Dimensionality and homogeneity of the Colombian version of the Cocaine Craving Questionnaire (CCQ-N-10)

Background and aimIt is essential to have a validated instrument to measure craving for cocaine use. However, in Colombia, there is no instrument to screen cocaine craving. The study aimed to determine the homogeneity and dimensionality of the CCQ-N-10 in patients with cocaine use disorder in Colombia.Materials and methodsAn adaptation and subsequent analysis of the psychometric properties of the CCQ-N-10 scale was carried out with 102 hospitalized or outpatient adults diagnosed with substance use disorders in addiction units in Bucaramanga, Colombia. Internal consistency and construct validity were estimated by confirmatory factor analysis and correlation analysis with scales with similar objectives.ResultsAn omega coefficient of 0.93 was obtained, and adjustment indicators of the confirmatory model were acceptable (RMSEA of 0.08, CFI and TLI of 0.99) when two of the original scale items were removed from the original scale analysis.ConclusionsThis study shows that the craving scale reduced to eight items can be helpful to assess the construct in the Colombian population; However, the small sample size makes it challenging to carry out other analyzes to corroborate its psychometric properties.

Preclinical evidence to support repurposing everolimus for craving reduction during protracted drug withdrawal

Cue-elicited drug-craving is a cardinal feature of addiction that intensifies (incubates) during protracted withdrawal. In a rat model, these addiction-related behavioral pathologies are mediated, respectively, by time-dependent increases in PI3K/Akt1 signaling and reduced Group 1 metabotropic glutamate receptor (mGlu) expression, within the ventromedial prefrontal cortex (vmPFC). Herein, we examined the capacity of single oral dosing with everolimus, an FDA-approved inhibitor of the PI3K/Akt effector mTOR, to reduce incubated cocaine-craving and reverse incubation-associated changes in vmPFC kinase activity and mGlu expression. Rats were trained to lever-press for intravenous infusions of cocaine or delivery of sucrose pellets and then subjected to tests for cue-reinforced responding during early (3 days) or late (30–46 days) withdrawal. Rats were gavage-infused with everolimus (0–1.0 mg/kg), either prior to testing to examine for effects upon reinforcer-seeking behavior, or immediately following testing to probe effects upon the consolidation of extinction learning. Single oral dosing with everolimus dose-dependently blocked cocaine-seeking during late withdrawal and the effect lasted at least 24 h. No everolimus effects were observed for cue-elicited sucrose-seeking or cocaine-seeking in early withdrawal. In addition, everolimus treatment, following initial cue-testing, reduced subsequent cue hyper-responsivity exhibited observed during late withdrawal, arguing a facilitation of extinction memory consolidation. everolimus’ “anti-incubation” effect was associated with a reversal of withdrawal-induced changes in indices of PI3K/Akt1/mTOR activity, as well as Homer protein and mGlu1/5 expression, within the prelimbic (PL) subregion of the prefrontal cortex. Our results indicate mTOR inhibition as a viable strategy for interrupting heightened cocaine-craving and facilitating addiction recovery during protracted withdrawal.

Reward-related responses and tonic craving in cocaine addiction: an imaging study of the monetary incentive delay task

Background Cocaine addiction is associated with altered sensitivity to natural reinforcers and intense drug craving. However, previous findings on reward-related responses are mixed and few studies have examined whether reward responses relate to tonic cocaine craving. Methods We combined fMRI and a monetary incentive delay task to investigate these issues. Imaging data were processed with published routines and the results were evaluated with a corrected threshold. We compared reward responses of 50 cocaine dependent individuals (CDs) and 45 healthy controls (HCs) for the ventral striatum (VS) and the whole brain. We also examined the regional responses in association with tonic cocaine craving, as assessed by the Cocaine Craving Questionnaire (CCQ) in CDs. We performed mediation analyses to evaluate the relationship between regional responses, CCQ score, and recent cocaine use. Results The VS showed higher activation to large as compared to small or no wins but this reward-related activity did not differ between CDs and HCs. The precentral gyrus (PCG), anterior insula, and supplementary motor area showed higher activation during large vs. no wins in positive correlation with the CCQ score in CDs. Mediation analyses suggested that days of cocaine use in the prior month contributed to higher CCQ scores and, in turn, PCG reward responses. Conclusions The results highlight a unique relationship between reward responses of the primary motor cortex, tonic cocaine craving and recent cocaine use. The motor cortex may partake in the cognitive motor processes critical to drug seeking behavior in addicted individuals.

Sex differences in opioid and psychostimulant craving and relapse: a critical review

A widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies on sex differences in psychostimulant and opioid craving and relapse. Next, we review preclinical studies on sex differences in psychostimulant and opioid reinstatement of drug seeking after extinction of drug self-administration and incubation of drug craving (time-dependent increase in drug seeking during abstinence). We also discuss ovarian hormones’ role in relapse and craving in humans and animal models and speculate on brain mechanisms underlying their role in cocaine craving and relapse in rodent models. Finally, we discuss imaging studies on brain responses to cocaine cues and stress in men and women.The results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. However, this conclusion is tentative because most of the studies reviewed were correlational, not sufficiently powered, and/or not a priori designed to detect sex differences. Additionally, fMRI studies suggest sex differences in brain responses to cocaine cues and stress. The results of the preclinical studies reviewed provide evidence for sex differences in stress-induced reinstatement and incubation of cocaine craving, but not cue- or cocaine priming-induced reinstatement of cocaine seeking. These sex differences are modulated in part by ovarian hormones. In contrast, the available data do not support the notion of sex differences in craving and relapse/reinstatement for methamphetamine or heroin in rodent models.