Cannabis use among U.S. military veterans with subthreshold or threshold posttraumatic stress disorder: Psychiatric comorbidities, functioning, and strategies for coping with posttraumatic stress symptoms.

Cannabis use is common among individuals with posttraumatic stress disorder (PTSD) symptoms, but its impact on psychiatric symptoms and functioning in this population is unclear. To clarify the clinical and functional correlates of cannabis use in individuals with PTSD symptoms, we analyzed data from the 2019-2020 National Health and Resilience in Veterans Study, a nationally representative survey of U.S. military veterans. Participants with current subthreshold or full PTSD (N = 608) reported on their past-6-month cannabis use and current psychiatric symptoms, functioning, treatment utilization, and PTSD symptom management strategies. Veterans with subthreshold/full PTSD who used cannabis more than weekly were more likely to screen positive for co-occurring depression, anxiety, and suicidal ideation than those who did not use cannabis, ORs = 3.4-3.8, or used cannabis less than weekly, ORs = 2.7-3.7. Veterans who used cannabis more than weekly also scored lower in cognitive functioning than veterans with no use, d = 0.25, or infrequent use, d = 0.71, and were substantially more likely to endorse avoidance coping strategies, ORs = 8.2-12.2, including substance use, OR = 4.4, and behavioral disengagement, ORs = 2.7-9.1, to manage PTSD symptoms. Despite more psychiatric and functional problems, veterans with frequent cannabis use were not more likely to engage in mental health treatment, ORs = 0.87-0.99. The results suggest enhanced cannabis use screening, interventions targeting risky use, and strategies promoting treatment engagement may help ameliorate more severe clinical presentations associated with frequent cannabis use among veterans with subthreshold/full PTSD.

The Long-Term, Prospective, Therapeutic Impact of Cannabis on Post-Traumatic Stress Disorder.

Introduction: Given the increasing availability and use of cannabis among individuals with post-traumatic stress disorder (PTSD) and the addition of PTSD as an eligible diagnosis in several U.S. medical cannabis programs, the efficacy of dispensary-obtained cannabis needs to be thoroughly examined. Materials and Methods: This prospective study assessed PTSD symptoms and functioning every 3 months over the course of a year in two samples of participants diagnosed with PTSD: (1) those with PTSD using dispensary-obtained cannabis (cannabis users) and (2) those with PTSD, who do not use cannabis (controls). Linear mixed-effects models and generalized estimating equations tested whether trajectories of symptoms differed between the two subsamples. Results: A total of 150 participants (mean [standard deviation] age, 50.67 [15.26] years; 73% male) were enrolled in the study. Over the course of 1 year, the cannabis users reported a greater decrease in PTSD symptom severity over time compared to controls [group×time interaction=-0.32 (95% confidence interval [CI]=-0.59 to -0.05, R2=0.13; t=-2.35, p=0.02). Participants who used cannabis were 2.57 times more likely to no longer meet DSM-5 criteria for PTSD at the end of the study observation period compared to participants who did not use cannabis (95% CI=1.12-6.07; p=0.03). Conclusions: This study provides evidence that the types of cannabis available in recreational and medical cannabis dispensaries might hold promise as an alternative treatment for PTSD. Randomized placebo-controlled trials are needed to assess safety and determine how different preparations of cannabis impact PTSD and functioning.

A Cross-Sectional and Prospective Comparison of Medicinal Cannabis Users and Controls on Self-Reported Health.

Introduction: Despite widespread legalization, the impact of medicinal cannabis use on patient-level health and quality of life (QOL) has not been carefully evaluated. The objective of this study was to characterize self-reported demographics, health characteristics, QOL, and health care utilization of Cannabis Users compared with Controls. Methods: A longitudinal, cross-sectional web-based survey study was completed between April 2016 and February 2018. Study participants (n=1276) were a convenience sample of either patients with a diagnosed health condition or caregivers of a patient with a diagnosed health condition registered with the Realm of Caring Foundation (a nonprofit organization dedicated to therapeutic cannabis research and education). Participants were invited through e-mail to complete follow-up assessments every 3 months with 33% of participants completing one or more prospective follow-ups. Assessments included self-reported demographics, health care utilization, medication use, pain, anxiety, depression, sleep, and QOL. Cannabis Users (n=808) were compared with Controls (n=468) using negative binomial regression and linear mixed effects models testing the effect of initiation, cessation, and maintenance of medicinal cannabis use. Results: Cannabis Users self-reported significantly better QOL [t(1054)=-4.19, p<0.001], greater health satisfaction [t(1045)=-4.14, p<0.001], improved sleep [children: t(224)=2.90, p<0.01; adults: [t(758)=3.03, p<0.01], lower average pain severity [t(1150)=2.34, p<0.05], lower anxiety [t(1151)=4.38, p<0.001], and lower depression [t(1210)=5.77, p<0.001] compared with Controls. Cannabis Users reported using fewer prescription medications (rate ratio [RR]=0.86; 95% confidence interval [CI]: 0.77-0.96) and were less likely to have a past-month emergency department visit (RR=0.61; 95% CI: 0.44-0.84) or hospital admission (RR=0.54; 95% CI: 0.34-0.87). Controls who initiated cannabis use after baseline showed significant health improvements at follow-up, and the magnitude of improvement mirrored the between-group differences observed at baseline. Conclusions: Cannabis use was associated with improved health and QOL. Longitudinal testing suggests that group differences may be due to the medicinal use of cannabis. Although bias related to preexisting beliefs regarding the health benefits of cannabis in this sample should be considered, these findings indicate that clinical trials evaluating the efficacy of defined cannabinoid products for specific health conditions are warranted.

Prevalence of cannabis use, disorder, and medical card possession in U.S. military veterans: Results from the 2019-2020 National Health and Resilience in Veterans Study.

More than half of U.S. states legalized medical or recreational sale and possession of cannabis since the prevalence of cannabis use was last estimated among U.S. military veterans in 2014. To provide updated estimates of the prevalence and correlates of cannabis use, cannabis use disorder (CUD), and medical cannabis card possession in this population, data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, a nationally representative survey of 4,069 veterans ages 22-99 years who reported on their past-6-month cannabis use, CUD symptoms, and possession of a medical cannabis card. An estimated 11.9% [95% confidence interval (CI) = 10.9-12.9%)] of veterans reported using cannabis, 2.7% (95% CI = 2.3-3.3%) screened positive for CUD, and 1.5% (95% CI = 1.2-2.0%) reported possessing a medical card. Prevalence of cannabis use, CUD, and card possession were higher among younger veterans (use: 20.2%, CUD: 5.6%, card: 2.1%) and those with psychiatric conditions (use: 24.0%-30.0%, CUD: 8.9%-13.0%, card: 3.1%-4.0%). Younger age, alcohol use disorder, and childhood adversity explained a large proportion of variance in cannabis use and CUD, and depression was independently associated with CUD (odds ratio [OR] = 2.76). Physical disability (OR = 3.59), combat veteran status (OR = 2.84), and non-Hispanic black (OR = 0.23) relative to white race/ethnicity most strongly predicted using cannabis with a medical card. The estimated prevalence of cannabis use in veterans-nearly 12%-is higher than the most recently reported estimate (9% in 2014). Veteran cannabis use may be increasing and is particularly prevalent among veterans with psychiatric conditions.

The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial.

IMPORTANCE: There is a pressing need for development of novel pharmacology for the treatment of Posttraumatic Stress Disorder (PTSD). Given increasing use of medical cannabis among US military veterans to self-treat PTSD, there is strong public interest in whether cannabis may be a safe and effective treatment for PTSD. OBJECTIVE: The aim of the present study was to collect preliminary data on the safety and potential efficacy of three active concentrations of smoked cannabis (i.e., High THC = approximately 12% THC and < 0.05% CBD; High CBD = 11% CBD and 0.50% THC; THC+CBD = approximately 7.9% THC and 8.1% CBD, and placebo = < 0.03% THC and < 0.01% CBD) compared to placebo in the treatment of PTSD among military veterans. METHODS: The study used a double-blind, cross-over design, where participants were randomly assigned to receive three weeks of either active treatment or placebo in Stage 1 (N = 80), and then were re-randomized after a 2-week washout period to receive one of the other three active treatments in Stage 2 (N = 74). The primary outcome measure was change in PTSD symptom severity from baseline to end of treatment in Stage 1. RESULTS: The study did not find a significant difference in change in PTSD symptom severity between the active cannabis concentrations and placebo by the end of Stage 1. All three active concentrations of smoked cannabis were generally well tolerated. CONCLUSIONS AND RELEVANCE: The present study is the first randomized placebo-controlled trial of smoked cannabis for PTSD. All treatment groups, including placebo, showed good tolerability and significant improvements in PTSD symptoms during three weeks of treatment, but no active treatment statistically outperformed placebo in this brief, preliminary trial. Additional well-controlled and adequately powered studies with cannabis suitable for FDA drug development are needed to determine whether smoked cannabis improves symptoms of PTSD. TRIAL REGISTRATION: Identifier: NCT02759185; ClinicalTrials.gov.

Comparative associations of problematic alcohol and cannabis use with suicidal behavior in U.S. military veterans: A population-based study.

Alcohol use disorder (AUD) and cannabis use disorder (CUD) are each associated with increased suicidal behavior, but it is unclear how their comorbidity relates to suicide risk. Understanding these associations in U.S. military veterans is especially important, given their heightened risk for suicide, high prevalence of AUD, and increasing access to cannabis. We compared associations of probable AUD, CUD, and AUD/CUD with suicide ideation, plan(s), and attempt(s) in a nationally representative sample of 4,069 veterans surveyed in 2019-2020 as part of the National Health and Resilience in Veterans Study. Among veterans who screened positive for current AUD, 8.7% also screened positive for current CUD. Among veterans who screened positive for current CUD, 33.3% screened positive for current AUD. Current and lifetime positive screens for AUD, CUD, and AUD/CUD were each strongly and independently associated with past-year suicide ideation and lifetime suicide ideation, plan(s), and attempt(s) [odds ratios (ORs) = 1.6-8.7]. Relative to veterans who screened positive for AUD only, veterans who screened positive for AUD/CUD and CUD only had higher odds of past-year suicide ideation (AUD/CUD: OR = 3.3; CUD only: OR = 2.4), lifetime suicide ideation (AUD/CUD: OR = 1.9; CUD only: OR = 2.6) and lifetime suicide plan(s) (AUD/CUD: OR = 1.7; CUD only: OR = 6.1). Collectively, findings suggest that screening positive for CUD might be an especially strong indicator of suicide ideation and planning in veterans with and without AUD, independent of sociodemographic, military, trauma, and other psychiatric factors. These findings underscore the importance of routine screening for CUD in suicide prevention efforts, especially as cannabis becomes more widely available.

Burden of cannabis use and disorder in the U.S. veteran population: Psychiatric comorbidity, suicidality, and service utilization.

BACKGROUND: Cannabis use is associated with psychiatric illness and suicidality, which are prevalent among U.S. military veterans. However, the psychiatric burden of cannabis use and cannabis use disorder (CUD) among veterans is unclear. Using data from a nationally representative sample of veterans, we evaluated associations of lifetime cannabis use and CUD with psychiatric problems, suicidality, and treatment utilization. METHODS: Participants were 3,157 veterans aged 21 to 96 years from the National Health and Resilience in Veterans Study (NHRVS). Cannabis use and CUD were assessed using the Mini International Neuropsychiatric Interview. Psychiatric morbidities, suicidal ideation and attempts, and treatment utilization were assessed and compared between three cannabis groups: [1] no lifetime cannabis use (never-use); [2] lifetime cannabis use but never met criteria for CUD (non-CUD cannabis use); [3] lifetime CUD (CUD). RESULTS: Relative to the never-use group, veterans who used cannabis had elevated odds of current and lifetime posttraumatic stress disorder (PTSD), mood, anxiety, and substance use disorders, current suicidal ideation, lifetime suicide attempts, and current and lifetime mental health treatment utilization [odds ratios (ORs)=1.5-8.3]. Veterans with CUD had higher odds of current and lifetime PTSD, mood, and anxiety disorders, lifetime nicotine and alcohol dependence, and current suicidal ideation, relative to veterans who used cannabis but never met criteria for CUD (ORs=1.6-2.7). LIMITATIONS: The cross-sectional design of this study precludes causal inference. CONCLUSIONS: Cannabis use and CUD are associated with substantial psychiatric and suicide-related burden among veterans, highlighting the need for screening, education, and treatment to mitigate potential cannabis-related harm.

The state of clinical outcome assessments for cannabis use disorder clinical trials: A review and research agenda.

There is considerable variability in the use of outcome measures in clinical trials for cannabis use disorder (CUD), and a lack of consensus regarding optimal outcomes may have hindered development and approval of new pharmacotherapies. The goal of this paper is to summarize an evaluation of assessment measures and clinical endpoints for CUD clinical trials, and propose a research agenda and priorities to improve CUD clinical outcome assessments. The primary recommendation is that sustained abstinence from cannabis should not be considered the primary outcome for all CUD clinical trials as it has multiple limitations. However, there are multiple challenges to the development of a reliable and valid indicator of cannabis reduction, including the lack of a standard unit of measure for the various forms of cannabis and products and the limitations of currently available biological and self-report assessments. Development of a core toolkit of assessments is needed to both allow flexibility for study design, while facilitating interpretation of outcomes across trials. Four primary agenda items for future research are identified to expedite development of improved clinical outcome assessments for this toolkit: (1) determine whether minimally invasive biologic assays could identify an acute level of cannabis use associated with psychomotor impairment or other cannabis-related harms; (2) create an indicator of quantity of cannabis use that is consistent across product types; (3) examine the presence of cannabis-specific functional outcomes; and (4) identify an optimal duration to assess changes in CUD diagnostic criteria.

Aversiveness and Meaningfulness of Uncomfortable Experiences with Edible Cannabis.

Cannabis remains the most frequently used illicit drug in the United States. As its legal status has changed, more people have turned to oral administration ("edibles"). 172 individuals who reported an uncomfortable experience with edible cannabis completed an online survey. Despite the aversive nature of the experience, 62.9% of the sample reported that the edible experience was at least somewhat meaningful and the majority of participants (95.2%) did not report any medical problems. The most common non-medical problem reported was going to bed early or lying down (75.8%). Most participants (69.2%) reported that dose was the key contributor to their negative experience. Participants who rated the experience as more aversive were less likely to use edibles again, r (167) = - .180, p < . 05. In addition, the duration of the aversive experience correlated positively with aversiveness rating, r (167) = . 244, p < . 05. With increased legalization of cannabis, edible use may rise. Dose seems to be associated with uncomfortable experiences with edible cannabis. Notwithstanding these uncomfortable experiences, the vast majority of the sample used cannabis edibles again, reported that the experience was at least somewhat meaningful, and did not report significant problems associated with the experience.

A cross-sectional examination of choice and behavior of veterans with access to free medicinal cannabis.

Background: With a rise in public pressure to increase veteran access to medicinal cannabis, free cannabis collectives for military veterans are proliferating across the US. Objectives: The aim of the current study was to document which cannabis formulations and routes of administration are chosen by veterans with increased access to cannabis, and to determine whether cannabis is being used as a substitute for other licit and illicit drugs. Method: The current study collected cross-sectional self-report data on cannabis use, cannabinoid constituent composition, primary indication of use, and substitution practices among a sample of 93 US military veterans (84.9% male) with access to free cannabis. Result: Most of the sample reported using cannabinoids as a substitute for either alcohol, tobacco, prescription medications, or illicit substances, reported that they use cannabis frequently (Modal frequency >4x/day, Modal quantity = 5 to 8 grams/week), and primarily select higher-risk cannabis formulations (i.e., high THC/low CBD, smoked). The majority of the sample reported that they use cannabis to self-treat multiple physical and mental health conditions/symptoms. Conclusions: Results of the current study suggest that military Veterans with reduced barriers to access cannabis could be making both helpful and harmful choices regarding their cannabis use. These findings suggest that more guidance on the selection of cannabis-based products in this population is warranted, particularly as barriers to medicinal cannabis access are reduced.

Navigating Blind in the Green Rush: Clinical Considerations and Harm Reduction Practices for Cannabis.

BACKGROUND: The United States has recently experienced extensive changes in state policy regarding the use of cannabis for recreational and medicinal purposes. Despite its rapidly increasing accessibility and social acceptance, there is a striking dearth of research on cannabis as a treatment for medical and psychological conditions. Research on cannabis is difficult to conduct as it is classified as a schedule I drug with high potential for abuse and currently no accepted medical use in treatment. As a result, no standard dosing procedures exist and the lack of conclusive scientific evidence has left clinical providers without evidence-based guidelines about if, when, and how to guide clients on using cannabis safely. OBJECTIVE: To (1) provide critical psychoeducational information about cannabis and cannabis problems to guide client-provider conversations about cannabis use and (2) describe common clinical concerns around cannabis use, highlight special considerations for vulnerable populations, and review harm reduction techniques and practical resources that may help clinicians and their clients navigate safer cannabis use. CONCLUSION: The removal of regulatory barriers would enable researchers to address key public health questions about the potential therapeutic and adverse effects of cannabis use. Additionally, funds for research, clinician education, and public health education initiatives are necessary to reduce risk around cannabis use in the United States.

Cannabis and cannabinoid drug development: evaluating botanical versus single molecule approaches.

Accumulating evidence suggests that the endocannabinoid system is a promising target for the treatment of a variety of health conditions. Two paths of cannabinoid drug development have emerged. One approach is focused on developing medications that are directly derived from the cannabis plant. The other utilizes a single molecule approach whereby individual phytocannabinoids or novel cannabinoids with therapeutic potential are identified and synthesized for pharmaceutical development. This commentary discusses the unique challenges and merits of botanical vs single molecule cannabinoid drug development strategies, highlights how both can be impacted by legalization of cannabis via legislative processes, and also addresses regulatory and public health considerations that are important to consider as cannabinoid medicine advances as a discipline.

Assessment of the validity of the CUDIT-R in a subpopulation of cannabis users.

BACKGROUND: The Cannabis Use Disorders Identification Test-Revised (CUDIT-R) is an 8-item measure used to screen for cannabis use disorders (CUD). Despite widespread use of the tool, assessments of the CUDIT-R's validity in subpopulations are limited. OBJECTIVES: The current study tested the structural validity and internal consistency of one of the most widely used screening measures for CUD (i.e., CUDIT-R) among a sample of military veterans who use cannabis for medicinal purposes. METHODS: The present study used confirmatory factor analysis (CFA) to test the internal consistency and validity of the single-factor structure of the original screener among a sample of veterans who use cannabis for medicinal purposes (n = 90 [90% male]; Mage = 55.31, SD = 15.37). Measures included demographics and the CUDIT-R, obtained from the baseline assessment of an ongoing longitudinal study. RESULTS: The CFA revealed that the single-factor model previously validated in recreational using samples only accounted for 38.34% of total variance in responses on the CUDIT-R (χ2 = 66.09, df = 28, p < 0.05; RMSEA = 0.06) and demonstrated acceptable but modest internal consistency (Cronbach's α = 0.73). CONCLUSION: More psychometric work is needed to determine the reliability and validity of using the CUDIT-R to screen for CUD among military veterans who use medicinal cannabis and other subpopulations of cannabis users.

Placebo Effects of Edible Cannabis: Reported Intoxication Effects at a 30-Minute Delay.

Previous research has demonstrated the ability of non-active smoked cannabis cigarettes to induce subjective effects of intoxication (i.e., placebo effect). No studies have been conduced to test whether edible forms of cannabis, which are associated with a significant delay in onset of effect, are able to induce a placebo effect. In the present study, 20 participants were told that they would receive an edible cannabis lollipop containing a high dose of tetrahydrocannabinol (THC), but were instead given a placebo control. Measures of intoxication and mood were taken at baseline, 30 minutes, and 60 minutes post-ingestion of the placebo lollipop. Results of four repeated-measures ANOVAs found significant and quadratic changes across time in cannabis (ARCI m-scale) intoxication (F(2,18) = 4.90, p = .01, η2 = .22) and negative mood (F(2,18) = 3.99, p = .05, η2 = .19). Changes in positive mood and the overall measure of general intoxication (ARCI) failed to reach significance. The present study provides preliminary evidence that a placebo effect can be induced with inert edible agents when participants are told that they are receiving active THC. This is the first known study to demonstrate an edible cannabis intoxication placebo effect.

Cannabinoids as therapeutic for PTSD.

Limited efficacy for current pharmacotherapy for PTSD indicates that improved pharmacological treatments are needed. Neurobiological research points to cannabinoids as possible therapeutic agents of interest. Moreover, observational reports indicate that there is growing popular interest in therapeutic use of cannabinoids for the alleviation of trauma symptoms. The aim of this review was to present an up-to-date look at current research on the possible therapeutic value of cannabinoids for PTSD. Experimental, preclinical, and clinical findings are discussed.

Medicinal versus recreational cannabis use: Patterns of cannabis use, alcohol use, and cued-arousal among veterans who screen positive for PTSD.

INTRODUCTION: The present study is the first to test whether veterans who use cannabis specifically for the purposes of self-medication for their reported PTSD symptoms differ from veterans who use cannabis medicinally for other reasons, or recreationally, in terms of patterns of cannabis use, use of alcohol, and reactivity to written combat trauma reminders. METHODS: Assessment measures were administered online to a sample of veterans with a history of cannabis use (n=1971). Cued arousal was assessed pre/post via a prompt about combat experiences. Hypotheses were tested using a series of Bonferroni corrected one-way analyses of variance, t-tests, bivariate and partial correlations, and a Chi-square test. RESULTS: Compared to recreational users, veterans who identify as medicinal cannabis users reported greater combat exposure (d=0.56), PTSD symptoms (d=1.02), subjective arousal when cued (d=0.25), and cannabis use (dfrequency=0.40; ddensity=0.42), but less alcohol use (d=0.28). Few differences were observed between medicinal users who reported using for PTSD versus those who reported using for other reasons. CONCLUSIONS: Compared to those who use cannabis recreationally, veterans who report that they use cannabis medicinally use more cannabis and endorse significantly more symptoms of arousal following a prompt about combat trauma experiences.