s threat response fails to adequately disengage after he or she has experienced a traumatic event. The areas of the brain responsible for engaging and then disengaging our threat responses have been shown to be high in ECS activity in healthy individuals, while being much less active in people who suffer from PTSD. It follows that cannabis would be expected to help address symptoms of PTSD. Much preclinical work has, indeed, established this potential. To date, clinical evidence supporting the efficacy of cannabis for PTSD has been positive in nature but weak in power; hopefully stronger clinical evidence will be forthcoming.

References

(1) Posttraumatic Stress Disorder. (2013) American Psychiatric Association. Retrieved from www.psychiatry.org/File%20Library/Psychiatrists/Practice/DSM/APA_DSM-5-PTSD.pdf

(2) G. Fraser,. (2009). The Use of a Synthetic Cannabinoid in the Management of Treatment-Resistant Nightmares in Posttraumatic Stress Disorder (PTSD). CNS Neuroscience & Therapeutics. Retrieved from www.ncbi.nlm.nih.gov/pmc/articles/PMC6494011/pdf/CNS-15-84.pdf

(3) V. Trezza and P. Campolongo, (2013). The endocannabinoid system as a possible target to treat both the cognitive and emotional features of post-traumatic stress disorder (PTSD). Front Behav Neurosci. Retrieved from pubmed.ncbi.nlm.nih.gov/23950739/

(4) S. Chan, et al (2017). Medical cannabis use for patients with post-traumatic stress disorder (PTSD). Journal of Pain Management. Retrieved from www.researchgate.net/publication/324088961_Medical_cannabis_use_for_patients_with_post-traumatic_stress_disorder_PTSD

(5) S. Maren. and A. Holmes, (2016). Stress and Fear Extinction. Neuropsychopharmacology. Retrieved from www.nature.com/articles/npp2015180.pdf

(6) M. Steenkamp, et al (2016). Marijuana and other cannabinoids as a treatment for posttraumatic stress disorder: A literature review. Depress Anxiety. Retrieved from pubmed.ncbi.nlm.nih.gov/28245077/

(7) L. Elms, et al (2019). Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series. Journal of Alternative and Complementary Medicine. Retrieved from pubmed.ncbi.nlm.nih.gov/30543451/

(8) T. Passie, et al (2012). Mitigation of post-traumatic stress symptoms by Cannabis resin: A review of the clinical and neurobiological evidence. Drug Test Anal. Retrieved from pubmed.ncbi.nlm.nih.gov/22736575/

(9) C. Bailey, et al (2013). Recent Progress in Understanding the Pathophysiology of Post-Traumatic Stress Disorder: Implications for Targeted Pharmacological Treatment. CNS Drugs. https://pubmed.ncbi.nlm.nih.gov/23483368/

(10) L. Orsolini, et al (2019). Use of Medicinal Cannabis and Synthetic Cannabinoids in Post-Traumatic Stress Disorder (PTSD): A Systematic Review. Medicina (Kaunas). Retrieved from pubmed.ncbi.nlm.nih.gov/31450833/

(11) P. Roitman, et al (2014). Preliminary, Open-Label, Pilot Study of Add-On Oral D9-Tetrahydrocannabinol in Chronic Post-Traumatic Stress Disorder. Clin Drug Investig. Retrieved from pubmed.ncbi.nlm.nih.gov/24935052/

(12) S. Stoner, (2017). Effects of Marijuana on Mental Health: Posttraumatic Stress Disorder (PTSD). University of Washington. Retrieved from adai.uw.edu/pubs/pdf/2017mjptsd.pdf

(13) L. Shishko, et al (2018). A review of medical marijuana for the treatment of posttraumatic stress disorder: Real symptom re-leaf or just high hopes? Mental Health Clinician. Retrieved from www.researchgate.net/publication/326089217_A_review_of_medical_marijuana_for_the_treatment_of_posttraumatic_stress_disorder_Real_symptom_re-leaf_or_just_high_hopes

(14) S. Yarnell, (2015). The Use of Medicinal Marijuana for Posttraumatic Stress Disorder: A Review of the Current Literature. Prim Care Companion CNS Discord. Retrieved from www.ncbi.nlm.nih.gov/pmc/articles/PMC4578915/

(15) S. Ahmad, (2020). The Science of Memory Extinction. Psychology Today. Retrieved from www.psychologytoday.com/us/blog/balanced/202002/the-science-memory-extinction

(16) A. Berardi, G. Schelling, and P. Campolongo, (2016). The endocannabinoid system and Post Traumatic Stress Disorder (PTSD): From preclinical findings to innovative therapeutic approaches in clinical settings. Pharmacol Res. Retrieved from pubmed.ncbi.nlm.nih.gov/27456243/

(17) S. Smith and W. Vale, (2006). The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci. Retrieved from www.ncbi.nlm.nih.gov/pmc/articles/PMC3181830/

(18) Stress System Malfunction Could Lead to Serious, Life Threatening Disease. (2002, Sep 9) National Institute of Child Health and Human Development. Retrieved from www.nichd.nih.gov/newsroom/releases/stress

(19) L. Ruglass, et al. (2017). Impact of Cannabis Use on Treatment Outcomes among Adults Receiving Cognitive-Behavioral Treatment for PTSD and Substance Use Disorders. City University of New York. Retrieved from academicworks.cuny.edu/cgi/viewcontent.cgi?article=1520&context=cc_pubs

(20) R. Das et al. (2013). Cannabidiol enhances consolidation of explicit fear extinction in humans. Psychopharmacology. Retrieved from link.springer.com/article/10.1007/s00213-012-2955-y

(21) C. Rabinak, et al. (2012). Cannabinoid facilitation of fear extinction memory recall in humans. Neuropharmacology. Retrieved from www.ncbi.nlm.nih.gov/pmc/articles/PMC3445738/

(22) I. Reznik (2011). Medical cannabis use in post-traumatic stress disorder: a naturalistic observational study. The journal of the European College of Neuropsychopharmacology. Retrieved from www.researchgate.net/publication/288356711_P4a011_Post-traumatic_stress_disorder_and_medical_cannabis_use_a_naturalistic_observational_study

(23) K. Villagonzalo et al. (2010). The relationship between substance use and posttraumatic stress disorder in a methadone maintenance treatment program. Comprehensive Psychiatry. Retrieved from www.sciencedirect.com/science/article/abs/pii/S0010440X10001689

About the Author

Ruth Fisher, PHD, is a systems design researcher and analyst. She analyzes markets to determine how environments shape outcomes. She is co-founder of CannDynamics, Inc., and author of The Medical Cannabis Primer and Winning the Hardware-Software Game: Using Game Theory to Optimize the Pace of New Technology Adoption. Dr. Fisher has worked in the technology and healthcare sectors on behalf of technology companies, early-stage researchers, physicians, and technology start-ups.