The Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving.

BACKGROUND: Naltrexone is a nonselective opioid receptor antagonist used as a treatment for alcohol use disorder. However, only modest clinical effects have been observed, possibly because of limited knowledge about the biological variables affecting the efficacy of naltrexone. We investigated the potential role of the kappa opioid receptor (KOR) in the therapeutic effect of naltrexone. METHODS: A total of 48 non-treatment-seeking heavy drinkers (16 women) who met DSM-IV criteria for alcohol dependence participated in two alcohol drinking paradigms (ADPs) separated by a week of open-label naltrexone (100 mg daily). Craving, assessed with the Alcohol Urge Questionnaire and the Yale Craving Scale, and drinking behavior were recorded in each ADP. Prior to naltrexone initiation, KOR availability was determined in the amygdala, hippocampus, pallidum, striatum, cingulate cortex, and prefrontal cortex using positron emission tomography with [11C]LY2795050. RESULTS: Participants reported lower levels of craving (Yale Craving Scale: -11 ± 1, p < .0001; Alcohol Urge Questionnaire: -6 ± 0.6, p < .0001) and consumed fewer drinks (-3.7 ± 4, p < .0001) during the second ADP following naltrexone therapy. The observed reduction in drinking was negatively associated with baseline KOR availability in the striatum (p = .005), pallidum (p = .023), and cingulate cortex (p = .018). Voxelwise analysis identified clusters in the bilateral insula, prefrontal, and cingulate cortex associated with the reduction in drinking (p < .0001). In addition, KOR availability in all evaluated brain regions was associated with craving measured in both ADPs. CONCLUSIONS: The KOR is implicated in drinking and craving following naltrexone therapy in alcohol use disorder.

PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age.

Opioid receptors are implicated in alcoholism, other addictions, withdrawal, and depression, and are considered potential pharmacological targets for treatment. Our goal in the present study was to compare the availability of kappa opioid receptors (KOR) between an alcohol-dependent cohort (AD) and a healthy control cohort (HC). Sixty-four participants-36 AD and 28 HC-underwent PET scans with [11C]LY2795050, a selective kappa antagonist tracer. Partial-volume correction was applied to all PET data to correct for atrophy. Volume of distribution (VT) of the tracer was estimated regionally as a measure of KOR availability. VT values of AD versus HC were compared for 15 defined ROIs. Multivariate analysis showed a main effect of group on VT across these 15 ROIs. Post hoc tests showed that AD had significantly lower VT and thus a lower KOR availability than HC in amygdala and pallidum (corrected for multiple comparisons). Exploratory analysis of change in VT with age was conducted; VT was not found to vary significantly with age in any region. Our findings of lower VT in AD versus HC in multiple regions are in contrast to findings in the mu and delta opioid receptor systems of higher VT in AD versus HC. Although age-related decline in receptors has previously been observed in the mu opioid receptor system, we found that KOR availability does not change with age.

Blunt Use among Adolescents and Young Adults: Informing Cigar Regulations.

OBJECTIVES: We used focus groups to understand cigar product features that increase the appeal of blunts (hollowed out cigars filled with marijuana) among adolescents and young adults. METHODS: With a standardized focus group guide, we assessed cigar use behaviors and perceptions among lifetime cigar users (N = 47; 8 focus groups separated by sex and age group [adolescents, young adults]) in 2016. We analyzed data related to blunts. RESULTS: Overall, 85.5% of the participants had smoked a blunt in the past 30 days (38% used daily). Participants perceived that cheap cigar brands were used primarily for blunts. Cigar product features that made them useful for blunts included wide availability, easy accessibility (easy to bypass underage purchasing restrictions), attractive flavors, inexpensive cost, perforated wrappers that make cigars easy to open, and ability to remove the inner wrapper (also referred to as "cancer paper") to reduce the risk of harm. CONCLUSIONS: Various product features of cigars make it easy for adolescents and young adults to manipulate them to create blunts. Tobacco regulations that include restrictions on product characteristics, as well as enforcement of prohibition of sales of cigars to underage minors are needed. Youth also need to be educated about harms of blunt use.

An open-label pilot study of an intervention using mobile phones to deliver contingency management of tobacco abstinence to high school students.

This pilot study assessed the feasibility, acceptability, and preliminary efficacy of a smoking cessation intervention that used mobile phones to remotely deliver reinforcements contingent on tobacco abstinence (contingency management [CM]) and weekly in-person cognitive-behavioral therapy to adolescent smokers. Daily adolescent smokers (N = 15; 12 completed study procedures, 3 dropped out) were recruited to participate in a 4-week study. During the first 2 weeks, daily text messages sent at random times prompted participants to transmit a video of themselves providing a carbon monoxide (CO) sample. During the last 2 weeks, text messages sent on 3 randomly chosen days each week prompted participants to transmit a video of themselves providing a saliva sample. Negative samples (CO ≤8 ppm; cotinine ≤100 ng/ml) were reinforced with monetary incentives. Feasibility was assessed using the number of on-time, valid videos, and acceptability was determined using participant perceptions of the intervention. Seven-day point-prevalence (PP) abstinence (self-reported abstinence, cotinine <100 ng/ml) was assessed at end of treatment (EOT) and at a 1-month follow-up. The study findings indicate that remote delivery of CM using mobile phones was feasible (85.8% of the CO videos and 67% of the saliva cotinine videos were on time) and acceptable (positive perceptions of the CM procedures). Seven-day PP was 60% at EOT and 46.7% at the follow-up. Although larger randomized controlled trials are needed to evaluate efficacy, this pilot study suggests that the use of mobile phones to deliver CM for smoking cessation among adolescent smokers was acceptable and feasible. (PsycINFO Database Record