Computer-Based Training for Cognitive Behavioural Therapy for Substance Use Disorder: A Randomized Controlled Trial Including Quantitative and Qualitative Health and Economic Outcomes: Formation informatisée pour la thérapie cognitivo-comportementale pour les troubles liés à l'usage de substances : un essai randomisé contrôlé y compris les résultats quantitatifs et qualitatifs en matière de santé et d'économie.

OBJECTIVES: Heavy alcohol and drug use is reported by a substantial number of Canadians; yet, only a minority of those experiencing substance use difficulties access specialized services. Computer-Based Training for Cognitive Behavioural Therapy (CBT4CBT) offers a low-cost method to deliver accessible and high-quality CBT for substance use difficulties. To date, CBT4CBT has primarily been evaluated in terms of quantitative outcomes within substance use disorder (SUD) samples in the United States. A comparison between CBT4CBT versus standard care for SUDs in a Canadian sample is critical to evaluate its potential for health services in Canada. We conducted a randomized controlled trial of CBT4CBT versus standard care for SUD. METHODS: Adults seeking outpatient treatment for SUD (N = 50) were randomly assigned to receive either CBT4CBT or treatment-as-usual (TAU) for 8 weeks. Measures of substance use and associated harms and quality of life were completed before and after treatment and at 6-month follow-up. Qualitative interviews were administered after treatment and at follow-up, and healthcare utilization and costs were extracted for the entire study period. RESULTS: Participants exhibited improvements on the primary outcome as well as several secondary outcomes; however, there were no differences between groups. A cost-effectiveness analysis found lower healthcare costs in CBT4CBT versus TAU in a subsample analysis, but more days of substance use in CBT4CBT. Qualitative analyses highlighted the benefits and challenges of CBT4CBT. DISCUSSION: Findings supported an overall improvement in clinical outcomes. Further investigation is warranted to identify opportunities for implementation of CBT4CBT in tertiary care settings.Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03767907.

Evaluating a digital intervention targeting substance use difficultiesPlain Language SummaryWhy was the study done?Heavy alcohol and drug use is frequent in the Canadian population, although very few people have access to treatment. The digital intervention, Computer-Based Training for Cognitive Behavioural Therapy (CBT4CBT), may provide a low-cost, high-quality, and easily accessible method of treatment for substance use difficulties. Limited research on this digital intervention has been conducted in Canadian populations, and few studies thus far have evaluated participants' subjective experience using the intervention, along with the cost on the Canadian healthcare system.What did the researchers do?The research team recruited participants and provided access to either CBT4CBT or to standard care at a mental health hospital for 8 weeks. Participants were asked questions about their substance use and related consequences, quality of life, and thoughts on the treatment they received. Information regarding healthcare use and the cost to the healthcare system was also gathered.What did the researchers find?Participants in both groups improved with regards to their substance use, some related consequences, and psychological quality of life. Participants provided insight on the benefits and challenges of both types of treatment. It was also found that the CBT4CBT intervention was less costly.What do these findings mean?These findings support that adults receiving CBT4CBT and standard care both improved to a similar degree in this sample. Participant feedback may inform future studies of how best to implement this intervention in clinical studies. Future studies with larger samples are needed to further examine whether CBT4CBT can increase access to supports and be beneficial in the Canadian healthcare system.

Cannabis use in adolescents and anxiety symptoms and disorders: a systematic review and meta-analysis.

Background: The use of cannabis is highly prevalent during adolescence compared to the general adult population. In addition to the high comorbidity between cannabis use and anxiety disorders, early evidence suggests that cannabis may precede the development of anxiety. Moreover, adolescence represents a major developmental period for both neurobiological and psychological processes, placing these individuals at a heightened vulnerability to the influence of cannabis.Objectives: This systematic review and meta-analysis examined the prospective associations between adolescent cannabis use and subsequent anxiety outcomes (i.e. anxiety disorders and/or symptoms).Methods: Following PRISMA guidelines, a systematic review and meta-analysis were conducted encompassing data from articles published between database inception and September 2022.Results: Six longitudinal studies were identified for quantitative analysis, while twelve non-overlapping longitudinal studies were identified for qualitative review (total N = 18; 33380 subjects). Meta-analytical findings supported an association between adolescent cannabis use and the development of a subsequent anxiety disorder (Odds Ratio = 2.14, 95% CI: 1.37-3.36, p < .01). These findings were consistent with our qualitative synthesis where nine of the twelve longitudinal studies observed a significant relationship between adolescent cannabis use and exacerbation of anxiety symptoms later in life, irrespective of an anxiety disorder diagnosis.Discussion: In summary, the current evidence suggests a prospective association between adolescent cannabis use and later anxiety symptoms and disorders. These findings underscore the importance of refining research methodologies, considering sex-based differences and controlling for confounding factors, as well as implementing educational initiatives and developing clinical interventions to address the mental health risks associated with cannabis use among adolescents.

Cannabis cravings predict cigarette use in schizophrenia: a secondary analysis from two cannabis abstinence studies.

CLINICAL TRIAL NAME: Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cannabis Use and Cognitive Outcomes in SchizophreniaURL: www.clinicaltrials.gov; Registration Number: NCT03189810.

Feasibility and effectiveness of extended-release buprenorphine (XR-BUP) among correctional populations: a systematic review.

Background: Medications for opioid use disorder (MOUD) reduce risks for overdose among correctional populations. Among other barriers, daily dosing requirements hinder treatment continuity post-release. Extended-release buprenorphine (XR-BUP) may therefore be beneficial. However, limited evidence exists.Objectives: To conduct a systematic review examining the feasibility and effectiveness of XR-BUP among correctional populations.Methods: Searches were carried out in Pubmed, Embase, and PsychINFO in October 2023. Ten studies reporting on feasibility or effectiveness of XR-BUP were included, representing n = 819 total individuals (81.6% male). Data were extracted and narratively reported under the following main outcomes: 1) Feasibility; 2) Effectiveness; and 3) Barriers and Facilitators.Results: Studies were heterogeneous. Correctional populations were two times readier to try XR-BUP compared to non-correctional populations. XR-BUP was feasible and safe, with no diversion, overdoses, or deaths; several negative side effects were reported. Compared to other MOUD, XR-BUP significantly reduced drug use, resulted in similar or higher treatment retention rates, fewer re-incarcerations, and was cost-beneficial, with a lower overall monthly/yearly cost. Barriers to XR-BUP, such as side effects and a fear of needles, as well as facilitators, such as a lowered risk of opioid relapse, were also identified.Conclusion: XR-BUP appears to be a feasible and potentially effective alternative treatment option for correctional populations with OUD. XR-BUP may reduce community release-related risks, such as opioid use and overdose risk, as well as barriers to treatment retention. Efforts to expand access to and uptake of XR-BUP among correctional populations are warranted.

Relationship between number of prior lumbar spine surgeries and outcomes following spinal cord stimulator implantation: A multisite, retrospective pooled analysis.

OBJECTIVES: Lumbar spine surgery is a common procedure for treating disabling spine-related pain. In recent decades, both the number and cost of spine surgeries have increased despite technological advances and modification in surgical technique. For those patients that have continued uncontrolled back and/or lower extremity pain following lumbar spine surgery, spinal cord stimulation (SCS) has emerged as a viable treatment option. However, the impact of lumbar spine surgical history remains largely unstudied. Specifically, the current study considers the impact of number of prior lumbar spine surgeries on pain relief outcomes following SCS implantation. MATERIALS AND METHODS: We queried the electronic medical record of five separate pain practices for all patients who have undergone a SCS implant between January 1, 2017, and March 1, 2020. Inclusion criteria consisted of any patients with an SCS implant who underwent a prior lumbar spine surgery. The primary outcome was the mean calculated percentage pain relief in patients based on number of prior lumbar spine surgeries. RESULTS: There was a total of 1974 total SCS implant cases identified across five separate pain clinics. There was no difference in mean calculated pain relief in patients with one prior spine surgery versus those with two or more prior spine surgeries (28.2% vs. 25.8%, adjusted ß-coefficient -3.1, 95% CI -8.9 to 2.7, p = 0.290). Similarly, when analyzing number of spine surgeries as a continuous variable, there was no association between number of spine surgeries and calculated pain relief (adjusted ß-coefficient -1.5, 95% CI -4.0 to 1.1, p = 0.257). Additionally, after patients were stratified based on waveform, there was no association between number of prior lumbar spine surgeries (analyzed both as a categorical and continuous variable) and calculated percentage pain relief. CONCLUSIONS: This multicentered retrospective study found that there was no significant difference in pain scores in individuals who received SCS following one or more lumbar spine surgeries. Additionally, the waveform of the SCS device had no statistically significant impact on post-operative pain scores following one or more lumbar spine surgeries.

Deep brain stimulation of the nucleus accumbens in the treatment of severe alcohol use disorder: a phase I pilot trial.

Alcohol use disorder (AUD) is a highly prevalent, often refractory, medical illness. The symptoms of AUD are driven by dysfunction in several neurocircuits centered on the nucleus accumbens (NAc). Case reports and animal studies suggest NAc-DBS may be an effective harm-reduction treatment in severe AUD. Six patients with severe, refractory AUD underwent NAc-DBS. Safety metrics and clinical outcomes were recorded. Positron emission tomography (FDG-PET) was used to measure glucose metabolism in the NAc at baseline and 6 months. Functional magnetic resonance imaging (fMRI) was used to characterize postoperative changes in NAc functional connectivity to the rest of the brain, as well as NAc and dorsal striatal reactivity to alcoholic visual cues. This study was registered with ClinicalTrials.gov, NCT03660124. All patients experienced a reduction in craving. There was a significant reduction in alcohol consumption, alcohol-related compulsivity, and anxiety at 12 months. There was no significant change in depression. FDG-PET analysis demonstrated reduced NAc metabolism by 6 months, which correlated with improvements in compulsive drinking behaviors. Clinical improvement correlated with reduced functional connectivity between the NAc and the visual association cortex. Active DBS was associated with reduced activation of the dorsal striatum during passive viewing of alcohol-containing pictures. NAc-DBS is feasible and safe in patients with severe, otherwise refractory AUD. It is associated with a reduction in cravings and addictive behavior. A potential mechanism underlying this process is a down-regulation of the NAc, a disruption of its functional connectivity to the visual association cortex, and interference of cue-elicited dorsal striatum reactivity. Trial Registration NCT03660124 ( www.clinicaltrials.gov ).

Does tobacco dependence worsen cannabis withdrawal in people with and without schizophrenia-spectrum disorders?

BACKGROUND AND OBJECTIVES: Rates of cannabis use disorder (CUD) are higher in people with schizophrenia than in the general population. Irrespective of psychiatric diagnosis, tobacco co-use is prevalent in those with CUD and leads to poor cannabis cessation outcomes. The cannabis withdrawal syndrome is well-established and increases cannabis relapse risk. We investigated whether cannabis withdrawal severity differed as a function of high versus no/low tobacco dependence and psychiatric diagnosis in individuals with CUD. METHOD: Men with CUD (N = 55) were parsed into four groups according to schizophrenia diagnosis and tobacco dependence severity using the Fagerstrom Test for Nicotine Dependence (FTND): men with schizophrenia with high tobacco dependence (SCT+, n = 13; FTND ≥ 5) and no/low tobacco dependence (SCT-, n = 22; FTND ≤ 4), and nonpsychiatric controls with high (CCT+, n = 7; FTND ≥ 5) and no/low (CCT-, n = 13; FTND ≤ 4) tobacco dependence. Participants completed the Marijuana Withdrawal Checklist following 12-h of cannabis abstinence. RESULTS: There was a significant main effect of tobacco dependence on cannabis withdrawal severity (p < .001). Individuals with high tobacco dependence had significantly greater cannabis withdrawal severity (M = 13.85 [6.8]) compared to individuals with no/low tobacco dependence (M = 6.49, [4.9]). Psychiatric diagnosis and the interaction effects were not significant. Lastly, cannabis withdrawal severity positively correlated with FTND (r = .41, p = .002). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Among individuals with CUD and high tobacco dependence, cannabis withdrawal severity was elevated twofold, irrespective of diagnosis, relative to individuals with CUD and no/low tobacco dependence. Findings from this study emphasize the importance of addressing tobacco co-use when treating CUD.

Marked Increase in Amphetamine-Related Emergency Department Visits and Inpatient Admissions in Toronto, Canada, 2014-2021.

BACKGROUND: We report emergency department and inpatient amphetamine-related trends focusing on co-occurring substance use and psychiatric diagnoses at the Centre for Addiction and Mental Health, the largest mental health teaching hospital in Canada. METHODS: We describe yearly trends in amphetamine-related Centre for Addiction and Mental Health emergency department visits and inpatient admissions out of all emergency department visits and inpatient admissions between 2014 and 2021, along with proportions of concurrent substance-related admissions and mental/psychotic disorders emergency department visits and inpatient admissions among amphetamine-related contacts; joinpoint regression analyses assessed changes in amphetamine-related emergency department visits and inpatient admissions. RESULTS: Amphetamine-related emergency department visits rose from 1.5% in 2014 to 8.3% in 2021, with a peak of 9.9% in 2020. Amphetamine-related inpatient admissions rose from 2.0% to 8.8% in 2021, with a peak of 8.9% in 2020. Significant increasing trends in the percentage of amphetamine-related emergency department visits happened especially between the second and the fourth quarter of 2014 (quarterly percent change = + 71.4, P <0.01). Similarly, the percentage of amphetamine-related inpatient admissions increased mostly between the second quarter of 2014 and the third quarter of 2015 (quarterly percent change = + 32.6, P <0.01). The proportion of concurrent opioid-related contacts among amphetamine-related emergency department visits and inpatient admission increased markedly between 2014 and 2021; psychotic disorders in amphetamine-related inpatient admissions more than doubled from 2015 to 2021. DISCUSSION: Prevalence of amphetamine use, mostly from methamphetamine, has been increasing in Toronto as have co-occurring psychiatric disorders and opioid use. Our findings highlight the need for increases in accessible efficacious treatments for complex populations with polysubstance use and co-occurring disorders.

A systematic review of gender-responsive and integrated substance use disorder treatment programs for women with co-occurring disorders.

Background: Integrated and gender-responsive interventions, designed to target co-occurring substance use and psychiatric disorders in women, may be effective in addressing gender-specific challenges.Objectives: This systematic review aims to identify integrated gender-responsive substance use disorder treatments for women, summarize evaluations of these treatments, and address gaps in the literature.Methods: We searched PsycINFO, PubMed, and MEDLINE on September 24, 2021, and March 10, 2022. Included articles were randomized-controlled trials, secondary analyses of naturalistic studies, or open-label studies of integrated and gender-responsive treatments from any year that assessed both substance use and mental health/trauma outcomes.Results: We identified N = 24 studies (participants = 3,396; 100% women) examining Seeking Safety, Helping Women Recover and Beyond Trauma, A Woman's Path to Recovery, Modified Trauma Recovery and Empowerment Model (TREM), Breaking the Cycle, VOICES, Understanding and Overcoming Substance Misuse, Women's Recovery Group, Female Specific Cognitive Behavioral Therapy, and Moment by Moment in Women's Recovery. Across treatments there were significant improvements over time; Seeking Safety, Helping Women Recover, and TREM were associated with significantly better substance use and mental health outcomes relative to the comparison groups.Conclusions: Integrated gender-responsive treatments are a promising approach to treating women with co-occurring substance use and mental health concerns, and broad clinical implementation stands to benefit women. However, there remains a lack of studies evaluating substance use treatments in women with severe mental illness (e.g., psychotic-spectrum disorders) who differ in their needs and capacity.

Genome-wide association meta-analysis of nicotine metabolism and cigarette consumption measures in smokers of European descent.

Smoking behaviors, including amount smoked, smoking cessation, and tobacco-related diseases, are altered by the rate of nicotine clearance. Nicotine clearance can be estimated using the nicotine metabolite ratio (NMR) (ratio of 3'hydroxycotinine/cotinine), but only in current smokers. Advancing the genomics of this highly heritable biomarker of CYP2A6, the main metabolic enzyme for nicotine, will also enable investigation of never and former smokers. We performed the largest genome-wide association study (GWAS) to date of the NMR in European ancestry current smokers (n = 5185), found 1255 genome-wide significant variants, and replicated the chromosome 19 locus. Fine-mapping of chromosome 19 revealed 13 putatively causal variants, with nine of these being highly putatively causal and mapping to CYP2A6, MAP3K10, ADCK4, and CYP2B6. We also identified a putatively causal variant on chromosome 4 mapping to TMPRSS11E and demonstrated an association between TMPRSS11E variation and a UGT2B17 activity phenotype. Together the 14 putatively causal SNPs explained ~38% of NMR variation, a substantial increase from the ~20 to 30% previously explained. Our additional GWASs of nicotine intake biomarkers showed that cotinine and smoking intensity (cotinine/cigarettes per day (CPD)) shared chromosome 19 and chromosome 4 loci with the NMR, and that cotinine and a more accurate biomarker, cotinine + 3'hydroxycotinine, shared a chromosome 15 locus near CHRNA5 with CPD and Pack-Years (i.e., cumulative exposure). Understanding the genetic factors influencing smoking-related traits facilitates epidemiological studies of smoking and disease, as well as assists in optimizing smoking cessation support, which in turn will reduce the enormous personal and societal costs associated with smoking.

Evaluating Treatment Mechanisms of Varenicline: Mediation by Affect and Craving.

INTRODUCTION: Negative reinforcement models posit that relapse to cigarette smoking is driven in part by changes in affect and craving during the quit attempt. Varenicline may aid cessation by attenuating these changes; however, this mediational pathway has not been formally evaluated in placebo-controlled trials. Thus, trajectories of negative affect (NA), positive affect (PA), and craving were tested as mediators of the effect of varenicline on smoking cessation. AIMS AND METHODS: Secondary data analysis was conducted on 828 adults assigned to either varenicline or placebo in a randomized controlled trial for smoking cessation (NCT01314001). Self-reported NA, PA, and craving were assessed 1-week pre-quit, on the target quit day (TQD), and 1 and 4 weeks post-TQD. RESULTS: Across time, NA peaked 1-week post-quit, PA did not change, and craving declined. Less steep rises in NA (indirect effect 95% CI: .01 to .30) and lower mean craving at 1-week post-quit (CI: .06 to .50) were mediators of the relationship between varenicline and higher cessation rates at the end of treatment. PA was associated with cessation but was not a significant mediator. CONCLUSIONS: These results partially support the hypothesis that varenicline improves smoking cessation rates by attenuating changes in specific psychological processes and supported NA and craving as plausible treatment mechanisms of varenicline. IMPLICATIONS: The present research provides the first evidence from a placebo-controlled randomized clinical trial that varenicline's efficacy is due, in part, to post-quit attenuation of NA and craving. Reducing NA across the quit attempt and craving early into the attempt may be important treatment mechanisms for effective interventions. Furthermore, post-quit NA, PA, and craving were all associated with relapse and represent treatment targets for future intervention development.

Videoconferencing-delivered psychological intervention for the treatment of COVID-19 related psychological distress in University students: study protocol for a randomised controlled trial in India.

BACKGROUND: The mental health impacts of the COVID-19 pandemic have been profound. This paper outlines the study protocol for a trial that tests the efficacy of a brief group-based psychological intervention (Coping with COVID; CWC), relative to Supportive Counselling, to reduce distress associated with COVID-19 in a young adult population in Bangalore, India. METHODS: A single-blind, parallel, randomized controlled trial will be carried out via video conferencing in a small group format. Following informed consent, adults that screen positive for levels of psychological distress (Kessler 10 (K-10 score ≥ 20) and have access to a videoconferencing platform will be randomised to an adapted version of CWC (n = 90) or Supportive Counselling (SC) (n = 90). The primary outcome will be reduction in psychological distress including anxiety and depression at 2-months post treatment. Secondary outcomes include worry, positive wellbeing, and stress in relation to COVID-19. DISCUSSION: This treatment trial will assess whether CWC will result in reduced distress relative to Supportive Counselling in a young adult population in Bangalore, India. This study will yield important insights into the role of nonspecific factors versus the intervention's components in impacting COVID-19 related distress. TRIAL REGISTRATION: This trial was prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN12621001064897). ETHICS AND DISSEMINATION: Ethics approval has been obtained from the participating institution, CHRIST University in Bangalore. Results of the trial will be submitted for publication in peer reviewed journals and findings presented at scientific conferences and to key service providers and policy makers.

Effects of 28 days of cannabis abstinence on cognition in major depressive disorder: A pilot study.

BACKGROUND AND OBJECTIVES: Cannabis is a widely used substance that may impair select cognitive domains, including attention and memory. Problematic cannabis use is a common clinical problem among patients with major depressive disorder (MDD). Few studies have investigated the effects of cannabis abstinence on cognition in MDD. Thus, our study aimed to determine whether a 28-day period of cannabis abstinence is associated with improvements in cognition in patients with MDD and comorbid cannabis use disorder (CUD). METHODS: We evaluated the effects of 28 days of cannabis abstinence on cognition in MDD patients with comorbid CUD facilitated by contingency management, motivational interviewing, psychoeducation, and coping-skills training (N = 11). Primary outcomes included Baseline to Day 28 changes in verbal memory and learning, while secondary outcomes included Baseline to Day 28 changes in working memory, visuospatial working memory (VSWM), visual search speed, mental flexibility, response inhibition, attention, manual dexterity, and fine motor movement. RESULTS: Eight participants (72.7%) met the pre-specified criteria for cannabis abstinence and three participants significantly reduced their cannabis use (≥90%). Visual search speed, selective attention, and VSWM improved over the study period. These improvements were not associated with changes in cannabis metabolite levels from baseline to endpoint. DISCUSSION AND CONCLUSIONS: Our findings suggest that 28 days of cannabis abstinence may improve select cognitive domains in patients with MDD and comorbid CUD. SCIENTIFIC SIGNIFICANCE: This is the first study to longitudinally examine the effects of cannabis on cognition in MDD. CLINICAL TRIAL: Effects of Cannabis Abstinence on Symptoms and Cognition in Depression (NCT03624933; https://www. CLINICALTRIALS: gov).

Does cannabis use predict aggressive or violent behavior in psychiatric populations? A systematic review.

Background: Despite an increase in information evaluating the therapeutic and adverse effects of cannabinoids, many potentially important clinical correlates, including violence or aggression, have not been adequately investigated.Objectives: In this systematic review, we examine the published evidence for the relationship between cannabis and aggression or violence in individuals with psychiatric disorders.Methods: Following PRISMA guidelines, articles in English were searched on PubMed, Google Scholar, MEDLINE, and PsycINFO from database inception to January 2022. Data for aggression and violence in people with psychiatric diagnoses were identified during the searches.Results: Of 391 papers identified within the initial search, 15 studies met inclusion criteria. Cross-sectional associations between cannabis use and aggression or violence in samples with post-traumatic stress disorder (PTSD) were found. Moreover, a longitudinal association between cannabis use and violence and aggression was observed in psychotic-spectrum disorders. However, the presence of uncontrolled confounding factors in the majority of included studies precludes any causal conclusions.Conclusion: Although cannabis use is associated with aggression or violence in individuals with PTSD or psychotic-spectrum disorders, causal conclusions cannot be drawn due to methodological limitations observed in the current literature. Well-controlled, longitudinal studies are needed to ascertain whether cannabis plays a causal role on subsequent violence or aggression in mental health disorders.

Comparing the Rate of Nicotine Metabolism Among Smokers With Current or Past Major Depressive Disorder.

BACKGROUND AND OBJECTIVES: Persons with current or past major depressive disorder (MDD) vs those without have higher smoking rates. The nicotine metabolite ratio (NMR) represents variation in the rate of nicotine metabolism and has been associated with smoking behaviors and response to tobacco treatments. We compared NMR between smokers with current or past MDD (MDD+) vs smokers without MDD (MDD-). We also assessed correlates of NMR and compared withdrawal and craving between MDD+ and MDD- smokers. METHODS: Using baseline data from two clinical trials and propensity score weighting based on sex, race, body mass index, and smoking rate, we compared NMR between MDD+ (N = 279) and MDD- (N = 1575) smokers. We also compared groups on and nicotine withdrawal and craving. RESULTS: Mean NMR (ß = -.02, 95% confidence interval [CI]: -0.05 to 0.01, P = .13) and the distribution of smokers across NMR quartiles (odds ratio [OR] = 0.76, 95% CI: 0.50 to 1.16, P = .21) were similar between MDD+ and MDD- samples. This relationship was not affected by antidepressant medication. In the MDD+ sample, African Americans had significantly lower mean NMR, while older smokers and smokers with lower education had higher mean NMR (Ps < .05). MDD+ smokers had significantly higher withdrawal and craving than MDD- smokers (Ps < .05). DISCUSSION AND CONCLUSIONS: While variability in NMR may not explain differences in smoking rates between MDD+ and MDD- smokers, MDD+ smokers report increased withdrawal and craving. SCIENTIFIC SIGNIFICANCE: In this first study to assess NMR among MDD+ smokers, the findings underscore the need to address withdrawal and craving within smoking cessation treatments for those with MDD. (Am J Addict 2021;00:00-00).

A systematic review and meta-analysis of sex differences in cannabis use disorder amongst people with comorbid mental illness.

BACKGROUND: While males are more likely diagnosed with cannabis use disorder (CUD), females are more susceptible to developing and maintaining CUD. Yet, for both sexes, CUD is associated with high rates of comorbid mental illness (MI). OBJECTIVES: To identify and compare sex differences in the prevalence of comorbid CUD amongst individuals with/without MIs. METHODS: This systematic review generated pooled odds ratios (OR) and 95% confidence intervals (CI) from 37 studies (including clinical trials, cohort, and case-control studies) among individuals with and without MIs, quantifying sex differences in rates of comorbid CUD. A meta-analysis was also completed. RESULTS: In the CUD-only group, males were twice as likely to have CUD than females (OR = 2.0, CI = 1.9-2.1). Among MIs, males were more likely than females to have CUD comorbid with schizophrenia (OR ~2.6, CI = 2.5-2.7) and other psychotic, mood, and substance use disorders (1> OR <2.2, CI = 0.7-2.6). The reverse association (females > males) was observed for anxiety disorders and antisocial personality disorder (OR = 0.8, CI = 0.7-1.0). Among females, MIs increased the likelihood of having CUD, except for psychotic disorders and depression. A meta-analysis was inconclusive due to high heterogeneity across studies. Thus, comparisons across MI groups were not possible. CONCLUSION: While males are more likely to be diagnosed with CUD, there are important sex differences in the prevalence of CUD across MI diagnoses that should be taken into account when approaching CUD prevention and determining treatment efficacy.

Cannabis and Cannabinoids in Mood and Anxiety Disorders: Impact on Illness Onset and Course, and Assessment of Therapeutic Potential.

BACKGROUND AND OBJECTIVES: Cannabis use is common in people with and mood and anxiety disorders (ADs), and rates of problematic use are higher than in the general population. Given recent policy changes in favor of cannabis legalization, it is important to understand how cannabis and cannabinoids may impact people with these disorders. We aimed to assess the effects of cannabis on the onset and course of depression, bipolar disorder, ADs, and post-traumatic stress disorder (PTSD), and also to explore the therapeutic potential of cannabis and cannabinoids for these disorders. METHODS: A systematic review of the literature was completed. The PubMed® database from January 1990 to May 2018 was searched. We included longitudinal cohort studies, and also all studies using cannabis or a cannabinoid as an active intervention, regardless of the study design. RESULTS: Forty-seven studies were included: 32 reported on illness onset, nine on illness course, and six on cannabinoid therapeutics. Cohort studies varied significantly in design and quality. The literature suggests that cannabis use is linked to the onset and poorer clinical course in bipolar disorder and PTSD, but this finding is not as clear in depression and anxiety disorders (ADs). There have been few high-quality studies of cannabinoid pharmaceuticals in clinical settings. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These conclusions are limited by a lack of well-controlled longitudinal studies. We suggest that future research be directed toward high-quality, prospective studies of cannabis in clinical populations with mood and ADs, in addition to controlled studies of cannabinoid constituents and pharmaceuticals in these populations. (Am J Addict 2019;00:00-00).

Pharmacotherapies for co-occurring substance use and bipolar disorders: A systematic review.

OBJECTIVES: Substance use disorders (SUDs), including those for alcohol, stimulants, tobacco, opioids and cannabis, in patients with bipolar disorder are a major clinical and public health problem, and are present in the majority of these patients. Nonetheless, the development of effective pharmacological treatments for co-occurring SUDs in bipolar illness have not been well-developed and may be an important practical reason for the reduced effectiveness of these medications in community practice. METHODS: We conducted a systematic review of the literature (PubMed, Medline, Google Scholar), and identified N = 29 clinical studies, which evaluated both mental health and SUD outcomes in patients with co-occurring bipolar disorders and SUDs. RESULTS: Our findings suggest the potential of valproate sodium and lamotrigine as preferred pharmacological agents for the treatment of co-occurring psychiatric and substance use outcomes in these patients. However, many of the reviewed studies are of open-label designs and of modest sample sizes. CONCLUSIONS: Thus, given the gaps in our knowledge, recommendations for treatment of this common and important co-morbidity are preliminary. Accordingly, the conduct of larger, randomized controlled trials for this co-morbidity is clearly needed.

Cannabis and mental illness: a review.

With the increasing push to legalize cannabis in Western nations, there is a need to gage the potential impact of this policy change on vulnerable populations, such as those with mental illness, including schizophrenia, mood, and anxiety disorders. This is particularly important as there are strong motives in these individuals to seek short-term reward (e.g., "getting high"). Nonetheless, data to support the beneficial effects of cannabis use in psychiatric populations are limited, and potential harms in patients with psychotic and mood disorders have been increasingly documented. This article reviews the effects of cannabis in people with mental illness. Then, we provide a reconciliation of the addiction vulnerability and allostatic hypotheses to explain co-morbidity addiction in mentally ill cannabis users, as well as to further aid in developing a rational framework for the assessment and treatment of problematic cannabis use in these patients.

Effects of Tobacco Smoking Status on Verbal Learning and Memory in Patients With Schizophrenia and Non-Psychiatric Controls.

BACKGROUND AND OBJECTIVES: Patients with schizophrenia have higher rates of tobacco smoking compared to the general population. Moreover, these patients have deficits in cognition, including verbal learning and memory. However, it is not clear whether smoking status alters verbal learning and memory in schizophrenia. We examined the effects of smoking abstinence and reinstatement on verbal learning and memory in people with schizophrenia and nonpsychiatric controls and other cognitive domains as exploratory. METHODS: Smoking participants (N = 28; 14 schizophrenia smokers; 14 nonpsychiatric smokers) were studied under smoking satiated, overnight abstinence and smoking reinstatement conditions. Nonsmokers ( n = 30; 15 schizophrenia nonsmokers; 15 nonpsychiatric nonsmokers) were also studied. A comprehensive cognitive battery was administered including verbal learning and memory using the Hopkins Verbal Learning Test-Revised (HVLT-R). RESULTS: A 2 (diagnosis) × 2 (smoking status) repeated measures analysis of variance with time (session) as the within-subjects factor and diagnosis and smoking status as the between-subject factors was performed for HVLT-R and other cognitive outcomes. Smoking abstinence produced a decline in verbal memory of the HVLT discrimination index in smokers with schizophrenia that was partially revised by reinstatement, although trends for other HVLT measures were not statistically significant. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Acute cigarette smoking and abstinence may selectively alter verbal learning and memory deficits in smokers with schizophrenia compared to nonpsychiatric smoking controls and nonsmokers, but additional studies are needed to confirm the preliminary findings in this small sample. (Am J Addict 2019;00:1-9).