Short and Long-Term Effects of Cannabis on Symptoms of Post-Traumatic Stress Disorder

Emily M. LaFrance, Nicholas C. Glodosky, Marcel Bonn-Miller, Carrie Cuttler

Journal of Affective Disorders, 2020, 274, 298–304

Doi : 10.1016/j.jad.2020.05.132

 

A B S T R A C T

Background : Many individuals use cannabis to manage symptoms of post-traumatic stress disorder (PTSD), and evidence indicates that the endocannabinoid system represents a viable target for treating these symptoms.

Method : Data from 404 medical cannabis users who self-identified as having PTSD were obtained from Strainprint®, a medical cannabis app that patients use to track changes in symptoms as a function of different strains and doses of cannabis across time. This sample collectively used the app 11,797 times over 31 months to track PTSD-related symptoms (intrusive thoughts, flashbacks, irritability, and/or anxiety) immediately before and after inhaling cannabis. Latent change score models were used to examine changes in symptom severity and predictors of these changes (gender, dose, cannabis constituents, time). Multilevel models were used to explore long-term consequences of repeatedly using cannabis to manage these symptoms.

Results : All symptoms were reduced by more than 50% immediately after cannabis use. Time predicted larger decreases in intrusions and irritability, with later cannabis use sessions predicting greater symptom relief than earlier sessions. Higher doses of cannabis predicted larger reductions in intrusions and anxiety, and dose used to treat anxiety increased over time. Baseline severity of all symptoms remained constant across time.

Limitations : The sample was self-selected, self-identified as having PTSD, and there was no placebo control group.

Conclusions : Cannabis provides temporary relief from PTSD-related symptoms. However, it may not be an effective long-term remedy as baseline symptoms were maintained over time and dose used for anxiety increased over time, which is indicative of development of tolerance.

Keywords : Cannabis, PTSD, Intrusions, Flashbacks, Anxiety, Irritability

 

1. Introduction

Post-traumatic stress disorder (PTSD) is a disorder of recovery following the experience of a traumatic event, characterized by alterations in arousal and reactivity including irritability, sleep disturbances, and hypervigilance; intrusion symptoms including intrusive distressing memories, flashbacks, and nightmares; persistent avoidance of stimuli associated with the traumatic event(s); and disturbances in cognition and mood (APA, 2013). Lifetime prevalence of PTSD has been estimated to be around 6.8% to 8.7% of the U.S. population (APA, 2013; Kessler, Berglund, et al., 2005), with past-year prevalence of approximately 3.5% (APA, 2013; Kessler, Chiu et al., 2005). Epidemiological studies have demonstrated an over two-fold greater lifetime prevalence of PTSD among women (9.7%) compared to men (3.6%) (NCS, 2005).

While a number of effective behavioral treatments are available for individuals with PTSD (e.g., cognitive processing therapy, prolonged exposure), pharmacological interventions typically involve the use of selective serotonin reuptake inhibitors (SSRIs) which generally have small effect sizes and have been associated with various undesirable side effects, low rates of symptom remission, and high rates of dropout (Berger et al., 2009; Cipriani et al., 2018). As such, many organizations (e.g., the International Society for Traumatic Stress Studies [ISTSS, nd], 2018 Department of Veteran Affairs/Department of Defense [VA/DOD, 2017] recommend therapy as the first-line treatment for PTSD, rather than SSRIs or other pharmacological interventions.

While documented evidence of therapeutic effects of cannabis on PTSD symptoms remains somewhat sparse, emerging evidence indicates that the endocannabinoid system may represent a viable target for treating PTSD. Specifically, there is evidence that PTSD may be related to deficiencies in the endocannabinoid system (Hill et al., 2018; Neumeister et al., 2013) and these deficiencies have been associated with more severe symptoms of PTSD including anxiety and extinction of aversive memories (Bluett et al., 2014; Hill et al., 2013). Indeed there is now solid evidence that cannabinoids reduce responses to conditioned fear cues, impair retrieval of emotionally aversive memories, and promote the extinction of fear memories (Atsak et al., 2012; Bitencourt et al., 2008; Das et al., 2013; Do Monte et al., 2013; Gomes et al., 2012; Lemos et al., 2010; Pamplona et al., 2006) suggesting that targeting the endocannabinoid system may hold promise for reducing PTSD-related intrusions and flashbacks. Indeed, a recent double-blind placebo-controlled trial found that inhibition of fatty acid amide 31 hydrolase (FAAH; which inhibits the breakdown of the endocannabinoid anandamide) increased levels of anandamide in healthy cadults which in turn enhanced fear extinction and attenuated autonomic stress reactivity (Mayo et al., 2019).

Consistent with this largely preclinical evidence, an open label clinical trial provided evidence that nabilone (a synthetic analogue of delta-9-tetrahydrocannabinol; THC) reduced nightmares, improved sleep, and reduced flashbacks in patients diagnosed with PTSD (Fraser et al., 2009). Similarly, a retrospective study indicated that nabilone is effective in reducing insomnia, nightmares, and other PTSD symptoms (Cameron et al., 2014). Moreover, the results of a doubleblind placebo-controlled cross-over study indicated that nabilone significantly reduced nightmares, improved PTSD symptom severity, and enhanced general wellbeing in 10 men with PTSD (Jetly et al., 2015). However, the sample sizes used in these studies are modest and most of the aforementioned studies relied on synthetic THC or other cannabinoids rather than examining the potential therapeutic effects of whole plant cannabis or phytocannabinoids (i.e., cannabinoids obtained from the cannabis plant).

Nevertheless, a growing number of individuals with PTSD are using cannabis (Bonn-Miller et al., 2012; Bonn-Miller & Rousseau, 2014), with both trauma exposure and PTSD diagnosis having been associated with increased odds of cannabis use in nationally representative samples (Cougle et al., 2011; Kevorkian et al., 2015). Studies have suggested that those with PTSD turn to cannabis when existing psychological or pharmacological interventions fail (Bonn-Miller et al., 2011). Indeed, cannabis appears to be used by this population, specifically, to cope with negative affect and sleep difficulties (Betthauser et al., 2015; Bonn-Miller et al., 2007; 2014). A recent study that utilized ecological momentary assessment (EMA) to determine the antecedents and consequences of cannabis use among trauma-exposed young adults exhibiting PTSD symptoms demonstrated that PTSD hyperarousal symptoms were predictive of subsequent cannabis use, which in turn was associated with reductions in state anxiety (Buckner et al., 2018).

However, the cannabinoid content of the cannabis used by participants was not assessed and ratings were not taken immediately prior to and following use of cannabis, preventing the analysis of acute, withinmoment effects (Buckner et al., 2018). Another major limitation of the body of research on PTSD and cannabis/cannabinoids has been the paucity of longitudinal data which has obscured understanding of whether cannabinoids need to be administered chronically, or if acute doses are sufficient to reduce PTSD symptoms (Loflin et al., 2017). Failures to consider long-term effects of cannabis use on PTSD is particularly concerning given that the chronic cannabis use is associated with a broad range of negative outcomes (Karila et al., 2014). Therefore, two recent studies have extended prior work by examining the short- (3 week) and long-term (12 month) effects of cannabis with different ratios of THC and cannabidiol (CBD) on PTSD symptomatology (Bonn-Miller, Brunstetter et al., submitted; Bonn-Miller, Sisley et al., submitted). Findings suggest that THCdominant, CBD-dominant, and balanced THC:CBD cannabis preparations were associated with short-term reductions in PTSD symptoms, though none separated from placebo ((Bonn-Miller, Sisley et al., submitted).

However, long-term use of primarily THC-dominant cannabis was associated with lower PTSD symptomatology (primarily driven by reductions in hyperarousal symptoms) as well as a greater than two-fold reduction in the likelihood of PTSD diagnosis at 12 months, relative to non-users (Bonn-Miller, Brunstetter et al., submitted).

The present study was designed to address the limitations of the extant literature by using a very large dataset to examine changes in PTSD symptomatology (intrusions, flashbacks, irritability, anxiety) from immediately before, to shortly after, cannabis use as well as potential predictors of these symptom changes including gender, dose, THC concentrations, CBD concentrations, and THC x CBD interactions. We further sought to explore potential long-term consequences of repeatedly using cannabis to manage symptoms of PTSD by investigating changes in the efficacy of cannabis, changes in dose, and changes in baseline PTSD symptoms (i.e., symptom severity ratings before each cannabis use session) across cannabis use sessions over a 31-month time period.

(…)

ptsd.main