Cue-induced Craving Research Articles

Alcohol and cannabis co-use: Probing subjective response in eliciting cross-substance craving

The co-use of alcohol and cannabis is rising in prevalence, yet the mechanisms driving individuals to co-use are not well understood. Subjective response to alcohol or cannabis may predict the desire to use either substance. However, which specific facets of subjective response predict cross-substance craving remains unclear. The present study investigated whether acute administration of alcohol or cannabis facilitates cue-induced craving for the other substance, with an emphasis on the underlying subjective response mechanisms contributing to co-use. This is a secondary analysis of a behavioral pharmacology study that combined alcohol/cannabis administration with a cross-substance cue-reactivity paradigm in individuals who were heavy alcohol and heavy cannabis co-users. Over two sessions, twenty-nine individuals (17M/12F) self-administered alcohol or cannabis (in a crossover design), and then completed a cue-reactivity exercise with the other substance. Analyses tested how changes in subjective response variables following substance administration predicted cross-substance cue-induced craving. Following alcohol administration, greater subjective ratings of positive mood predicted significantly greater cue-induced cannabis craving (β = 1.14, SE = 0.41, t = 2.80, p = 0.010). Following cannabis administration, lower subjective effects ratings of positive mood/arousal predicted significantly greater cue-induced alcohol craving (β = −1.08, SE = 0.38, t = −2.85, p = 0.009; β = −2.38, SE = 1.13, t = −2.10, p = 0.047). This study identified subject response mechanisms contributing to cross-substance cue induced craving. These mechanisms include increases in positive mood following alcohol use and decreases in positive mood and arousal, akin to increases in relaxation, following cannabis use.

Effectiveness of Transcranial-Direct Current Stimulation in Individuals with Methamphetamine Use Disorder: A Systematic Review and Meta-Analysis

Context: Non-alcoholic substance abuse is a major public health concern worldwide, with methamphetamine being the second most widely used non-alcoholic substance globally, and Iran ranks fifth in methamphetamine addiction. To date, no approved pharmacological or non-pharmacological treatment by the Food and Drug Administration has been introduced for methamphetamine use disorder (MUD). Therefore, various treatment methods are currently utilized. One non-pharmacological approach that has gained attention is transcranial-direct current stimulation (tDCS), with various clinical evaluations focused on it. Objectives: The aim of this review is to assess the effectiveness of this method in improving symptoms in individuals with MUD. Methods: Databases were reviewed up to October 10, 2023, in both Persian and English languages, using PubMed, Scopus, Web of Science, Google Scholar, Science Direct, Scientific Information Database (SID), and Noormags. Keywords were MUD, tDCS, Addiction, Craving, and Cognitive Function. Studies were included based on Population, Intervention, Comparison (sham or active control), Outcomes (craving or cognition), and Study Design (randomized controlled trial). Studies were excluded if they involved brain mapping or neuroimaging. Meta-analysis was conducted based on Standardized Mean Difference (SMD) to compare tDCS to sham intervention (P ≤ 0.05, two-tailed). Random effects models were used for individual MUD data from studies that reported end-of-treatment craving data. The risk of bias was calculated using the Cochrane Risk-of-Bias Tool (RoB-2), and meta-analysis was conducted using Comprehensive Meta-Analysis Software. Results: A total of 870 studies were initially identified; twenty-three studies (mean age 30.13 ± 6.67) were identified that examined the effects of tDCS on MUD outcomes (e.g., craving, cognition). After removing heterogeneous studies, meta-analyses were performed for tDCS vs. sham control studies in the craving domain. We found that tDCS reduced craving, indicated by medium to large effect sizes (Hedges' g: -0.64; SMD -0.58, 95% CI -0.85 to -0.30; I² = 10.71%, Q value: 8.96). Results showed that complementary treatment with tDCS can be useful. The DLPFC (F3, F4) was the most commonly targeted brain region for stimulation or inhibition. However, the number of sessions and their duration varied significantly across studies. Conclusions: This systematic review and meta-analysis found that tDCS can reduce momentary and cue-induced cravings. However, the studies varied in quality and sample size and used different scales for assessing cravings and cognitive functions, leading to inconsistencies. The review highlighted the importance of targeting the DLPFC due to its role in executive functions and self-control, with right-sided stimulation showing greater effectiveness. Emotional dysregulation in MUD, such as anxiety and depression, was also noted, with tDCS showing limited support for emotion regulation. The review identified the need for larger RCTs, standardized measurement tools, and detailed participant information to improve the understanding and effectiveness of tDCS in treating MUD.

The acute effect of mindfulness-based regulation on neural indices of cue-induced craving in smokers

Mindfulness has garnered attention for its potential in alleviating cigarette cravings; however, the neural mechanisms underlying its efficacy remain inadequately understood. This study (N=46, all men) aims to examine the impact of a mindfulness strategy on regulating cue-induced craving and associated brain activity. Twenty-three smokers, consuming over 10 cigarettes daily for at least 2 years， were compared to twenty-three non-smokers. During a regulation of craving task, participants were asked to practice mindfulness during smoking cue-exposure or passively view smoking cues while fMRI scans were completed. A 2 (condition: mindfulness-cigarette and look-cigarette) × 2 (phase: early, late of whole smoking cue-exposure period) repeated measures ANOVA showed a significant interaction of the craving scores between condition and phase, indicating that the mindfulness strategy dampened late-phase craving. Additionally, within the smoker group, the fMRI analyses revealed a significant main effect of mindfulness condition and its interaction with time in several brain networks involving reward, emotion, and interoception. Specifically, the bilateral insula, ventral striatum, and amygdala showed lower activation in the mindfulness condition, whereas the activation of right orbitofrontal cortex mirrored the strategy-time interaction effect of the craving change. This study illuminates the dynamic interplay between mindfulness, smoking cue-induced craving, and neural activity, offering insights into how mindfulness may effectively regulate cigarette cravings.

S139 - The Effect of Opioid-Stimulant Co-Use on Tonic and Cue Induced Cravings

S139 - The Effect of Opioid-Stimulant Co-Use on Tonic and Cue Induced Cravings

The mediating role of trait impulsivity in the relation between cue-induced craving and functional connectivity within the salience network among abstinent patients with methamphetamine use disorder

The mediating role of trait impulsivity in the relation between cue-induced craving and functional connectivity within the salience network among abstinent patients with methamphetamine use disorder

Neural Correlates of Stress and Alcohol Cue-Induced Alcohol Craving and of Future Heavy Drinking: Evidence of Sex Differences.

Stress and alcohol cue reactivity are associated with poor treatment outcomes in alcohol use disorder (AUD), but sex-specific neural correlates of stress and alcohol cue-induced craving compared with neutral cue-induced craving and of heavy drinking outcomes in AUD have not been examined. Thus, this study prospectively examined these associations and assessed sex differences. Treatment-seeking adults with AUD (N=77; 46 men and 31 women) completed a functional MRI task involving stress, alcohol, and neutral cue exposure with repeated assessments of alcohol craving. Most of these participants (N=72; 43 men and 29 women) then participated in an 8-week standardized behavioral AUD treatment program, during which the percentage of heavy drinking days was assessed. Significant increases in both stress and alcohol cue-induced craving relative to neutral cue-induced craving were observed, with a greater alcohol-neutral contrast in craving relative to the stress-neutral contrast among men and equivalent stress-neutral and alcohol-neutral contrasts in craving among women. Whole-brain voxel-based regression analyses showed craving-associated hyperactivation in the neutral condition, but hypoactive prefrontal (ventromedial and lateral prefrontal, supplementary motor, and anterior cingulate regions) and striatal responses during exposure to stressful images (stress-neutral contrast) and alcohol cues (alcohol-neutral contrast), with significant sex differences. Additionally, a higher percentage of heavy drinking days was associated with hypoactivation of the subgenual anterior cingulate cortex and the bed nucleus of the stria terminalis in the stress-neutral contrast among women, hyperactivation of the hypothalamus in the stress-neutral contrast among men, and hyperactivation of the hippocampus in the alcohol-neutral contrast among men. Sex differences in stress- and alcohol cue-induced responses in the cortico-striatal-limbic network related to subjective alcohol craving and to heavy drinking indicated that distinct brain circuits underlie alcohol use outcomes in women and men. These findings underscore the need for sex-specific therapeutics to address this neural dysfunction effectively.

Data-driven connectivity profiles relate to smoking cessation outcomes.

At a group level, nicotine dependence is linked to differences in resting-state functional connectivity (rs-FC) within and between three large-scale brain networks: the salience network (SN), default mode network (DMN), and frontoparietal network (FPN). Yet, individuals may display distinct patterns of rs-FC that impact treatment outcomes. This study used a data-driven approach, Group Iterative Multiple Model Estimation (GIMME), to characterize shared and person-specific rs-FC features linked with clinically-relevant treatment outcomes. 49 nicotine-dependent adults completed a resting-state fMRI scan prior to a two-week smoking cessation attempt. We used GIMME to identify group, subgroup, and individual-level networks of SN, DMN, and FPN connectivity. Regression models assessed whether within- and between-network connectivity of individual rs-FC models was associated with baseline cue-induced craving, and craving and use of regular cigarettes (i.e., "slips") during cessation. As a group, participants displayed shared patterns of connectivity within all three networks, and connectivity between the SN-FPN and DMN-SN. However, there was substantial heterogeneity across individuals. Individuals with greater within-network SN connectivity experienced more slips during treatment, while individuals with greater DMN-FPN connectivity experienced fewer slips. Individuals with more anticorrelated DMN-SN connectivity reported lower craving during treatment, while SN-FPN connectivity was linked to higher craving. In conclusion, in nicotine-dependent adults, GIMME identified substantial heterogeneity within and between the large-scale brain networks. Individuals with greater SN connectivity may be at increased risk for relapse during treatment, while a greater positive DMN-FPN and negative DMN-SN connectivity may be protective for individuals during smoking cessation treatment.

Age moderates the association of optimism on craving during substance use disorder treatment

BackgroundOptimism, characterized by a positive expectancy toward future outcomes, has garnered attention for its potential role in influencing well-being and may be a protective factor in substance use disorder (SUD) treatment. This study evaluated the relationship of optimism and craving among those in substance use disorder SUD treatment. MethodsDrawing from a cohort of 4201 individuals in residential SUD treatment programs, this study used both cross-sectional and longitudinal assessment to examine tonic (steady-state) and cue-induced (phasic) cravings across individuals primarily using eight classes of substances. Previous research established that optimism increases during adulthood and peaks during an individual's 50s. This study sought to establish if the association between optimism and craving is moderated by age during the first week of treatment and if that relationship changes over the course of treatment both within and between-person. ResultsThis study found a negative correlation between optimism and craving intensity. Elevated optimism scores correlated with substantially reduced levels of both tonic (β = −0.31, p < 0.001) and cue-induced (β = −0.29, p < 0.001) cravings. Age was a significant moderator of the relationship between optimism and craving such that as individuals age, the potency of optimism in mitigating cravings gradually attenuates (interaction for tonic craving: β = 0.06, p < 0.001; interaction for cue-induced craving: β = 0.05, p < 0.001). Reflected in the fact that in older individuals' cravings tended to converge toward lower or moderate levels, regardless of their optimism scores. ConclusionsBy delineating the contemporaneous association between high optimism and lower cravings, the study suggests that interventions aimed at fostering optimism may represent an avenue to improve the effectiveness of SUD treatment, especially in emerging adults.

The association of individual cognition and social environment of smoking with autonomy over tobacco: A survey from rural China.

This study explores the association of individual cognition and social environment of smoking with autonomy over tobacco, providing evidence and insights to help smokers effectively prevent and reduce tobacco dependence. Data were collected from 1389 participants, aged ≥15 years, by face-to-face interviews from June 2018 to November 2019 in central China. We assessed autonomy over tobacco using the Autonomy Over Smoking Scale (AUTOS), including Withdrawal Symptoms (WS), Psychological Dependence (PD) and Cue-induced Cravings (CC), and examined factors of individual cognition and social environment, as well as covariates, including demographic characteristics, health status, and smoking behavior. AUTOS total score was 16.92 ± 9.05, WS score was the lowest (4.40 ± 3.36) in the three subscales, and CC score was the highest (6.88 ± 3.2). After adjustment, WS score of having a greater awareness of smoking hazards to one's own health was lower than those who had no awareness (β=0.14; 95% CI: -0.31-0.00), and the total score of AUTOS, the score of PD and CC for those who thought smoking was 'more helpful (high)' to interpersonal communication were higher than 'not helpful (not at all)' (β=0.14; 95% CI: 0.01-0.28 with β=0.16; 95% CI: 0.02-0.29; and β=0.14; 95% CI: 0.00-0.28; respectively). Having a greater difficulty in smoking cessation was associated with higher AUTOS total and subscale scores (p<0.001). Notably, none of the social-environmental factors included had a significant association with AUTOS scores. Interventions targeting individual cognitive factors of tobacco dependence seem to be more effective in smoking cessation. Future research may explore the influence of family and workplace among social environmental factors, which may reveal the effect of a binding force.

Neural correlates of drinking reduction during a clinical trial of cognitive behavioral therapy for alcohol use disorder.

Cognitive behavioral therapy (CBT) is an effective treatment for alcohol use disorder (AUD). We hypothesized that the dorsolateral prefrontal cortex (DLPFC), a region implicated in cognitive control and goal-directed behavior, plays a role in behavior change during CBT by facilitating the regulation of craving (ROC). Treatment-seeking participants with AUD (N = 22) underwent functional magnetic resonance imaging (fMRI) scanning both before and after a 12-week, single-arm trial of CBT, using an ROC task that was previously shown to engage the DLPFC. We found that both the percentage of heavy drinking days (PHDD) and the overall self-reported alcohol craving measured during the ROC task were significantly reduced from pre- to post-CBT. However, we did not find significant changes over time in either the ability to regulate craving or regulation-related activity in any brain region. We found a significant 3-way interaction between the effects of cue-induced craving, cue-induced brain activity and timepoint of assessment (pre- or post-CBT) on PHDD in the left DLPFC. Follow-up analysis showed that cue-induced craving was associated with cue-induced activity in the left DLPFC among participants who ceased heavy drinking during CBT, both at pre-CBT and post-CBT timepoints. No such associations were present at either timepoint among participants who continued to drink heavily. These results suggest that patients in whom DLPFC functioning is more strongly related to cue-induced craving may preferentially respond to CBT.

Frontal EEG response to alcohol craving elicited by individually tailored video cues.

Most findings on the pathophysiology of alcoholism are based on studies using resting-state electroencephalography (EEG). There are few studies on cue-induced craving and on its utility as an electrophysiological index. We examined quantitative EEG (qEEG) activities in alcoholics and social drinkers exposed to video cues and compared their association with subjective alcohol craving and other related psychiatric symptoms, including anxiety and depression. This is a between-subjects design. Adult male alcoholics (n=34) and healthy social drinkers (n=33) participated. In a laboratory, EEGs were recorded while the participants were presented with craving-inducing video stimuli. Measures used were the Visual Analog Scale (VAS) for subjective alcohol craving, Alcohol Urge Questionnaire (AUQ), Michigan Alcoholism Screening Test (MAST), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) scores. One-way analysis of covariance with age showed that alcoholics had significantly increased beta activity in the right DLPFC region (F4) (F=4.029, p=0.049), compared to social drinkers when craving-inducing stimuli were presented. Beta activity at the F4 electrode was positively correlated with AUQ (r=.284, p=0.021), BAI (r=.398, p=0.001), BDI (r=.291, p=0.018), and changes in VAS (r=.292, p=0.017) scores in both alcoholics and social drinkers. In alcoholics, beta activity was significantly correlated with BAI (r=.392, p=0.024). These findings imply functional importance of hyperarousal and negative emotions upon exposure to craving-inducing cues. Frontal EEG indices with beta power could serve as an objective electrophysiological index of craving induced by individually tailored video cues in alcohol consumption behavior.

Immediate and lasting effects of different regulation of craving strategies on cue-induced craving and the late positive potential in smokers.

Craving, induced by substance-related cues, contributes to continued substance use and relapse. Therefore, regulation of craving (ROC) is important for treatment success. Distraction involves disengaging from craving-inducing cues; whereas, reappraisal requires engaging with potential risks of substance use. Given this difference in elaboration, we addressed the question whether reappraisal entails lasting advantages over distraction in successful ROC. To elucidate how this is implemented neurally, we examined the late positive potential (LPP) as an electrocortical indicator of motivated attention to cues. N= 62 smokers viewed smoking-related pictures and indicated the degree of craving each picture induced. While viewing the pictures, EEG was recorded, and the participants focused on the long-term negative (LATER) or short-term positive (NOW) consequences of smoking or performed an arithmetic task to distract themselves from processing the pictures (DISTRACT). After a break, all pictures were presented again without regulation instruction (re-exposure). Results revealed that LATER and DISTRACT achieved similar degrees of immediate ROC success, but only LATER had a sustained effect during re-exposure. In contrast, LPP amplitudes were more prominently reduced during DISTRACT than LATER, and there was no difference in LPP amplitudes during re-exposure. These findings imply that it may be beneficial to engage with the risks of drug use (reappraisal) rather than avoiding triggers of craving (distraction). However, these effects do not seem to be mediated by lasting changes in cue-related motivated attention (LPP).

Are medication effects on subjective response to alcohol and cue-induced craving associated? A meta regression study

RationaleAlcohol administration and cue-reactivity paradigms are frequently used to screen for the initial efficacy of medications for alcohol use disorder (AUD). While medication effects on the primary outcomes for these paradigms are assumed to be qualitatively related, there is a critical lack of quantitative evidence to support this hypothesis.ObjectivesThe study aims to test the relationship between medication effect sizes on subjective response to alcohol administration and medication effect sizes for cue-induced craving to cue exposure, using meta-analysis.MethodsSystematic literature searches were conducted to identify randomized trials, wherein AUD medications were tested using the alcohol administration and/or cue-reactivity paradigms. From these studies, descriptive statistics were collected to compute medication effect sizes on the primary outcomes for each respective paradigm. With medication as the unit of analysis, medication effect sizes in alcohol administration studies were compared with medication effect sizes in cue-reactivity studies using the Williamson-York regression which allows for meta-regression across independent samples.ResultsMedication effect sizes on alcohol-induced stimulation and alcohol-induced craving were not significantly associated with medication effect sizes on cue-induced alcohol craving (k stimulation = 10 medications, widehat{beta }=0.272 left(mathrm{SE}=0.263right), p=0.150 and k craving = 11 medications, widehat{beta }=0.217 (SE = 0.237), p=0.181), respectively. Medication effect sizes on alcohol-induced sedation were significantly associated with medication effects on cue-induced craving (k = 10 medications, widehat{beta }=-0.600 (SE = 0.258), p=0.010), such that medications that increased alcohol-induced sedation were more likely to reduce cue-induced alcohol craving.ConclusionsWith the exception of alcohol-induced sedation, there is little quantitative evidence of medication effects on subjective response domains measured during alcohol administration parallel medication effects on cue-induced alcohol craving. To provide additional context to the current study, future work should examine whether cue-reactivity findings predict clinical trial outcomes.

Association of Cortico-Striatal Engagement During Cue Reactivity, Reappraisal, and Savoring of Drug and Non-Drug Stimuli With Craving in Heroin Addiction.

The authors investigated cortico-striatal reactivity to drug cues (as compared with neutral and food cues), drug cue reappraisal, food cue savoring, and their correlations with heroin craving in individuals with heroin use disorder compared with healthy control subjects. Cross-sectional changes in functional MRI blood-oxygen-level-dependent signal during a novel cue reactivity task were assessed in 32 individuals with heroin use disorder (mean age, 40.3 years; seven women) and 21 age- and sex-matched healthy control subjects (mean age, 40.6 years; eight women). Drug cue reactivity (vs. neutral cues) was significantly higher in the nucleus accumbens in the heroin use disorder group compared with the control group and nominally significantly higher in the orbitofrontal cortex (OFC); ventromedial prefrontal cortex (vmPFC) activity positively correlated with drug craving. Drug cue reactivity (vs. salient food cues) was also higher in the inferior frontal gyrus (IFG) in the heroin use disorder group compared with the control group. Drug reappraisal and food savoring (vs. passive viewing) showed increased IFG and supplementary motor area activity in all participants; in the heroin use disorder group, higher IFG/dorsolateral PFC (dlPFC) activity during drug reappraisal and rostral anterior cingulate cortex (ACC) activity during food savoring were associated with lower drug cue-induced craving and longer treatment, respectively. A direct comparison of regulation of reactivity to both salient cues revealed widespread group differences such that drug reappraisal activity was higher in the heroin use disorder group and food savoring activity was higher in the control group in both cortical (e.g., OFC, IFG, ACC, vmPFC, and insula) and subcortical (e.g., dorsal striatum and hippocampus) regions. Higher drug reappraisal versus food savoring in the dlPFC was associated with higher self-reported methadone dosage in the heroin use disorder group. The results demonstrate cortico-striatal upregulation during drug cue exposure and impaired reactivity during processing of alternative non-drug rewards in the heroin use disorder group. Normalizing cortico-striatal function by reducing drug cue reactivity and enhancing natural reward valuation may inform therapeutic mechanisms for reducing drug craving and seeking in heroin addiction.

Menstrual cycle influences on cue-induced smoking cravings and heart rate variability.

Women experience greater difficulties in quitting smoking than men, though the hormonal factors contributing to this sex difference remain to be clarified. The current study aimed to examine menstrual cycle effects on smoking cue-induced cravings as well as examine dynamic reproductive hormone change as a potential mediator underlying any cycle effects observed. Twenty-one women who smoke underwent two laboratory sessions - one in the mid-follicular phase and the other in the late luteal phase - involving an in-vivo smoking cue task, administered before and after exposure to a psychosocial laboratory stressor. Heart rate variability (HRV) and subjective smoking cravings were assessed in response to the cue task. The degree of change in the urinary metabolites of estradiol and progesterone from 2 days before to the day of each laboratory session was measured. Results revealed that both before and following exposure to psychosocial stress, highly nicotine-dependent women exhibited smaller cue-induced increases in HRV relative to the follicular phase. In contrast, less nicotine-dependent women exhibit an increase in HRV in both menstrual cycle phases. Results furthermore suggest that menstrual cycle effects seen in highly nicotine-dependent women are driven by the decline in estradiol and progesterone occurring in the late luteal phase. Though limited by a small sample size, this study suggests that withdrawal from reproductive hormones in the late luteal phase may alter highly nicotine-dependent women's physiological response to smoking cues, which may reflect greater difficulty resisting temptation. These findings may provide some insight regarding women's greater difficulty in maintaining abstinence after quitting smoking.

The impact of opioid-stimulant co-use on tonic and cue-induced craving

The twin opioid-stimulant epidemics have led to increased overdose deaths and present unique challenges for individuals entering treatment with opioid-stimulant polysubstance use. This study examined tonic and cue-induced craving as a primary outcome among persons in substance use treatment who reported primary substances of opioids, methamphetamine, or cocaine. The sample consisted of 1974 individuals in 55 residential substance-use treatment centers in the United States in 2021. Weekly surveys were delivered via a third-party outcomes tracking system, including measures of tonic and cue-induced craving. Initial comparisons on tonic and cue-induced craving were made among those who primarily used opioids, cocaine, or methamphetamine. Further, the effect of opioid/stimulant polysubstance use on tonic and cue-induced craving was evaluated using marginal effect regression models. Primary methamphetamine use was associated with decreased tonic craving compared to primary opioid use (β = −5.63, p < 0.001) and primary cocaine use was also associate with decreased tonic craving compared to primary opioid use (β = −6.14, p < 0.001). Primary cocaine use was also associated with lower cue-induced cravings compared to primary opioid use (β = −0.53, p = 0.037). Opioid-methamphetamine polysubstance use was associated with higher tonic craving (β = 3.81, p = <0.001) and higher cue-induced craving (β = 1.55, p = 0.001); however, this was not the case for opioid-cocaine polysubstance use. The results of this study indicate that individuals who primarily use opioids and have secondary methamphetamine use experience higher cue-induced and tonic-induced craving, suggesting that these individuals may benefit from additional interventions that target craving and mitigate relapse risk and other negative sequelae.

277. Reductions in Cue-Induced Craving are Associated With Reductions in Dorsolateral Prefrontal Cortex Activation in Absence of Heavy Drinking During Cognitive Behavioral Therapy for Alcohol Use Disorder

277. Reductions in Cue-Induced Craving are Associated With Reductions in Dorsolateral Prefrontal Cortex Activation in Absence of Heavy Drinking During Cognitive Behavioral Therapy for Alcohol Use Disorder

568. Stress Exposure and Cue-Induced Craving Exert Distinct Time-Dependent Influences on Subjective Valuation

568. Stress Exposure and Cue-Induced Craving Exert Distinct Time-Dependent Influences on Subjective Valuation

Brain glucose metabolism and dopamine transporter changes in rats with morphine-induced conditioned place preference.

Addiction to morphine is a chronic brain disease leading to compulsive abuse. Drug addiction animal models with and without conditioned place preference (CPP) training have been used to investigate cue-elicited drug craving. We used 18 F-fluorodeoxyglucose (18 F-FDG) and 11 C-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane (11 C-CFT) micro-PET/CT scans to examine the regional changes in brain glucose metabolism and dopamine transporter (DAT) availability to study their relationship underlying drug memory in morphine-treated rat models with and without CPP. Standardized uptake value ratio (SUVr) of 18 F-FDG significantly decreased in the medial prefrontal cortex (mPFC) and cingulate with short-term morphine administration compared with the baseline condition. Voxelwise analysis indicated glucose metabolism alterations in the somatosensory cortex, hippocampus and cingulate in morphine-treated rats and in the striatum, thalamus, medial prefrontal cortex, primary motor cortex and many regions in the cortex in the CPP group compared with the baseline condition. Alterative glucose metabolism was also observed in the striatum, primary somatosensory cortex and some cortical regions in the CPP group compared with morphine alone group. DAT expression alterations were only observed in the long-term morphine compared with the short-term morphine group. This study shows that cerebral glucose metabolism significantly altered during morphine administration and CPP process mainly in the mPFC, striatum and hippocampus, which indicates that the function of these brain regions is involved in cue-induced craving and memory retrieval.

Impact of cannabidiol on reward- and stress-related neurocognitive processes among individuals with opioid use disorder: A pilot, double-blind, placebo-controlled, randomized cross-over trial.

Opioid use disorder (OUD) continues to be a significant public health concern. Medications for OUD (MOUD) such as buprenorphine reduce overdose mortality, but relapses occur often, leading to adverse outcomes. Preliminary data suggest that cannabidiol (CBD) may be a potential adjunctive treatment to MOUD by attenuating cue-reactivity. This pilot study sought to evaluate the impact of a single dose of CBD on reward- and stress-related neurocognitive processes implicated in relapse among those with OUD. The study was a pilot, double-blind, placebo-controlled, randomized cross-over trial aimed at assessing the effects of a single dose of CBD (Epidiolex®) 600 mg or matching placebo administered to participants with OUD receiving either buprenorphine or methadone. Vital signs, mood states, pain, opioid withdrawal, cue-induced craving, attentional bias, decision-making, delayed discount, distress tolerance, and stress-reactivity were examined at each testing session on two separate testing days at least 1 week apart. Ten participants completed all study procedures. Receipt of CBD was associated with a significant decrease in cue-induced craving (0.2 vs. 1.3, p = 0.040), as well as reduced attentional bias toward drug-related cues as measured by the visual probe task (-80.4 vs. 100.3, p = 0.041). No differences were found among all the other outcomes examined. CBD may have promise as an adjunct to MOUD treatment by attenuating the brain response to drug-related cues, which, in turn, may reduce the risk of relapse and overdoses. Further research is warranted to evaluate the potential for CBD as an adjunctive therapy for individuals in treatment for OUD. https://clinicaltrials.gov/ct2/show/NCT04982029.