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.

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.

Neuromodulation to Treat Substance Use Disorders in People With Schizophrenia and Other Psychoses: A Systematic Review.

BACKGROUND: Substance use disorders (SUDs) are a common yet poorly studied comorbidity in individuals with psychotic disorders. The co-occurrence of the two complicates recovery and interferes with pharmacological and behavioral treatment response and adherence. Recently, researchers have been exploring both invasive and non-invasive neuromodulation techniques as potential treatment methods for SUDs. We review the evidence that neuromodulation may reduce substance craving and consumption in individuals with schizophrenia. METHODS: A comprehensive literature search of PubMed, MEDLINE, and PsycINFO databases was conducted (N = 1,432). Of these, we identified seven studies examining the effects of repetitive transcranial magnetic stimulation (rTMS) and two studies using transcranial direct current stimulation (tDCS) on drug consumption and craving in schizophrenia or schizoaffective disorders. RESULTS: Despite the limited number of studies in this area, the evidence suggests that rTMS to the dorsolateral prefrontal cortex (DLPFC) may reduce cannabis and tobacco use in patients with schizophrenia and schizoaffective disorder. Findings with tDCS, however, were inconclusive. DISCUSSION: Our systematic review suggests that rTMS applied to DLPFC is a safe and promising therapeutic technique for the management of comorbid schizophrenia and SUDs, with the majority of the evidence in tobacco use disorder. However, there was substantial heterogeneity in study methods, underscoring the need to optimize stimulation parameters (e.g., frequency, duration, and target regions). Larger clinical trials are needed to establish the efficacy of rTMS in reducing drug consumption and craving in psychotic patients, ideally in comparison to existing pharmacological and behavioral interventions.