Comparing Adult Cannabis Treatment-Seekers Enrolled in a Clinical Trial with National Samples of Cannabis Users in the United States

Background—Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment Episodes Data Set – Admissions. Methods—Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. Results—Results showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users. Conclusions—These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings

A Randomized Placebo-Controlled Trial of \u3cem\u3eN\u3c/em\u3e-Acetylcysteine for Cannabis Use Disorder in Adults

Background—Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. Methods—In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18–50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200 mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. Results—There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio = 1.00, 95% confidence interval 0.63 – 1.59; p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. Conclusions—In contrast with prior findings in adolescents, there is no evidence that NAC 1200 mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors

An Open-Label Trial Of Aripiprazole Treatment In Dual Diagnosis Individuals: Safety And Efficacy

This open-label study evaluated the safety and efficacy of aripiprazole in the treatment of 20 patients with co-morbid schizophrenia, schizoaffective disorder, or bipolar disorder and alcohol, cocaine, and/or marijuana use disorders. Primary outcomes were substance use, measured by the Timeline Followback, and score on the Clinical Global Impression scale for psychiatric and substance use symptoms. The data suggest that aripiprazole may reduce substance use and improve psychiatric symptoms in patients with co-morbid disorders; however, limitations are noted. Subsequent randomized studies are needed to further explore these findings. Copyright © Taylor & Francis Group, LLC

Modeling Cannabis Use Disorder Treatment Progression: Evidence of Differential Mechanisms Underlying Functional Improvements

The exclusive focus on abstinence, rigid parameters, and lack of population moderation studies limits evidence of mechanisms of behavior change (MOBCs) that explain functional improvements in cannabis use disorder (CUD) treatments. We aimed to surpass these limitations by examining: 1) two untested non-abstinent MOBCs, 2) end-of-treatment (EOT; i.e., proximal) outcomes simultaneously functioning as MOBCs for follow-up (i.e., distal) outcomes, and 3) gender-moderated outcome predictors and MOBCs. Treatment-seeking individuals with CUD (n = 186; 70.1% male; 57.2% White) between ages 18-50 (M = 30.90, SD = 8.95) participated in a 12-week multi-site clinical trial with a four-week follow-up. We collected self-reported data and creatinine-corrected cannabinoid urine concentrations. We modeled treatment progression using moderated multigroup longitudinal path analyses to examine: H1) if mid-treatment, non-abstinent MOBCs (craving and use reductions) mediated the direct effect of CUD severity at the screening visit on proximal outcomes (anxiety, depression, and cannabis-related problems), H2) if proximal outcomes mediated the direct effect of mid-treatment MOBCs on a four-week distal outcome (quality of life challenges), and H3) if gender moderated these effects. We found that craving reduction may be a MOBC for the full and men samples. In women, depression may concurrently function as a proximal outcome and MOBC for quality of life challenges (distal outcome). Further, gender-moderated outcome predictors and MOBCs; for men, it may be craving reduction, and for women, reduced cannabis use. These nontraditional, differential explanations of functional improvements suggest that our understanding of CUD treatments may be more nuanced than currently indicated in the literature

Sleep and substance use disorder treatment: A preliminary study of subjective and objective assessment of sleep during an intensive outpatient program

Background and Objectives: Characteristics of sleep concerns and their relationship to mental health in heterogeneous substance use disorder (SUD) treatment settings are not well understood. The purpose of this preliminary study was to assess sleep using subjective and objective measures at two time points during SUD treatment and compare sleep changes to changes in mental health measures. Methods: Treatment-seeking participants completed an assessment battery at the beginning of treatment (Time 1, N = 30) and again upon treatment completion (Time 2, approximately 4 weeks later, N = 22). The majority of participants were White (80%), male (63%), and presenting for alcohol use disorder (60.0%), though almost half reported polysubstance abuse (43%). Comorbidity was common (53%). Sleep and mental health questionnaires with 1 week of actigraphy and sleep diaries were completed at both time points. Results: Most participants met the criteria for a sleep disorder and mean scores on questionnaires showed poor sleep quality, insomnia symptoms, and frequent nightmares, with sleep quality and insomnia improving over time but remaining clinically significant. Nightmares did not improve. Actigraphy indicated poor sleep at both time points. Improvement in insomnia was related to improvement in measures of mental health while changes in actigraphy variables were not related to these measures. Discussion and Conclusions: Multiple types of sleep disturbance are prevalent in this population, with nightmares persisting throughout treatment and insomnia symptoms showing a relationship with mental health symptoms. Scientific Significance: This was the first study to longitudinally assess mental health with subjective and objective measures of sleep across multiple types of SUDs in a community SUD treatment setting.12 month embargo; first published: 23 June 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Oxytocin moderates corticolimbic social stress reactivity in cocaine use disorder and healthy controls

Social stress can contribute to the development of substance use disorders (SUDs) and increase the likelihood of relapse. Oxytocin (OT) is a potential pharmacotherapy that may buffer the effects of social stress on arousal and reward neurocircuitry. However, more research is needed to understand how OT moderates the brain's response to social stress in SUDs. The present study examined the effect of intransasal OT (24 IU) versus placebo (PBO) on corticolimbic functional connectivity associated with acute social stress in individuals with cocaine use disorder (CUD; n = 67) and healthy controls (HC; n = 52). Psychophysiological interaction modeling used the left and right amygdala as seed regions with the left and right orbitofrontal and anterior cingulate cortex as a priori regions of interest. Moderators of the OT response included childhood trauma history and biological sex, which were examined in independent analyses. The main finding was that OT normalized corticolimbic connectivity (left amygdala-orbitofrontal and left amygdala-anterior cingulate) as a function of childhood trauma such that connectivity was different between trauma-present and trauma-absent groups on PBO, but not between trauma groups on OT. Effects of OT on corticolimbic connectivity were not different as a function of diagnosis (CUD vs HC) or sex. However, OT reduced subjective anxiety during social stress for CUD participants who reported childhood trauma compared to PBO and normalized craving response as a function of sex in CUD. The present findings add to some prior findings of normalizing effects of OT on corticolimbic circuitry in individuals with trauma histories and provide some initial support that OT can normalize subjective anxiety and craving in CUD