Cannabidiol as a candidate pharmacotherapy for sleep disturbance in alcohol use disorder.

Among individuals with alcohol use disorder (AUD), it is estimated that the majority suffer from persistent sleep disturbances for which few candidate medications are available. Our aim wass to critically review the potential for cannabidiol (CBD) as a treatment for AUD-induced sleep disturbance. As context, notable side effects and abuse liability for existing medications for AUD-induced sleep disturbance reduce their clinical utility. CBD modulation of the endocannabinoid system and favorable safety profile have generated substantial interest in its potential therapeutic use for various medical conditions. A number of preclinical and clinical studies suggest promise for CBD in restoring the normal sleep-wake cycle and in enhancing sleep quality in patients diagnosed with AUD. Based on its pharmacology and the existing literature, albeit primarily preclinical and indirect, CBD is a credible candidate to address alcohol-induced sleep disturbance. Well-designed RCTs will be necessary to test its potential in managing this challenging feature of AUD.

Melatonin for Treatment-Seeking Alcohol Use Disorder patients with sleeping problems: A randomized clinical pilot trial.

A high percentage of subjects diagnosed with alcohol use disorder (AUD) suffer from sleeping difficulties. Lack of sleep could lead AUD patients to relapse or, sometimes, to suicide. Most of the currently prescribed medications to treat this complex problem retain a high risk of side effects and/or dependence. Therefore, the aim of the current clinical trial is to investigate the possibility of the use of a safer treatment, such as the natural health product melatonin, to treat alcohol-related sleeping problems. Sixty treatment-seeking AUD subjects were assigned to melatonin (5 mg) or placebo for 4 weeks of treatment. Change in sleeping quality which is the primary outcome of the study was assessed using the Pittsburgh sleep quality index (PSQI) scale. Linear mixed models were used to statistically analyze the difference in scores before and after 4 weeks of treatment. There was a reduction in the global PSQI score in both groups with no significant drug effect between groups. In conclusion, the use of melatonin (5 mg)/day didn't differ from placebo in decreasing sleeping problems in a sample of AUD subjects after 4 weeks of treatment. However, higher doses are worth exploring in future research.

Randomized Clinical Trials Investigating Innovative Interventions for Smoking Cessation in the Last Decade.

Every year, billions of dollars are spent treating smoking and related conditions, yet smoking-related morbidity and mortality continue to rise. There are currently only three FDA-approved medications for smoking cessation: nicotine replacement therapy, bupropion, and varenicline. Although these medications increase abstinence rates, most individuals relapse following treatment. This chapter reviews clinical trials published within the past 10 years investigating novel smoking cessation pharmacotherapies. Among these pharmacotherapies, some showed promising results, such as cytisine and endocannabinoid modulators, whereas others failed to produce significant effects. More research is needed to develop drugs that produce higher rates of long-term abstinence and to determine which subgroups of patients benefit from a given treatment.

Association Study of OPRM1 Gene in a Sample of Schizophrenia Patients With Alcohol Dependence or Abuse.

Alcohol use disorder is a complex disorder that is influenced by genetic factors. The non-synonymous single-nucleotide polymorphism (SNP) rs1799971 in exon 1 in opioid receptor OPRM1 was extensively studied in patients with alcohol dependence with mixed findings. Moreover, studies showed that opioid receptor polymorphism might play a role in the pathophysiology of schizophrenia. Our results suggest that rs1799971 SNP is not significantly associated with alcohol dependence in our sample of Schizophrenia patients of European ancestry.

Testing the PPAR hypothesis of tobacco use disorder in humans: A randomized trial of the impact of gemfibrozil (a partial PPARα agonist) in smokers.

Previous pre-clinical studies demonstrated a promising role of alpha-type peroxisome proliferator-activated receptors (PPARα) agonists in decreasing nicotine self-administration and nicotine-seeking behavior in animals. Our goal was to investigate the potential of gemfibrozil, a PPARα agonist, on reducing tobacco smoking in humans. METHODS: This was a double-blind, placebo-controlled, crossover study evaluating the effects of gemfibrozil (1200 mg/day) on smoking in 27 treatment-seeking smokers. The study had two 2-week phases separated by a washout period of at least 1 week. In each phase and after 1 week on medication, participants underwent a lab session where cue reactivity and forced choice paradigms were conducted. Physiological responses and self-reported craving were monitored during the presentation of smoking and neutral cues. In addition, two types of cigarettes were used in the forced choice paradigms: the Nicotinized cigarettes (Nic) and the Denicotinized cigarettes (Denic). The goal of the forced choice was to calculate the percentage of choice of Nic cigarettes while taking gemfibrozil or placebo. The number of quit days was calculated during the two quit attempts weeks (one while taking gemfibrozil and one while taking placebo) of the study. RESULTS: There were no significant differences between gemfibrozil and placebo groups in the percentage of choice of Nic cigarettes, the cue-reactivity (both physiological and subjective measures), or in the number of days of abstinence. CONCLUSIONS: Although preclinical studies with PPAR α agonists showed promising results, this preliminary study did not demonstrate positive effect of gemfibrozil on tobacco use and cessation indices.