Gender differences in the prevalence of stimulant misuse in the United States: 2015-2019.

BACKGROUND AND OBJECTIVES: The gender gap in prevalence of substance-use disorders has narrowed. However, gender differences in stimulant misuse have not been well-characterized in recent years. The aim of this study was to quantify gender differences in past-year stimulant misuse and stimulant-use disorder, separated by stimulant type (cocaine/crack, prescription stimulants, and methamphetamine). In an exploratory aim, we investigated whether gender differences were moderated by age or sexual orientation. METHODS: We combined data from the National Survey on Drug Use and Health from 2015 to 2019 (unweighted N = 282,768) to test gender differences in the prevalence of past-year stimulant misuse. RESULTS: Results indicated that stimulant misuse was significantly more prevalent in men than women for all stimulant types for both past-year use and past-year use disorder. The magnitude of this sex difference was smallest for prescription stimulants, where men had 1.37 times higher odds of past-year misuse and no gender difference was observed in the prevalence of prescription stimulant-use disorder. The magnitude of gender differences also varied based on both age and sexual orientation. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Illicit stimulant misuse continues to be more common in men than in women; however, gender differences are more modest for prescription stimulant misuse, suggesting a narrowing of this historical gender difference.

Permutation Tests for Assessing Potential Non-Linear Associations between Treatment Use and Multivariate Clinical Outcomes.

In many psychometric applications, the relationship between the mean of an outcome and a quantitative covariate is too complex to be described by simple parametric functions; instead, flexible nonlinear relationships can be incorporated using penalized splines. Penalized splines can be conveniently represented as a linear mixed effects model (LMM), where the coefficients of the spline basis functions are random effects. The LMM representation of penalized splines makes the extension to multivariate outcomes relatively straightforward. In the LMM, no effect of the quantitative covariate on the outcome corresponds to the null hypothesis that a fixed effect and a variance component are both zero. Under the null, the usual asymptotic chi-square distribution of the likelihood ratio test for the variance component does not hold. Therefore, we propose three permutation tests for the likelihood ratio test statistic: one based on permuting the quantitative covariate, the other two based on permuting residuals. We compare via simulation the Type I error rate and power of the three permutation tests obtained from joint models for multiple outcomes, as well as a commonly used parametric test. The tests are illustrated using data from a stimulant use disorder psychosocial clinical trial.

Effects of a trauma-informed mindful recovery program on comorbid pain, anxiety, and substance use during primary care buprenorphine treatment: A proof-of-concept study.

BACKGROUND: A mindfulness-based intervention that reduces comorbid pain, anxiety, and substance use during office-based opioid treatment (OBOT) could enhance retention and prevent overdose. We conducted a pilot study of the Mindful Recovery OUD Care Continuum (M-ROCC), a 24-week trauma-informed program with a motivationally-sensitive curriculum. METHODS: Patients prescribed buprenorphine (N = 18) enrolled in M-ROCC. We collected urine toxicology biweekly. At 0, 4, and 24 weeks, participants completed PROMIS-Pain, PROMIS-Anxiety, Mindfulness (FFMQ), Experiential Avoidance (BEAQ), Interoceptive Awareness (MAIA), and Self-Compassion (SCS-SF) scales. We estimated changes over time using mixed models. Participants completed qualitative interviews at 4 and 24 weeks. RESULTS: Positive urine toxicology decreased over time for cocaine (ß = -.266, p = .008) and benzodiazepines (ß = -.208, p = .028). M-ROCC reduced PROMIS-Pain (Z = -2.29; p = .022), BEAQ (Z = -2.83; p = .0005), and increased FFMQ (Z = 3.51; p < .001), MAIA (Z = 3.40; p = .001), and SCS-SF (Z = 2.29; p = .022). Participants with co-morbid anxiety had decreased PROMIS-Anxiety (Z = -2.53; p = .012). Interviewed participants commonly used mindfulness practices for stress and anxiety (12/12, 100%), and to reduce pain catastrophizing and rumination (7/12, 58%). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This is the first study to report the effects of a 24-week mindfulness program during buprenorphine treatment on common comorbidities, including pain interference, anxiety, cocaine, and benzodiazepine use. The findings that M-ROCC is associated with reduced experiential avoidance, as well as increased interoceptive awareness and self-compassion, align with proposed mechanisms that are now extended to OUD treatment. Future larger randomized controlled trials are needed before effectiveness can be established and the role of these mechanisms can be confirmed.

Assessment of the Short Grit Scale in patients with substance use disorder: Psychometric properties and patient characteristics.

Background: Recovery from substance use disorder requires sustained effort and perseverance. Hence, the resilience factor of grit may be important for people in recovery. Little research has been conducted on grit in patients with substance use disorder (SUD), especially in a large and varied sample.Objectives: To analyze the psychometric properties of the Short Grit Scale (Grit-S) in patients with SUD and to use demographic and clinical characteristics to predict variance in Grit-S scores.Methods: Participants completed the Grit-S and other self-report measures. Psychometric properties of the Grit-S were assessed in outpatients (N = 94, 77.7% male) and a hierarchical regression predicted Grit-S variance in inpatients (N = 1238, 65.0% male).Results: The Grit-S demonstrated good internal consistency (α=.75) and strong test-retest reliability (adjusted r = .79, p < .001). Mean Grit-S score was 3.15, lower than other clinical samples reported in the literature. Regression modeling indicated a moderate, statistically significant association between demographic and clinical characteristics and Grit-S scores (R2 = 15.5%, p < .001). Of particular interest, the positive factor of recovery protection showed the strongest association with Grit-S of all variables assessed (ß=.185 vs. ß = .052-.175 for the remaining significant independent variables).Conclusion: The psychometric properties of the Grit-S in patients with SUD support its use in this population. Moreover, the particularly low grit scores among inpatients with SUDs and the association of grit scores with substance use risk and recovery factors suggest that grit could be useful as a treatment target in this population.

Benzodiazepine-Involved Overdose Deaths in the USA: 2000-2019.

BACKGROUND: Despite the focus on overdose deaths co-involving opioids and benzodiazepines, little is known about the epidemiologic characteristics of benzodiazepine-involved overdose deaths in the USA. OBJECTIVE: To characterize co-involved substances, intentionality, and demographics of benzodiazepine-involved overdose deaths in the USA from 2000 to 2019. DESIGN: Cross-sectional study using national mortality records from the National Vital Statistics System. SUBJECTS: US residents in the 50 states and District of Columbia who died from a benzodiazepine-involved overdose from 2000 to 2019. MAIN MEASURES: Demographic characteristics, intention of overdose, and co-involved substances KEY RESULTS: A total of 118,208 benzodiazepine-involved overdose deaths occurred between 2000 and 2019 (median age, 43 [IQR, 32-52]; male, 58.6%; White, 93.3%; Black, 4.9%; American Indian and Alaska Native, 0.9%; Asian American and Pacific Islander, 0.9%; Hispanic origin, 6.4%). Opioids were co-involved in 83.5% of the deaths. Nine percent of benzodiazepine-involved overdose deaths did not involve opioids, cocaine, other psychostimulants, barbiturates, or alcohol. Overdose deaths were classified as suicides in 8.5% of cases with benzodiazepine and opioid co-involvement and 36.2% of cases with benzodiazepine but not opioid involvement. Rates of benzodiazepine-involved overdose deaths increased from 0.46 per 100,000 individuals in 2000 to 3.55 per 100,000 individuals in 2017 before decreasing to 2.96 per 100,000 individuals in 2019. Benzodiazepine-involved overdose mortality rates increased from 2000 to 2019 among all racial groups, both sexes, and individuals of Hispanic and non-Hispanic origin. Rates of benzodiazepine-involved overdose deaths decreased among White individuals, but not Black individuals, from 2017 to 2019. CONCLUSIONS: Interventions to reduce benzodiazepine-involved overdose mortality should consider the demographics of, co-involved substances in, and presence of suicides among benzodiazepine-involved overdose deaths.

Correlates of optimism among patients in substance use disorder inpatient treatment.

BACKGROUND AND OBJECTIVES: Early recovery from substance use disorder (SUD) is often characterized by hopelessness and despair about the future. Optimism, or the expectation that good things will happen, may provide a buffer against despair, and motivate adaptive goal engagement and coping. Study objectives were to (1) compare levels of optimism among individuals in substance use disorder inpatient treatment to other populations and (2) examine correlates of optimism. METHODS: This exploratory study utilized a cross-sectional survey design. Participants (n = 355) completed self-report measures assessing sociodemographic and clinical characteristics. The main variable of interest, optimism, was assessed by Life Orientation Test-Revised scores. Multivariate regression was used to examine the association among sociodemographic and clinical variables and optimism. RESULTS: Our sample (n = 342) scored lower on optimism (mean = 11.7) than general population and SUD patients reported in the literature (range = 13.0-18.5). Optimism was higher for SUD inpatients who were college-educated and those with higher scores on the recovery protection factor, while greater anxiety severity was associated with lower optimism scores. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This study contributes to emerging research on the association between optimism and SUDs. Optimism has not been previously studied among patients in acute, short-term inpatient SUD treatment and doing so may be clinically useful in addressing low optimism as an obstacle to motivation for treatment. Bolstering optimism may be a promising target for intervention and future research.

Are Pain and Negative Affect Coping Distinct Motives for Opioid Misuse?

Background: Coping with pain is a commonly reported motive for opioid misuse. Opioids also provide relief of stress and negative affect and thus are often misused to cope with these emotional states. Although several studies have investigated coping motives in people who misuse opioids, it remains unclear whether pain coping and negative affect coping are distinct or overlapping motives for misuse. Objectives: In this study, we examined opioid use motives (enhancement, social, negative affect coping, and pain coping) in a sample of 52 adults seeking treatment for opioid use disorder. We used an adaptation of the Drug Use Motives Questionnaire that included an additional 5 items to assess pain coping motives for use. Results: Results indicated that pain coping was not significantly associated with other motives for use, including negative affect coping. Pain coping motives were strongly correlated with both pain severity (r = .51) and pain interference (r = .39), but not anxiety severity. Conversely, negative affect coping motives were strongly correlated with anxiety severity (r = .45), but not pain severity or interference. Conclusions: These results suggest that pain coping motives may be distinct from negative affect coping motives and should be assessed separately.

Patients' perceptions of telehealth services for outpatient treatment of substance use disorders during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: The rapid scale-up of telehealth services for substance use disorders (SUDs) during the COVID-19 pandemic presented a unique opportunity to investigate patient experiences with telehealth. This study examined patient perceptions of telehealth in an outpatient SUD treatment program offering individual therapy, group therapy, and medication management. METHODS: Two hundred and seventy adults receiving SUD outpatient treatment were eligible to complete a 23-item online survey distributed by clinicians; 58 patients completed/partially completed the survey. Data were summarized with descriptive statistics. RESULTS: Participants were predominately male, White, and well-educated. The majority (86.2%) were "very satisfied" or "satisfied" with the quality of telehealth care. "Very satisfied" ratings were highest for individual therapy (90%), followed by medication management (75%) and group therapy (58%). Top reasons for liking telehealth included the ability to do it from home (90%) and not needing to spend time commuting (83%). Top reasons for disliking telehealth were not connecting as well with other members in group therapy (28%) and the ability for telehealth to be interrupted at home or work (26%). DISCUSSION AND CONCLUSIONS: Telehealth visits were a satisfactory treatment modality for most respondents receiving outpatient SUD care, especially those engaging in individual therapy. Challenges remain for telehealth group therapy. SCIENTIFIC SIGNIFICANCE: This is the first study examining patients' perceptions of telehealth for outpatient SUD treatment during the COVID-19 pandemic by treatment service type. Importantly, while many participants found telehealth more accessible than in-person treatment, there was variability with respect to the preferred mode of treatment delivery.

Associations between Childhood Abuse and Chronic Pain in Adults with Substance Use Disorders.

BACKGROUND: Both childhood abuse and chronic pain are common in people with substance use disorders (SUDs). Studies have found that exposure to childhood abuse is associated with chronic pain in adulthood; however, few studies have examined this association in people with SUDs. Objectives: This study aimed to characterize the association between childhood abuse and chronic pain presence and severity in adults with SUDs. Methods: Data were obtained from 672 treatment-seeking participants with SUDs on an inpatient detoxification unit. Regression models evaluated whether childhood physical or sexual abuse was associated with the likelihood of chronic pain and severity of several pain-related characteristics: pain catastrophizing, pain severity, and pain interference. Results: Childhood physical and sexual abuse were significantly associated with a greater likelihood of chronic pain in adulthood. In the adjusted analyses, childhood physical abuse was associated with worse pain severity, whereas childhood sexual abuse was associated with greater pain catastrophizing and worse pain interference. Conclusions: Childhood physical and sexual abuse were associated with a greater likelihood of chronic pain in adults with SUDs. Among those with chronic pain, exposure to childhood abuse was associated with a more severe symptom profile, characterized by greater pain severity, more catastrophic interpretations of pain, and more pain-related interference with daily life. People with SUDs and a history of childhood abuse may benefit from screening for pain and interventions to reduce pain catastrophizing. These findings highlight the importance of longitudinal research to understand mechanisms linking childhood abuse exposure to later pain and substance misuse.

A Research Agenda for Advancing Strategies to Improve Opioid Safety: Findings from a VHA State of the Art Conference.

US military Veterans have been disproportionately impacted by the US opioid overdose crisis. In the fall of 2019, the Veterans Health Administration (VHA) convened a state-of-the-art (SOTA) conference to develop research priorities for advancing the science and clinical practice of opioid safety, including both use of opioid analgesics and managing opioid use disorder. We present the methods and consensus recommendations from the SOTA. A core group of researchers and VA clinical stakeholders defined three areas of focus for the SOTA: managing opioid use disorder, long-term opioid therapy for pain including consideration for opioid tapering, and treatment of co-occurring pain and substance use disorders. The SOTA participants divided into three workgroups and identified key questions and seminal studies related to those three areas of focus. The strongest recommendations included testing implementation strategies in the VHA for expanding access to medication treatment for opioid use disorder, testing collaborative tapering programs for patients prescribed long-term opioids, and larger trials of behavioral and exercise/movement interventions for pain among patients with substance use disorders.

Establishing the First Annual Meetings of the American Academy of Addiction Psychiatry.

This paper describes the initial meetings of the American Academy of Addiction Psychiatry, and it compares and contrasts these relatively small meetings with the much larger meetings today. The paper is centered on the organization's initial focus on establishing itself in the mainstream of medicine and psychiatry. (Am J Addict 2020;00:00-00).

Impact of Medications for Opioid Use Disorder on Discharge Against Medical Advice Among People Who Inject Drugs Hospitalized for Infective Endocarditis.

BACKGROUND AND OBJECTIVES: The impact of medications for opioid use disorder (MOUD) on against medical advice (AMA) discharges among people who inject drugs (PWID) hospitalized for endocarditis is unknown. METHODS: A retrospective review of all PWID hospitalized for endocarditis at our institution between 2016 and 2018 (n = 84). RESULTS: PWID engaged with MOUD at admission, compared with those who were not, were less likely to be discharged AMA but this did not reach statistical significance in adjusted analysis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.033-1.41; P = .11). Among out-of-treatment individuals, newly initiating MOUD did not lead to significantly fewer AMA discharges (OR, 0.98; 95% CI, 0.26-3.7; P = .98). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: PWID hospitalized for endocarditis are at high risk for discharge AMA but more research is needed to understand the impact of MOUD. (Am J Addict 2020;29:155-159).

Pain catastrophizing and distress intolerance: prediction of pain and emotional stress reactivity.

Exposure to stress is associated with poor outcomes in people with chronic pain. Dispositional variables, such as pain catastrophizing and distress intolerance, may impact reactivity to stressors. Importantly, these variables can be modified with treatment. The aim of this study was to investigate whether pain catastrophizing and distress intolerance were associated with tolerance of a pain stressor or a psychosocial stressor, and heightened negative affect following these stressors. A sample of 50 adults with chronic pain completed self-report measures and pain and psychosocial stress inductions. Results indicated that pain catastrophizing was associated with heightened anxiety during pain induction. Distress intolerance was associated with negative affect following a psychosocial stressor, and with poorer tolerance of the psychosocial stressor. Pain catastrophizing and distress intolerance are related factors, however, they exhibit distinct associations with amplification of pain and psychosocial stress reactivity. These variables may be important treatment targets in people with chronic pain.

Pain interference and catastrophizing are not associated with polysubstance use among treatment-seeking patients with substance use disorders and chronic pain.

Background: People with substance use disorders (SUD) and co-occurring chronic pain report the use of myriad substances, which is concerning due to the heightened risk of overdose associated with polysubstance use. Identifying malleable factors associated with polysubstance use in this population can inform interventions. In this study, we examined whether two pain processes - pain interference and pain catastrophizing - were associated with polysubstance use. Objectives: We examined the cross-sectional associations among self-reported pain interference and catastrophizing and polysubstance use. We also determined if sex and primary SUD moderated these associations. Methods: Participants were 236 (36% female) adults receiving inpatient treatment for SUD (58% alcohol use disorder, 42% opioid use disorder) who met criteria for chronic pain. We utilized negative binomial regression to examine associations between pain interference and catastrophizing (focal independent variables) and the number of substances used in the month before treatment (i.e., polysubstance use; outcome). Results: Participants used three substances, on average, in the month prior to treatment. Neither pain interference (IRR = 1.05, p = .06) nor pain catastrophizing (IRR = 1.00, p = .37) were associated with polysubstance use. The association between pain interference and polysubstance use was moderated by sex and primary SUD (ps<0.01), such that these variables were positively related in men and those with alcohol use disorder. Conclusion: Pain interference and catastrophizing were not uniformly associated with polysubstance use, underscoring the need to examine other factors associated with polysubstance use in this population. However, men and those with alcohol use disorder might benefit from interventions targeting pain interference to reduce polysubstance use.

Clinical Correlates of Smoking Status in Men and Women with Opioid Use Disorder.

Background: Smoking is highly prevalent in people with opioid use disorder (OUD) and is a significant contributor to morbidity and mortality in this population. However, little is known about the differences between those with OUD who do and do not smoke cigarettes. Objectives: Our aim was to investigate differences between treatment-seeking adults with OUD who did and did not smoke. Methods: Participants (N = 568; 30% female) completed a battery of self-report questionnaires including measures of current smoking status and number of cigarettes smoked per day as well as measures of clinical characteristics (e.g. craving, anxiety). Results: Of the total sample, 77% were current smokers. Multivariable logistic regression identified heroin use (OR = 2.20, 95% CI = 1.38, 3.53) and younger age (OR = 0.97, 95% CI = 0.95, 0.997) as strong correlates of smoking status; other characteristics were not significant. Older age and opioid craving were associated with more cigarettes smoked per day. Notably, these patterns differed for males and females; opioid craving (B = 0.62, SEB = 0.24) was associated with the number of cigarettes smoked among men, and anxiety (B = 0.39, SEB = 0.19) was associated with the number of cigarettes smoked among women. Conclusion: Adults with OUD who used heroin in the past month were more likely to be current smokers. No sex differences were observed in likelihood of smoking; however, the predictors of smoking status and severity differed between men and women.

Associations between pain catastrophizing and clinical characteristics in adults with substance use disorders and co-occurring chronic pain.

Background: Pain catastrophizing refers to the tendency to interpret pain as harmful, intolerable, or uncontrollable. Greater pain catastrophizing is associated with more pain-related negative phenomena, such as pain reactivity, pain disability, and emotional distress related to pain. Several studies of patients seeking chronic pain treatment have identified an association between pain catastrophizing and misuse of opioids and alcohol; however, it is unknown whether this association would be similarly present in patients with chronic pain seeking substance use disorder treatment. Objectives: The current study examined whether pain catastrophizing is associated with worse pain-related outcomes and psychological functioning in individuals receiving inpatient substance use disorder treatment who endorsed current chronic pain. Methods: In a series of regression models, we tested the associations between pain catastrophizing and functioning, specifically pain interference, craving, anxiety, and days of mood difficulties in a cross-sectional sample of patients seeking substance use disorder treatment with co-occurring chronic pain (N = 244, 67.6% female). Results: Greater pain catastrophizing was associated with more pain interference, higher levels of craving, more anxiety symptoms and more days of mood difficulties, adjusted for demographic characteristics and pain severity. Conclusion: In patients with comorbid substance use disorder and chronic pain, pain catastrophizing may offer a potential therapeutic target to improve substance use treatment outcomes.

Nonmedical benzodiazepine use in adults with alcohol use disorder: The role of anxiety sensitivity and polysubstance use.

BACKGROUND AND OBJECTIVES: The nonmedical use of benzodiazepines-defined as use without a prescription or at a dose or frequency higher than prescribed-is increasing among adults in substance use disorder treatment and is associated with risk for overdose. The aim of the current study was to characterize the prevalence of nonmedical benzodiazepine use among adults seeking treatment for alcohol use disorder and to examine whether nonmedical benzodiazepine use was associated with: (1) polysubstance use and (2) greater anxiety sensitivity. METHODS: A sample of 461 treatment-seeking adults with alcohol use disorder who were recruited for a cross-sectional study were included in this analysis. RESULTS: A total of 89 participants (19%) reported nonmedical benzodiazepine use in the previous 30 days. Results of a logistic regression indicated that polysubstance use (number of substances used in the past month) was associated with nonmedical benzodiazepine use. The association between anxiety sensitivity and nonmedical benzodiazepine misuse was moderated by gender; anxiety sensitivity was associated with benzodiazepine use among women, but not men. DISCUSSION AND CONCLUSIONS: These results replicate findings from research on opioid use disorder suggesting that anxiety sensitivity is associated with nonmedical benzodiazepine use in women and not men. SCIENTIFIC SIGNIFICANCE: Targeted intervention to those with polysubstance use-including education on overdose risk when benzodiazepines are combined with other substances-is indicated in men and women with alcohol use disorder. Anxiety sensitivity may be a potential therapeutic target to reduce nonmedical benzodiazepine use among women with alcohol use disorder. (Am J Addict 2018;27:485-490).

Focus Group Study to Examine Content of Family Meetings in Short-term Substance Use Disorder Treatment.

This study explores the content family members find helpful in family meetings that occur while patients are in short-term treatment for substance use disorders. Three focus groups were conducted; two with 23 family members and one with 10 patients who were asked to identify those topics that are helpful or unhelpful for families with and without prior treatment experiences. Families identified education about substance use disorders and an overview of treatment options as useful for family members new to treatment, and an emphasis on response to relapse and family supports as important for those with prior treatment experiences.

Religious coping in patients with severe substance use disorders receiving acute inpatient detoxification.

BACKGROUND AND OBJECTIVES: Religious coping, one of the most widely studied components of spirituality among psychiatric populations, has rarely been addressed in patients with severe substance use disorders (SUD). The aim of our study was to elucidate whether religious coping is related to symptom expression and mutual-help participation. METHODS: Self-reported religious coping was assessed in individuals sequentially admitted to a private psychiatric hospital for inpatient detoxification. Target symptoms of SUD included severity of substance use prior to admission and craving during detoxification. Three hundred thirty-one patients (68.6% male) participated in the survey; mean age was 38.0 years, and primary presenting diagnosis was most commonly alcohol use disorder (n = 202; 61%), followed by opioid use disorder (n = 119; 36%). RESULTS: Positive religious coping was associated with significantly greater mutual-help participation, fewer days of drug use prior to admission, and was modestly, yet significantly associated with lower drug craving. Negative religious coping was associated with lower confidence in the ability to remain abstinent post-discharge and higher drug craving. CONCLUSIONS: Consistent with hypotheses, greater positive religious coping was associated with greater mutual-help participation, lower severity of pre-admission drug use, and lower substance craving during detoxification. Use of positive religious coping may modify the course of SUD recovery by promoting engagement in mutual-help activities. SCIENTIFIC SIGNIFICANCE: The findings of this study suggest that positive and negative religious coping are linked with several key SUD recovery variables. Further research to replicate this finding and to assess mechanisms within this potential association is warranted. (Am J Addict 2017;26:744-750).

Nabilone pharmacotherapy for cannabis dependence: A randomized, controlled pilot study.

BACKGROUND AND OBJECTIVES: We assessed the safety, tolerability, and preliminary efficacy of nabilone, a cannabinoid agonist, to treat cannabis dependence. METHODS: Eighteen adults with DSM-IV cannabis dependence were randomized to receive either 2 mg/day of nabilone (n = 10) or placebo (n = 8) for 10 weeks in addition to medication management. Twelve participants, six in each group, completed treatment. The safety and tolerability of nabilone was assessed at each visit. Any side effects from nabilone or the placebo were documented. Cannabis use outcomes were assessed via self-report of days of use and twice-weekly urine cannabinoid tests; secondary outcomes included cannabis craving and anxiety. RESULTS: We assessed safety and tolerability at each study visit. A total of eight adverse events, all mild or moderate, were reported in two participants in the nabilone group, and six events were reported in four participants in the placebo group during study treatment. A total of eight adverse events were reported in two participants in the nabilone group and six events were reported in four participants in the placebo group during study treatment. All reported adverse events were rated mild-to-moderate. There were no side effects deemed serious enough to be classified as an FDA-defined serious adverse event. In general, participants in both groups reported reduced cannabis use according to self-report over the course of the study, although these reductions were not statistically discernible. Moreover, there was no difference in cannabis use between the nabilone group and the placebo group as measured by self-report. DISCUSSION AND CONCLUSIONS: Nabilone pharmacotherapy was safe and well-tolerated in participants with cannabis dependence. Future studies might evaluate a higher dose of nabilone to determine its effects on cannabis use outcomes in participants with cannabis dependence. SCIENTIFIC SIGNIFICANCE: There remains a clear need for additional pharmacotherapy trials for cannabis dependence, and nabilone remains a candidate for such trials. (Am J Addict 2017;26:795-801).