Trajectories of craving in the course of pharmacotherapy trials for methamphetamine use disorder.

AIMS: The aim of this study was to measure trajectories of craving for methamphetamine during the course of pharmacotherapy trials for methamphetamine use disorder. DESIGN, SETTING AND PARTICIPANTS: Craving trajectories were identified using Group-Based Trajectory Modeling. The association of craving trajectories with drug use trajectories was examined using a dual trajectory model. Association of craving trajectories with other health and social outcomes was also examined. The study used pooled data from five randomized controlled pharmacotherapy trials for methamphetamine use disorder. A total of 866 adults with methamphetamine use disorder participated in randomized controlled pharmacotherapy trials. MEASUREMENT: Craving was assessed weekly using the Brief Substance Craving Scale. Drug use was assessed using urine toxicology. Alcohol- and drug-related problems, as well as psychiatric, medical, legal, employment and relationship problems, were measured using the Addiction Severity Index. FINDINGS: A three-trajectory model with high, medium and low craving trajectories was selected as the most parsimonious model. Craving trajectories were associated with methamphetamine use trajectories in the course of trial; 88.4% of those in the high craving trajectory group had a consistently high frequency of methamphetamine use compared with 18.7% of those in the low craving group. High craving was also associated with less improvement in most other outcomes and higher rate of dropout from treatment. In turn, low craving was associated with a rapidly decreasing frequency of methamphetamine use, greater improvement in most other outcomes and a lower rate of dropout. Participants on modafinil daily and ondansetron 1 mg twice daily were less likely to be in the high craving group compared with those on placebo. CONCLUSIONS: Trajectories of methamphetamine craving in the course of clinical trials for methamphetamine use disorder appear to be both highly variable and strongly associated with greater frequency of drug use, other drug-related outcomes and dropout from trials. Two medications, modafinil daily and ondansetron at a dose of 1 mg two times daily, appear to be associated with greater reduction in craving in the course of treatment compared with placebo. A decrease in methamphetamine craving shows promise as an early indicator of recovery from methamphetamine use disorder.

Explaining child maltreatment and aggression among Chinese drug user: The mediating and moderating roles of drug craving and impulsivity.

BACKGROUND: The cycle of violence highlights a strong correlation between child maltreatment and aggression. However, there remains a significant gap in the pathway models of the cycle of violence. Given the exceptionally high rates of child maltreatment and violent crime among Chinese drug users, it is essential to examine the mechanisms of the cycle of violence within this group. OBJECTIVE: The current study incorporates drug craving and impulsivity into the child maltreatment-aggression mechanism. We explore the potential mediating and moderating roles of these variables and further examine the heterogeneity. PARTICIPANTS AND SETTING: A total of 894 participants (Meanage = 38.30, SDage = 8.38) were recruited as the final sample. METHODS: We employed moderated mediation and serial mediation models to explore the roles of drug craving and impulsivity. The Johnson-Neyman method was utilized to investigate moderating effects. Rich demographic variables and depression were controlled. RESULTS: There was no direct relationship between child maltreatment and aggression. The moderated mediation model indicated that drug craving played a mediating role, and there was a substitutive relationship between impulsivity and drug craving. The serial mediation model showed that child maltreatment could only affect drug craving (not impulsivity) and could ultimately influence aggression through a chain relationship. Heterogeneity tests revealed that the mechanisms might differ among various types of maltreatment. CONCLUSION: Drug craving holds a significant position in the cycle of violence. Compared to impulsivity, it is a more proximal factor to child mistreatment. Future research should also focus on the heterogeneity of child maltreatment for targeted interventions.

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.

Given the widespread use and relapse of methamphetamine (METH), it has caused serious public health burdens globally. However, the neurobiological basis of METH addiction remains poorly understood. Therefore, this study aimed to use magnetic resonance imaging (MRI) to investigate changes in brain networks and their connection to impulsivity and drug craving in abstinent individuals with METH use disorder (MUDs). A total of 110 MUDs and 55 age- and gender-matched healthy controls (HCs) underwent resting-state functional MRI and T1-weighted imaging scans, and completed impulsivity and cue-induced craving measurements. We applied independent component analysis to construct functional brain networks and multivariate analysis of covariance to investigate group differences in network connectivity. Mediation analyses were conducted to explore the relationships among brain-network functional connectivity (FC), impulsivity, and drug craving in the patients. MUDs showed increased connectivity in the salience network (SN) and decreased connectivity in the default mode network compared to HCs. Impulsivity was positively correlated with FC within the SN and played a completely mediating role between METH craving and FC within the SN in MUDs. These findings suggest alterations in functional brain networks underlying METH dependence, with SN potentially acting as a core neural substrate for impulse control disorders.

Effects of exercise interventions on negative emotions, cognitive performance and drug craving in methamphetamine addiction.

Introduction: Methamphetamine is currently one of the most commonly used addictive substances with strong addiction and a high relapse rate. This systematic review aims to examine the effectiveness of physical activity in improving negative emotions, cognitive impairment, and drug craving in people with methamphetamine use disorder (MUD). Methods: A total of 17 studies out of 133 found from Embase and PubMed were identified, reporting results from 1836 participants from MUD populations. Original research using clearly described physical activity as interventions and reporting quantifiable outcomes of negative mood, cognitive function and drug craving level in people with MUD were eligible for inclusion. We included prospective studies, randomized controlled trials, or intervention studies, focusing on the neurological effects of physical activity on MUD. Results: Taken together, the available clinical evidence showed that physical activity-based interventions may be effective in managing MUD-related withdrawal symptoms. Discussion: Physical exercise may improve drug rehabilitation efficiency by improving negative emotions, cognitive behaviors, and drug cravings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024530359.

Substance use patterns, quantities, and associated risk factors in women with polysubstance misuse.

Polysubstance use (PSU), the use of two or more substances proximally, is highly prevalent and has amplified the risk for morbidity and mortality. However, PSU patterns and associated risk factors are not well characterized. This may be especially relevant to women who are known to be vulnerable to stress/trauma, craving, pain, and anxious and depressive symptoms as associated risk factors for PSU. A cross-sectional observational study was conducted to characterize substance use patterns in women who regularly used cocaine, opioids, marijuana, alcohol, benzodiazepines and/or nicotine and were being assessed for a placebo-controlled study of guanfacine treatment (n = 94; ages 19-65). Data on stress/traumatic life events, drug cravings for each substance, pain ratings, and anxiety and depressive symptoms were also obtained using standardized well-validated surveys. High use per day of two or more drugs was observed (72.7% ± 33.3%) and opioid amounts were high relative to other drug amounts (p's < 0.001). Notably, higher stress/trauma events and higher cravings are each associated with cumulative PSU days, amounts and probability of an individual PSU day (p's < 0.02). This remained when PSU versus single substance use was compared. Pain, anxiety and depressive symptoms were not associated with PSU metrics. These findings characterize specific patterns of PSU in women and show that average drug craving and stress/trauma events are associated with PSU. Interventions that focus on stress/trauma and craving management could be of benefit in reducing PSU risk in women.

Association between drug craving and aggression in Chinese male methamphetamine-dependent patients with and without depressive symptoms.

Depressive symptoms and aggression are common in patients with substance use disorder. Drug craving is one of the main drivers of drug-seeking behavior. This study aimed to explore the relationship between drug craving and aggression in methamphetamine use disorder (MAUD) patients with and without depressive symptoms. Totally, 613 male patients with MAUD were recruited in this study. Patients with depressive symptoms were identified by the 13-item Beck Depression Inventory (BDI-13). Drug craving and aggression were assessed by the Desires for Drug Questionnaire (DDQ) and the Buss & Perry Aggression Questionnaire (BPAQ), respectively. 374 patients (61.01%) were confirmed to meet the criteria of depressive symptoms. Patients with depressive symptoms had significantly higher DDQ and BPAQ total scores than those without depressive symptoms. DDQ desire and intention were positively correlated with verbal aggression and hostility in patients with depressive symptoms, whereas they were correlated with self-directed aggression in patients without depressive symptoms. In patients with depressive symptoms, DDQ negative reinforcement and a history of suicide attempts were independently associated with BPAQ total score. Our study suggests that male MAUD patients have a high incidence of depressive symptoms and that patients with depressive symptoms may have greater drug cravings and aggression. Depressive symptoms may play a role in the association between drug craving and aggression in patients with MAUD.

The anterior insula and its projection to amygdala nuclei modulate the abstinence-exacerbated expression of conditioned place preference.

RATIONALE: Relapse into substance use is often triggered by exposure to drug-related environmental cues. The magnitude of drug seeking depends on the duration of abstinence, a phenomenon known as the incubation of drug craving. Clinical and preclinical research shows that the insular cortex is involved in substance use disorders and cue-induced drug seeking. However, the role of the insula on memory retrieval and motivational integration for cue-elicited drug seeking remains to be determined. OBJECTIVES: We investigated the role of the anterior insular cortex (aIC) and its glutamatergic projection to amygdala nuclei (aIC-AMY) on the expression of conditioned place preference (CPP) during early and late abstinence. METHODS: Male adult C57BL/6J mice underwent amphetamine-induced CPP, and their preference was tested following 1 or 14 days of abstinence. aIC and aIC-AMY functional role in CPP expression was assessed at both abstinence periods by employing optogenetic silencing and behavioral pharmacology. RESULTS: Compared to a single day, an exacerbated preference for the amphetamine-paired context was observed after 14 days of abstinence. Photoinhibition of either aIC or aIC-AMY projection reduced CPP expression following late but not early abstinence. Similarly, the antagonism of aIC NMDA receptors reduced CPP expression after 14 days of abstinence but not 1 day. CONCLUSIONS: These results suggest that aIC and its glutamatergic output to amygdala nuclei constitute critical neurobiological substrates mediating enhanced motivational cue reactivity during the incubation of amphetamine craving rather than contextual memory recall. Moreover, cortical NMDA receptor signaling may become sensitized during abstinence, ultimately modulating disproportioned drug seeking.

Efficacy of a Brief Mindfulness Intervention in Underserved Individuals Receiving Inpatient Treatment for Opioid Use Disorder: A Pilot Study.

Introduction A mindfulness intervention is a mind-body complementary health approach that focuses on the relationships between mind, body, brain, and behavior. Mindfulness-Based Stress Reduction (MBSR) and similar mindfulness programs have been shown to decrease drug craving and relapse and improve emotional regulation, stress, pain, and anxiety. To our knowledge, a very limited number of studies have examined its efficacy in individuals from underserved populations. Underserved populations experience disparities in healthcare access, and as a result, see poorer addiction-related outcomes. The goal of this pilot study was to utilize an evidence-based, neuroscience-informed brief mindfulness intervention to improve mental health and decrease substance use behavior in a vulnerable, underserved population in New Jersey suffering from opioid use disorder (OUD). Methods We implemented a brief MBSR intervention in 15 underserved individuals undergoing inpatient medication-assisted treatment (MAT) for OUD. Individuals received weekly intervention sessions lasting one hour over six weeks. Furthermore, they practiced mindfulness for 10 minutes daily. Participants completed pre-and post-mindfulness intervention surveys to examine their mental well-being, drug craving, perceived stress, and emotional regulation. Results Within-subjects t-test results showed that compared to pre-intervention, participants showed significantly decreased perceived stress (t(14) =2.401, p=.015) and significantly decreased difficulty in emotional regulation (t(13) =3.426, p=.002 ) at post-intervention. They also showed significantly decreased drug craving post-intervention (t(14) =5.501, p=.<001). Anxiety decreased post-intervention but was not statistically significant (t(14) =1.582, p=.068). Conclusion This pilot study demonstrates that a brief mindfulness intervention can be effective for underserved individuals with OUD. Consistent with our hypothesis, results showed that a six-week mindfulness intervention could reduce everyday stress, drug craving, and difficulties in emotional regulation. In the future, a large-scale randomized control trial should be conducted with a control group to demonstrate the efficacy of this useful intervention.

Association between rumination and drug craving in Chinese male methamphetamine use disorder patients with childhood trauma.

BACKGROUND: In China, males make up the majority of methamphetamine (MA) dependent individuals and the majority of treatment seekers. Childhood trauma (CT) and rumination are associated with an increased risk of MA use. However, the association between CT, rumination, and drug craving remains largely unknown. OBJECTIVE: The present study aims to explore the association between rumination and drug craving in methamphetamine use disorder (MAUD) patients with CT. PARTICIPANTS AND SETTING: This study recruited 404 male participants with MAUD from a male drug rehabilitation center in Southwest China. METHODS: Patients with CT were identified by the short form of Childhood Trauma Questionnaire (CTQ-SF). Rumination and drug craving were assessed by the Ruminative Responses Scale (RRS) and the Obsessive Compulsive Drug Use Scale (OCDUS), respectively. RESULTS: 188 patients (46.5 %) experienced CT. Patients who had experienced CT showed significantly higher RRS symptom rumination score and OCDUS total score than those who had not. In patients with CT, RRS total and all subscale scores were positively associated with OCDUS interference of drug. Furthermore, the RRS brooding (ß = 0.34, p < 0.001) and total scores (ß = 0.38, p < 0.001) were determined to be separate contributors to the OCDUS total score in patients with CT. CONCLUSIONS: Our study suggests that CT is common in male MAUD patients, and those who have suffered CT may exhibit higher levels of rumination and drug craving. Moreover, CT may play an influential role in the association between rumination and drug craving in patients with MAUD.

Cannabidiol as a Harm Reduction Strategy for People Who Use Drugs: A Rapid Review.

OBJECTIVE: The drug poisoning crisis throughout North America necessitates novel harm reduction approaches. Emerging evidence suggests that cannabidiol (CBD) may have some utility as a harm reduction modality for those with problematic substance use. This rapid review aimed to synthesize available evidence on CBD as a potential harm reduction tool for people who use drugs while providing clinical and research insights. METHOD: A systematic search in EMBASE, MEDLINE, CENTRAL, and CINAHL was completed in July 2022. For inclusion, studies had to meet the following criteria: (1) drawn from an adult population of people who use drugs; (2) investigates CBD as an intervention for problematic substance use or harm reduction-related outcomes; (3) be published after the year 2000 and in English; and (4) be primary research or a review article. A narrative synthesis was used to group outcomes relevant to harm reduction and provide clinical and research insights. RESULTS: We screened 3,134 records, of which 27 studies (5 randomized trials) were included. The evidence remains limited, but available studies support the potential utility of CBD to reduce drug-induced craving and anxiety in opioid use disorder. There were low-quality studies suggesting that CBD may improve mood and general well-being of people who use drugs. Evidence suggests that CBD monotherapy may not be an adequate harm reduction strategy for problematic substance use but rather an adjunct to the standard of care. CONCLUSION: Low-quality evidence suggests that CBD may reduce drug cravings and other addiction-related symptoms and that CBD may have utility as an adjunct harm reduction strategy for people who use drugs. However, there is a significant need for more research that accurately reflects CBD dosing and administration regimens used in a real-world context.

Gut-derived bacterial LPS attenuates incubation of methamphetamine craving via modulating microglia.

BACKGROUND: The microbiota-gut-brain axis plays a critical role in the pathophysiology of neuropsychiatric disorders, and the compositions of gut microbiota are altered by addictive drugs. However, the role of gut microbiota in the incubation of methamphetamine (METH) craving remains poorly understood. METHODS: 16S rRNA gene sequencing was performed to assess the richness and diversity of gut microbiota in METH self-administration model. Hematoxylin and eosin staining was performed to evaluate the integrity of intestinal barrier. Immunofluorescence and three-dimensional reconstruction were performed to assess the morphologic changes of microglia. Serum levels of lipopolysaccharide (LPS) were determined using the rat enzyme-linked immunosorbent assay kits. Quantitative real-time PCR was performed to assess transcript levels of dopamine receptor, glutamate ionotropic AMPA receptor 3 and brain-derived neurotrophic factor. RESULTS: METH self-administration induced gut microbiota dysbiosis, intestinal barrier damage and microglia activation in the nucleus accumbens core (NAcc), which was partially recovered after prolonged withdrawal. Microbiota depletion via antibiotic treatment increased LPS levels and induced a marked change in the microglial morphology in the NAcc, as indicated by the decreases in the lengths and numbers of microglial branches. Depleting the gut microbiota also prevented the incubation of METH craving and increased the population of Klebsiella oxytoca. Furthermore, Klebsiella oxytoca treatment or exogenous administration of the gram-negative bacterial cell wall component LPS increased serum and central LPS levels, induced microglial morphological changes and reduced the dopamine receptor transcription in the NAcc. Both treatments and NAcc microinjections of gut-derived bacterial LPS significantly decreased METH craving after prolonged withdrawal. CONCLUSIONS: These data suggest that LPS from gut gram-negative bacteria may enter circulating blood, activate microglia in the brain and consequently decrease METH craving after withdrawal, which may have important implications for novel strategies to prevent METH addiction and relapse.

Towards Device Agnostic Detection of Stress and Craving in Patients with Substance Use Disorder.

Novel technologies have great potential to improve the treatment of individuals with substance use disorder (SUD) and to reduce the current high rate of relapse (i.e. return to drug use). Wearable sensor-based systems that continuously measure physiology can provide information about behavior and opportunities for real-time interventions. We have previously developed an mHealth system which includes a wearable sensor, a mobile phone app, and a cloud-based server with embedded machine learning algorithms which detect stress and craving. The system functions as a just-in-time intervention tool to help patients de-escalate and as a tool for clinicians to tailor treatment based on stress and craving patterns observed. However, in our pilot work we found that to deploy the system to diverse socioeconomic populations and to increase usability, the system must be able to work efficiently with cost-effective and popular commercial wearable devices. To make the system device agnostic, methods to transform the data from a commercially available wearable for use in algorithms developed from research grade wearable sensor are proposed. The accuracy of these transformations in detecting stress and craving in individuals with SUD is further explored.

The Effect of Different Transcranial Direct Current Stimulation (tDCS) Protocols on Drug Craving and Cognitive Functions in Methamphetamine Addicts.

Introduction: Drug craving is a major problem in addiction treatment. Neuroimaging research has revealed various areas for drug craving, among which two key areas are the Dorsolateral Prefrontal Cortex (DLPFC) and the cerebellum. The DLPFC is involved in different cognitive tasks, such as inhibitory control over seductive options that promise an immediate reward. The cerebellum is related to cognition and memory and activated by drug-related cues. Therefore, we decided to study the effect of Transcranial Direct Current Stimulation (tDCS) on six different protocols in reducing drug craving and increasing cognitive functions in methamphetamine addicts. Methods: The present study is quasi-experimental, with a pre-test-post-test design and a control group. Based on a simple sampling method, 15 male methamphetamine addicts were recruited from two rehabilitation centers in Tehran City, Iran. The participants were aged 18-65 years with a minimum of 12-month history of methamphetamine dependence. The Visual Analog Scale (VAS), the go/no-go task and the n-back task were administered before and after a single session of tDCS. The tDCS was applied on six protocols: 1) the right DLPFC anodal and the left DLPFC cathodal stimulation, 2) the right DLPFC cathodal and the left DLPFC anodal stimulation, 3) the right DLPFC anodal and the right arm cathodal stimulation, 4) the left DLPFC anodal and the left arm cathodal stimulation, 5) the right cerebellar hemisphere (O2) anodal and the left cerebellar hemisphere (O1) cathodal stimulation, and 6) the right cerebellar hemisphere (O2) cathodal and the left cerebellar hemisphere (O1) anodal stimulation. The data were analyzed by covariance method using SPSS software v. 22. Results: Study results indicated that while single-session tDCS effects on craving were not significant, it increased cognitive inhibition, especially in protocol 2: the right DLPFC cathodal and the left DLPFC anodal stimulation. Conclusion: Single-session tDCS affects craving insignificantly, but it can increase cognitive inhibition significantly. These findings support the results of previous studies on the effects of brain stimulation on reducing drug craving in other drug-type settings. Highlights: One session of Transcranial Direct Current Stimulation (tDCS) intervention is ineffective for reducing addiction craving in methamphetamine addicts.DCS intervention significantly increases cognitive inhibition.The best results with tDCS intervention in addiction recovery are use of the right DLPFC cathodal stimulation and left DLPFC anodal stimulation protocol. Plain Language Summary: One of the primary concerns in treating addiction is to choose an effective intervention for reducing craving. tDCS is a non-invasive and safe way of reducing craving, which can be used in different ways to decrease addiction craving and treat addiction. While his study founds that one session of tDCS protocols is not effective in reducing the methamphetamine craving, They are effective for increasing cognitive inhibition, which is essential in addiction recovery and saying no to cravings. This effect on the cognitive inhibition ability has important implications for those seeking new and non-invasive addiction recoveries, especially in methamphetamine addiction.

Incubation of cocaine craving coincides with changes in dopamine terminal neurotransmission.

Relapse to drug use is one of the major challenges in treating substance use disorders. Exposure to drug-related cues and contexts triggers drug craving, which drives cocaine seeking, and increases the probability of relapse. Clinical and animal studies have shown a progressive intensification of cocaine seeking and craving that develops over the course of abstinence, a phenomenon commonly referred to as incubation of cocaine craving. Although the neurobiology underlying incubation of cocaine craving has been examined - particularly within the context of glutamate plasticity- the extent to which increased cocaine craving engenders mesolimbic dopamine (DA) changes has received relatively little attention. To assess whether incubation of cocaine craving is associated with alterations in DA terminal neurotransmission in the nucleus accumbens core (NAc), we used ex vivo fast scan cyclic voltammetry in female and male rats to assess DA dynamics following short access, long access, or intermittent access to cocaine self-administration followed by 28 days of abstinence. Results indicated that both long access and intermittent access to cocaine produced robust incubation of cocaine craving, which was associated with increases in cocaine potency. In addition, intermittent access self-administration also produced a robust increase in DA uptake rate at baseline. In contrast, short access to cocaine did not engender incubation of cocaine craving, nor produce changes in DA neurotransmission. Together these observations indicate that incubation of cocaine craving coincides with changes in DA transmission, suggesting that underlying changes in mesolimbic DA signaling may contribute to the progressive intensification of drug craving that occurs across periods of abstinence.

Attention bias and alcohol craving: Differential effects via biological sex and mood.

BACKGROUND: Attentional bias (AB) has been linked to alcohol use, mood, and alcohol craving, with key differences across different types of mood and biological sex. However, further exploration of the role of AB across these alcohol variables is needed. The current study examined the relationship between mood and AB as predictors of alcohol craving using ecological momentary assessment (EMA). Exploratory analysis examined these effects as a function of biological sex. METHODS: Participants (n = 69) from a Midwestern University carried a mobile device for 15 days and provided ratings of momentary mood (positive mood, anxious mood, and sad mood), alcohol craving, and AB. Data were analyzed using a two-level multilevel regression model, with associations between craving, mood, and AB examined at both the momentary and between-subjects levels. RESULTS: Across assessments, positive and negative moods were positively associated with momentary craving, with AB found to operate differently between men and women. At the within-subjects level, increases in positive mood among men strengthened the AB-craving association, while women showed stronger AB-craving associations when positive mood decreased. At the between-subjects level, trait-like sadness led to positive AB-craving associations for men, however, this was the opposite for women. Similarly, AB-craving associations were positive and robust for men with trait-like positive mood but again the opposite was observed for women. CONCLUSIONS: The findings highlight the importance and nuances of biological sex in the context of mood, AB, and craving. Interventions targeting AB and/or emotion regulation may yield different outcomes for men and women.

Theta-Burst Stimulation Combined With Virtual-Reality Reconsolidation Intervention for Methamphetamine Use Disorder: Study Protocol for a Randomized-Controlled Trial.

Background: Craving associated with drug-related memory is one of the key factors that induce the relapse of methamphetamine (MA). Disruption or modulation of the reconsolidation of drug-related memory may serve as an option for clinical treatment of MA addiction. This protocol proposes to use virtual reality (VR) to retrieve drug-associated memory and then use transcranial magnetic stimulation (TMS) at the neural circuit that encodes the reward value of drug cues to provide a non-invasive intervention during reconsolidation. We aim to evaluate the effectiveness of TMS treatment after VR retrieval on the reduction of cue reactivity and craving of MA. Methods: This is a randomized, double-blind, sham-controlled, parallel group trial, targeting participants with MA use disorder aged from 18 to 45 years old. Forty-five eligible volunteers in Shanxi Drug Rehabilitation Center will be recruited and be randomly allocated into three parallel groups, receiving either 1) MA-related cues retrieval in VR combined with active TMS (MA VR scene + TBS) or 2) sham TMS (MA VR scene + sham TBS), or 3) neutral cues retrieval in VR combined with active TMS (neutral VR scene + TBS). Two sessions of post-VR-retrieval TBS will be scheduled on two separate days within 1 week. The primary outcome will detect the memory-related activity by the electroencephalography (EEG) reactivity to drug cues in VR scenes. Secondary outcomes are the self-reported MA craving in VR scene, the physiological parameter (cue-induced heart rate) and the scores of psychological questionnaires including anxiety, depression, and mood. All primary and secondary outcomes will be assessed at baseline, 1-week, and 1-month post-intervention. Assessments will be compared between the groups of 1) MA VR scene + TBS, 2) MA VR scene + sham TBS and 3) neutral VR scene + TBS. Discussion: This will be the first study to examine whether the TMS modulation after VR retrieval can reduce self-reported craving and drug-related cue reactivity. It will promote the understanding of the neural circuit mechanism of the reconsolidation-based intervention and provide an effective treatment for MA use disorder patients. Clinical Trial Registration: [Chinese Clinical Trial Registry], identifier [ChiCTR1900026902]. Registered on 26 October 2019.

How drug cravings affect metacognitive monitoring in methamphetamine abusers.

BACKGROUND AND OBJECTIVE: Metacognitive monitoring refers to the process in which an individual analyzes their own mental state, then monitors and adjusts cognitive activities to achieve a predetermined goal. Recent research has suggested a strong link between metacognition and drug cravings. Conversely, few studies on the impact of metacognitive monitoring on methamphetamine (MA) cravings exist. Thus, this study investigated whether drug cravings would impair MA abusers' metacognitive monitoring and explored the prediction effects of drug cravings. METHOD: Seventy MA abusers from the Zhejiang Compulsory Isolation Drug Rehabilitation Center and 65 non-users from the Wenzhou Medical University were recruited for this experimental study. The judgment of learning (JOL) paradigm was used to examine metacognitive monitoring, and cue-induced pictures were used to induce MA abusers' drug cravings. Analysis of covariance (ANCOVA), partial correlation, and regression analysis were performed. RESULTS: Compared with non-users, MA abusers had significantly poorer metacognitive monitoring and tended to overestimate their performance. Furthermore, there was a significant correlation between the accuracy of JOLs and drug cravings, which indicated that metacognitive monitoring was weakened by drug cravings with higher cravings imposing more severe impacts. In addition, the regression analysis suggested that drug cravings can predict metacognitive monitoring.

The Relationship between Different Amounts of Physical Exercise, Internal Inhibition, and Drug Craving in Individuals with Substance-Use Disorders.

PURPOSE: To explore the relationship between different amounts of physical exercise and drug craving in individuals with substance-use disorders (SUD), and to reveal the mediating role of internal inhibition between physical activity and drug craving. METHOD: This study adopted the Physical Activity Rating Scale, Internal Inhibition Scale, and Drug Craving Scale to assess 438 cases of SUD in a compulsory isolation detoxification center in southwest China. RESULTS: (1) The amount of physical exercise individuals with SUD engaged in was positively correlated with internal inhibition and negatively correlated with drug craving, while the amount of physical exercise was negatively correlated with drug craving. (2) The amount of physical exercise was able to negatively predict drug craving in addicts, the amount of physical exercise and internal inhibition were able to jointly predict drug craving, and internal inhibition played a mediating role between the amount of physical exercise and drug craving (the mediating effect was 0.22). (3) There was a dose-effect relationship regarding different amounts of physical exercises and drug craving. Internal inhibition did not mediate between a low amount of physical exercise and drug craving, it played a partial mediating role between a moderate amount of physical exercise and drug craving (the mediating effect was -0.19), and it played a partial mediating role between a high amount of physical exercise and drug craving (the mediating effect was -0.15). CONCLUSIONS: Physical activity has a positive effect on reducing drug craving in individuals with SUD. Moreover, in the process of sports rehabilitation for SUD, medium or high amounts of physical activity were required in order to effectively reduce and alleviate drug cravings.

The cue-reactivity paradigm: An ensemble of networks driving attention and cognition when viewing drug and natural reward-related stimuli.

The cue-reactivity paradigm is a widely adopted neuroimaging probe engendering brain activity linked with attentional, affective, and reward processes following presentation of appetitive stimuli. Given the multiple mental operations invoked, we sought to decompose cue-related brain activity into constituent components employing emergent meta-analytic techniques when considering drug and natural reward-related cues. We conducted coordinate-based meta-analyses delineating common and distinct brain activity convergence across cue-reactivity studies (N = 196 articles) involving drug (n = 133) or natural (n = 63) visual stimuli. Across all studies, convergence was observed in limbic, cingulate, insula, and fronto-parieto-occipital regions. Drug-distinct convergence was observed in posterior cingulate, dorsolateral prefrontal, and temporo-parietal regions, whereas distinct-natural convergence was observed in thalamic, insular, orbitofrontal, and occipital regions. We characterized connectivity profiles of identified regions by leveraging task-independent and task-dependent MRI datasets, grouped these profiles into subnetworks, and linked each with putative mental operations. Outcomes suggest multifaceted brain activity during cue-reactivity can be decomposed into elemental processes and indicate that while drugs of abuse usurp the brain's natural-reward-processing system, some regions appear distinct to drug cue-reactivity.

Anxiety, Loneliness, Drug Craving, and Depression Among Substance Abusers in Sichuan Province, China.

Studies have reported that anxiety had a positive effect on depression among substance abusers in males. However, little is known about the mechanism underlying this relationship in substance abusers in males. The purpose of this study was to investigate the mediating effect of loneliness and drug craving between anxiety and depression in substance abusers in males. State-Trait Anxiety Inventory, The UCLA Loneliness Scale, Drug Craving Scale, and The Center for Epidemiologic Studies Depression Scale were employed into this study to investigate 585 substance abusers in males (age range of 20-58 years: M = 33.21, SD = 6.97). Structural equation modeling and the bootstrap approach were used to analyze the mediating effect of loneliness and drug craving on the relationship between anxiety and depression. The results indicated that: Loneliness had a significant positive correlation with anxiety (r = 0.37, p < 0.001) and depression (r = 0.49, p < 0.001); Drug craving had a significant positive correlation with anxiety (r = 0.28, p < 0.001) and depression (r = 0.39, p < 0.001). Loneliness and drug craving mediated the link between anxiety and depression. There was a significant positive correlation between substance abusers in male's anxiety, loneliness, drug craving, and depression. Loneliness and drug craving had a significant mediating effect on the relationship between anxiety and depression. Therefore, it was suggested that substance abusers in male's anxiety and depression might be improved and driven by decreasing loneliness and drug craving. Targeted interventions to decrease substance abusers in male's loneliness and drug craving should be developed, implemented, and help them to recover.