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Cannabis use disorder (CUD) presents differently in men and women, particularly in symptoms of cannabis withdrawal. Novel pharmacotherapeutic interventions for CUD, such as those that target the endocannabinoid (eCB) system, must be developed in a manner consistent with these sex differences. The present pilot study sought to prospectively assess sex differences in cannabis withdrawal in a small sample of adults with moderate-to-severe CUD and to determine if withdrawal was associated with peripheral eCB and eCB congener tone. Men and women (n = 5/sex) completed 2 weeks of study participation separated by 1 month; in the latter week, participants abstained from cannabis use. Each week, participants attended in-person laboratory visits during which blood was drawn repeatedly to assess plasma eCB and eCB congener tone. Participants also completed multiple daily ambulatory assessments to assess cannabis use and withdrawal symptoms. As anticipated, women reported a greater increase in withdrawal symptoms during the abstinent week [Δ = 9.4 (SE = 1.1); p < 0.001] than men [Δ = 1.2 (SE = 1.2); p = 0.35]. Sex differences in levels of the eCB N-arachidonoylethanolamide (AEA), as well as the eCB congeners stearoylethanolamide (SEA) and linoleylethanolamide (LEA), were evident during abstinence at the morning time point only (p's < 0.05). LEA was associated with withdrawal symptom expression in both sexes [β = 0.16 (SE = 0.09)] and palmitoylethanolamide (PEA) [β = 0.22 (SE = 0.13)] and 2-arachidonoylglycerol (2-AG) [β = 0.32 (SE = 0.15)] were associated with withdrawal symptoms in women only. Pharmacotherapeutic development for CUD should consider evident sex differences in eCB and eCB congener tone during abstinence and their associations with cannabis withdrawal, as eCB-based interventions may produce differential effects by sex., (© 2023 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Hedonic dysregulation is a core mechanism of addiction. There is a dearth of research on hedonic dysregulation in cannabis use disorder (CUD). The current study tested whether personalized scripted imagery may be an efficacious approach to remediate reward functioning in adults with CUD., Methods: Adults with CUD (n=10) and non-CUD controls (n=12) completed a single session personalized scripted imagery procedure. Non-drug (i.e. natural) reward and neutral scripts were transcribed and participants listened to the scripts in counterbalanced order. Primary outcomes included positive affect (PA), galvanic skin response (GSR), and cortisol and were assessed at four timepoints. Mixed effects models were used to compare between and within subject effects., Results: Mixed effects models revealed a Condition (reward vs. neutral) X Group (CUD vs. control) interaction (p=0.01) on PA response, indicating blunted PA response to the neutral script relative to the reward script in CUD participants. Likewise, GSR response in CUD participants was decreased in response to the neutral script relative to the reward script (p=0.034; interaction n.s.). An interaction effect of Group X PA on cortisol response was found (p=.036) indicating that cortisol was positively correlated with PA in healthy control participants, but not CUD participants., Conclusions: Adults with CUD may demonstrate acute deficits in hedonic tone under neutral conditions relative to healthy controls. Personalized scripted imagery may be an efficacious tool to remediate hedonic dysregulation in CUD. Cortisol may play a role in healthy positive affect regulation warranting further investigation., Competing Interests: Declaration of Competing Interest All authors declare they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Adverse childhood experiences (ACEs) show a graded association with the development of substance use disorders (SUDs) and engagement in risky substance use behaviors. Women are overrepresented among individuals with more severe childhood adversity (≥4 types of ACEs) and may be at particular risk for aberrant substance use. Objectives: To assess the prevalence of ACEs among men and women with cannabis, opioid, cocaine, and tobacco use disorders. Methods: Non-treatment-seeking individuals participating in clinical addiction research at a single site completed the ACE questionnaire and provided a detailed substance use history. Data were analyzed using proportional odds models and logistic regression. Results: Most participants (424/565; 75%) reported at least one ACE, and more than one-quarter (156/565; 27%) reported severe childhood adversity. Relative to men ( n  = 283), women ( n  = 282) reported more ACEs (OR = 1.49; p  = .01) and more experiences of emotional/physical abuse (OR = 1.52; p  = .02), sexual abuse (OR = 4.08; p  = .04), and neglect (OR = 2.30; p  < .01). Participants in the cocaine (OR = 1.87; n = .01) and opioid (OR = 2.21; p  = .01) use disorder, but not cannabis use disorder (OR = 1.46; p  = .08), studies reported more severe adversity relative to the tobacco group. Relative to tobacco users, emotional/physical abuse (OR = 1.92; p  = .02) and neglect (OR = 2.46; p  = .01) scores were higher in cocaine users and household dysfunction scores were higher in opioid users (OR = 2.67; p  = .01). Conclusion: The prevalence of ACEs differs with respect to both participant gender and primary substance used. Novel SUD treatment strategies that incorporate ACEs may be uniquely beneficial in specific subpopulations of people with SUDs.

Background: Several evidence-based tobacco cessation treatment strategies exist, though significant barriers to cessation remain which must be addressed to improve abstinence rates for sub-populations of those smoking cigarettes. Cannabis co-use among those who use tobacco is common and appears to be increasing among adults in the United States (US). The literature evaluating the impact of cannabis use on tobacco cessation has been mixed and has several important limitations, which precludes development of treatment recommendations specific to individuals who use tobacco and co-use cannabis. To date, no prospective studies have evaluated the impact of cannabis use and severity on tobacco cessation or quantified cannabis use changes during tobacco treatment to assess for concurrent reductions, abstinence, or compensatory (i.e., increased) cannabis use. This study's aims are to: (1) evaluate tobacco cessation outcomes among participants who co-use cannabis compared to participants only using tobacco, (2) using daily diaries and biochemical verification, assess changes in cannabis use during tobacco treatment, and (3) assess for a dose-dependent impact of cannabis use on tobacco cessation., Method: A multi-site, prospective, quasi-experimental 12-week tobacco treatment trial enrolling treatment-seeking adults (ages 18-40; N = 208) from three sites across South Carolina (US) who use tobacco daily and oversampling (2:1) those who co-use cannabis. Participants receive tobacco cessation pharmacotherapy (varenicline) paired with behavioral support, while cannabis use is not addressed as part of treatment. The primary outcome is 7-day point prevalence tobacco abstinence at the week 12 end of treatment visit, measured via biochemical verification and self-report. Secondary outcome measures include changes in cannabis use (via biochemical verification and self-report) during tobacco cessation treatment., Discussion: Results from this trial have the potential to inform tobacco treatment among those co-using cannabis, which may require a tailored approach to address the role of cannabis in quitting tobacco., Trial Registration: The trial is registered with ClinicalTrials.gov: NCT04228965. January 14th, 2020., (© 2023. The Author(s).)

Background: Individuals with alcohol use disorder (AUD) do not always respond to currently available treatments, and evaluation of new candidate pharmacotherapies is indicated. N-acetylcysteine (NAC), an over-the-counter supplement, has shown promise in treating a variety of substance use disorders, but little research has evaluated its merits as a treatment for AUD. This secondary analysis from the National Drug Abuse Treatment Clinical Trials Network examined the effects of NAC versus placebo on alcohol use among participants with cannabis use disorder (CUD) enrolled in a 12-week, multi-site cannabis cessation trial., Methods: Participants (N = 302, ages 18-50) were randomized to double-blind NAC (1200 mg, twice daily) or placebo. Neither alcohol use nor desire for alcohol cessation were requirements for participation. Participants that returned for at least one treatment visit and had recorded alcohol use data (i.e., total drinks per week, drinking days per week, and binge drinking days per week) were included in the analysis (n = 277)., Results: Compared to the placebo group, participants in the NAC group had increased odds of between-visit alcohol abstinence [OR = 1.37; 95% CI = 1.06-1.78; p = 0.019], fewer drinks per week [RR = 0.67; 95% CI = 0.48-0.99; p = 0.045], and fewer drinking days per week [RR = 0.69; 95% CI = 0.51-0.92; p = 0.014]. Changes in concurrent cannabis use amounts were not correlated to any of the alcohol use variables., Discussion: These findings indicate that NAC may be effective at reducing consumption of alcohol by ∼30% among treatment-seeking adults with CUD, suggesting a need for further trials focused on the effects of NAC on alcohol consumption among individuals seeking treatment for AUD., (Published by Elsevier B.V.)

Background: Quantifying cannabis use is complex due to a lack of a standardized packaging system that contains specified amounts of constituents. A laboratory procedure has been developed for estimating physical quantity of cannabis use by utilizing a surrogate substance to represent cannabis, and weighing the amount of the surrogate to determine typical use in grams., Method: This secondary analysis utilized data from a multi-site, randomized, controlled pharmacological trial for adult cannabis use disorder (N=300), sponsored by the National Drug Abuse Treatment Clinical Trials Network, to test the incremental validity of this procedure. In conjunction with the Timeline Followback, this physical scale-based procedure was used to determine whether average grams per cannabis administration predicted urine cannabinoid levels (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) and problems due to use, after accounting for self-reported number of days used (in the past 30 days) and number of administrations per day in a 12-week clinical trial for cannabis use disorder., Results: Likelihood ratio tests suggest that model fit was significantly improved when grams per administration and relevant interactions were included in the model predicting urine cannabinoid level (X 2 =98.3; p<0.05) and in the model predicting problems due to cannabis use (X 2 =6.4; p<0.05), relative to a model that contained only simpler measures of quantity and frequency., Conclusions: This study provides support for the use of a scale-based method for quantifying cannabis use in grams. This methodology may be useful when precise quantification is necessary (e.g., measuring reduction in use in a clinical trial)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

BackgroundCannabis 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.MethodsIn 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 1200mg (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.ResultsThere 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.ConclusionsIn contrast with prior findings in adolescents, there is no evidence that NAC 1200mg 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.

Background: It is common for cannabis users to also use tobacco. While data suggest that tobacco users have more difficulty achieving cannabis cessation, secondary analyses of clinical trial data sets may provide insight into the moderating variables contributing to this relationship, as well as changes in tobacco use during cannabis treatment. Those were the aims of this secondary analysis.Methods: The parent study was a multi-site trial of N-acetylcysteine for cannabis dependence conducted within the National Drug Abuse Treatment Clinical Trials Network. Participants were treatment-seeking adults (ages 18-50) who met criteria for cannabis dependence (N = 302). For cigarette smokers (n = 117), tobacco use was assessed via timeline follow-back and nicotine dependence was assessed via the Fagerström Test for Nicotine Dependence (FTND). Outcome measures included: 1) changes in tobacco use based on treatment assignment, nicotine dependence, and concurrent cannabis reduction/abstinence, and 2) independent associations between nicotine dependence and cannabis abstinence.Results: Cigarette smokers accounted for 39% of the sample (117/302), with a median FTND score of 3.0 (10-point scale). Among those with lower baseline nicotine dependence scores, cigarette smoking was reduced in the active treatment group compared to placebo. Those with moderate/high levels of nicotine dependence showed slight increases in smoking following active treatment. Nicotine dependence did not affect cannabis cessation.Conclusions: Cigarette smoking during cannabis treatment was affected, but depended on baseline nicotine dependence severity, though dependence levels did not impact cannabis abstinence. Interventions that address both tobacco and cannabis are needed, especially due to an increasing prevalence of cannabis use. [ABSTRACT FROM AUTHOR]

Background: The agreement between self-reported cannabis abstinence with urine cannabinoid concentrations in a clinical trials setting is not well characterized. We assessed the agreement between various cannabinoid cutoffs and self-reported abstinence across three clinical trials, one including contingency management for abstinence.Methods: Three cannabis cessation clinical trials where participants reported use and provided weekly urine samples for cannabis and creatinine concentration measurements were included. Bootstrapped data were assessed for agreement between self-reported 7+ day abstinence and urine cannabinoid tests using generalized linear mixed effects models for clustered binary outcomes. One study implemented contingency management for cannabis abstinence. Four hundred and seventy-three participants with 3787 valid urine specimens were included. Urine was analyzed for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol and creatinine using immunoassay methods Biological cutoffs of 50, 100, and 200 ng/ml, as well as changes in CN normalized THCCOOH (25%/50% decrease), were assessed for agreement with self-reported abstinence during the three clinical trials.Results: Agreement between measured THCCOOH and self-reported abstinence increases with increasing cutoff concentrations, while the agreement with self-reported non-abstinence decreases with increasing cutoff concentrations. Combining THCCOOH cutoffs with recent changes in CN-THCCOOH provides a better agreement in those self-reporting abstinence. Participants in the studies that received CM for abstinence had a lower agreement between self-reported abstinence and returned to use than those in studies that did not have a contingency management component.Conclusion: Using combinations of biological measurements and self-reported abstinence, confirmation of study related abstinence may be verifiable earlier and with greater accuracy than relying on a single measurement. [ABSTRACT FROM AUTHOR]

Background: More effective treatments for cannabis use disorder (CUD) are needed. Evidence suggests that biases in cognitive processing of drug-related stimuli are central to the development and maintenance of addiction. The current study examined the feasibility and effect of a novel intervention - approach bias modification (ApBM) - on cannabis approach bias and cue-reactivity.Methods: A randomized, double-blind, sham-controlled proof-of-principle laboratory experiment investigated the effect of a four-session computerized ApBM training protocol on cannabis approach bias and cue-reactivity in non-treatment seeking adults age 18-65 with CUD (N = 33). ApBM procedures involved responding to cannabis or neutral stimuli using a computer joystick to model approach or avoidance behavior. Reactivity to tactile, olfactory, and auditory cue sets was assessed with physiological (blood pressure and heart rate) and subjective (cannabis craving) measures. Cannabis use was assessed via self-report.Results: Participants receiving ApBM showed blunted cannabis cue-induced craving at the end of training compared to those in the sham-ApBM condition (p = .05). A preliminary gender effect on cannabis use was also found; men receiving ApBM reported fewer cannabis use sessions per day at the end of training compared to women (p = .02), while there were no differences between men and women in the sham condition. ApBM did not attenuate cannabis approach bias following training.Conclusion: Preliminary results indicate that ApBM may be efficacious in reducing cannabis cue-reactivity and improving cannabis use outcomes. While encouraging, the results should be interpreted with caution. Investigation of ApBM as an adjunct to psychosocial treatments for treatment-seeking adults with CUD is warranted. [ABSTRACT FROM AUTHOR]

Background: Cannabis use disorder (CUD) is a common condition with few treatments. Several studies in other substance use disorders have found that applying repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) decreases cue-elicited craving and possibly decreases use. To date, there have been no studies attempting to use rTMS in CUD.Objectives: This study was conducted to determine if rTMS could be feasibly delivered to a group of non-treatment seeking CUD participants. Secondarily, the study aimed to estimate the effect of rTMS on craving.Methods: In a double-blind, sham-controlled, crossover design, a single session of active or sham rTMS (Left DLPFC, 10 Hz, 110% rMT, 4000 pulses) was delivered during a validated cannabis cue paradigm. Participants crossed over to complete the other condition one week later. The feasibility and tolerability were measured by the rate of retention, and the percentage of participants able to tolerate full dose rTMS, respectively. Craving was measured using the Marijuana Craving Questionnaire (MCQ).Results: Eighteen non-treatment seeking CUD participants were recruited from the community; 16 (three women) completed the trial (89% retained for the three study visits). All of the treatment completers tolerated rTMS at full dose without adverse effects. There was not a significant reduction in the total MCQ when participants received active rTMS as compared to sham rTMS.Conclusion: rTMS can be safely and feasibly delivered to CUD participants, and treatment is well tolerated. A single session of rTMS applied to the DLPFC may not reduce cue-elicited craving in heavy cannabis users. [ABSTRACT FROM AUTHOR]

Introduction: Gender differences in cannabis use and cannabis use disorder have been established. Regarding treatment, some evidence suggests that women are less responsive, though the mechanisms are not well understood. Motivation to change and self-efficacy are associated with better outcomes overall, and may help explain gender differences in cannabis use outcomes.Methods: A secondary data analysis of a double-blind placebo controlled trial of buspirone treatment for cannabis dependence (N=175) was conducted. Self-report assessments of motivation to change, self-efficacy, and other clinical correlates were completed at baseline, and cannabis use was measured throughout the study.Results: There was a significant interaction between gender and taking steps on abstinence. Counter to hypothesis, higher taking steps reduced likelihood of achieving abstinence among women; there was no association among men. Subsequently, taking steps was associated with self-efficacy and quantity of use among men, and cannabis related problems among women. There was a significant interaction between gender and readiness to change on creatinine adjusted cannabinoid levels. Change readiness was positively associated with cannabinoid levels among women, but not men.Conclusions: Motivation to change and initiation of change behavior predict worse cannabis outcomes in women. Men and women differ in what motivates change behavior. Social desirability, neurobiology, and treatment type may impact these effects. Gender differences in cannabis use and treatment responsiveness must be considered in future studies. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the efficacy of buspirone, a partial 5-HT1A agonist, for treatment of cannabis dependence.Methods: One hundred seventy-five cannabis-dependent adults were randomized to receive either up to 60mg/day of buspirone (n=88) or placebo (n=87) for 12 weeks combined with a brief motivational enhancement therapy intervention and contingency management to encourage study retention. Cannabis use outcomes were assessed via weekly urine cannabinoid tests.Results: Participants in both groups reported reduced cannabis craving over the course of the study; however, buspirone provided no advantage over placebo in reducing cannabis use. Significant gender by treatment interactions were observed, with women randomized to buspirone having fewer negative urine cannabinoid tests than women randomized to placebo (p=0.007), and men randomized to buspirone having significantly lower creatinine adjusted cannabinoid levels as compared to those randomized to placebo (p=0.023). An evaluation of serotonin allelic variations did not find an association with buspirone treatment response.Conclusions: Buspirone was not more efficacious than placebo in reducing cannabis use. Important gender differences were noted, with women having worse cannabis use outcomes with buspirone treatment. Considerations for future medication trials in this challenging population are discussed. [ABSTRACT FROM AUTHOR]

Motivational enhancement therapy (MET) is efficacious in reducing cannabis use, yet benefits are generally short-lived. Oxytocin is a hypothalamic neuropeptide that promotes prosocial behaviors and plays a role in drug-related neuroadaptations; as such, oxytocin may enhance the effect of MET on cannabis outcomes. Cannabis dependent adults were randomized to receive MET plus oxytocin ( n =8) or placebo ( n =8). Participants receiving oxytocin showed reductions in amount of cannabis used daily and number of sessions per day. Participants receiving placebo did not evidence significant reductions. Powered clinical trials of oxytocin-enhanced MET for cannabis use disorder are warranted. [ABSTRACT FROM AUTHOR]

Background and objectives: Tobacco and cannabis use are both highly prevalent worldwide. Their co-use is also common in adults and adolescents. Despite this frequent co-occurrence, cessation from both substances is rarely addressed in randomized clinical trials. Given evidence that tobacco use may increase during cannabis cessation attempts, and additionally that tobacco users have poorer cannabis cessation outcomes, we explored tobacco outcomes, specifically cigarette smoking, from an adolescent cannabis cessation trial that tested the efficacy of N-acetylesteine (NAC). Methods: Cannabis-dependent adolescents (ages 15-21; n = 116) interested in cannabis treatment were randomized to NAC (1200 mg bid) or matched placebo for 8 weeks. Participants did not need to be cigarette smokers or be interested in smoking cessation to qualify for inclusion. Results: Approximately 59% of enrolled participants were daily and non-daily cigarette smokers, and only differed from non-smoking participants on the compulsion sub-scale of the Marijuana Craving Questionnaire. Among cigarette smokers who were retained in the study, there was no change in cigarettes per day for either NAC or placebo groups during the eight-week treatment phase. Being a cigarette smoker did not appear to influence the effects of NAC on cannabis abstinence, though there was a trend in the placebo group of poorer cannabis outcomes for cigarette smokers vs. non-smokers. Conclusions: No evidence was found of compensatory cigarette smoking during this cannabis cessation trial in adolescents. Further work assessing interventions to reduce both cannabis and tobacco use in this population is greatly needed. [ABSTRACT FROM AUTHOR]

Background: Time from first cannabis use to cannabis dependence (latency) may be an important prognostic indicator of cannabis-related problems and treatment outcomes. Gender differences in latency have been found; however, research in this general area is limited. As cannabis use increases and perceived risk declines, a better understanding of how these factors interact in predicting treatment outcomes is critical.Methods: A secondary data analysis of a randomized, double-blind, placebo-controlled pharmacotherapy trial for cannabis dependence (N = 302) examined the associations between age of cannabis use onset, time to cannabis dependence (latency), and gender on cannabis use during the trial. Mediation analysis tested whether the association between age of onset and cannabis use during the trial was mediated by latency to cannabis dependence differentially for men and women.Results: Age of use initiation was inversely correlated with latency to dependence prior to treatment [HR(95% CI) = 1.18 (1.06, 1.30); p = .002] and cannabis use during treatment (β=-1.27; SE = 0.37; p < .001). There was a significant mediation effect between age of onset, latency, and cannabis use that varied by gender. Earlier age of onset predicted longer latency, and subsequently, greater cannabis use during the trial in men (21.4% mediated; p < .05), but not women. Other substance use, race, and past psychiatric diagnosis did not predict latency either independently or in interaction models.Conclusion: Findings support existing evidence that early cannabis use onset is associated with worse outcomes and add new knowledge on the differential associations between age of onset, latency to cannabis dependence, and treatment outcomes for men and women. [ABSTRACT FROM AUTHOR]

Cannabis use disorder (CUD) is a common and consequential disorder. When applied to the dorsolateral prefrontal cortex (DLPFC), repetitive transcranial magnetic stimulation (rTMS) reduces craving across substance use disorders and may have therapeutic clinical effects when applied in serial-sessions. The present study sought to preliminarily determine whether serial-sessions of rTMS applied to the DLPFC had a therapeutic effect in CUD. This study was a two-site, phase-2, double-blind, randomized-controlled-trial. Seventy-two treatment-seeking participants (37.5% Women, mean age 30.2±9.9 SD) with ≥moderate-CUD were randomized to active or sham rTMS (Beam-F3, 10 Hz, 20-total-sessions, two-sessions-per-visit, two-visits-per-week, with cannabis cues) while undergoing a three-session motivational enhancement therapy intervention. The primary outcome was the change in craving between pre- and post- treatment (Marijuana Craving Questionnaire Short-Form—MCQ-SF). Secondary outcomes included the number of weeks of abstinence and the number of days-per-week of cannabis use during 4-weeks of follow-up. There were no significant differences in craving between conditions. Participants who received active-rTMS reported numerically, but not significantly, more weeks of abstinence in the follow-up period than those who received sham-rTMS (15.5%-Active; 9.3%-Sham; rate ratio = 1.66 [95% CI: 0.84, 3.28]; p =0.14). Participants who received active-rTMS reported fewer days-per-week of cannabis use over the final two-weeks of the follow-up period than those receiving sham-rTMS (Active vs. Sham: −0.72; Z=−2.33, p =0.02). This trial suggests rTMS is safe and feasible in individuals with CUD and may have a therapeutic effect on frequency of cannabis use, though further study is needed with additional rTMS-sessions and a longer follow-up period. • This phase-2 RCT tested the efficacy of prefrontal rTMS for cannabis use disorder. • The study paradigm was safe and feasible, and participants tolerated rTMS well. • The active-group had numerically more weeks of abstinence during follow-up. • The active-group had fewer days-per-week of cannabis use during follow-up. • More rTMS and a longer follow-up may result in a larger effect in future studies.. [ABSTRACT FROM AUTHOR]

Background: An efficacious pharmacotherapy for cannabis use disorder (CUD) has yet to be established. This study preliminarily evaluated the safety and efficacy of varenicline for CUD in a proof-of-concept clinical trial.Methods: Participants in this 6-week randomized, placebo-controlled pilot trial received either varenicline (n = 35) or placebo (n = 37), added to a brief motivational enhancement therapy intervention. Outcomes included cannabis withdrawal, cannabis abstinence, urine cannabinoid levels, percent cannabis use days, and cannabis sessions per day.Results: Both treatment groups noted significant decreases in self-reported cannabis withdrawal, percentage of days used, and use sessions per day during treatment compared to baseline. While this pilot trial was not powered to detect statistically significant between-group differences, participants randomized to varenicline evidenced numerically greater rates of self-reported abstinence at the final study visit [Week 6 intent-to-treat (ITT): Varenicline: 17.1% vs. Placebo: 5.4%; RR = 3.2 (95% CI: 0.7,14.7)]. End-of-treatment urine creatinine corrected cannabinoid levels were numerically lower in the varenicline group and higher in the placebo group compared to baseline [Change from baseline: Varenicline -1.7 ng/mg (95% CI: -4.1,0.8) vs. Placebo: 1.9 ng/mg (95% CI: -0.4,4.3); Δ = 3.5 (95% CI: 0.1,6.9)]. Adverse events related to study treatment did not reveal new safety signals.Conclusions: Findings support the feasibility of conducting clinical trials of varenicline as a candidate pharmacotherapy for CUD, and indicate that a full-scale efficacy trial, powered based on effect sizes and variability yielded in this study, is warranted. [ABSTRACT FROM AUTHOR]

Given the popularity and ease of single-item craving assessments, we developed a multi-item measure and compared it to common single-item assessments in an ecological momentary assessment (EMA) context. Two weeks of EMA data were collected from 48 emerging adults (56.25% female, 85.42% White) who frequently used cannabis. Eight craving items were administered, and multilevel factor analyses were used to identify the best fitting model. The resulting scale’s factors represented purposefulness/general desire and emotionality/negative affect craving. Convergent validity was examined using measures of craving, cannabis use disorder symptoms, frequency of use, cannabis cue reactivity, cannabis use, negative affect, and impulsivity. The scale factors were associated with cue-reactivity craving, negative affect, impulsivity, and subfactors of existing craving measures. For researchers interested in using a single item to capture craving, one item performed particularly well. However, the new scale may provide a more nuanced assessment of mechanisms underlying craving. [ABSTRACT FROM AUTHOR]

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 1200mg (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 1200mg 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. [ABSTRACT FROM AUTHOR]