Test-retest reliability of the Epworth Sleepiness Scale in clinical trial settings.

The present analysis examined the test-retest reliability of the Epworth Sleepiness Scale in participants with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea in three clinical trials. Intraclass correlation coefficient estimates for Epworth Sleepiness Scale scores from two solriamfetol 12-week placebo-controlled trials (one narcolepsy, one obstructive sleep apnea) and one long-term open-label extension trial (narcolepsy or obstructive sleep apnea) were calculated using postbaseline time-point pairs for the overall population in each trial, by treatment, and by primary obstructive sleep apnea therapy adherence. In the 12-week narcolepsy trial, intraclass correlation coefficients (95% confidence intervals) were 0.83 (0.79, 0.87) for weeks 4 and 8 (n = 199), 0.87 (0.83, 0.90) for weeks 8 and 12 (n = 196), and 0.81 (0.76, 0.85) for weeks 4 and 12 (n = 196). In the 12-week obstructive sleep apnea trial, intraclass correlation coefficients (95% confidence intervals) were 0.74 (0.69, 0.78) (n = 416), 0.80 (0.76, 0.83) (n = 405), and 0.74 (0.69, 0.78) (n = 405), respectively. In the open-label extension trial, intraclass correlation coefficients (95% confidence intervals) were 0.82 (0.79, 0.85) for weeks 14 and 26/27 (n = 495), 0.85 (0.82, 0.87) for weeks 26/27 and 39/40 (n = 463), and 0.78 (0.74, 0.81) for weeks 14 and 39/40 (n = 463). Placebo/solriamfetol treatment or adherence to primary obstructive sleep apnea therapy did not affect reliability. In conclusion, across three large clinical trials of participants with narcolepsy or obstructive sleep apnea, Epworth Sleepiness Scale scores demonstrated a robust acceptable level of test-retest reliability in evaluating treatment response over time.

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.

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.

Cannabis, Cannabinoids, and Sleep: a Review of the Literature.

PURPOSE OF REVIEW: The current review aims to summarize the state of research on cannabis and sleep up to 2014 and to review in detail the literature on cannabis and specific sleep disorders from 2014 to the time of publication. RECENT FINDINGS: Preliminary research into cannabis and insomnia suggests that cannabidiol (CBD) may have therapeutic potential for the treatment of insomnia. Delta-9 tetrahydrocannabinol (THC) may decrease sleep latency but could impair sleep quality long-term. Novel studies investigating cannabinoids and obstructive sleep apnea suggest that synthetic cannabinoids such as nabilone and dronabinol may have short-term benefit for sleep apnea due to their modulatory effects on serotonin-mediated apneas. CBD may hold promise for REM sleep behavior disorder and excessive daytime sleepiness, while nabilone may reduce nightmares associated with PTSD and may improve sleep among patients with chronic pain. Research on cannabis and sleep is in its infancy and has yielded mixed results. Additional controlled and longitudinal research is critical to advance our understanding of research and clinical implications.

The interaction between anxiety sensitivity and cigarette smoking level in relation to sleep onset latency among adolescent cigarette smokers.

Cigarette smoking during adolescence is linked to a number of sleep disturbances and has been consistently linked to sleep onset latency among adults. However, little research has examined factors that may influence the relation between cigarette smoking level and sleep onset latency among adolescents. One factor that may be particularly important in this regard is anxiety sensitivity (AS). The current study examined whether cigarette smoking level interacted with AS in its association with sleep onset latency among 94 adolescent (Mage = 15.72) cigarette smokers. As hypothesized, AS interacted with smoking level to relate to sleep onset latency, even after controlling for age and gender. This relation was specific to sleep onset latency as opposed to other types of sleep disturbances, and that adolescents who smoked at higher levels tended to go to sleep later and wake up later than adolescents who smoked at relatively lower levels.

Physical activity and cannabis cessation.

BACKGROUND AND OBJECTIVES: Based on recent empirical and theoretical work suggesting that physical activity (PA) activates many of the same physiological systems as cannabis, the present study sought to investigate the impact of PA level (ie, low [including none] vs. moderate/high) on a cannabis cessation attempt during the first 7 days post-quit. METHODS: The present study was a 2 time-point prospective study of 84 cannabis dependent military veterans (3 female) who responded to study flyers, within a Veterans Affairs Medical Center, seeking individuals interested in engaging in a self-guided cessation attempt. All study measures were self-report. RESULTS: Though no baseline differences between those with low and those with moderate/high levels of physical activity were observed, results revealed that participants who reported low levels of physical activity, versus moderate/high levels, were significantly more likely to report a cannabis lapse during the week following a quit attempt, particularly within the first 4 days of the cessation period. Further, individuals with low levels of PA were also more likely to report greater mean cannabis use during the first 4 days of the cessation period. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Findings suggest that early interventions aimed at increasing physical activity may be useful among individuals with cannabis dependence who are engaged in a cessation attempt.

Interactions between disordered sleep, post-traumatic stress disorder, and substance use disorders.

Disordered sleep is associated with a number of adverse health consequences and is an integral component of many psychiatric disorders. Rates of substance use disorders (SUDs) are markedly higher among individuals with post-traumatic stress disorder (PTSD), and this relationship may be partly mediated by disturbed sleep. Sleep disturbances (e.g. insomnia, daytime sleepiness, vivid nightmares) are hallmark features of PTSD and there is evidence that individuals with PTSD engage in substance use as a means of coping with these symptoms. However, prolonged substance use can lead to more severe sleep disturbances due to the development of tolerance and withdrawal. Behavioural or pharmacological treatment of disordered sleep is associated with improved daytime symptoms and psychosocial functioning among individuals who have developed PTSD. Initial research also suggests that improving sleep could be similarly beneficial in reducing coping oriented substance use and preventing relapse among those seeking treatment for SUDs. Together, these findings suggest that ameliorating sleep disturbance among at-risk individuals would be a viable target for the prevention and treatment of PTSD and associated SUDs, but prospective research is needed to examine this hypothesis. Enhanced understanding of the interrelation between sleep, PTSD, and SUDs may yield novel prevention and intervention approaches for these costly, prevalent and frequently co-occurring disorders.

Self-reported cannabis use characteristics, patterns and helpfulness among medical cannabis users.

OBJECTIVES: Little research has investigated the demographic and symptom profile of medical cannabis users in states in the USA that have legalized cannabis use. METHODS: In the present cross-sectional study, we investigated the demographic profile of 217 adults currently receiving medical cannabis, as well as differences in problematic use and perceived helpfulness in terms of (i) symptoms of psychological disorders and pain, and (ii) motives for use. RESULTS: Findings indicated that medical cannabis users (i) use and perceive cannabis to be beneficial for multiple conditions, some for which cannabis is not specifically prescribed or allowed at the state level; and (ii) report similar rates of disordered use as compared with population estimates among regular users. Furthermore, problematic cannabis use was predicted by several symptoms of psychological disorders (e.g. depression) and a variety of use motives (e.g. coping), while cannabis was reported as particularly helpful among those with several psychological symptoms (e.g. traumatic intrusions), as well as those reporting use for social anxiety reasons. CONCLUSIONS: Results are discussed in terms of future directions for research given the current debates regarding legalization of cannabis for medical purposes and, more generally, the lack of empirical data to inform such debates.

Pubertal maturation and cortisol level in response to a novel social environment among female adolescents.

Research indicates changes in HPA-axis activity across puberty. The current study extends existing work by evaluating pubertal status and cortisol level in a novel social environment (research laboratory) while controlling for several important biological, behavioral, and psychological variables. Participants were 30 girls (ages 9-16 years) from the United States. Pubertal status was assessed via the Pubertal Development Scale. Salivary samples were collected at laboratory-introduction and a matched at-home period; laboratory-introduction levels were regressed on basal cortisol levels to create standardized residual scores. After controlling for covariates, pubertal status was positively associated with residualized cortisol values. Findings indicate more advanced puberty related to greater cortisol response to the laboratory; data are discussed in terms of future research and building biopsychosocial models of the puberty-psychopathology linkage.

Posttraumatic stress disorder and cannabis use characteristics among military veterans with cannabis dependence.

BACKGROUND AND OBJECTIVES: The present study is the first to explore links between PTSD and cannabis use characteristics immediately prior to a cannabis quit attempt, including motives, use problems, withdrawal, and craving. METHODS: Measures of PTSD diagnosis, symptom severity, and cannabis use characteristics were administered to a sample of cannabis dependent military veterans (n = 94). Hypotheses were tested with a series of analyses of variance and covariance and hierarchical multiple regressions with Bonferroni corrections. Analyses were conducted with and without adjusting for variance shared with substance use (cannabis, alcohol, tobacco) in the previous 90 days, and co-occurring mood, anxiety, and substance use diagnoses. RESULTS AND CONCLUSIONS: Compared to participants without PTSD, participants with PTSD reported significantly increased: (a) use of cannabis to cope, (b) severity of cannabis withdrawal, and (c) experiences of craving related to compulsivity, emotionality, and anticipation, with findings regarding coping and craving remaining significant after adjusting for covariates. Among the total sample, PTSD symptom severity was positively associated with (a) use of cannabis to cope, (b) cannabis use problems, (c) severity of cannabis withdrawal, and (d) experiences of craving related to compulsivity and emotionality, with findings regarding withdrawal and emotion-related craving remaining significant after adjusting for covariates. Thus, links between PTSD and using cannabis to cope, severity of cannabis withdrawal, and especially craving appear robust across measures of PTSD and analytical method. SCIENTIFIC SIGNIFICANCE: The results of this study provide support for models that posit a pernicious feedback loop between PTSD symptomatology and cannabis use.

Anxiety sensitivity and sleep quality: independent and interactive predictors of posttraumatic stress disorder symptoms.

A cardinal feature of posttraumatic stress disorder (PTSD) is decreased sleep quality. Anxiety sensitivity (AS) is one factor that has shown early theoretical and empirical promise in better understanding the relation between sleep quality and PTSD outcomes. The current study is the first to test the independent and interactive effects of sleep quality and AS on PTSD symptoms. Consistent with hypotheses, AS and sleep quality were found to be independent and interactive predictors of PTSD symptom severity in our sample of male military veterans seeking treatment for PTSD. Slope analyses revealed that AS was differentially related to PTSD symptom severity as a function of quality of sleep. The veterans with good sleep quality and relatively lower levels of AS had the lowest level of PTSD symptoms, whereas the veterans with poor sleep quality and low AS evidenced severity of PTSD symptoms similar to those with high AS.

Sleep quality moderates the relation between depression symptoms and problematic cannabis use among medical cannabis users.

OBJECTIVES: This study sought to extend research on the relation between depression symptoms and problematic cannabis use by evaluating the potential moderating role of perceived sleep quality among medical cannabis users. METHODS: This employed a cross-sectional design. The sample consisted of 162 adults (mean age = 42.05 years, SD = 14.8; 22% female), with current recommendations from a doctor for medical cannabis, recruited from a medical cannabis dispensary. RESULTS: Consistent with previous research, individuals with heightened depression symptoms had greater problematic cannabis use. In addition, perceived sleep quality moderated this relation, such that depression symptoms differentially related to problematic cannabis use as a function of perceived quality of sleep (ΔR(2) = .03, p = .02). Participants with higher levels of depression and good perceived sleep quality had the greatest rates of problematic cannabis use. CONCLUSIONS: These results suggest that individuals with heightened depression may have higher rates of problematic cannabis use, in part, because of the beneficial effects of cannabis in terms of perceived sleep quality.

The relationship of sleep quality and PTSD to anxious reactivity from idiographic traumatic event script-driven imagery.

Poor sleep quality has been linked to posttraumatic stress disorder (PTSD). This study provided a test of how poor sleep quality relates to real-time assessment of anxious reactivity to idiographic traumatic event cues. Script-driven imagery (SDI) was employed to examine reactivity to traumatic event cues among 46 women (mean age = 27.54 years, SD = 13.62; 87% Caucasian) who had experienced either physical or sexual assault. We tested 3 hypotheses: (a) individuals with PTSD would report greater anxiety reactions to SDI than trauma-exposed individuals without PTSD, (b) poorer sleep quality would be positively related to anxiety reactions to SDI, and (c) there would be an interaction between PTSD and sleep quality such that individuals with PTSD and relatively poor sleep quality would report greater anxious reactivity to SDI than would be expected from each main effect alone. Poor sleep quality and PTSD were related to elevated anxious reactivity to trauma cues (sr(2) = .06). In addition, sleep quality was negatively associated with anxious reactivity among people without PTSD (sr(2) =.05). The current findings, in combination with longitudinal evidence, suggest that poor sleep quality following exposure to a traumatic event may be a risk factor for anxious reactivity to traumatic event cues.

Sleep quality among U.S. military veterans with PTSD: a factor analysis and structural model of symptoms.

Poor sleep quality among individuals with posttraumatic stress disorder (PTSD) is associated with poorer prognosis and outcomes. The factor structure of the most commonly employed measure of self-reported sleep quality, the Pittsburgh Sleep Quality Index (PSQI), has yet to be evaluated among individuals with PTSD. The current study sought to fill this gap among a sample of 226 U.S. military veterans with PTSD (90% with co-occurring mood disorders, 73.5% with substance use disorders). We evaluated the factor structure of the PSQI by conducting an exploratory factor analysis (EFA) in approximately half of the sample (n = 111). We then conducted a second EFA in the other split half (n = 115). Lastly, we conducted a path analysis to investigate the relations between sleep factors and PTSD symptom severity, after accounting for the relation with depression. Results suggested sleep quality can best be conceptualized, among those with PTSD, as a multidimensional construct consisting of 2 factors, Perceived Sleep Quality and Efficiency/Duration. After accounting for the association between both factors and depression, only the Perceived Sleep Quality factor was associated with PTSD (ß = .51). The results provide a recommended structure that improves precision in measuring sleep quality among veterans with 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.

Solriamfetol treatment of excessive daytime sleepiness in participants with narcolepsy or obstructive sleep apnea with a history of depression.

Given the high rate of depression associated with narcolepsy or obstructive sleep apnea (OSA), this analysis compared effects of solriamfetol treatment of excessive daytime sleepiness (EDS) in participants with/without a history of depression (DHx+/DHx-). This secondary analysis included data from two randomized, controlled trials in which participants were randomized to 12 weeks placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg/day. Efficacy/safety (combined solriamfetol doses) was summarized for DHx+/DHx-subgroups. 27.5% (65/236) with narcolepsy and 23.4% (111/474) with OSA were DHx+. In narcolepsy (DHx+ and DHx-), 40-min Maintenance of Wakefulness Test (MWT40) mean sleep latency increased (5.4 and 7.0 min), Epworth Sleepiness Scale (ESS) score decreased (3.8 and 3.5 points), and percentage of participants improved on Patient Global Impression of Change (PGI-C) was higher (31.7% and 39.4%) relative to placebo. In OSA (DHx+ and DHx-), MWT40 mean sleep latency increased (7.7 and 10.7 min), ESS decreased (3.5 and 3.7 points), and percentage of participants improved on PGI-C was higher (41.1% and 29.4%) relative to placebo. Common treatment-emergent adverse events (headache, decreased appetite, nausea, anxiety) were similar in DHx+/DHx-. This study suggests that safety and efficacy of solriamfetol for treating EDS in narcolepsy and OSA are not affected by depression history. Moreover, the findings emphasize the high prevalence of depression in people with sleep disorders and suggest that increased awareness of this association may have clinical significance.

The predictive validity of the progress assessment, a clinician administered instrument for use in measurement-based care for substance use disorders.

We tested the predictive validity of the Progress Assessment (PA), a brief counselor administered tool for use in measurement-based care for substance use disorders. The PA includes 5 items assessing relapse risk and 5 items assessing factors protective against relapse. Data were drawn from a completed study of continuing care for cocaine dependence (McKay et al., 2013) and includes 12 months of follow-up on158 participants (76% male) who received brief telephone or face-to-face sessions. Each session began with the administration of the PA, followed by cognitive-behavioral counseling tied to the results of the PA and anticipated risky situations. Outcome was assessed via urine toxicology every 3 months. As administered in an effectiveness trial, average PA risk and protective scales within each 3-month segment of the study predicted urine toxicology results at the end of that period, with higher risk scores and lower protective scores predicting greater rates of cocaine positive urine drug screens. PA scores did not predict dropout from continuing care participation. The 10-item PA shows promise as a pragmatic clinical tool for ongoing monitoring during continuing care for substance dependence.

Test of the role of nicotine dependence in the relation between posttraumatic stress disorder and panic spectrum problems.

Posttraumatic stress disorder (PTSD) frequently co-occurs with panic spectrum problems. Relatively little empirical work has tested possible mechanisms accounting for this association. Nicotine dependence often ensues subsequent to PTSD onset and research suggests smoking high numbers of cigarettes daily may lead to panic problems. The current study tested the hypotheses that nicotine dependence partially mediates the relations between PTSD and both panic attacks and panic disorder within a nationally representative sample of 5,692 (3,020 women; M(Age) = 45, SD = 18) adults from the National Comorbidity Survey-Replication. Results were consistent with hypotheses. These findings support the theory suggesting smoking among people with PTSD may be involved in the development of panic problems.

Unique and Interactive Relations among Posttraumatic Stress, Distress Tolerance, and Anger Responding to Traumatic Event Cues.

Experimental and clinical studies have demonstrated an association between posttraumatic stress symptoms (PTSS) and anger. Expanding upon past research, the current study examined the interactive associations among PTSS, distress tolerance (DT), and anger responding among a sample of 95 trauma-exposed adults. This study used a personalized script-driven imagery procedure to gauge emotional responses. Results from a hierarchical linear regression demonstrated a main effect of PTSS and an interaction between PTSS and DT. Simple slope analyses indicated that PTSS level was unrelated to anger responding among traumatic event-exposed people relatively low in DT, while anger responses were positively correlated with levels of PTSS among those relatively higher in DT. These findings highlight the need for future research to consider distress tolerance as well as other emotional vulnerability factors in assessing PTSD-related anger.

Nicotine dependence mediates the relations between insomnia and both panic and posttraumatic stress disorder in the NCS-R sample.

Although a growing literature has demonstrated elevations in insomnia symptoms among persons with either panic disorder (PD) or posttraumatic stress disorder (PTSD) relative to people without psychopathology, comparably little is known about processes underlying these associations. In recognition of this important gap in the literature, this study tested nicotine dependence as a partial mediator of the relations between insomnia symptoms and both PD and PTSD among a nationally representative sample of 5,692 (3,311 females; M(age)=43.33, SD=16.55) adults from the National Comorbidity Survey-Replication. Consistent with hypotheses, nicotine dependence partially mediated the relations between insomnia and both PD and PTSD after controlling for variance accounted for by diagnoses of major depressive episodes, drug and alcohol dependence, and gender. Overall, results suggest nicotine dependence may be a possible mechanism that underlies insomnia among those with PD and PTSD.