Cue-provoked Craving Research Articles

Mindfulness-oriented recovery enhancement in opioid use disorder: Extended emotional regulation and neural effects and immediate effects of guided meditation in a pilot sample

ObjectiveMindfulness-Oriented Recovery Enhancement (MORE) is an efficacious intervention to aid recovery from substance use disorder. This study in a pilot sample of individuals in treatment for opioid use disorder (OUD) characterizes longer-term changes after the MORE intervention and immediate effects of a brief MORE guided meditation session. DesignTwelve female participants in residential treatment for OUD completed an 8-week MORE intervention. Participants completed two sessions: one before and one after the 8-week MORE intervention. Each session included an emotional regulation questionnaire outside an MRI scanner first and then a 10-minute guided MORE meditation inside the scanner during which functional magnetic resonance imaging (fMRI) data were collected. Emotional regulation was measured after 8-weeks of MORE intervention. In addition, functional connectivity (i.e. correlated fMRI signal) between regions in a hypothesized affect regulation network was measured during the meditation state to assess change in brain network function due to 8-weeks of MORE. For each 10-min guided meditation, we also assessed their mood and opioid craving. ResultsNine participants completed all measurements. Participants’ emotional regulation difficulty significantly decreased after 8-weeks of MORE intervention. Furthermore, after 8-weeks of MORE, there was significantly increased connectivity between left ventromedial prefrontal cortex and left amygdala and between left ventrolateral prefrontal cortex and left nucleus accumbens captured during a meditation state. In both sessions, positive mood significantly increased after 10-min of guided mediation, however opioid craving was not significantly influenced. ConclusionsThis pilot study characterizes potential benefits of 8-week MORE intervention in improving emotional regulation difficulty and brain function. A 10-min guided MORE meditation may immediately improve mood, with potential to reduce acute stress- or cue-provoked craving. These results warrant future studies with larger sample size.

Smokers' Self-Report and Behavioral Reactivity to Combined Personal Smoking Cues (Proximal + Environment + People): A Pilot Study.

Cue reactivity (CR) among smokers exposed to smoking-related stimuli, both proximal (e.g., cigarettes, lighter) and distal (environments, people), has been well-demonstrated. Furthermore, past work has shown that combining proximal smoking cues with smoking environment cues increases cue-provoked craving and smoking behavior above that elicited by either cue type alone. In this pilot study, we examined the impact of combining three personal cues, proximal + environment + people, on subjective and behavioral cue reactivity among smokers. To further understand the impact of this method, we also tested reactivity under the conditions of both smoking satiety and deprivation. In addition, we examined the extent to which cue-induced craving predicted immediate subsequent smoking. Fifteen smokers completed six sessions, of which two focused on the intake and development of personal cues and four involved personal cue reactivity sessions: (1) deprived, smoking cue combination, (2) deprived, nonsmoking cue combination, (3) sated, smoking combination, and (4) sated, nonsmoking cue combination. Cue-provoked craving was greater and smokers were quicker to light a cigarette and smoked more during their exposure to smoking rather than nonsmoking cues and in deprived compared to sated conditions, with no interaction between these variables. While deprived, greater cue-provoked craving in response to smoking cues was correlated with a quicker latency to light a cigarette. This work supports the feasibility of presenting three personal smoking-related combinations of cues within a cue reactivity paradigm and highlights the robust reactivity that this methodology can evoke in smokers.

Smoking abstinence and neurocognition: implications for cessation and relapse.

In this chapter, we review the last decade of research on the effects of smoking abstinence on various forms of neurocognition, including executive function (working memory, sustained attention, response inhibition), reward processing, and cue-reactivity. In our review we identify smoking abstinence-induced deficits in executive function mediated by effects on frontal circuitry, which in turn is known to be affected by modulation of cholinergic, dopaminergic, and other neurotransmitter systems. We also review evidence that smoking abstinence blunts reactivity to non-drug reinforcers-a finding that is consistent with results in the animal literature. Finally, our review of cue-reactivity indicates that smoking abstinence does not appear to amplify cue-provoked craving, although it may increase attentional bias to smoking-related cues. Inconsistencies across findings and potential contributing factors are discussed. In addition, we review the literature on the effects of nicotine and non-nicotine factors in neurocognition. Finally, we provide a multi-factor model and an agenda for future research on the effects of smoking abstinence on neurocognition. The model includes four distinct yet interacting factors, including: Negative Reinforcement, Drug-Reward Bias, Goal and Skill Interference, and Non-Cognitive Factors. Additional research is needed to further evaluate the scope and time-course of abstinence-induced changes in neurocognition, the mechanisms that underlie these changes and the specific role of these processes in drug reinforcement, lapse, and relapse.

A Pilot Study to Investigate the Efficacy of Nicotine Oral Soluble Film, Lozenge and Gum in Relief of Acute Smoking Cue-provoked Craving for Cigarette in Low Dependence Smokers

Introduction: A new nicotine film that releases nicotine quickly may lead to faster craving relief.Aims: This study compares the efficacy of 2.5 mg nicotine film with 2 mg nicotine lozenge and 2 mg nicotine gum on relieving provoked craving in low dependence smokers.Methods: A randomised, open-label, active comparators controlled study was conducted in 120 subjects. Subjects were abstinent from smoking for 4 hours prior to being provoked with smoking cues. After post-provocation craving assessment, subjects were administered one dose of the 3 treatments: nicotine film, lozenge, or gum. Craving intensity was then assessed at 50 seconds, 3, 5, 7, 15, 20, 25 and 30 minutes after administration.Results/Findings: Three treatments reduced craving with similar maximum effects. The effect was maintained up to 30 minutes. Nicotine film significantly reduced more craving than lozenge at 50 seconds, 3 and 5 minutes. It also significantly reduced more craving than gum at 50 seconds and 3 minutes. There was no significant difference between lozenge and gum.Conclusions: Nicotine film, lozenge and gum have similar maximum craving relief. Nicotine film significantly reduced more craving than lozenge and gum at early time points. Nicotine film may be particularly useful to provide acute craving relief.

Perceived Medication Assignment during a Placebo-Controlled Laboratory Study of Varenicline: Temporal Associations of Treatment Expectancies with Smoking-Related Outcomes

Expectancies regarding treatment assignment may influence outcomes in placebo-controlled trials above and beyond actual treatment assignment. For smoking pharmacotherapies, guessing enrollment in the active medication treatment is associated with higher abstinence rates. However, placebo-controlled trials of smoking pharmacotherapies rarely assess perceived treatment assignment and those that do only collect this information after reaching full dosage. To determine the temporal relationship between treatment expectancies and smoking-related variables, we assessed the impact of treatment guess during a placebo-controlled laboratory study of varenicline on measures of craving, smoking reward, and smoking reinforcement. We hypothesized that treatment guess at mid-titration would influence smoking-related measures at full dosage, above and beyond actual medication effects. We also explored factors related to guess stability and differences in blind fidelity between mid-drug titration and full dosage. Eighty-eight participants completed laboratory assessments at baseline, mid-titration, and full dosage that involved self-report and behavioral measures of tonic craving, cue-provoked craving, smoking reward, and smoking reinforcement. Participants guessed treatment assignment at mid-titration and full dosage. Generalized linear models confirmed that, beyond actual treatment assignment, treatment guess improved model fit for both self-report and behavioral smoking-related measures. Further, accuracy of treatment guess improved from titration to full dosage, and specific demographic factors (e.g., gender, race) were associated with type of treatment guess and guess stability across time. These results reinforce the importance of assessing perceived treatment assignment repeatedly during placebo-controlled trials and suggest that treatment expectancies during titration can affect outcomes once full dosage has been reached.

Dissociable effect of acute varenicline on tonic versus cue-provoked craving in non-treatment-motivated heavy smokers

RationaleThe effectiveness of varenicline for smoking cessation has been established, but little is known about the psychological processes that mediate this clinical outcome. ObjectivesThis study evaluated the effect of a single dose of varenicline on tonic and cue-provoked changes in craving, withdrawal, and affect using a randomized, double-blind, placebo-controlled, cross-over design. MethodsFollowing overnight abstinence, 38 non-treatment-motivated smokers received either varenicline 2mg or matched placebo, then tonic measures of craving, withdrawal, and positive and negative affect were obtained at 30-min intervals. At 4-h post-administration, a cue exposure session obtained the same subjective measures at three time-points following the physical handling of a lit cigarette versus the sharpening and handling of a pencil. ResultsAt 4-h post-administration, varenicline reduced tonic craving as well as craving across the smoking and neutral cue conditions, relative to placebo. By contrast, the capacity of the smoking cue to enhance craving relative to the neutral cue was unaffected by varenicline. Measures of withdrawal and positive and negative affect produced mixed results. ConclusionsAcute varenicline selectively attenuates tonic but not cue-provoked craving. This dissociation provides insight into the specific psychological processes that might mediate the effectiveness of varenicline, and highlights cue-provoked craving as a discrete target for advancing smoking cessation pharmacotherapy.

Varenicline effects on craving, cue reactivity, and smoking reward

Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist that has been found to be effective for treating tobacco dependence. However, the subjective and behavioral mediators of its efficacy are not known. Using multiple sessions of laboratory-based assessment, this double-blind, placebo-controlled experiment was designed to test if varenicline reduced both tonic and cue-provoked tobacco cravings, and if it attenuated perceived reward from smoking. Participants in the present analysis include 100 smokers who were scheduled for three assessment sessions: at baseline, before receiving medication; at mid-run-in, 5-7 days after beginning medication; and after full dosage was reached, 12-15 days. Following overnight abstinence, each session included assessment of tonic craving, reactivity (including craving) to smoking cues, expected value of a cigarette, smoking behavior, and self-reported reward following smoking. Varenicline, compared to placebo, reduced tonic craving, cue-provoked craving by the final assessment, the expected value of cigarettes, number of puffs and time spent smoking, and self-reported reward (i.e., satisfaction) from smoking. Results showing that varenicline reduced tonic craving levels and perceived reward from smoking are consistent with reports from clinical trials, strengthening the evidence in support of these subjective mechanisms of action. This is the first placebo-controlled study to demonstrate that varenicline reduced cue-provoked cravings, thereby offering another potential mediator of its therapeutic effects. Findings may aid in the development of more targeted interventions for tobacco dependence.

Cumulative priming effects of cortical stimulation on smoking cue-induced craving

Smoking cue-provoked craving is an intricate behavior associated with strong changes in neural networks. Craving is one of the main reasons subjects continue to smoke; therefore interventions that can modify activity in neural networks associated with craving can be useful tools in future research investigating novel treatments for smoking cessation. The goal of this study was to use a neuromodulatory technique associated with a powerful effect on spontaneous neuronal firing – transcranial direct current stimulation (tDCS) – to modify cue-provoked smoking craving. Based on preliminary data showing that craving can be modified after a single tDCS session, here we investigated the effects of repeated tDCS sessions on craving behavior. Twenty-seven subjects were randomized to receive sham or active tDCS (anodal tDCS of the left DLPFC). Our results show a significant cumulative effect of tDCS on modifying smoking cue-provoked craving. In fact, in the group of active stimulation, smoking cues had an opposite effect on craving after stimulation – it decreased craving – as compared to sham stimulation in which there was a small decrease or increase on craving. In addition, during these 5 days of stimulation there was a small but significant decrease in the number of cigarettes smoked in the active as compared to sham tDCS group. Our findings extend the results of our previous study as they confirm the notion that tDCS has a specific effect on craving behavior and that the effects of several sessions can increase the magnitude of its effect. These results open avenues for the exploration of this method as a therapeutic alternative for smoking cessation and also as a mean to change stimulus-induced behavior.

Cortical Stimulation of the Prefrontal Cortex With Transcranial Direct Current Stimulation Reduces Cue-Provoked Smoking Craving

Because neuroimaging studies have shown that cue-provoked smoking craving is associated with changes in the activity of the bilateral dorsolateral prefrontal cortex (DLPFC), we aimed to investigate whether a powerful technique of noninvasive brain stimulation, transcranial direct current stimulation (tDCS), reduces cue-provoked smoking craving as indexed by a visual analog scale. We performed a randomized, sham-controlled crossover study in which 24 subjects received sham and active tDCS (anodal tDCS of the left and right DLPFC) in a randomized order. Craving was induced by cigarette manipulation and exposure to a smoking video. The study ran from January 2006 to October 2006. Smoking craving was significantly increased after exposure to smoking-craving cues (p < .0001). Stimulation of both left and right DLPFC with active, but not sham, tDCS reduced craving significantly when comparing craving at baseline and after stimulation, without (p = .007) and with (p = .005) smoking-craving cues. There were no significant mood changes in any of the conditions of stimulation. Adverse events were mild and distributed equally across all treatment conditions. Our findings extend the results of a previous study on the use of brain stimulation to reduce craving, showing that cortical stimulation with tDCS is beneficial for reducing cue-provoked craving, and thus support the further exploration of this technique for smoking cessation.

Comparative efficacy of rapid‐release nicotine gum versus nicotine polacrilex gum in relieving smoking cue‐provoked craving

Most relapse episodes occur when smokers are confronted with craving provoked by situational cues. Current nicotine gum can help relieve cue-provoked cravings, but faster effects may result in more rapid relief. We tested a prototype formulation of a new rapid-release nicotine gum (RRNG) that provides more rapid release and absorption of nicotine, for its ability to provide faster and better craving relief compared to current nicotine polacrilex gum (NPG). Random assignment to RRNG or NPG, used during a smoking cue provocation procedure. Participants and setting A total of 319 smokers were exposed to a smoking cue in the laboratory by being asked to light but not smoke a cigarette of their preferred brand. Subjects then chewed a piece of 2 mg RRNG (n = 159) or 2 mg NPG (n = 160) according to randomized assignment. Craving assessments were completed at regular intervals before and after cue exposure (baseline, pre-cue, and 3, 6, 9, 12, 15, 18, 21, 25, 30 and 35 minutes after the cue). Smokers chewing RRNG showed significantly lower craving than NPG subjects starting with the first assessment at 3 minutes (P < 0.025). Repeated-measures ANOVA revealed a significant treatment x time interaction (P < 0.05)-craving scores dropped more rapidly in RRNG subjects compared to NPG subjects. Survival analyses also indicated superiority of RRNG in achieving more rapid self-reported meaningful relief (P < 0.05) and complete relief (P < 0.05) of craving. Rapid-release nicotine gum reduced cue-provoked craving more rapidly compared to NPG, and thus merits further study in cessation efficacy trials.

Cue-Provoked Craving and Nicotine Replacement Therapy in Smoking Cessation.

Cue exposure paradigms have been used to examine reactivity to smoking cues. However, it is not known whether cue-provoked craving is associated with smoking cessation outcomes or whether cue reactivity can be attenuated by nicotine replacement therapy (NRT) in clinical samples. Cue-provoked craving ratings and reaction time responses were measured on the 1st day of abstinence among 158 smokers who had been randomized to high-dose nicotine (35 mg) or placebo patch. The nicotine patch reduced overall levels of craving but did not attenuate cue-provoked craving increases or reaction time responses. Cue-provoked craving predicted relapse among participants on the nicotine patch but not among those on placebo. In summary, NRT users could benefit from treatment that attenuates cue-provoked craving.