Cognitive Enhancer Donepezil Attenuates Heroin-Seeking Behavior Induced by Cues in Rats.

PURPOSE: Opioid use disorder is a significant global problem. Chronic heroin use is associated with impairment of cognitive function and conscious control ability. The cholinergic system can be disrupted following heroin administration, indicating that activation of the cholinergic system may prevent chronic heroin misuse. Donepezil as an inhibitor of cholinesterase has been reported to clinically improve cognition and attention. In this study, the inhibition of heroin self-administration and heroin-seeking behaviours by donepezil were evaluated in rats. METHODS: Rats were trained to self-administer heroin every four hours for 14 consecutive days under a fixed ratio 1 (FR1) reinforcement schedule, then underwent withdrawal for two weeks. A progressive ratio schedule was then used to evaluate the relative motivational value of heroin reinforcement. After withdrawal, a conditioned cue was introduced for the reinstatement of heroin-seeking behaviour. Donepezil (0.3-3 mg/kg, i.p.) was used during both the FR1 heroin self-administration and progressive ratio schedules. Immunohistochemistry was used to investigate the mechanism of action of donepezil in the rat brain. RESULTS: Pre-treatment with high dose donepezil (3 mg/kg) but not low doses (0.3-1 mg/kg) significantly inhibited heroin self-administration under the FR1 schedule. Donepezil decreased motivation values under the progressive ratio schedule in a dose-dependent manner. All doses of donepezil (1-3 mg/kg) decreased the reinstatement of heroin seeking induced by cues. Correlation analysis indicated that the inhibition of donepezil on heroin-seeking behaviour was positively correlated with an increased expression of dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) in the nucleus accumbens (NAc) and increased expression of choline acetyltransferase (ChAT) in the ventral tegmental area (VTA). CONCLUSIONS: The present study demonstrated that donepezil could inhibit heroin intake and heroin-seeking behaviour. Further, donepezil could regulate dopamine receptors in the NAc via an increase of acetylcholine. These results suggested that donepezil could be developed as a potential approach for the treatment of heroin misuse.

Structural violence and the need for compassionate use of methadone in Mexico.

BACKGROUND: Epidemiological data from Mexico have documented an increase in heroin use in the last decade. However, there is no comprehensive care strategy for heroin users, especially those who have been accused of a crime. The objective of this study was to describe the heroin and methadone use of intravenous heroin users of both sexes who have been in jail, to offer evidence for the formulation of health policy. METHODS: This study used an ethnographic approach, with open-ended interviews carried out from 2014 to the present. Heroin users of both sexes attending a private methadone clinic in Mexico City were invited to participate. The sample was non-probabilistic. All interviews were audiotaped and transcribed, and narratives were analyzed using thematic analysis. RESULTS: Participants in this study were 33 users of heroin, two of them women, who had been in prison. They ranged in age from 33 to 62 years, had used heroin for a period of 13-30 years, and were from three states: Michoacan, Oaxaca, and Mexico City. Three principal categories of analysis were structured: 1. Pilgrimage for help (dynamics of the drama of suffering, pain, and time through health care spaces); 2) methadone use as self-care; and 3) accessibility to methadone treatment. The impossibility of access to methadone treatment is a condition which motivates users in their journey. The dynamics of methadone use are interpreted as a form of self-care and care to avoid substance use. Reducing the psychological, physical, and harmful effects of the substance allows them to perform daily activities. The inability to access treatment leads to a significant effect on users who experience structural violence. CONCLUSION: Compassionate methadone treatment and holistic attention should be considered as a way to meet patients' needs and mitigate their suffering, based on public health policy that allows for human rights-based care.

Assessing the Role of Corticothalamic and Thalamo-Accumbens Projections in the Augmentation of Heroin Seeking in Chronically Food-Restricted Rats.

Drug addiction is a chronic disorder characterized by compulsive drug seeking, and involves repetitive cycles of compulsive drug use, abstinence, and relapse. In both human and animal models of addiction, chronic food restriction increases rates of relapse. Our laboratory has reported a robust increase in drug seeking following a period of withdrawal in chronically food-restricted rats compared with sated controls. Recently, we reported that activation of the paraventricular nucleus of the thalamus (PVT) abolished heroin seeking in chronically food-restricted rats. However, the precise inputs and outputs of the PVT that mediate this effect remain elusive. The goal of the current study was to determine the role of corticothalamic and thalamo-accumbens projections in the augmentation of heroin seeking induced by chronic food restriction. Male Long-Evans rats were trained to self-administer heroin for 10 d. Next, rats were removed from the self-administration chambers and were subjected to a 14 d withdrawal period while sated (unlimited access to food) or mildly food-restricted (FDR). On day 14, rats were returned to the self-administration context for a 3 h heroin-seeking test under extinction conditions during which corticothalamic and thalamo-accumbens neural activity was altered using chemogenetics. Surprisingly, chemogenetic activation or inhibition of corticothalamic projections did not alter heroin-seeking behavior. Chemogenetic activation of thalamo-accumbens shell, but not core, projectors attenuated heroin seeking in FDR rats. The results indicate an important role for the PVT to nucleus accumbens shell projections in the augmentation of heroin seeking induced by chronic food restriction.SIGNIFICANCE STATEMENT Relapse to heroin use is one of the major obstacles in the treatment of opiate addiction. Triggers for relapse are modulated by environmental challenges such as caloric restriction. Elucidating the brain mechanisms that underlie relapse is critical for evidence-based treatment development. Here we demonstrate a critical role for the input from the paraventricular thalamus (PVT), a hub for cortical, sensory, and limbic information, to the nucleus accumbens shell (an area known to be important for reward and motivation) in the augmentation of heroin seeking in food-restricted rats. Our findings highlight a previously unknown role for the PVT in heroin seeking following a period of abstinence.

The Association between Opioid Discontinuation and Heroin Use: A Nested Case-Control Study.

BACKGROUND: Opioid prescribing guidelines recommend reducing or discontinuing opioids for chronic pain if harms of opioid treatment outweigh benefits. As opioid discontinuation becomes more prevalent, it is important to understand whether opioid discontinuation is associated with heroin use. In this study, we sought to assess the association between opioid discontinuation and heroin use documented in the medical record. METHODS: A matched nested case-control study was conducted in an integrated health plan and delivery system in Colorado. Patients receiving opioid therapy in the study period (January 2006-June 2018) were included. Opioid discontinuation was defined as ≥45 days with no opioids dispensed after initiating opioid therapy. The heroin use onset date represented the index date. Case patients were matched to up to 20 randomly selected patients without heroin use (control patients) by age, sex, calendar time, and time between initiating opioid therapy and the index date. Conditional logistic regression models estimated matched odds ratios (mOR) for the association between an opioid discontinuation prior to the index date and heroin use. RESULTS: Among 22,962 patients prescribed opioid therapy, 125 patients (0.54%) used heroin after initiating opioid therapy, of which 74 met criteria for inclusion in the analysis. The odds of opioid discontinuation were approximately two times higher in case patients (n = 74) than control patients (n = 1045; mOR = 2.19; 95% CI 1.27-3.78). CONCLUSIONS: Among patients prescribed chronic opioid therapy, the observed increased risk for heroin use associated with opioid discontinuation should be balanced with potential benefits.

Smoking heroin with cannabis versus injecting heroin: unexpected impact on treatment outcomes.

BACKGROUND: In several countries, especially in Africa, the dominant method of heroin intake is smoking a joint of cannabis laced with heroin. There is no data exploring the impact of smoking heroin with cannabis on treatment outcomes. AIM: To compare treatment outcomes between people who inject heroin and people who smoke heroin with cannabis. METHODOLOGY: Three hundred heroin users were assessed on admission to inpatient rehabilitation and after treatment. We compared drug use, psychopathology, criminality, social functioning and general health between heroin injectors and heroin-cannabis smokers at treatment entry, and at 3 and 9 months after rehabilitation. RESULTS: The sample comprised 211 (70.3%) heroin-cannabis smokers and 89 (29.7%) heroin injectors. Eighty-four percent were followed up at 3 months and 75% at 9 months. At 9 months, heroin-cannabis smokers had a higher proportion of those who relapsed to heroin use compared with intravenous (IV) users (p = 0.036). The median number of heroin use episodes per day was lower for IV users than heroin-cannabis smokers at both follow-up points (p = 0.013 and 0.0019). A higher proportion of IV users was HIV positive (p = 0.002). There were no significant differences in psychopathology, general health, criminality and social functioning between IV users and heroin-cannabis smokers at all three time points. CONCLUSIONS: Heroin users who do not inject drugs but use other routes of administration may have increased risk for relapse to heroin use after inpatient rehabilitation and should therefore have equal access to harm reduction treatment services. Advocating a transition from injecting to smoking heroin in an African context may pose unique challenges.

2Hz-electroacupuncture attenuates heroin-seeking behaviors via adjusts CB1-Rs and CB2-Rs expression in relapse-relevant brain regions of heroin self-administration rats.

Opiate addiction has a high rate of relapse. The accumulating evidence shows that electroacupuncture (EA) may be effective for the treatment of opiate relapse. However, the change of expression of CB1-Rs and CB2-Rs involve in 2Hz EA anti-relapse pathway is still unclear. To explore the changes of expression of CB1-Rs and CB2-Rs, heroin self-administration (SA) model rats were adopted and treated using 2Hz EA. The expressions of CB1-Rs and CB2-Rs were observed using immunohistochemistry method. The results showed that, compared with the control group, active pokes in the heroin-addicted group increased, while the active pokes decreased significantly in 2Hz EA group compared with heroin-addicted group. Correspondingly, the expression of CB1-Rs in prefrontal cortex (PFC), hippocampus (Hip), nucleus accumbens (NAc) and ventral tegmental area (VTA) all increased significantly while the expression of CB2-Rs in those relapse-relevant brain regions decreased obviously in heroin-addicted group when compared with the control group. In addition, the expression of CB1-Rs obviously decreased in the 2Hz EA group while the expression of CB2-Rs in those relapse-relevant brain regions increased significantly when compared with the heroin-addicted group. It indicated that 2Hz EA could attenuate the heroin-evoked seeking behaviors effectively. The anti-relapse effects of 2Hz EA might be related to the decrease of CB1-Rs and increase of CB2-Rs expression in relapse-relevant brain regions of heroin SA rats.

Abstinence Following a Motivation-Skill-Desensitization-Mental Energy Intervention for Heroin Dependence: A Three-year Follow-up Result of a Randomized Controlled Trial.

The high rate of relapse among heroin users remains a significant public concern in China. In the present study, we utilized a Motivation-Skill-Desensitization-Mental Energy (MSDE) intervention and evaluated its effects on abstinence and mental health. Eighty-nine male heroin users in a drug rehabilitation center were enrolled in the study. The participants in the MSDE intervention group (n=46) received MSDE intervention, which included motivational interviewing, coping skills training, eye movement desensitization and reprocessing, and mindfulness-based psychotherapy. The participants in the control group (n=43) received a series of lectures on skills training. A significant increase in Contemplation Ladder score (P<0.001) and decreases in scores on the Obsessive Compulsive Drug Use Scale (P<0.001), Beck Depression Inventory (P<0.001), and Aggression Questionnaire (P=0.033) were found immediately after intervention. Compared to the control group, the MSDE intervention group reported significantly higher abstinence rates (P=0.027) and retention rates (P<0.001) at follow-up. Overall, the MSDE intervention, which uses a combined strategy for relapse prevention, could be a promising approach for preventing relapse among heroin users in China.

Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial.

OBJECTIVE: Despite the staggering consequences of the opioid epidemic, limited nonopioid medication options have been developed to treat this medical and public health crisis. This study investigated the potential of cannabidiol (CBD), a nonintoxicating phytocannabinoid, to reduce cue-induced craving and anxiety, two critical features of addiction that often contribute to relapse and continued drug use, in drug-abstinent individuals with heroin use disorder. METHODS: This exploratory double-blind randomized placebo-controlled trial assessed the acute (1 hour, 2 hours, and 24 hours), short-term (3 consecutive days), and protracted (7 days after the last of three consecutive daily administrations) effects of CBD administration (400 or 800 mg, once daily for 3 consecutive days) on drug cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder. Secondary measures assessed participants' positive and negative affect, cognition, and physiological status. RESULTS: Acute CBD administration, in contrast to placebo, significantly reduced both craving and anxiety induced by the presentation of salient drug cues compared with neutral cues. CBD also showed significant protracted effects on these measures 7 days after the final short-term (3-day) CBD exposure. In addition, CBD reduced the drug cue-induced physiological measures of heart rate and salivary cortisol levels. There were no significant effects on cognition, and there were no serious adverse effects. CONCLUSIONS: CBD's potential to reduce cue-induced craving and anxiety provides a strong basis for further investigation of this phytocannabinoid as a treatment option for opioid use disorder.

Experiences and perceptions of people who use heroin: public health lessons from Hermosillo, Mexico.

Heroin consumption in Mexico is low compared with its use in the United States; however, this practice is more common in the northern region of Mexico than in the rest of the country, being documented only in cities that are located exactly at the Mexico-U.S. border. The Mexican legal framework is focused on rehabilitation, but its effects on the lives of users are unknown. The objective of this research was to analyze how the regulatory Mexican framework is conceptualized and practiced in the daily life of a group of heroin users from a northern city, where consumption has recently spread and has not been documented. We collected the official registered data from users and conducted a qualitative study in Hermosillo, Sonora. A research on the legal framework was conducted, as well as on the city's context. Data on heroin users can be found at HIV health center, as there is no other source of such records. The Mexican legal framework aims at rehabilitation and at avoiding criminalization; however, the daily life of users drives them towards crime circuits: people commit crimes to stay in prison, where they can control the addiction and get heroin, in case of abstinence. The Mexican State has no empirical information to improve its programs and laws related to the use of heroin. The daily practices of users become not only epidemiological but social risks to the community and to the users themselves. Also, the lack of access due to stigmatization, criminalization and violence, increases the inequities, creating a cycle that reproduces poverty and suffering as part of a social structure. Therefore, changes are needed in the justice system.

The Affective and Neural Correlates of Heroin versus Cocaine Use in Addiction Are Influenced by Environmental Setting But in Opposite Directions.

Previous studies have shown that individuals with heroin and cocaine addiction prefer to use these drugs in distinct settings: mostly at home in the case of heroin and mostly outside the home in the case of cocaine. Here we investigated whether the context would modulate the affective and neural responses to these drugs in a similar way. First, we used a novel emotional task to assess the affective state produced by heroin or cocaine in different settings, based on the recollections of male and female drug users. Then we used fMRI to monitor neural activity during drug imagery (re-creating the setting of drug use) in male drug users. Consistent with our working hypothesis, the majority of participants reported a shift in the affective valence of heroin from mostly pleasant at home to mostly unpleasant outside the home (p < 0.0001). The opposite shift was observed for cocaine; that is, most participants who found cocaine pleasant outside the home found it unpleasant when taken at home (p < 0.0014). Furthermore, we found a double dissociation, as a function of drug and setting imagery, in BOLD signal changes in the left PFC and caudate, and bilaterally in the cerebellum (all p values <0.01), suggesting that the fronto-striatal-cerebellar network is implicated in the contextualization of drug-induced affect. In summary, we report that the same setting can influence in opposite directions the affective and neural response to psychostimulants versus opiates in humans, adding to growing evidence of distinct substrates for the rewarding effects of these two drug classes.SIGNIFICANCE STATEMENT The rewarding effects of addictive drugs are often thought to depend on shared substrates. Yet, environmental influences can unmask striking differences between psychostimulants and opiates. Here we used emotional tasks and fMRI to explore the influence of setting on the response to heroin versus cocaine in individuals with addiction. Simply moving from one setting to another significantly decreased heroin pleasure but increased cocaine pleasure, and vice versa. Similar double dissociation was observed in the activity of the fronto-striatal-cerebellar network. These findings suggest that the effects of opiates and psychostimulants depend on dissociable psychological and neural substrates and that therapeutic approaches to addiction should take into account the peculiarities of different drug classes and the settings of drug use.

Experiences and perceptions of people who use heroin: public health lessons from Hermosillo, Mexico / Experiencias y percepciones de personas que usan heroína: lecciones de salud pública desde Hermosillo, México / As experiências e percepções de usuários de heroína: lições de saúde pública de Hermosillo, México

Abstract: Heroin consumption in Mexico is low compared with its use in the United States; however, this practice is more common in the northern region of Mexico than in the rest of the country, being documented only in cities that are located exactly at the Mexico-U.S. border. The Mexican legal framework is focused on rehabilitation, but its effects on the lives of users are unknown. The objective of this research was to analyze how the regulatory Mexican framework is conceptualized and practiced in the daily life of a group of heroin users from a northern city, where consumption has recently spread and has not been documented. We collected the official registered data from users and conducted a qualitative study in Hermosillo, Sonora. A research on the legal framework was conducted, as well as on the city's context. Data on heroin users can be found at HIV health center, as there is no other source of such records. The Mexican legal framework aims at rehabilitation and at avoiding criminalization; however, the daily life of users drives them towards crime circuits: people commit crimes to stay in prison, where they can control the addiction and get heroin, in case of abstinence. The Mexican State has no empirical information to improve its programs and laws related to the use of heroin. The daily practices of users become not only epidemiological but social risks to the community and to the users themselves. Also, the lack of access due to stigmatization, criminalization and violence, increases the inequities, creating a cycle that reproduces poverty and suffering as part of a social structure. Therefore, changes are needed in the justice system.

Resumen: El consumo de heroína en México es bajo si se compara con su consumo en EE.UU.; no obstante, esta práctica es más común en la zona norte de México que en el resto del país, estando documentada solamente en ciudades que están localizadas exactamente en la frontera entre México y EE.UU. El marco legal mexicano está centrado en la rehabilitación, sin embargo sus efectos en las vidas de los consumidores son desconocidos. El objetivo de esta investigación fue analizar cómo se conceptualiza el marco regulatorio mexicano, y cómo se hace realidad en la vida diaria de un grupo de personas usuarias de heroína, procedentes de una ciudad del norte, donde recientemente el consumo se ha extendido y no se ha documentado. Nosotros recogimos datos oficiales registrados de consumidores y realizamos un estudio cualitativo en Hermosillo, Sonora. Se realizó una investigación sobre el marco legal, así como del contexto de la ciudad. Los datos sobre los consumidores de heroína sólo se pueden encontrar en centros de salud especializados en VIH, pues que no existe otra fuente para tales registros. El marco legal mexicano pretende la rehabilitación y evitar la criminalización; sin embargo, la vida diaria de los consumidores les conduce hacia los circuitos del crimen: la gente comete delitos para estar en prisión, donde pueden controlar la adicción y conseguir heroína, en caso de abstinencia. El estado mexicano no cuenta con información empírica para mejorar los programas y leyes relacionadas con el consumo de heroína. Las prácticas diarias de los consumidores se han convertido no sólo en riesgos epidemiológicas, sino tambiém en riesgos sociales para la comunidad y los propios consumidores. Asimismo, la falta de acceso debido a la estigmatización, la criminalización y la violencia, incrementa las inequidades, creando un círculo vicioso que reproduce la pobreza y el sufrimiento, como parte de la estructura social. Por ello, es necesario que se produzcan cambios en el sistema judicial.

Resumo: O consumo da heroína é baixo no México, comparado ao uso nos Estados Unidos, porém essa prática é mais comum na região Norte do México em comparação com o resto do país, sendo documentada apenas nas cidades localizadas justamente na fronteira com os Estados Unidos. A legislação mexicana visa principalmente a reabilitação, mas seus efeitos sobre a vida dos usuários não são conhecidos. Este estudo teve como objetivo analisar a maneira pela qual o arcabouço regulatório mexicano é conceituado e praticado na vida diária de um grupo de usuários de heroína de um município no Norte do México, onde o consumo tem sido disseminado recentemente, mas sem ter sido documentado até então. Foram coletados os dados oficiais sobre usuários, seguido por um estudo qualitativo em Hermosillo, no Estado de Sonora. Foram estudados a legislação pertinente e o contexto local em Hermosillo. Os dados sobre os usuários de heroína foram encontrados nos centros de atendimento a pessoas com HIV, uma vez que não existe outra fonte desses registros. A legislação mexicana visa a reabilitação dos usuários, evitando sua criminalização, mas sua vida cotidiana os empurra para os circuitos do crime. Assim, os indivíduos cometem crimes para permanecer na prisão, onde conseguem controlar a dependência e obter a droga em casos de síndrome de abstinência. O governo mexicano não dispõe de dados empíricos para melhorar os programas e leis relacionados ao uso da heroína. As práticas diárias dos usuários se transformam em riscos, não apenas epidemiológicos como também sociais, tanto para a comunidade quanto para os próprios usuários. Além disso, a falta de acesso a serviços, em função da combinação de estigmatização, criminalização e violência, aumenta as desigualdades, criando um ciclo que reproduz e o sofrimento enquanto parte de uma estrutura social. Portanto, são necessárias mudanças urgentes no sistema de justiça.

Polydrug use and its association with drug treatment outcomes among primary heroin, methamphetamine, and cocaine users.

BACKGROUND: Polydrug use may challenge effective treatment for substance use disorders. We evaluate whether secondary substance use modifies the association between treatment and primary drug use among primary heroin, cocaine and methamphetamine (MA) users. METHODS: Data were obtained from prospective cohort studies on people who use illicit drugs (PWUD) in California, USA. Using repeated monthly data on self-reported secondary substance use (heroin, cocaine, MA, alcohol or marijuana; ≥1day in a month), primary drug use (≥1day in a month), and treatment participation, collected via timeline follow-back, we fitted generalized linear mixed multiple regression models controlling for potential confounders to examine the interactions between treatment and secondary substance use on the odds of primary heroin, cocaine and MA use, respectively. RESULTS: Included in our study were 587 primary heroin, 444 primary MA, and 501 primary cocaine users, with a median of 32.4, 13.3 and 18.9 years of follow-up, respectively. In the absence of secondary substance use, treatment was strongly associated with decreased odds of primary drug use (adjusted odds ratios (aORs): 0.25, 95% CI: 0.24, 0.27, 0.07 (0.06, 0.08), and 0.07 (0.07, 0.09)) for primary heroin, MA, and cocaine users, respectively. Secondary substance use of any kind moderated these associations (0.82 (0.78, 0.87), 0.25 (0.21, 0.30) and 0.53 (0.45, 0.61), respectively), and these findings were consistent for each type of secondary substance considered. Moreover, we observed different associations in terms of direction and magnitude between secondary substance use and primary drug use during off-treatment periods across substance types. CONCLUSION: This study demonstrates secondary substance use moderates the temporal associations between treatment and primary drug use among primary heroin, MA and cocaine users. Disparate patterns of polydrug use require careful measurement and analysis to inform targeted treatment for polydrug users.

Suicidal Ideation Among Heroin-Abusing Mothers in Methadone Maintenance Treatment.

BACKGROUND: There is a dearth of information about mothers in methadone maintenance treatment (MMT), their parental stress, and suicidal ideation. AIM: To evaluate parenting stress and suicidal ideation among heroin-dependent mothers in MMT. METHOD: The study was conducted at an MMT center. Inclusion criteria were mothers with at least one child between 6-12 years of age. Mothers (n = 41) were interviewed about their background characteristics, drug use, parenting stress, and suicide ideation. RESULTS: The mothers' median age was 44 (27-63 years), 35% were single, 20% married or with a partner, 45% separated or divorced, 83% were Jewish, and about one-third completed elementary school only. Among the study participants, 52% reported ever thinking about suicide, 28% reported past-year ideation, and 15% indicated they were likely to complete suicide someday. Mothers who have used heroin and cannabis reported high levels of parenting stress. Mothers with high parenting stress levels were more likely to report suicidal ideation. Country of origin status did not differentiate those interviewed. CONCLUSION: This study provides insight into a hard-to-reach population of mothers needing treatment, parental skills training, and mental stress reduction. Further research is needed to generalize the findings for treatment, education, and training purposes.

Anxiety disorders are associated with early onset of heroin use and rapid transition to dependence in methadone maintained patients.

Early onset of heroin use is a severity marker of heroin use disorder. We studied the interaction between early onset and rapid transition to heroin dependence recorded with retrospective interviews in 213 patients with severe heroin dependence and history of methadone maintenance treatment. General linear models were used to identify independent factors associated with early onset, factors associated with rapid transition to dependence, and a multivariate model was used to study the interaction of those two dimensions. Lifetime history of anxiety disorders and age at onset of cannabis use are shared common risk factors and are associated with the interaction.

Efficacy of Group Motivational Interviewing in the Degree of Drug Craving in the Addicts Under the Methadone Maintenance Treatment (MMT) in South East of Iran.

BACKGROUND: Craving is one of the important factors having an effective role in the addiction relapse. As an important factor in the therapy failure, this clinical phenomenon has to be diagnosed and treated. OBJECTIVE: The present research aimed at determining the efficacy of group motivational interviewing in the degree of drug craving in the addicts under the Methadone Maintenance Treatment (MMT). METHOD: This is a quasi-experimental study carried out on 100 addicted men (aged 18-50 years), who were under the MMT in a drug abstinence clinic affiliated with University of Medical Sciences (Iran) in the second half of 2014. The research sample was selected by the availability criteria based on the inclusion and exclusion criteria, and upon matching, it was divided randomly into two groups of 50 (control and treatment). The treatment group first received 5 sessions of group motivational counseling; then it entered the therapy process. The control group received the usual treatment of the drug abstinence clinic. To assess the drug craving degree (in the pretest, 2, 6 and 12 months after the abstinence), the Visual Cue-induced Craving Task, scored 0 to 100, was used. The data were analyzed by the descriptive statistics through independent t-test, and repeated measures analysis of variance. RESULTS: The means of craving degrees in the control group, 2, 6 and 12 months after the abstinence (73.28 ± 7.52, 65.83 ± 6.69 and 61.25±5.17, respectively) were significantly (p=0.0001) higher than those in the treatment group (68.94 ± 10.53, 40.48 ± 11.78 and 32.51 ± 9.00). Moreover, the mean of retention in the treatment was 9.24 ± 2.45 months in the treatment group that was significantly (p=0.001) higher than the 4.88 ± 3.65 months of retention in the control group. CONCLUSION: The research results support the fact that motivational interviewing decreases the degree of drug craving, and increases the probability of the addicts' retention in long-term therapeutic abstinence programs. Therefore, the use of such an approach as a pretreatment and a complementary therapy in changing health behaviors is recommended.

An integrated model of depression, compulsion, and mindfulness among heroin abusers in Taiwan.

BACKGROUND AND OBJECTIVES: Prevailing literature explains how depression, compulsion, and mindfulness affect heroin use; however, there is no comprehensive framework that explains their overall relationships. We therefore proposed and examined a hypothetical depression-compulsion-heroin use and mindfulness (DCHm) model. METHODS: We recruited 234 male heroin users. Self-reported levels of depression, mindfulness, compulsion to use, and severity of heroin use were measured. Structural equation modeling was used to examine the proposed DCHm model. RESULTS: Compulsion was a mediator between depression and heroin use. In addition, the DCHm model had satisfactory model fit indices. Depression indirectly affected heroin use through compulsion to use. The moderating effects of mindfulness in the two competing models were compared between the high- and low-mindfulness groups. The DCHm model in the high-mindfulness group had more favorable model fit indices than it did in the low-mindfulness group. CONCLUSIONS: Through learned emotional regulation strategies, addicted people with higher mindfulness were less likely to compulsively take drugs because of a depressive mood than were those with lower mindfulness. Furthermore, effective emotion-regulation strategies should be developed and examined in future studies. SCIENTIFIC SIGNIFICANCE: These results raise questions about the effect of compulsion on heroin use disorders. Mindfulness-based approaches to emotional regulatory strategies should be developed based on these findings. Further experimentation and prospective studies are needed to more fully examine the moderating role of mindfulness on depression and compulsion.

Heroin craving and its correlations with clinical outcome indicators in people with heroin dependence receiving methadone maintenance treatment.

BACKGROUND: Craving for substance use has been added as one of the diagnostic criteria of substance use disorders in DSM-5. However, further research is necessary to examine and expand the clinical potential of craving in the assessment and treatment for heroin users. This study aimed to examine the psychometrics of the Desire for Drug Questionnaire-Chinese Mandarin version (DDQ-CM) and its clinical utility of assessing craving for heroin measured among heroin users with methadone maintenance treatment (MMT). METHOD: Self-reported craving for heroin use was measured on the DDQ-CM and visual analog scale among 314 intravenous heroin users receiving MMT. Self-reported heroin dependence, attitude toward heroin use, readiness to change heroin use, and depression were collected. RESULTS: The results found that although the original three-factor model was acceptable for applying the DDQ-CM for heroin users with MMT, only the concurrent validity of the subscales of Desire and Intention and Negative Reinforcement was supported but not that of Control. Meanwhile, the levels of craving on the subscales of Desire and Intention and of Negative Reinforcement on the DDQ-CM were positively associated with the levels of heroin dependence, positive and negative attitudes toward heroin use, and depression, but negatively associated with readiness to change heroin use. CONCLUSIONS: This study supported the application of the subscales of Desire and Intention and Negative Reinforcement on the DDQ-CM to measure heroin craving in Taiwanese-Chinese heroin users and supported the clinical implication of craving in heroin users with MMT.

Longitudinal changes of dopamine transporters in heroin users during abstinence.

RATIONALE: Chronic exposure to heroin results in decreased dopamine transporter levels. Jitai tablets, a traditional Chinese medicine, have been effective at increasing striatal dopamine transporter availability after 6 months of treatment. However, it remains unknown how long the heroin-induced impairment persists and whether dopamine transporter can be normalized following long-term abstinence or treatment. OBJECTIVES: This study was to evaluate the time course of dopamine transporter changes in heroin users undergoing long-term abstinence and treatment with Jitai tablets for 1 year. METHODS: Single-photon emission computed tomography using [(99m)Tc]TRODAT-1 was performed on 64 heroin users and 20 healthy subjects to assess striatal dopamine transporter availability at baseline, 3, 6, and 12 months. Heroin users were randomly assigned to treatment with either placebo or Jitai tablets. Depression and anxiety scores were measured before each imaging session. RESULTS: Compared with healthy controls, significant reduction in dopamine transporter availability was found in heroin users at baseline in both the right (by ∼ 31.6%) and left striatum (by ∼ 33.2%). At 6 months, dopamine transporter availability was significantly higher in Jitai tablet-treated group than placebo group in the bilateral striatum (p < 0.01). At 12 months, dopamine transporter levels in both groups were upregulated substantially from baseline but still not recovered to normal levels in the left striatum (p < 0.05). Depression and anxiety scores significantly decreased at 3, 6, and 12 months (p < 0.05). CONCLUSIONS: Our results confirmed that heroin abuse induces pronounced, long-term reduction in dopamine transporter. Treatment with Jitai tablets appears to stimulate recovery.

Stigma and its determinants among male drug dependents receiving methadone maintenance treatment.

BACKGROUND: The stigma attached to substance use is considered as a barrier to treatment, resulting in continued dependence and harmful consequences for the health of drug abusers and society. METHODS: In the current study, stigma and its relation with patient characteristics and secrecy was examined in people who were in treatment of drug dependency. Participants were 144 patients from two referral methadone treatment centers who completed a survey containing questionnaires about stigma, secrecy and other measures of drug use. RESULTS: Patients reported high levels of self-stigma and moderate levels of stigma-related rejection and perceived stigma as well as commonly using secrecy, as a way of coping. More experiencing of self -stigma was associated with unemployment, positive history of IV drug use, incarceration and heroin consumption, compared to opium use. IV drug users and unemployed persons also reported more contacts with stigma- related rejection. No association was found between stigma and previous history of treatment for substance abuse. CONCLUSION: Findings indicate stigma in individuals who are in the treatment for substance dependence and highlight the need for more studies to clarify all aspects of drug use stigma.

Methadone treatment improves tuberculosis treatment among hospitalized opioid dependent patients in Ukraine.

BACKGROUND: Ukraine's volatile syndemics of tuberculosis (TB) and HIV among people who inject drugs (PWIDs) introduces numerous treatment challenges for each condition, including high mortality and development of multi-drug resistant TB (MDR-TB). METHODS: A prospective, non-randomized 90-day observational study was conducted in six Ukrainian TB treatment sites to assess the effectiveness of integrating methadone maintenance (MMT) with TB treatment using: (1) 90-day TB treatment retention; (2) time to treatment discontinuation; (3) TB medication adherence; and (4) subject disposition, including mortality. Of the 110 participants enrolled, 57 received MMT and 53 did not (non-MMT). RESULTS: All of the primary outcomes were significantly better in MMT versus non-MMT groups, including 90-day TB treatment completion (89.5% versus 73.6%; p=0.031), time to TB treatment discontinuation (p=0.039) and TB medication adherence (97.1% versus 86.2%; p<0.001) after controlling for death. The major reasons for treatment non-completion in the non-MMT group included death (N=3), administrative discharge from the clinic (N=5), loss to follow-up (N=2), and arrest (N=4). Overall, 90-day mortality was high (8.2%). After controlling for covariates differing between the two groups at baseline, the only independent predictor of completing 90 days of TB treatment was receipt of MMT in an integrated treatment setting (AOR=3.05; 95% CI 1.08-8.66). CONCLUSIONS: MMT integrated into inpatient TB treatment significantly improves retention in TB treatment and TB medication adherence among PWIDs. These findings call for policy change to increase the number of MMT sites in TB facilities and make MMT a low-threshold treatment option for opioid dependence in Ukraine.