Prenatal Cannabis and Tobacco Co-Exposure and Its Association with Behavioural Outcomes in Middle Childhood: Co-exposition prénatale au cannabis et au tabac et son association avec les résultats comportementaux au cours de l'enfance intermédiaire.

OBJECTIVES: Cannabis legalization has triggered an increase in prenatal cannabis use. Given that tobacco is commonly co-used with cannabis, determining outcomes associated with prenatal cannabis and tobacco co-exposure is crucial. While literature exists regarding the individual effects of prenatal cannabis and tobacco exposure on childhood behaviour, there is a gap regarding their combined use, which may have interactive effects. Therefore, we investigated whether prenatal cannabis and tobacco co-exposure was associated with greater externalizing and internalizing problems in middle childhood compared to prenatal exposure to either substance alone or no exposure. METHODS: Baseline data from the Adolescent Brain Cognitive Development (ABCD) Study (collected in children ages 9-11) were used to explore differences in externalizing and internalizing scores derived from the Childhood Behavior Checklist across four groups: children with prenatal cannabis and tobacco co-exposure (CT, n = 290), children with prenatal cannabis-only exposure (CAN, n = 225), children with prenatal tobacco-only exposure (TOB, n = 966), and unexposed children (CTL, n = 8,311). We also examined if the daily quantity of tobacco exposure modulated the effect of cannabis exposure on outcomes. RESULTS: Adjusting for covariates, a 2 × 2 ANCOVA revealed significant main effects for prenatal cannabis (p = 0.03) and tobacco exposure (p < 0.001), and a significant interaction effect on externalizing scores (p = 0.032); no significant main effects or interactions were found for internalizing scores. However, interactions between daily quantity of cannabis and tobacco exposure significantly predicted both externalizing and internalizing scores (p < 0.01). CONCLUSIONS: These findings indicate that co-exposure is associated with greater externalizing problems than exposure to either substance alone, which did not differ from each other. Further, greater tobacco exposure may amplify the negative effect of cannabis exposure on both externalizing and internalizing behaviours in children. These findings underscore the need for interventions that target cannabis and tobacco co-use in pregnant women to circumvent their adverse impact on middle childhood behaviour.

Prenatal Cannabis and Tobacco Co-exposure and its Association with Middle Childhood BehavioursPlain Language SummaryGiven the high rates of both cannabis and tobacco use during pregnancy, we explored if their combined use was associated with greater problematic behaviour in 10-year-old children compared to either substance alone or no substance use. We found that children with prenatal co-exposure had greater externalizing behaviours, such as attention problems and aggression, compared to children with prenatal exposure to one of the substances or no exposure. Prenatal co-exposure, cannabis-only exposure and tobacco-only exposure had no effect on childhood internalizing behaviours (e.g., depression, anxiety). However, the amount of tobacco consumed by the mother amplified the negative effect of cannabis on both childhood externalizing and internalizing behaviours. These findings emphasize the need for specialized treatment for cannabis and tobacco co-use in pregnant women to circumvent the adverse impact of these substances on externalizing behaviours in middle childhood.

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.

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.

Common and gender-specific associations with cocaine use on gray matter volume: Data from the ENIGMA addiction working group.

Gray matter volume (GMV) in frontal cortical and limbic regions is susceptible to cocaine-associated reductions in cocaine-dependent individuals (CD) and is negatively associated with duration of cocaine use. Gender differences in CD individuals have been reported clinically and in the context of neural responses to cue-induced craving and stress reactivity. The variability of GMV in select brain areas between men and women (e.g., limbic regions) underscores the importance of exploring interaction effects between gender and cocaine dependence on brain structure. Therefore, voxel-based morphometry data derived from the ENIGMA Addiction Consortium were used to investigate potential gender differences in GMV in CD individuals compared to matched controls (CTL). T1-weighted MRI scans and clinical data were pooled from seven sites yielding 420 gender- and age-matched participants: CD men (CDM, n = 140); CD women (CDW, n = 70); control men (CTLM, n = 140); and control women (CTLW, n = 70). Differences in GMV were assessed using a 2 × 2 ANCOVA, and voxelwise whole-brain linear regressions were conducted to explore relationships between GMV and duration of cocaine use. All analyses were corrected for age, total intracranial volume, and site. Diagnostic differences were predominantly found in frontal regions (CD < CTL). Interestingly, gender × diagnosis interactions in the left anterior insula and left lingual gyrus were also documented, driven by differences in women (CDW < CTLW). Further, lower right hippocampal GMV was associated with greater cocaine duration in CDM. Given the importance of the anterior insula to interoception and the hippocampus to learning contextual associations, results may point to gender-specific mechanisms in cocaine addiction.

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).

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.

Does cannabis use moderate smoking cessation outcomes in treatment-seeking tobacco smokers? Analysis from a large multi-center trial.

BACKGROUND AND OBJECTIVE: Tobacco and cannabis are frequently used in combination and cannabis co-use may lead to poor tobacco cessation outcomes. Therefore, it is important to explore if cannabis co-use is associated with a reduced likelihood of achieving successful tobacco abstinence among treatment-seeking tobacco smokers. The present study examined whether current cannabis use moderated tobacco cessation outcomes after 12 weeks of pharmacological treatment (varenicline vs. nicotine patch vs. placebo) with adjunctive behavioral counseling. METHODS: Treatment-seeking tobacco smokers (N = 1,246) were enrolled in an intent-to-treat study, of which 220 were current cannabis users. Individuals were randomly assigned to 12 weeks of placebo (placebo pill plus placebo patch), nicotine patch (active patch plus placebo pill), or varenicline (active pill plus placebo patch), plus behavioral counseling. The primary endpoint was biochemically verified 7-day point prevalence abstinence at the end of treatment. RESULTS: Controlling for rate of nicotine metabolism, treatment arm, age, sex, alcohol, and level of nicotine dependence, cannabis users were as successful at achieving biochemically verified 7-day point prevalence abstinence compared to tobacco-only smokers. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Findings suggest that cannabis use does not hinder the ability to quit tobacco smoking. Future tobacco cessation studies should employ prospective, longitudinal designs investigating cannabis co-use over time and at different severity levels. (Am J Addict 2016;25:291-296).

Co-morbid tobacco use disorder and depression: A re-evaluation of smoking cessation therapy in depressed smokers.

BACKGROUND AND OBJECTIVES: To provide a critical evaluation of nicotine use disorder co-morbidity in persons with major depressive disorder (MDD) or its subsyndromal presentations. We focus on how a diagnosis of current or past MDD may shape access to smoking cessation therapy, and highlight the unique challenges that this group of smokers has to overcome to receive adequate treatment. METHODS: A literature search was performed using PubMed for studies published between January 1995 and March 2015 using the following keywords and combination of keywords (co-morbidity, co-occurrence, and dual-diagnosis) and (nicotine dependence, cigarette smoking, tobacco dependence, tobacco use disorder) and (depression, major depression, unipolar mood disorders) and (self-medication). A total of 93 articles were identified. Of these, 31 studies were included in the analysis. RESULTS: We found that: a) depressed smokers are motivated to quit; b) smoking cessation does not exacerbate symptoms of depression; c) depression does not have a negative impact on smoking cessation outcomes, and d) the self-medication hypothesis does not account for tobacco dependence and depression co-morbidity. DISCUSSION AND CONCLUSIONS: Our review of the relevant evidence suggests the importance and clinical significance of undertaking smoking cessation treatment for depressed smokers. SCIENTIFIC SIGNIFICANCE: Our findings support the need for increased attention to developing and implementing smoking cessation treatments for depressed smokers. SCIENTIFIC SIGNIFICANCE: Our findings support the need for increased attention to developing and implementing smoking cessation treatments for depressed smokers.

Relationship between tobacco and cannabis use status in outpatients with schizophrenia.

BACKGROUND AND OBJECTIVE: While high prevalence of tobacco and cannabis use are well established in schizophrenia, reports on their co-morbid use is limited. We explored the links between tobacco and cannabis use in an outpatient population meeting DSM-IV criteria for schizophrenia. METHODS: Cigarette smoking behaviors were assessed in an outpaitent population with schizophrenia (N=54) with current (n=18), former (n=24), and no lifetime cannabis dependence (n=12). RESULTS: We found significant differences in cigarettes per day (CPD) across groups: current dependent patients smoked less CPD than patients with former dependence and those with no history of dependence; former dependent patients smoked significantly less than patients with no history of cannabis dependence. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Preliminary results support an effect of cannabis use status on tobacco consumption. In the absence of cannabis, patients may increase cigarette smoking, suggesting state-dependent effects of cannabis on tobacco. Prospective designs should further examine this relationship between cannabis and tobacco in schizophrenia versus non-psychiatric controls.

Neuromelanin levels in individuals with substance use disorders: A systematic review and meta-analysis.

Dopamine's role in addiction has been extensively studied, revealing disruptions in its functioning throughout all addiction stages. Neuromelanin in the substantia nigra (SN) may reflect dopamine auto-oxidation, and can be quantified using neuromelaninsensitive magnetic resonance imaging (neuromelanin-MRI) in a non-invasive manner.In this pre-registered systematic review, we assess the current body of evidence related to neuromelanin levels in substance use disorders, using both post-mortem and MRI examinations. The systematic search identified 10 relevant articles, primarily focusing on the substantia nigra. An early-stage meta-analysis (n = 6) revealed varied observations ranging from standardized mean differences of -3.55 to +0.62, with a pooled estimate of -0.44 (95 % CI = -1.52, 0.65), but there was insufficient power to detect differences in neuromelanin content among individuals with substance use disorders. Our gap analysis highlights the lack of sufficient replication studies, with existing studies lacking the power to detect a true difference, and a complete lack of neuromelanin studies on certain substances of clinical interest. We provide recommendations for future studies of dopaminergic neurobiology in addictions and related psychiatric comorbidities.

Dose-dependent effects of Varenicline on tobacco craving and withdrawal in tobacco smokers with and without schizophrenia.

BACKGROUND: People with schizophrenia (SCZ) have significantly higher tobacco smoking rates and lower quit rates than the general population. Varenicline, a partial agonist at α4ß2 nicotinic acetylcholine receptors (nAChRs) is an effective smoking cessation pharmacotherapy, however, investigation into its effects in SCZ are less well-studied and mechanisms may differ from non-psychiatric controls due to dysregulation in nAChR neurotransmission associated with SCZ. Here, we investigate whether Varenicline attenuates acute abstinence-induced increases in craving and withdrawal in participants with and without SCZ. METHODS: Following biochemically-verified overnight abstinence and subsequent smoking reinstatement, individuals with nicotine-dependence (n = 13 SCZ or schizoaffective; n = 12 controls) were assessed on the Minnesota Nicotine Withdrawal Scale (MNWS) and Tiffany Questionnaire for Smoking Urges (TQSU). Participants were pretreated in a double-blind, counterbalanced manner with Varenicline (0, 1 or 2 mg/day x 3 days) over three separate weeks. Data were analyzed using linear mixed-effects modelling and estimated marginal means. RESULTS: Robust effects of smoking abstinence were observed on TQSU and MNWS scores in SCZ and control participants. Relative to 1 mg, 2 mg/day of Varenicline attenuated abstinence-induced increases in craving (TQSU Factor 1 d=-0.47, p = .006; TQSU Factor 2 d=-0.42, p = .008) and withdrawal (MNWS d=-0.35, p = .03) in both groups. CONCLUSION: Our preliminary findings suggest that subacute Varenicline treatment reduces abstinence-induced craving and withdrawal in participants with and without SCZ. The efficacy of Varenicline on tobacco withdrawal and craving requires further study.

Structural and functional brain recovery in individuals with substance use disorders during abstinence: A review of longitudinal neuroimaging studies.

BACKGROUND: Neuroimaging studies reveal structural and functional including neurochemical brain abnormalities in individuals with substance use disorders compared to healthy controls. However, whether and to what extent such dysfunction is reversible with abstinence remains unclear, and a review of studies with longitudinal within-subject designs is lacking. We performed a systematic review of longitudinal neuroimaging studies to explore putative brain changes associated with abstinence in treatment-seeking individuals with substance use disorders. METHODS: Following PRISMA guidelines, we examined articles published up to May 2021 that employed a neuroimaging technique and assessed neurobiological recovery in treatment-seeking participants at a minimum of two time-points separated by a period of abstinence (longer than 24 h apart) or significant reduction in drug use. RESULTS: Forty-five studies met inclusion criteria. Encouragingly, in this limited but growing literature, the majority of studies demonstrated at least partial neurobiological recovery with abstinence. Structural recovery appeared to occur predominantly in frontal cortical regions, the insula, hippocampus, and cerebellum. Functional and neurochemical recovery was similarly observed in prefrontal cortical regions but also in subcortical structures. The onset of structural recovery appears to precede neurochemical recovery, which begins soon after cessation (particularly for alcohol); functional recovery may require longer periods of abstinence. CONCLUSIONS: The literature is still growing and more studies are warranted to better understand abstinence-mediated neural recovery in individuals with substance use disorders. Elucidating the temporal dynamics between neuronal recovery and abstinence will enable evidence-based planning for more effective and targeted treatment of substance use disorders, potentially pre-empting relapse.

Emotion recognition in individuals with cocaine use disorder: the role of abstinence length and the social brain network.

RATIONALE: Emotion recognition is impaired in drug addiction. However, research examining the effects of cocaine use on emotion recognition yield mixed evidence with contradictory results potentially reflecting varying abstinence durations. OBJECTIVES: Therefore, we investigated emotion recognition and its neural correlates in individuals with cocaine use disorder (CUD) parsed according to abstinence duration. METHODS: Emotion recognition performance was compared between current cocaine users (CUD + , n = 28; cocaine-positive urine), short-term abstainers (CUD-ST, n = 23; abstinence < 6 months), long-term abstainers (CUD-LT, n = 20; abstinence ≥ 6 months), and controls (n = 45). A sample subset (n = 73) underwent structural magnetic resonance imaging to quantify regional gray matter volume (GMV) using voxel-based morphometry. RESULTS: CUD + demonstrated greater difficulty recognizing happiness than CUD-ST and controls, and sadness and fear compared to controls (p < 0.01). For fear, CUD-ST also performed worse than controls (p < 0.01), while no differences emerged between CUD-LT and controls. Whole-brain analysis revealed lower GMV in the bilateral cerebellum in CUD + compared to CUD-LT and controls; a similar pattern was observed in the amygdala (CUD + < CUD-LT) (pFWE < 0.01). Collapsed across all participants, poorer recognition for happiness was associated with lower right cerebellar GMV (pFWE < 0.05). CONCLUSIONS: Emotion recognition is impaired with current cocaine use, and selective deficits (in fear) may persist with up to 6 months of abstinence. Lower cerebellar GMV may underlie deficits in positive emotion recognition. Interventions targeting emotional-social-cognitive deficits, especially among active users, may enhance treatment success for individuals with CUD.

Neurocognitive moderation of repetitive transcranial magnetic stimulation (rTMS) effects on cannabis use in schizophrenia: a preliminary analysis.

Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for cannabis use disorder in schizophrenia; however, gaps in the literature remain as to the potential role of neurocognitive functioning in treatment response. We evaluated the moderating role of select cognitive functions including baseline executive functioning, verbal memory, and sustained attention, and we explore the mediating role of changes in task performance on changes in cannabis use in both active and sham rTMS groups. Participants underwent high-frequency (20 Hz) rTMS applied to the bilateral dorsolateral prefrontal cortex 5x/week for 4 weeks. Weekly self-report of cannabis use and semi-quantitative urinary carboxy-tetrahydrocannabinol levels were recorded. A neurocognitive battery assessing verbal memory, visuospatial working memory, verbal working memory, sustained attention, delayed discounting, and complex planning was administered pre- and post-treatment. Better baseline performance on tasks assessing sustained attention, delayed discounting, and complex planning moderated the extent to which participants in the active group reduced cannabis use. There were no significant indirect pathways between treatment, changes in neuropsychological performance, and changes in cannabis use; however, active rTMS improved complex planning and sustained attention. These preliminary findings suggest that there is a moderating role of sustained attention, delayed discounting, and complex planning on the effects of rTMS on cannabis use. Further, mediation models suggest rTMS may exert direct effects on cannabis use independent of its effects on cognitive functioning in people with SCZ. Trial Registration: clinicaltrials.gov: NCT03189810.

Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia.

Cannabis use disorder (CUD) occurs at high rates in schizophrenia, which negatively impacts its clinical prognosis. These patients have greater difficulty quitting cannabis which may reflect putative deficits in the dorsolateral prefrontal cortex (DLPFC), a potential target for treatment development. We examined the effects of active versus sham high-frequency (20-Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use in outpatients with schizophrenia and CUD. Secondary outcomes included cannabis craving/withdrawal, psychiatric symptoms, cognition and tobacco use. Twenty-four outpatients with schizophrenia and CUD were enrolled in a preliminary double-blind, sham-controlled randomized trial. Nineteen participants were randomized to receive active (n = 9) or sham (n = 10) rTMS (20-Hz) applied bilaterally to the DLPFC 5x/week for 4 weeks. Cannabis use was monitored twice weekly. A cognitive battery was administered pre- and post-treatment. rTMS was safe and well-tolerated with high treatment retention (~90%). Contrast estimates suggested greater reduction in self-reported cannabis use (measured in grams/day) in the active versus sham group (Estimate = 0.33, p = 0.21; Cohen's d = 0.72), suggesting a clinically relevant effect of rTMS. A trend toward greater reduction in craving (Estimate = 3.92, p = 0.06), and significant reductions in PANSS positive (Estimate = 2.42, p = 0.02) and total (Estimate = 5.03, p = 0.02) symptom scores were found in the active versus sham group. Active rTMS also improved attention (Estimate = 6.58, p < 0.05), and suppressed increased tobacco use that was associated with cannabis reductions (Treatment x Time: p = 0.01). Our preliminary findings suggest that rTMS to the DLPFC is safe and potentially efficacious for treating CUD in schizophrenia.

Treatment Implications Associated with Cannabis and Tobacco Co-Use.

PURPOSE OF THE REVIEW: The goal of this article is to summarize the treatment-focused literature on cannabis and tobacco co-use and the treatment implications of co-use. This review will focus on: 1) the impact of co-use on cessation outcomes, 2) compensatory use/substitution of the non-treated substance among co-users, and 3) treatment interventions to address co-use. This article will highlight the limitations to co-use captured in the literature and offer considerations and directives for co-use research and treatment moving forward. RECENT FINDINGS: The degree to which co-use affects cessation for a single, targeted substance remains in question, as the literature is largely mixed. Cannabis treatment trials are better equipped to answer these questions given that they do not typically exclude tobacco users. While the relationship between tobacco use and poorer cannabis outcomes appears to have some evidence, the reverse relationship (cannabis use affecting tobacco outcomes) is not consistently supported. SUMMARY: The co-use of cannabis and tobacco and its impact on single substance cessation and/or compensatory substance use during cessation is generally overlooked in treatment trials, while interventions to address both substances are rare. Capturing co-use adds burden for researchers, clinicians, and participants, but is warranted given the prevalence of co-use and a rapidly changing cannabis and tobacco regulatory environment, which may further complicate co-occurring substance use. Co-users are a heterogeneous population; trials focused on co-users, in addition to better data capture and consistent terminology, will aid in an understanding of nuanced patterns of co-use critical to inform treatment interventions.

Changes in tobacco consumption in cannabis dependent patients with schizophrenia versus non-psychiatric controls during 28-days of cannabis abstinence.

BACKGROUND: Tobacco and cannabis are highly co-morbid in the general population and in patients with schizophrenia. Given the putative causal mechanisms facilitating co-use, it is important to determine how cannabis cessation may influence concurrent tobacco use. Using a 28-day cannabis abstinence paradigm, we prospectively examined changes in tobacco consumption in patients with schizophrenia and controls with cannabis dependence and daily cigarette use. METHODS: Cannabis dependent patients with schizophrenia (n = 19) and controls (n = 20) completed the study with abstinence rates of 42% and 55%, respectively. Participants completed measures of substance use, withdrawal, and clinical symptoms weekly. Urine samples were collected twice weekly to biochemically verify abstinence. RESULTS: Patients reported a greater increase in cigarettes smoked per day (CPD) on Day 7 relative to baseline (2.97 cigarette increase for abstinent subgroup, p < .01) compared to controls (.06 cigarette increase for abstinent subgroup, p = .95). Initially, greater reductions in cannabis use related to greater increases in CPD relative to baseline in the patient subsample (simple slope = -2.31, p = .05), but by Day 28, CPD returned to baseline levels independent of cannabis use. CPD changes were unrelated to cannabis withdrawal. Results were similar for changes in caffeine consumption, but not for alcohol. CONCLUSIONS: Findings suggest transient tobacco substitution for cannabis in patients with schizophrenia. This provides further support for a strong association between cannabis and tobacco in schizophrenia. Future studies should focus on targeting underlying mechanisms that promote co-use to better address potential changes in concurrent substance use during treatment interventions.

Effects of extended cannabis abstinence on clinical symptoms in cannabis dependent schizophrenia patients versus non-psychiatric controls.

BACKGROUND: Rates of cannabis use among patients with schizophrenia are high, however little is understood about clinical effects of continued cannabis use and cessation after illness onset. Therefore, we investigated the effects of 28-days of cannabis abstinence on psychotic and depressive symptomatology in cannabis dependent patients with schizophrenia. METHOD: Males with cannabis dependence and co-morbid schizophrenia (n=19) and non-psychiatric controls (n=20) underwent 28-days of monitored cannabis abstinence. Clinical symptoms were assessed at baseline and then weekly. Abstinence was encouraged using weekly therapy sessions and contingency reinforcement, confirmed by twice-weekly urine assays. RESULTS: Forty-two percent (8/19) of patients and 55% (11/20) of controls achieved 28-days of sustained cannabis abstinence. In patients, PANSS subscores did not change over time irrespective of abstinence status. In contrast, patient abstainers demonstrated a more pronounced reduction in depression scores compared to non-abstainers, however, the Abstinence Status x Time interaction was non-significant. DISCUSSION: Short-term (28-days) cannabis abstinence is not associated with improvement in psychotic symptoms, but may be associated with improvement in depressive symptomatology in patients with schizophrenia. Future studies employing larger samples as well as a continuous cannabis-using group may help to better characterize the causal effects of cannabis on symptom outcomes in this disorder.

A method to achieve extended cannabis abstinence in cannabis dependent patients with schizophrenia and non-psychiatric controls.

BACKGROUND: Cannabis use disorders (CUD) are common in schizophrenia (~25%) compared to the general population (~3%). Tetrahydrocannabinol (THC), the principal psychoactive component in cannabis is fat-soluble, resulting in an extended period for cannabinoid elimination. While detection of cannabinoids in urine is indicative of prior cannabis exposure, time of last use is difficult to verify sustained abstinence for extended periods (e.g., 28-days) in chronic cannabis users. Therefore, we evaluated the utility of a sustained cannabis abstinence paradigm in patients with schizophrenia and non-psychiatric controls. METHODS: Cannabis dependent patients (n=19) and controls (n=20) underwent 28-days of monitored cannabis abstinence facilitated with contingency management. Urine samples were taken twice weekly. Abstinence was evaluated using 1) Self-report; 2) Qualitative biochemical confirmation using MEDTOX; and 3) in a subset of participants (schizophrenia, n=13; controls, n=13) gas chromatography-mass spectrometry (GC-MS) was performed to obtain quantitative creatinine-normalized carboxy-THC (THC-COOH) metabolite levels <20ng/mL). Subjective assessments were used to assess behavioral correlates of cannabis abstinence and further supported time-dependent abstinence trajectories. RESULTS: Abstinence rates of 42.1% (8/19) in patients and 55% (11/19) in controls (p=0.53) were observed. Increased cannabis withdrawal symptoms in both patients and controls supported abstinence. DISCUSSION: Our results suggest a feasible method for identification of short-term cannabis abstinence in individuals with schizophrenia at rates comparable to controls. Monitoring sustained abstinence may have implications for potential interventions for CUDs in schizophrenia.