Psychosocial stress and methamphetamine use: A mixed-methods study of intersectional stigma and Aboriginal and Torres Strait Islander methamphetamine use.

BACKGROUND: Regular methamphetamine use can cause a range of physical, psychological and social harms. Stigma is one factor that impacts engagement and successful completion of treatment. In Australia, Aboriginal and Torres Strait Islander people who regularly use methamphetamine experience multiple stigmas, which further compounds access to treatment and quality of life. This paper explores the cumulative and compounding effects of participating in a stigmatised activity such as illicit drug use in relation to the stigma experienced by Aboriginal and Torres Strait Islander people as a population marginalised through colonisation. METHODS: Ten sites nationally participated in a cross-sectional survey measuring a range of factors including psychosocial stress in methamphetamine users. The survey sample size was 734, with 59% identifying as Aboriginal and Torres Strait Islander (n = 433). In addition, a total of 147 mainly Aboriginal and Torres Strait Islander people who use methamphetamine, community and family members, and service providers took part in a total of 19 focus groups and 7 interviews. RESULTS: Aboriginal and Torres Strait Islander participants experienced multiple psychosocial stressors at significantly higher rates than non-Indigenous participants. These stressors include diminished access to health care (33%), experiences of racism (34%), grief and sorrow (39%), worry for family (46%), and child welfare experiences (46%). The qualitative findings highlight the cumulative impact of historical, political and social stressors on an already stigmatised population. CONCLUSIONS: The findings of this unique analysis demonstrate the disruptive impact of methamphetamine use on the lives of those who use methamphetamines and their family members. They also illustrate challenges, such as stigma, that may confront those seeking assistance for drug-related issues. Aboriginal and Torres Strait Islander community involvement is necessary to provide support and education for the individual, the family, and the community as a whole. Stigma reduction is therefore a worthy target for intervention.

Perspectives and sentiments on contingency management from people who use methamphetamine.

INTRODUCTION: Contingency management (CM) is currently the most efficacious treatment for methamphetamine use, yet it is rarely available in routine care. We examined the viewpoints of people who use methamphetamine on CM as a potential treatment for methamphetamine use disorder. METHODS: Semi-structured qualitative interviews with 30 Australians aged 18 years or older who had used methamphetamine at least weekly in the past 6 months. RESULTS: Participants reported overall positive attitudes towards CM as a potential treatment option for methamphetamine use disorder. However, there was need for greater flexibility in meeting participant treatment goals (e.g., reduced use or complete abstinence), with particular concern about the viability of initiating abstinence, both in terms of the sufficiency of the initial financial incentive and managing withdrawal symptoms. There was strong interest in the use of digital technologies to provide remote CM, particularly around the convenience and flexibility this offered. Despite this, participants remained keen to access adjunctive treatment and support services but stressed that engagement with these additional services should not be mandatory. Marketing of CM will need to address preconceptions about drug-testing used in abstinence-based CM being punitive (especially urine testing) and its connotations with criminal justice interventions. DISCUSSION AND CONCLUSION: Positive attitudes towards CM bode well for potential uptake should CM be made available in routine clinical practice. However, there is a need to adapt CM to ensure it is feasible and attractive to people who are seeking treatment for methamphetamine use disorder.

A wide range of Deep Brain Stimulation of the nucleus accumbens shell time independently reduces the extinction period and prevents the reinstatement of methamphetamine-seeking behavior in rats.

Methamphetamine (METH) addiction is a significant public health issue, and standard medical therapies are often not curative. Deep Brain Stimulation (DBS) has recently shown the potential to cure addiction by modulating neural activity in specific brain circuits. Recent studies have revealed that the nucleus accumbens shell (NAcSh) could serve as a promising target in treating addiction. Therefore, the present study aimed to investigate the therapeutic effects of NAcSh high- or low-frequency stimulation (HFS or LFS) in the different time points of application on the extinction and reinstatement of the METH-conditioned place preference (CPP). LFS or HFS (10 or 130 Hz, 150-200 µA, 100 µs) was delivered to the NAcSh for 30 min non-simultaneous (in a distinct non-drug environment) or simultaneous (in a drug-paired context) of the drug-free extinction sessions. The obtained results showed that both non-simultaneous and simultaneous treatments by HFS and LFS notably reduced the extinction period of METH-induced CPP. Furthermore, the data indicated that both non-synchronous and synchronous HFS prevented METH-primed reinstatement, while only the LFS synchronized group could block the reinstatement of METH-seeking behavior. The results also demonstrated that HFS was more effective than LFS in attenuating METH-primed reinstatement, and applying HFS synchronous was significantly more effective than HFS non-synchronous in reducing the relapse of drug-seeking. In conclusion, the current study's results suggest that DBS of the NAcSh in a wide range of frequencies (LFS and HFS) could affect addiction-related behaviors. However, it should be considered that the frequency and timing of DBS administration are among the critical determining factors.

Social issues, crisis, and care coordination: First responders experience responding to people affected by methamphetamines.

Methamphetamines remain a public health problem due to the extensive burden of illicit drug use on society. Callout events in the pre-hospital environment related to methamphetamine use is increasing. In addition, there has been an increase in reported mental health side effects and breakdown in relationships and social networks. Descriptive phenomenology research design was undertaken and data analysed using thematic analysis. Semi-structured interviews were utilized to collect data exploring the experience of first responders attending callouts to people affected by methamphetamines in the pre-hospital environment. Interviews included paramedics (8) and police officers (10) from across Australia. Overall, participants reported responding to people affected by methamphetamines was complex in nature. Complexity was affected by extensive social circumstances, people presenting in states of crisis, lack of coordinated approach, and unsuitable care environments. The social impact of methamphetamine addiction is extensive. Staff working as first responders have an opportunity to help reduce the social impact and crises, referring people to follow-up care and drug and alcohol support services. Further research is needed to determine if a standardized approach, between first responders and EDs, should be developed to help streamlines services and improve how the individual services respond as a group to people affected by substances.

Virtual Digital Psychotherapist App-Based Treatment in Patients With Methamphetamine Use Disorder (Echo-APP): Single-Arm Pilot Feasibility and Efficacy Study.

BACKGROUND: Substance use disorder is one of the severe public health problems worldwide. Inequitable resources, discrimination, and physical distances limit patients' access to medical help. Automated conversational agents have the potential to provide in-home and remote therapy. However, automatic dialogue agents mostly use text and other methods to interact, which affects the interaction experience, treatment immersion, and clinical efficacy. OBJECTIVE: The aim of this paper is to describe the design and development of Echo-APP, a tablet-based app with the function of a virtual digital psychotherapist, and to conduct a pilot study to explore the feasibility and preliminary efficacy results of Echo-APP for patients with methamphetamine use disorder. METHODS: Echo-APP is an assessment and rehabilitation program developed for substance use disorder (SUD) by a team of clinicians, psychotherapists, and computer experts. The program is available for Android tablets. In terms of assessment, the focus is on the core characteristics of SUD, such as mood, impulsivity, treatment motivation, and craving level. In terms of treatment, Echo-APP provides 10 treatment units, involving awareness of addiction, motivation enhancement, emotion regulation, meditation, etc. A total of 47 patients with methamphetamine dependence were eventually enrolled in the pilot study to receive a single session of the Echo-APP-based motivational enhancement treatment. The outcomes were assessed before and after the patients' treatment, including treatment motivation, craving levels, self-perception on the importance of drug abstinence, and their confidence in stopping the drug use. RESULTS: In the pilot study, scores on the Stages of Change Readiness and Treatment Eagerness Scale and the questionnaire on motivation for abstaining from drugs significantly increased after the Echo-APP-based treatment (P<.001, Cohen d=-0.60), while craving was reduced (P=.01, Cohen d=0.38). Patients' baseline Generalized Anxiety Disorder-7 assessment score (ß=3.57; P<.001; 95% CI 0.80, 2.89) and Barratt Impulsiveness Scale (BIS)-motor impulsiveness score (ß=-2.10; P=.04; 95% CI -0.94, -0.02) were predictive of changes in the patients' treatment motivation during treatment. Moreover, patients' baseline Generalized Anxiety Disorder-7 assessment score (ß=-1.607; P=.03; 95% CI -3.08, -0.14), BIS-attentional impulsivity score (ß=-2.43; P=.004; 95% CI -4.03, -0.83), and BIS-nonplanning impulsivity score (ß=2.54; P=.002; 95% CI 0.98, 4.10) were predictive of changes in craving scores during treatment. CONCLUSIONS: Echo-APP is a practical, accepted, and promising virtual digital psychotherapist program for patients with methamphetamine dependence. The preliminary findings lay a good foundation for further optimization of the program and the promotion of large-scale randomized controlled clinical studies for SUD.

Methamphetamine-associated cardiomyopathy: an addiction medicine perspective.

Methamphetamine-associated cardiomyopathy (MaCM) is an increasingly recognised serious complication from methamphetamine (MA) use. It is characterised as the development of otherwise unexplained heart failure in the context of MA use. MaCM predominantly affects a young and vulnerable population with high morbidity and mortality. It is the second leading cause of mortality in patients with MA use disorder (MUD). Our understanding of MaCM pathogenesis is based on observational cohorts and autopsy studies. Currently, the treatment of MaCM is predicated on abstinence. Medical therapies offer some benefit to a minority of patients; however, without abstinence, medical therapies are often ineffective. Abstinence is difficult for most patients to achieve; all clinicians require an understanding of MaCM and how to educate patients on the risks of ongoing use. Where available, referral to addiction medicine specialists to assist with treatment of MUD is recommended. This review aims to: (i) explain the proposed pathologic mechanisms of MaCM; (ii) summarise recent recommendations of the screening and treatment of MaCM; and (iii) highlight the role of addiction medicine in the management of patient with MaCM.

Evaluation of the BEAT Meth Intervention for Emergency Department Patients with Methamphetamine Psychosis.

OBJECTIVES: Methamphetamine is the second leading cause of overdose death in America and a leading cause of emergency department (ED) visits. Methamphetamine-induced psychosis is a dangerous and difficult-to-treat consequence of methamphetamine use. We describe the pilot implementation and outcomes of a multimodal treatment intervention for ED patients with methamphetamine psychosis, Beginning Early and Assertive Treatment for Methamphetamine Psychosis (BEAT Meth). METHODS: BEAT Meth was implemented in an urban safety net health system. The protocol includes early identification and treatment of methamphetamine psychosis, a protocolized hospitalization, and support for transitioning patients to specialty addiction treatment. Patients receiving BEAT Meth were compared with ED patients with methamphetamine psychosis who were discharged. Implementation fidelity was measured to assess feasibility. RESULTS: BEAT Meth patients were nearly 3 times more likely to attend an outpatient specialty addiction appointment in the 30 days after discharge than comparison patients (32% vs 11%, P < 0.01). Subsequent ED utilization was common among all patients, and there was no significant difference in 30-day ED return rates between BEAT Meth and comparison patients (28% vs 37%, P = 0.10). Exploratory analyses suggested that increased attendance at outpatient treatment reduced ED utilization. CONCLUSIONS: BEAT Meth is an intervention framework to support identification, management, and treatment engagement of ED patients with methamphetamine psychosis. Treatment strategies like BEAT Meth are necessary to manage the unique challenges of methamphetamine addiction. These findings will guide clinical care, program development, and research.

Effectiveness of Mindfulness - Based Therapy and Counseling programs (MBTC) on relapses to methamphetamine dependence at a substance dependency treatment center.

This non-concurrent controlled intervention study aimed to examine the effectiveness of the Mindfulness - Based Therapy and Counseling programs (MBTC) on the treatment of methamphetamine use disorder among 70 individuals (37 females) receiving methamphetamine dependency treatment. Participants were divided into a control group undergoing the usual program and an experimental group using MBTC plus the usual program at a treatment center in Thailand. The study was conducted using the Methamphetamine Craving Questionnaire, urine Color Immunochromatographic Assay and the Mini-International Neuropsychiatric Interview. Stress, depression, and mindfulness were also assessed. MBTC comprised of practicing mindfulness for 90-120 min weekly for eight weeks. Participants were assessed before and after the treatment(s) and at follow-ups visits at 2, 4, 8, 12, and 24 weeks. Mean age (30.3 ± 5.8 years), age of first methamphetamine use (18.2 ± 4.5 years) and other demographics did not differ between groups. At six-month follow-up, the experimental group had significantly lower craving (-7.89, 95%CI = -15.47, -0.32), stress (-7.44, 95%CI = -12.21, -2.67), and depression (-2.95, 95%CI = -5.31, -0.6) and statistically significant higher mindfulness scores (12.86, 95%CI = 9.37, 16.35) than the control group. In addition, methamphetamine relapse in the MBTC group (5/35, 14.3%) was significantly lower than the control group (16/35, 45.7%).

Methamphetamine induced neurotoxic diseases, molecular mechanism, and current treatment strategies.

Methamphetamine (MA) is a extremely addictive psychostimulant drug with a significant abuse potential. Long-term MA exposure can induce neurotoxic effects through oxidative stress, mitochondrial functional impairment, endoplasmic reticulum stress, the activation of astrocytes and microglial cells, axonal transport barriers, autophagy, and apoptosis. However, the molecular and cellular mechanisms underlying MA-induced neurotoxicity remain unclear. MA abuse increases the chances of developing neurotoxic conditions such as Parkinson's disease (PD), Alzheimer's disease (AD) and other neurotoxic diseases. MA increases the risk of PD by increasing the expression of alpha-synuclein (ASYN). Furthermore, MA abuse is linked to high chances of developing AD and subsequent neurodegeneration due to biological variations in the brain region or genetic and epigenetic variations. To date, there is no Food and Drug Administration (FDA)-approved therapy for MA-induced neurotoxicity, although many studies are being conducted to develop effective therapeutic strategies. Most current studies are now focused on developing therapies to diminish the neurotoxic effects of MA, based on the underlying mechanism of neurotoxicity. This review article highlights current research on several therapeutic techniques targeting multiple pathways to reduce the neurotoxic effects of MA in the brain, as well as the putative mechanism of MA-induced neurotoxicity.

Craving among individuals with stimulant use disorder in residential social model-based treatment - Can exercise help?

BACKGROUND: In a randomized controlled 8-week trial, we examined the efficacy of aerobic and resistance exercise in reducing craving for methamphetamine (MA) among individuals with MA-use disorder during residential treatment. METHODS: Individuals with MA use disorder (138) who were newly enrolled in residential treatment volunteered for random assignment to either an 8-week exercise intervention (EX) or health education control (HE), with both conditions meeting 3 times weekly; 3 dropped out of the trial, bringing the analysis sample to 135. The majority of participants were male (80%), and 48% were Latino/Hispanic. The mean age of the sample was 31.7 (SD = 6.9) years. Using multivariate mixed models, differences between conditions were examined in: (1) craving for MA, measured by self-reported ratings on a Visual Analog Scale over the 8-week trial and, (2) MA use, measured by self-report and urine drug screens at baseline and 30 and 60 days after discharge from the 8-week study. RESULTS: Results revealed significantly lower craving scores among the participants in the EX group than those in the HE group over the 8-week trial (median daily craving score for EX = 13.5, for HE = 21.8; p = .009). In addition, participants with less craving during treatment had significantly lower rates of MA use after discharge than participants with high craving measured at 30-days (p = .004) and 60-days post-discharge (p < .001). CONCLUSIONS: Results support the utility of incorporating a structured exercise program for individuals with MA-use disorder to reduce craving and improve MA-use outcomes.

A transcranial magnetic stimulation protocol for decreasing the craving of methamphetamine-dependent patients.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique. Many substance use disorders lack effective treatments, and TMS is expected to reduce cravings and risk of relapse by regulating brain function. Here, we introduce three alternative TMS settings and specific operations to interfere with methamphetamine use disorders. Theoretically, this protocol can also be applied to diseases with similar brain damage characteristics. For complete details on the use and execution of this protocol, please refer to Chen et al. (2020).

Oxytocin increases physiological linkage during group therapy for methamphetamine use disorder: a randomized clinical trial.

Patients and psychotherapists often exhibit behavioral, psychological, and physiological similarity. Here, we test whether oxytocin-a neuropeptide that can enhance expressivity and social perception-influences time-lagged "linkage" of autonomic nervous system responses among participants and facilitators during group therapy. Physiological linkage estimates (n = 949) were created from ten cohorts, each with two facilitators (n = 5) and four to six participants (n = 48), over six weekly sessions of group therapy for methamphetamine use disorder. All participants of a cohort received oxytocin or placebo intranasally in a randomized double-blind procedure before each session. Cardiac interbeat intervals (IBI) were measured continuously during sessions to estimate physiological linkage, operationalized as one cohort-mate's IBI reactivity during one minute predicting another cohort-mate's IBI reactivity during the following minute. In oxytocin cohorts, participants and facilitators experienced significant physiological linkage to their cohort-mates (i.e., their physiological responses were predicted by the prior responses of their cohort-mates) and significantly more linkage than people in placebo cohorts. Both effects occurred during the first and second sessions but not later sessions. Results suggest that oxytocin may enhance psychosocial processes often associated with linkage-such as social engagement-in groups and highlight oxytocin's potential to improve group cohesion during group therapy.Clinical Trials Registration: NCT02881177, First published on 26/08/2016.

Methamphetamine-Associated Heart Failure Hospitalizations Across the United States: Geographic and Social Disparities.

Background Although methamphetamine abuse is associated with the development of heart failure (HF), nationwide data on methamphetamine-associated HF (MethHF) hospitalizations are limited. This study evaluates nationwide HF hospitalizations associated with substance abuse to better understand MethHF prevalence trends and the clinical characteristics of those patients. Methods and Results This cross-sectional period-prevalence study used hospital discharge data from the National Inpatient Sample to identify adult primary HF hospitalizations with a secondary diagnosis of abuse of methamphetamines, cocaine, or alcohol in the United States from 2002 to 2014. All 2014 MethHF admissions were separated by regional census division to evaluate geographical distribution. Demographics, payer information, and clinical characteristics of MethHF hospitalizations were compared with all other HF hospitalizations. Total nationwide MethHF hospitalizations increased from 547 in 2002 to 6625 in 2014 with a predominance on the West Coast. Methamphetamine abuse was slightly more common among primary HF hospitalizations compared with all-cause hospitalizations (7.4 versus 6.4 per 1000; Cohen h=0.012; P<0.001). Among HF hospitalizations, patients with MethHF were younger (mean age, 48.9 versus 72.4 years; Cohen d=1.93; P<0.001), more likely to be on Medicaid (59.4% versus 8.8%; Cohen h=1.16; P<0.001) or uninsured (12.0% versus 2.6%; Cohen h=0.36; P<0.001), and more likely to present to urban hospitals (43.8% versus 28.3%; Cohen h=0.32; P<0.001) than patients with non-methamphetamine associated HF. Patients with MethHF had higher rates of psychiatric comorbidities and were more likely to leave the hospital against medical advice. Conclusions MethHF hospitalizations have significantly increased in the United States, particularly on the West Coast. Coordinated public health policies and systems of care are needed to address this rising epidemic.

Current and Emerging Treatments for Methamphetamine Use Disorder.

Almost two decades have passed since the last methamphetamine (METH) abuse epidemic. In recent years, METH abuse in the United States has been rapidly increasing and is currently one of the leading causes of death in our country. Available statistical data indicates reemergence of METH popularity and suggest an impending third epidemic of METH abuse. Alarmingly, there is no FDA-approved medication for METH use disorder (MUD). This disorder is currently treated with behavioral therapies; however, these therapies have limitations and would benefit from the addition of a MUD pharmacotherapy. Unfortunately, clinical trials have not yet found consistently effective pharmacotherapy for MUD. This review outlines the history of METH use, provides information on current prevalence of METH abuse and MUD, describes medications that have been in clinical trials for MUD, and addresses current as well as potential new treatments for MUD.

Four-week Tai Chi intervention decreases attention bias to drug cues in individuals with methamphetamine use disorder.

Background: Mind-body exercise is used for the rehabilitation of individuals with methamphetamine use disorder (MUD). Attention bias to substances is an important index of MUD. However, whether a mind-body exercise intervention can decrease attention bias is unclear.Objective: This study aimed to test the effect of a four-week Tai Chi (a Chinese traditional mind-body exercise) exercise program on the attention bias of individuals with MUD.Methods: Thirty-two men with MUD and without Tai Chi practice experience were recruited and randomly assigned to either a Tai Chi exercise group or a control group. The Tai Chi group received four-week Tai Chi training, while the control group engaged in daily exercise (including radio gymnastics and Jianxincao, two kinds of free-hand exercises). During a drug-related Stroop task, participants were instructed to respond to the color of the word ignoring the word type (drug-related or neutral words). The reaction time and d' (the index of sensitivity) were measured.Results: The participants showed attention bias to substance cues; the reaction time was slower for drug-related words than for neutral words (p < .05). After the Tai Chi intervention, the Tai Chi group showed a faster reaction time (ps < .05) and a smaller d' (ps < .05) than the baseline across all the word types. In contrast, the control group showed no differences (ps > .05).Conclusion: Four-week Tai Chi intervention reduced sensitivity and attentional bias to drug-related cues in individuals with MUD, suggesting that mind-body exercise might enhance recovery from MUD via attention control.

Effects of Acute Dance and Aerobic Exercise on Drug Craving and Food Reward in Women with Methamphetamine Dependence.

INTRODUCTION: Drug dependence causes an overestimation of drug-related stimuli and an underestimation of non-drug-related stimuli, such as food. The purpose of this study was to investigate the effects of acute moderate-intensity dance and aerobic exercise on drug craving, appetite, prefrontal neural activation to food cues, and food reward in women with methamphetamine MA dependence. METHODS: Thirty-nine women who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition MA dependence criteria participated in the experiment and were randomly assigned to either a dance (n = 20) or exercise (n = 19) group. A moderate-intensity (65%-75% maximum heart rate) 35-min dance or treadmill intervention counterbalanced with a reading control session was conducted. After the intervention or control, subjective drug craving was measured before and after exposure to drug-related cues. Visual analog scales were used to measure subjective feelings of appetite. Participants then completed a visual food cue paradigm while using functional near-infrared spectroscopy to monitor prefrontal blood oxygen changes. Finally, the Leeds Food Preference Questionnaire was used to measure reward responses to different categories of food. RESULTS: The results showed that the dance and exercise interventions reduced subjective craving for drugs after being exposed to drug cues (P = 0.019). Implicit wanting (P < 0.001) and relative preferences (P = 0.001) for high-calorie savory foods were all increased after interventions relative to control. Compared with the control session, the left dorsolateral prefrontal cortex (P = 0.020) was activated when viewing high-calorie foods after moderate-intensity aerobic exercise. CONCLUSIONS: The current results support the use of moderate-intensity exercise as a therapeutic intervention to restore the balance between drug and nondrug rewards by decreasing cue-induced MA craving and increasing food reward.

A mindfulness-based, stress and coping model of craving in methamphetamine users.

There is increasing interest in the role of mindfulness and mindfulness-based interventions to optimize recovery from a substance use disorder (SUD). However, relatively little is known about the theory-based psychological and social pathways whereby mindfulness could have beneficial effects for managing a chronic, relapsing SUD. Informed by Revised Stress and Coping Theory, the present cross-sectional study examined affective, cognitive, and social pathways whereby mindfulness is associated with lower methamphetamine craving. A total of 161 HIV-positive, methamphetamine-using sexual minority men completed a screening visit for a randomized controlled trial. Using a hybrid structural equation model, we examined pathways whereby mindfulness is associated with lower methamphetamine craving. We found that greater mindfulness was directly associated with lower negative affect and higher positive affect as well as indirectly associated with less methamphetamine craving. Interestingly, the indirect association between mindfulness and methamphetamine craving appeared to be uniquely attributable to positive affect. Only positive affect was indirectly associated with lower methamphetamine craving via higher positive re-appraisal coping and greater self-efficacy for managing triggers for methamphetamine use. Methamphetamine craving was supported by moderate associations with greater substance use severity and more frequent methamphetamine use. These findings support the role of mindfulness in cultivating positive affect, which could be crucial to build the capacity of individuals to manage methamphetamine craving as a chronic stressor that threatens recovery from SUD.

Cannabidiol prevents amphetamine relapse and modulates D1- and D2-receptor levels in mesocorticolimbic brain areas of rats.

Amphetamine (AMPH) is an addictive psychostimulant highly used worldwide and its consumption is related to neurotoxic effects. Currently, there is no pharmacotherapy approved for treating AMPH or other psychostimulant drug addiction. Different studies have shown promising properties of cannabidiol (CBD) for treating many neurological and psychiatric diseases, and recently, CBD is being considered a potential strategy for the treatment of drug addiction disorders. Thus, we investigated possible CBD beneficial effects on relapse symptoms following AMPH re-exposure considering drug relapse is the most difficult clinical factor to control during addiction treatment. Rats received d,l-AMPH (4 mg/kg, i.p.) or vehicle in the conditioned place preference (CPP) paradigm (8 days), when each experimental group was re-assigned to receive CBD at two different doses (5 or 10 mg/kg, i.p) or control, for 5 days. Subsequently, animals were re-exposed to AMPH-CPP (4 mg/kg, i.p.) for 3 additional days to assess relapse behavior. Besides locomotor and anxiety-like behaviors, dopaminergic molecular parameters were quantified in both prefrontal cortex and ventral striatum. Regarding molecular levels, CBD modulated at basal levels the dopaminergic targets (D1R, D2R, DAT, and TH) in the assessed brain areas, preventing AMPH relapse and decreasing anxiety-like behavior per se and in AMPH-CPP animals. The current findings give evidence about CBD-induced AMPH-relapse prevention, which may be linked to dopaminergic mesocorticolimbic system modulation. Although future and clinical studies are needed, our outcomes show that CBD may be a useful alternative to prevent AMPH relapse.