HighlightsWe studied the extent that cigarette smoking predicts level of cannabis addiction.We tested whether cigarette smoking mediates the effect of cannabis use on dependence.We interviewed 298 cannabis and tobacco users, of which 65 were followed up.Cigarette smoking accounted for 29% of the variance in cannabis dependence.Cigarette smoking mediated the relationship between cannabis use and dependence.

Maladaptive reward memories (MRMs) are involved in the development and maintenance of acquired overconsumption disorders, such as harmful alcohol and drug use. The process of memory reconsolidation - where stored memories become briefly labile upon retrieval - may offer a means to disrupt MRMs and prevent relapse. However, reliable means for pharmacologically weakening MRMs in humans remain elusive. Here we demonstrate that the N-methyl D-aspartate (NMDA) antagonist ketamine is able to disrupt MRMs in hazardous drinkers when administered immediately after their retrieval. MRM retrieval + ketamine (RET + KET) effectively reduced the reinforcing effects of alcohol and long-term drinking levels, compared to ketamine or retrieval alone. Blood concentrations of ketamine and its metabolites during the critical ‘reconsolidation window’ predicted beneficial changes only following MRM reactivation. Pharmacological reconsolidation interference may provide a means to rapidly rewrite maladaptive memory and should be further pursued in alcohol and drug use disorders.

Maladaptive reward memories (MRMs) can become unstable following retrieval under certain conditions, allowing their modification by subsequent new learning. However, robust (well-rehearsed) and chronologically old MRMs, such as those underlying substance use disorders, do not destabilize easily when retrieved. A key determinate of memory destabilization during retrieval is prediction error (PE). We describe a retrieval procedure for alcohol MRMs in hazardous drinkers that specifically aims to maximize the generation of PE and therefore the likelihood of MRM destabilization. The procedure requires explicitly generating the expectancy of alcohol consumption and then violating this expectancy (withholding alcohol) following the presentation of a brief set of prototypical alcohol cue images (retrieval + PE). Control procedures involve presenting the same cue images, but allow alcohol to be consumed, generating minimal PE (retrieval-no PE) or generate PE without retrieval of alcohol MRMs, by presenting orange juice cues (no retrieval + PE). Subsequently, we describe a multisensory disgust-based counterconditioning procedure to probe MRM destabilization by re-writing alcohol cue-reward associations prior to reconsolidation. This procedure pairs alcohol cues with images invoking pathogen disgust and an extremely bitter-tasting solution (denatonium benzoate), generating gustatory disgust. Following retrieval + PE, but not no retrieval + PE or retrieval-no PE, counterconditioning produces evidence of MRM rewriting as indexed by lasting reductions in alcohol cue valuation, attentional capture, and alcohol craving.

Maladaptive reward memories (MRMs) are involved in the development and maintenance of acquired overconsumption disorders, such as harmful alcohol and drug use. The process of memory reconsolidation-where stored memories become briefly labile upon retrieval-may offer a means to disrupt MRMs and prevent relapse. However, reliable means for pharmacologically weakening MRMs in humans remain elusive. Here we demonstrate that the Nmethyl D-aspartate (NMDA) antagonist ketamine is able to disrupt MRMs in hazardous drinkers when administered immediately after their retrieval. MRM retrieval + ketamine (RET + KET) effectively reduced the reinforcing effects of alcohol and long-term drinking levels, compared to ketamine or retrieval alone. Blood concentrations of ketamine and its metabolites during the critical 'reconsolidation window' predicted beneficial changes only following MRM reactivation. Pharmacological reconsolidation interference may provide a means to rapidly rewrite maladaptive memory and should be further pursued in alcohol and drug use disorders.

The psychological flexibility model (PFM) provides a framework for understanding and treating behavioural dysregulation in addictions. Rather than modulating the intensity of subjective experience, interventions based on, or consistent with, the PFM (PFM interventions) seek to alter the individual’s relationship to internal states, such as craving, negative affect and drug-related thoughts, using mindfulness, acceptance and related strategies. Experimental (non-clinical) studies in smokers have examined the effects of specific isolated strategies informed by or consistent with the PFM (PFM strategies). Here, we systematically review these studies and determine the extent to which they conform to methodological standards indicative of high levels of internal validity. Eligible studies were identified through electronic database searches and assessed for the presence of specific methodological features. Provisional aggregate effect sizes were determined depending on availability of data. Of 1499 screened publications, 12 met the criteria. All examined aspects of private subjective experience relevant to abstinence (craving n = 12; negative affect n = 10), demonstrating effects favouring PFM strategies relative to inactive control conditions. However, only six assessed outcome domains consistent with the PFM and provided no consistent evidence favouring PFM strategies. Overall, most studies had methodological limitations. As such, high-quality experimental studies continue to be needed to improve our understanding of necessary and/or sufficient constituents of PFM-guided smoking cessation interventions. Recommendations for future research are discussed.