Substance Abuse Relapse Research Articles

A two-state comparative implementation of peer-support intervention to link veterans to health-related services after incarceration: a study protocol

BackgroundApproximately 600,000 persons are released from prison annually in the United States. Relatively few receive sufficient re-entry services and are at risk for unemployment, homelessness, poverty, substance abuse relapse and recidivism. Persons leaving prison who have a mental illness and/or a substance use disorder are particularly challenged. This project aims to create a peer mentor program to extend the reach and effectiveness of reentry services provided by the Department of Veterans’ Affairs (VA). We will implement peer support for reentry veterans sequentially in two states. Our outcome measures are 1) fidelity of the intervention, 2) linkage to VA health care and, 3) continued engagement in health care.The aims for this project are as follows: (1) Conduct contextual analysis to identify VA and community reentry resources, and describe how reentry veterans use them. (2) Implement peer-support, in one state, to link reentry veterans to Veterans’ Health Administration (VHA) primary care, mental health, and SUD services. (3) Port the peer-support intervention to another, geographically, and contextually different state.DesignThis intervention involves a 2-state sequential implementation study (Massachusetts, followed by Pennsylvania) using a Facilitation Implementation strategy. We will conduct formative and summative analyses, including assessment of fidelity, and a matched comparison group to evaluate the intervention’s outcomes of veteran linkage and engagement in VHA health care (using health care utilization measures). The study proceeds in 3 phases.DiscussionWe anticipate that a peer support program will be effective at improving the reentry process for veterans, particularly in linking them to health, mental health, and SUD services and helping them to stay engaged in those services. It will fill a gap by providing veterans with access to a trusted individual, who understands their experience as a veteran and who has experienced justice involvement. The outputs from this project, including training materials, peer guidebooks, and implementation strategies can be adapted by other states and regions that wish to enhance services for veterans (or other populations) leaving incarceration. A larger cluster-randomized implementation-effectiveness study is planned.Trial registrationThis protocol is registered with clinicaltrials.gov on November 4, 2016 and was assigned the number NCT02964897.

The Efficacy of Dog Assisted Therapy in Detained Drug Users: A Pilot Study in an Italian Attenuated Custody Institute.

Drug addiction is a major care and safety challenge in prison context. Nowadays, rehabilitation and specific therapeutic programs are suggested to improve health and well-being of inmates during their detention time and to reduce substance abuse relapse after release from prison. Among these programs, several studies reported the benefits for inmates coming from animal assisted interventions. In this pilot controlled study, we investigated the efficacy of a dog assisted therapy program addressed to 22 drug addicted male inmates housed in an attenuated custody institute in Italy. The study lasted six months, the treated group (12 inmates) was involved once a week for one hour in 20 dog assisted therapy sessions, whereas the control group (10 inmates) followed the standard rehabilitation program. One week before the beginning and one week after the end of the sessions, all inmates involved were submitted to symptom checklist-90-revised and Kennedy axis V. Inmates involved in the dog assisted therapy sessions significantly improved their social skills, reducing craving, anxiety and depression symptoms compared to the control group. Despite the limitation due to the small number of inmates enrolled and to the absence of follow up, we found these results encouraging to the use of dog assisted therapy as co-therapy in drug addicted inmates rehabilitation programs, and we claim the need of more extensive study on this subject.

The Importance of Mindfulness in Preventing Substance-Abuse Relapse: A Literature Review

This study discusses how to use information on mindfulness and its applications as a method for coping with difficult emotions in order to prevent a relapse of drug addiction. Mindfulness practices, while supporting healthy development, also reduce stress, improve well-being, and provide emotional balance. Its use in substance abuse treatment is quite new. Mindfulness helps one to be able to cope with their state of mind in the moment of stress related to substance withdrawal by supporting learning and well-being, and by enabling a direct relationship to be established among self-awareness, self-control, and emotion regulation. In the working group of this study on the prevention of substance abuse relapse, sessions consisted of experimental exercises and discussions. The objective is to keep key points such as the person’s current experiences, relapse, improvement or lifestyle in the center of the discussion. The attention of the participants, through mindfulness application, is a continual in “the moment” review of their surroundings and can prevent them from getting lost in their history. As another strong side of the program, the importance of an individual addressing one’s self before judging or being made to feel guilty is gently encouraged in these applications. In this way, difficulties that emerge in the practice are assessed not as failures but as a sign of tendencies related to the mind, and people’s motivations are protected by normalizing the difficulties they experience. Perhaps the most crucial point of the mindfulness-based relapse prevention program, unlike other therapies, is that labeling in any manner is not performed. Instead of people experiencing the worth of being forgiven, people are required to only observe and accept. Through all of these practices, the target is to ensure a person becomes more aware and accepting towards their actions.

Abstract 247: STEMI 365: Creating a Yearlong Program to Reduce Cardiac Recidivism After STEMI

Survivors of myocardial infarctions are at increased risk of recurrent infarctions and have an annual death rate of 5%, six times that in people of the same age who do not have coronary heart disease. Despite the existence of published interventions and clinical recommendations aimed at secondary and tertiary prevention their application and adherence statistics in post-myocardial infarction patients are woeful. The objective of this paper is to detail the creation of a template curriculum that gives best practice recommendations to post STEMI patients in an effort to reduce recidivism by combining current medical methodology with lessons learned from other fields currently addressing the problem of recidivism and relapse. STEMI 365 is a yearlong program that aims to reduce cardiac recidivism in STEMI survivors. STEMI 365 is composed of three parts: best practice guidelines, evaluation toolkit, and template curriculum. The best practice guidelines document is broken into sections on cardiac rehabilitation, lifestyle modification, drug therapy, patient follow-up and screening, and patient education. All guidelines are informed by the latest recommendations and research in the fields of medicine and relapse prevention. The evaluation toolkit is composed of the cardiac recidivism risk tool, the self-evaluation tool, and the global evaluation tool. The goal of the toolkits is to guide resource allocation by understanding a patient’s unique cardiac recidivism risk, internal sources of potential relapse, and external sources of potential relapse. The Federal Post Conviction Risk Assessment developed by the Administrative Office of the United States Courts informs the toolkits’ construction. The template curriculum is a summation of the programs and interventions that can be utilized by a health system to decrease cardiac recidivism in STEMI survivors. The curriculum addresses one year of time divided into three phases: inpatient, outpatient, and maintenance. The interventions rage in scope from training a patient’s family members in bystander CPR to the creation of a centralized patient monitoring program and post-myocardial infarction clinic. Each phase combines the best modalities in treatment found in the fields of post-myocardial infarction care, hospital re-admission prevention, substance abuse relapse prevention, scholastic dropout prevention, and criminal justice. Personal interviews were conducted with leaders in each field to ensure the correct application of their methodologies. STEMI 365 provides tools to identify patients at highest risk of cardiovascular relapse, to apply local and regional resources in an effective way based on patient risk, and to customize interventions to a health system’s available resources. STEMI 365 is beginning an application phase at this institution, and will be available to other health systems in the near future.

Madde Bağımlılığında Nüksü Önlemede Bilinçli Farkındalığın Önemi: Bir Derleme Çalışması

Madde Bağımlılığında Nüksü Önlemede Bilinçli Farkındalığın Önemi: Bir Derleme Çalışması

Validation of relapse timeline followback interview among Narcotics Anonymous clients

Background: Relapse is commonly defined as a return to substance use after a period of abstinence. The aim of this study was to investigate the psychometric properties of the timeline followback interview for substance abuse among the Narcotics Anonymous clients Methods: In this cross-sectional methodological study, 385 clients presenting to Narcotics Anonymous centers of Qom city were selected by convenience sampling. Data were collected by demographic variables questionnaire and Timeline Followback Interview (TLFB). To validate the questionnaire, its reliability was first calculated by SPSS software and exploratory factor analysis was performed afterwards. Then, confirmatory factor analysis was done by Lisrel software. Results: All subjects were male and 61.56% of them were married. The results indicated that the internal consistency of 0.93 for the questionnaire. Further, the findings of exploratory and confirmatory factor analysis demonstrated the acceptable construct validity of this questionnaire among the study sample. Conclusion: The timeline followback interview enjoyed acceptable psychometric properties among the Iranian clients who joined Narcotics Anonymous groups. Therefore, researchers and clinicians can use the above mentioned questionnaire as a valid tool for assessing vulnerability to substance abuse relapse.

Survival Analysis of Drug Abuse Relapse in Addiction Treatment Centers.

Background:Drug abuse is a chronic and enduring phenomenon, which is among the important challenging public health problems. One of the main aspects in drug abuse is the relapse.Objectives:The aims of this study were to estimate the time to relapse (survival rate) and to evaluate some of its associated variables by survival analysis.Patients and Methods:This research was conducted in four addiction treatment centers on 140 self-referred addicts in Ilam city, Iran, in 2012. Cluster sampling method was used for selecting the samples and data were collected by interview and referring to the subjects’ records. The gathered data were analyzed through the life table, Kaplan-Meier analysis, log rank test, and Cox regression.Results:The relapse rate was 30.42%, mean and median of the time to relapse (survival time) were 27.40 ± 1.63 months (CI 95%: 24.19 - 30.60) and 25 ± 2.25 months (CI 95%: 22.5 - 27.5), respectively. In the first six months, the cumulative survival rate was 83%, while in the 24th month it was 46% and the following time was consistent. Job status (OR = 2.64), marital status (OR = 1.55), family size (OR = 1.20) and age (OR = 0.23) were statistically significant in Cox regression model.Conclusions:In the initial treatment, it seems necessary to supervise and monitor the treatment process through staff in addiction treatment centers together with the company of the addicts’ families to reduce relapse rate.

C7β-methyl analogues of the orvinols: the discovery of kappa opioid antagonists with nociceptin/orphanin FQ peptide (NOP) receptor partial agonism and low, or zero, efficacy at mu opioid receptors.

Buprenorphine is a successful analgesic and treatment for opioid abuse, with both activities relying on its partial agonist activity at mu opioid receptors. However, there is substantial interest in its activities at the kappa opioid and nociceptin/orphanin FQ peptide receptors. This has led to an interest in developing compounds with a buprenorphine-like pharmacological profile but with lower efficacy at mu opioid receptors. The present article describes aryl ring analogues of buprenorphine in which the standard C20-methyl group has been moved to the C7β position, resulting in ligands with the desired profile. In particular, moving the methyl group has resulted in far more robust kappa opioid antagonist activity than seen in the standard orvinol series. Of the compounds synthesized, a number, including 15a, have a profile of interest for the development of drug abuse relapse prevention therapies or antidepressants and others (e.g., 8c), as analgesics with a reduced side-effect profile.

The Feasibility and Acceptability of "Arise": An Online Substance Abuse Relapse Prevention Program.

The purpose of this study was to test the feasibility and acceptability of a novel online adolescent substance abuse relapse prevention tool, "Arise" (3C Institute, Cary, NC). The program uses an innovative platform including interactive instructional segments and skill-building games to help adolescents learn and practice coping skills training strategies. We conducted a pilot test with nine adolescents in substance abuse treatment (44 percent female) and a feasibility test with treatment providers (n=8; 50 percent female). Adolescents interacted with the program via a secure Web site for approximately 30 minutes for each of two instructional units. Treatment providers reviewed the same material at their own pace. All participants completed a questionnaire with items assessing usability, acceptability, understanding, and subjective experience of the program. Regarding feasibility, recruitment of this population within the study constraints proved challenging, but participant retention in the trial was high (no attrition). Adolescents and treatment providers completed the program with no reported problems, and overall we were able to collect data as planned. Regarding acceptability, the program received strong ratings from both adolescents and providers, who found the prototype informative, engaging, and appealing. Both groups strongly recommended continuing development. We were able to deliver the intervention as intended, and acceptability ratings were high, demonstrating the feasibility and acceptability of online delivery of engaging interactive interventions. This study contributes to our understanding of how interactive technologies, including games, can be used to modify behavior in substance abuse treatment and other health areas.

Predicting Substance Abuse Relapse: The Role of Social Interest and Social Bonding

Substance abuse relapse has been linked to a number of internal and external vulnerability factors. The authors explored the internal construct of Adlerian social interest (Adler, ) and the external construct of Hirschi's () social bonding to provide a holistic risk profile of relapse.

Drug Abuse Relapse Rates Linked to Level of Education: Can We Repair Hypodopaminergic-Induced Cognitive Decline With Nutrient Therapy?

It is well known that athletes and other individuals who have suffered painful injuries are at increased risk for all reward deficiency syndrome (RDS) behaviors, including substance use disorder (SUD). Comparing patient demographics and relapse rates in chemical dependence programs is pertinent because demographics may affect outcomes. Increased risk for relapse and lower academic achievement were found to have a significant association in recent outcome data from a holistic treatment center (HTC) located in North Miami Beach, FL. Relapse outcomes from the Drug Addiction Treatment Outcome Study (DATOS; n = 1738) and HTC (n = 224) were compared for a 12-month period. Post-discharge relapse was reported by 26% of HTC patients and 58% of patients in DATOS. When broken out by education level—less than high school, high school diploma, college degree, and graduate degree—HTC patient relapse was 50%, 36%, 33%, and 16%, respectively, and demonstrated an inverse linear association (F = 5.702; P = 0.017). Looking at DATOS patient relapse rates broken down by educational grades/years completed, patients who attended school between 7th grade and 4 years of college also demonstrated an inverse linear association (F = 5.563; P = 0.018). Additionally, the lowest performers, patients who reported their academic performance as “not so good,” had the highest relapse (F = 4.226; P = 0.04). Albeit certain limitations, compared with DATOS patients, HTC patients produced significantly larger net differences in relapse rates (X2 = 84.09; P = 0.0001), suggesting that other variables, such as the treatment model may also affect patient relapse. Our results implicate the use of vitamin and mineral supplements coupled with a well-researched natural dopamine agonist nutrient therapy; both have been shown to improve cognition and behavior, and thus academic achievement. That relapse is highest among addicts who have less education and who report lower grades is a factor that can be useful when considering treatment type and controlled for when comparing treatment outcomes.

Mindfulness Therapy May Help Prevent Substance-Abuse Relapse in Long Term

Mindfulness Therapy May Help Prevent Substance-Abuse Relapse in Long Term

Methamphetamine-Associated Memory Is Regulated by a Writer and an Eraser of Permissive Histone Methylation

Memories associated with drugs of abuse, such as methamphetamine (METH), increase relapse vulnerability to substance use disorder by triggering craving. The nucleus accumbens (NAc) is essential to these drug-associated memories, but underlying mechanisms are poorly understood. Posttranslational chromatin modifications, such as histone methylation, modulate gene transcription; thus, we investigated the role of the associated epigenetic modifiers in METH-associated memory. Conditioned place preference was used to assess the epigenetic landscape in the NAc supporting METH-associated memory (n = 79). The impact of histone methylation (H3K4me2/3) on the formation and expression of METH-associated memory was determined by focal, intra-NAc knockdown (KD) of a writer, the methyltransferase mixed-lineage leukemia 1 (Mll1) (n = 26), and an eraser, the histone lysine (K)-specific demethylase 5C (Kdm5c) (n = 38), of H3K4me2/3. A survey of chromatin modifications in the NAc of animals forming a METH-associated memory revealed the global induction of several modifications associated with active transcription. This correlated with a pattern of gene activation, as revealed by microarray analysis, including upregulation of oxytocin receptor (Oxtr) and FBJ osteosarcoma oncogene (Fos), the promoters of which also had increased H3K4me3. KD of Mll1 reduced H3K4me3, Fos and Oxtr levels and disrupted METH-associated memory. KD of Kdm5c resulted in hypermethylation of H3K4 and prevented the expression of METH-associated memory. The development and expression of METH-associated memory are supported by regulation of H3K4me2/3 levels by MLL1 and KDM5C, respectively, in the NAc. These data indicate that permissive histone methylation, and the associated epigenetic writers and erasers, represent potential targets for the treatment of substance abuse relapse, a psychiatric condition perpetuated by unwanted associative memories.

Brain Potentials Measured During a Go/NoGo Task Predict Completion of Substance Abuse Treatment

U.S. nationwide estimates indicate that 50% to 80% of prisoners have a history of substance abuse or dependence. Tailoring substance abuse treatment to specific needs of incarcerated individuals could improve effectiveness of treating substance dependence and preventing drug abuse relapse. We tested whether pretreatment neural measures of a response inhibition (Go/NoGo) task would predict which individuals would or would not complete a 12-week cognitive behavioral substance abuse treatment program. Adult incarcerated participants (n = 89; women n = 55) who volunteered for substance abuse treatment performed a Go/NoGo task while event-related potentials (ERPs) were recorded. Stimulus- and response-locked ERPs were compared between participants who completed (n = 68; women = 45) and discontinued (n = 21; women = 10) treatment. As predicted, stimulus-locked P2, response-locked error-related negativity (ERN/Ne), and response-locked error positivity (Pe), measured with windowed time-domain and principal component analysis, differed between groups. Using logistic regression and support-vector machine (i.e., pattern classifiers) models, P2 and Pe predicted treatment completion above and beyond other measures (i.e., N2, P300, ERN/Ne, age, sex, IQ, impulsivity, depression, anxiety, motivation for change, and years of drug abuse). Participants who discontinued treatment exhibited deficiencies in sensory gating, as indexed by smaller P2; error-monitoring, as indexed by smaller ERN/Ne; and adjusting response strategy posterror, as indexed by larger Pe. The combination of P2 and Pe reliably predicted 83.33% of individuals who discontinued treatment. These results may help in the development of individualized therapies, which could lead to more favorable, long-term outcomes.

Intrastriatal gene delivery of GDNF persistently attenuates methamphetamine self-administration and relapse in mice

Relapse of drug abuse after abstinence is a major challenge to the treatment of addicts. In our well-established mouse models of methamphetamine (Meth) self-administration and reinstatement, bilateral microinjection of adeno-associated virus vectors expressing GDNF (AAV-Gdnf) into the striatum significantly reduced Meth self-administration, without affecting locomotor activity. Moreover, the intrastriatal AAV-Gdnf attenuated cue-induced reinstatement of Meth-seeking behaviour in a sustainable manner. In addition, this manipulation showed that Meth-primed reinstatement of Meth-seeking behaviour was reduced. These findings suggest that the AAV vector-mediated Gdnf gene transfer into the striatum is an effective and sustainable approach to attenuate Meth self-administration and Meth-associated cue-induced relapsing behaviour and that the AAV-mediated Gdnf gene transfer in the brain may be a valuable gene therapy against drug dependence and protracted relapse in clinical settings.

Mesoaccumbens dopamine signaling alteration underlies behavioral transition from tolerance to sensitization to morphine rewarding properties during morphine withdrawal

Although the firing activity of dopamine (DA) neurons in the ventral tegmental area (VTA) and the behavioral response to morphine rewarding properties alter as opiate withdrawal, little is known about the dynamic changes in DA signal pathway from the VTA to the nucleus accumbens (NAc) during prolonged withdrawal, and whether the changes are indicative of vulnerability to relapse of drug abuse. Here we report that morphine spontaneously withdrawn (SW) rats are incapable of responding to small dose of morphine-induced conditioned place preference (CPP) from 24h-SW to 30d-SW, but recover response at 45d-SW. Interestingly, mesoaccumbens DA signaling, including the firing of DA neurons in the VTA, contents of DA and its metabolic ratio, and the membrane level of dopamine D1 receptor in the NAc elicited by morphine challenge, display a similar pattern of time-dependent changes during morphine withdrawal. Moreover, blockade of D1 receptor abolishes this behavioral transition. In addition, a strong correlation was found between % change in CPP score and membrane D1 receptor level induced by morphine challenge. These results indicate a time-dependent behavioral switch from tolerance to sensitization during the prolonged withdrawal, which could offer a window for therapeutic intervention via manipulations of D1 receptors.

Substance use disorders in Saudi Arabia: review article

Objective: The objective was to review all the available published studies and reports with particular reference to substance abuse in Saudi Arabia.Methods: Data were collected from a PubMed search and reviewing national journals, the United Nations Office on Drug and Crime (UNODC) reports, World Health Organization (WHO) reports and conference presentations over the last two decades.Results: Among Saudi patients in addiction treatment settings, the most commonly abused substances were amphetamine (4–70.7%,), heroin (6.6–83.6%), alcohol (9–70.3%) and cannabis (1–60%). Over the past decade, there was an increase in the use of cannabis and amphetamine and decrease in the use of heroin and volatile substances. Peer pressure and psychosocial stresses were risk factors for initiation as well as relapse of substance abuse. Anxiety, depression and hepatitis were the most common co-morbid disorders among the Saudi patients.Conclusion: Substance abuse is a public health problem in Saudi Arabia. It was associated with many psychiatric disorders, medical diseases and educational, occupational, legal and social consequences. School- and community-based prevention programmes are highly required in Saudi Arabia as a first-line strategy in the fight against substance abuse.

Treating and preventing relapse of drug abuse by healthcare providers

였던 것으로 보인다. 미국에서도 의료인의 약물 오남용은 체 Drug abuse by healthcare providers is a serious public problem affecting not only the providers themselves but also their families, colleagues, and patients. It is not a new problem, but the medical community has historically been unwilling to accept and publicly acknowledge the problem, particularly a problem of its own members. Therefore, drug abuse by healthcare providers has either gone unnoticed or has been treated punitively, which has led to high prevalence and mortality. In South Korea, drug-abusing healthcare providers are considered criminals rather than patients. However, many studies have reported that punitive action alone is ineffective. This article describes the treatment principles, prognosis, and possibilities of returning to practice for drug-abusing healthcare providers. Early detection of drug abuse is key to subsequent treatment and prognosis. Furthermore, why relapse prevention as well as treatment is significant and which factors intensify the risk of relapse will be discussed. The use of opioids, coexisting psychiatric illness, and a family history of drug abuse are statistically significant factors. Finally, continuous and close monitoring is effective for relapse prevention, so it is considered another kind of therapy. An organized system for treating drug abuse is currently lacking in South Korea, not only for the general population but also for healthcare providers. In the future, a systematic approach and management by the medical community is necessary to resolve drug abuse by healthcare providers.

Comparison of the efficacy of buprenorphine and clonidine in detoxification of opioid-dependents.

Since the number of drug users is increasing, applying a method of detoxification with fewer side effects during withdrawal from opioids and greater reliability seems to be necessary. In addition, without maintenance treatment, there will be limited success of treatment. This study aimed to compare success rates of detoxification with sublingual buprenorphine and clonidine and to evaluate addiction relapse in patients using naltrexone in a six-month follow-up. This double-blind trial was carried out on opioid dependent patients in a psychiatric hospital in Kerman (Iran) during 2007-09. The subjects were randomly selected from individuals who had referred for detoxification. They were allocated to two groups to receive either clonidine (n = 21) or buprenorphine (n = 14). The success rates of the two methods were assessed at the end of the course and patients were discharged while prescribed with 25 mg daily use of naltrexone. They were followed up for six months and the continuous use of naltrexone and relapse of substance abuse were evaluated. A total number of 35 patients entered the study. Success of detoxification with naltrexone was confirmed in all cases. One person (8.4%) in the clonidine group and no patient in the buprenorphine group had a clinical opiate withdrawal scale (COWS) score of more than 12 (P > 0.05). The mean levels of objective signs and subjective symptoms of withdrawal and the desire for drug abuse had significant reductions during detoxification period in both groups (P < 0.001). However, the difference in these variables between the two groups was not statistically significant (P > 0.05). Naltrexone was used for an average of one month in 43% and 64% of subjects in the clonidine and buprenorphine groups, respectively. In addition, 62% of patients in the clonidine group and 92.8% of subjects in the buprenorphine group received maintenance treatment. Nevertheless, the mean number of days staying in treatment was not significantly difference between the two groups (P > 0.05). Buprenorphine is as effective as clonidine in controlling withdrawal symptoms. A greater percentage of patients detoxified by buprenorphine received maintenance treatment, but there was not a significant difference in relapse rates between the two methods.

Cues predicting drug or food reward restore morphine-induced place conditioning in mice lacking delta opioid receptors

The exact role of delta opioid receptors in drug-induced conditioned place preference (CPP) remains debated. Under classical experimental conditions, morphine-induced CPP is decreased in mice lacking delta opioid receptors (Oprd1 (-/-)). Morphine self-administration, however, is maintained, suggesting that drug-context association rather than drug reward is deficient in these animals. This study further examined the role of delta opioid receptors in mediating drug-cue associations, which are necessary for the expression of morphine-induced CPP. We first identified experimental conditions under which Oprd1 (-/-) mice are able to express CPP to morphine (5, 10 or 20 mg/kg) in a drug-free state and observed that, in this paradigm, CPP was dependent on circadian time conditions. We then took advantage of this particularity to assess the ability of various cues (internal or discrete), predicting either drug or food reward, to restore CPP induced by morphine (10 mg/kg) in Oprd1 (-/-) mice in conditions under which they normally fail to express CPP. We found that presentation of circadian, drug or auditory cues, predicting morphine or food reward, restored morphine CPP in Oprd1 (-/-) mice, which then performed as well as control mice. This study reveals that, in contrast to spatial cues, internal or discrete morphine-predicting stimuli permit full expression of morphine CPP in Oprd1 (-/-) mice. Delta receptors, therefore, appear to play a crucial role in modulating spatial contextual cue-related responses. This activity may be critical when context gains control over behavior, as is the case for context-induced relapse in drug abuse.