Assessing the reinforcing effects of caffeine : the self-administrtion of caffeine by rats

Caffeine is the most widely consumed psychoactive drug, with the prevalence of use approaching 80% of the world's population. In stark contrast to most stimulants, caffeine is considered an innocuous agent with advantageous behavioral effects. Nonetheless, the sustained use of caffeine can result in tolerance or sensitization to the pharmacologic and behavioral effects of the drug effects shared with other stimulants including amphetamine and cocaine. Moreover, unlike cocaine, caffeine abstinence results in unique withdrawal symptoms that are easily identified. The observation of withdrawal, dependence, and tolerance, notions usually associated with drug abuse, suggest caffeine consumption may provide an intriguing model of substance abuse. To this end, the aims of this work were to delineate environmental factors that establish caffeine self-administration in rats. The self-administration of caffeine was established and modified by a combination of behavioral and pharmacological factors including food restriction, drug dose, and infusion rate. The results suggest caffeine-maintained behavior is comparable to nicotine self-administration, but distinct from that of cocaine or heroin. These findings highlight the role of non-pharmacological factors in substance abuse and suggest that further investigations evaluating the reinforcing effects of caffeine can enhance the understanding and treatment of drug abuse

Oral Cannabidiol Does Not Produce a Signal for Abuse Liability in Frequent Marijuana Smokers

Background—Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability. Methods—Healthy, frequent marijuana users (n=31) were enrolled in this within subject, randomized, placebo-controlled, double-blind, multisite study that administered oral cannabidiol (0, 200, 400, 800 mg) alone and in combination with smoked marijuana (0.01%, 5.3-5.8% THC). Participants received one dose combination across 8 once-weekly outpatient sessions (7.5 hrs). The primary findings on the drug interaction effects were previously reported (Haney et al., 2016). The present study is a secondary analysis of the data to examine the abuse liability profile of oral cannabidiol (200, 400, 800 mg) in comparison to oral placebo and active smoked marijuana (5.3-5.8% THC). Results—Active marijuana reliably produced abuse-related subjective effects (e.g., high) (p \u3c .05). However, CBD was placebo-like on all measures collected (p \u3e .05). Conclusions—Overall, CBD did not display any signals of abuse liability at the doses tested and these data may help inform U.S. regulatory decisions regarding CBD schedule on the CSA

A Randomized Placebo-Controlled Trial of \u3cem\u3eN\u3c/em\u3e-Acetylcysteine for Cannabis Use Disorder in Adults

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 1200 mg (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 1200 mg 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