The association between interleukin-8 levels and the development of withdrawal symptoms during methamphetamine abstinence.

OBJECTIVE: Withdrawal symptoms are common during methamphetamine (METH) abstinence. This study aimed to explore the association between serum interleukins and withdrawal symptoms during METH abstinence. METHODS: This study recruited 120 METH users, and 94 of them completed the 2-week follow-up. Serum interleukin-1ß, 6,8,10 were tested at admission. Withdrawal symptoms were assessed by the Methamphetamine Withdrawal Questionnaire (MAWQ). RESULTS: Serum IL-8 levels were positively correlated with MAWQ scores at the 2-week endpoint (r = .257, p = .013). The variation of the MAWQ scores during the 2-week follow-up was negatively correlated with serum IL-8 levels at admission (r = -.249, p = .026). Serum IL-8 levels remained associated with the severity of METH withdrawal symptoms (ß = .363, p = .023), after adjusting for potential confounders. LIMITATIONS: This study did not include normal controls. Most patients were male and cigarette smokers. Patients were only followed up for 2 weeks, and their toxicology data were not collected. Interleukins were only measured at admission, and were tested in serum, not in the cerebrospinal fluid. CONCLUSIONS: Our study demonstrated that higher serum IL-8 levels may predict more severe withdrawal symptoms at 2 weeks after METH abstinence.

From opiates to methamphetamine: building new harm reduction responses in Jakarta, Indonesia.

BACKGROUND: Despite the rise of stimulant use, most harm reduction programs still focus on people who inject opioids, leaving many people who use methamphetamine (PWUM) underserviced. In Asia, especially, where methamphetamine prevalence has overtaken opioids prevalence, harm reduction programs assisting PWUM are rare. The few existing innovative practices focusing on methamphetamine use lie underreported. Understanding how these programs moved their focus from opiates to methamphetamine could help inspire new harm reduction responses. Hence, this paper analyzes a newly implemented outreach program assisting methamphetamine users in Jakarta, Indonesia. It addresses the program's critical learning points when making the transition to respond to stimulant use. METHODS: This case study is part of a more extensive research on good practices of harm reduction for stimulant use. For this case study, data was collected through Indonesian contextual documents and documents from the program, structured questionnaire, in-depth interviews with service staff and service users, a focus group discussion with service users, and in-loco observations of activities. For this paper, data was reinterpreted to focus on the key topics that needed to be addressed when the program transitioned from working with people who use opioids to PWUM. RESULTS: Four key topics were found: (1) getting in touch with different types of PWUM and building trust relationships; (2) adapting safer smoking kits to local circumstances; (3) reframing partnerships while finding ways to address mental health issues; and (4) responding to local law enforcement practices. CONCLUSIONS: The meaningful involvement of PWUM was essential in the development and evaluation of outreach work, the planning, and the adaptation of safer smoking kits to local circumstances. Also, it helped to gain understanding of the broader needs of PWUM, including mental health care and their difficulties related to law enforcement activities. Operating under a broad harm reduction definition and addressing a broad spectrum of individual and social needs are preferable to focusing solely on specific interventions and supplies for safer drug use. Since many PWUM smoke rather than inject, securing funding for harm reduction focused on people who do not inject drugs and/or who do not use opioids is fundamental in keeping programs sustainable.

Bouncing back: Brain rehabilitation amid opioid and stimulant epidemics.

Recent methamphetamine and opioid use epidemics are a major public health concern. Chronic stimulant and opioid use are characterized by significant psychosocial, physical and mental health costs, repeated relapse, and heightened risk of early death. Neuroimaging research highlights deficits in brain processes and circuitry that are linked to responsivity to drug cues over natural rewards as well as suboptimal goal-directed decision-making. Despite the need for interventions, little is known about (1) how the brain changes with prolonged abstinence or as a function of various treatments; and (2) how symptoms change as a result of neuromodulation. This review focuses on the question: What do we know about changes in brain function during recovery from opioids and stimulants such as methamphetamine and cocaine? We provide a detailed overview and critique of published research employing a wide array of neuroimaging methods - functional and structural magnetic resonance imaging, electroencephalography, event-related potentials, diffusion tensor imaging, and multiple brain stimulation technologies along with neurofeedback - to track or induce changes in drug craving, abstinence, and treatment success in stimulant and opioid users. Despite the surge of methamphetamine and opioid use in recent years, most of the research on neuroimaging techniques for recovery focuses on cocaine use. This review highlights two main findings: (1) interventions can lead to improvements in brain function, particularly in frontal regions implicated in goal-directed behavior and cognitive control, paired with reduced drug urges/craving; and (2) the targeting of striatal mechanisms implicated in drug reward may not be as cost-effective as prefrontal mechanisms, given that deep brain stimulation methods require surgery and months of intervention to produce effects. Overall, more studies are needed to replicate and confirm findings, particularly for individuals with opioid and methamphetamine use disorders.

Methamphetamine Use: A New Wave in the Opioid Crisis?

BACKGROUND: The ongoing drug crisis in the United States continues to be headlined with numbers of deaths related to opioid overdose. Less known to the public and health care providers is the rise in methamphetamine use, often in conjunction with opioids or adulterated with fentanyl. An old practice with a new twist is the use of methamphetamine in conjunction with an opioid such as heroin. PURPOSE: Although there are no Food and Drug Administration-approved medications to treat individuals with stimulant use disorders, a review of available studies suggests a few promising medications that may be helpful for patients in early recovery from methamphetamine. OUTCOME: Some individuals are more likely to respond to medications such as long-acting naltrexone, bupropion, and mirtazapine, who have light-to-moderate use of methamphetamine. Naloxone kits should be considered for all patients who are actively using stimulants because of a high potential of adulterated methamphetamine.

The Effect of Saffron on Depression among Recovered Consumers of Methamphetamine Living with HIV/AIDS.

BACKGROUND: From one hand, depression is one of the symptoms that occur after abstinence from methamphetamine. On the other people living with HIV/AIDS are in isolation due to the nature of their illness and depression is one of the most common mental health problems they experience. OBJECTIVES: This study was aimed at determining the effectiveness of saffron on reducing depression among recovered consumers of methamphetamine living with HIV/AIDS. METHODS: The design of this study was semi-experimental with pre-test, post-test and control (placebo) groups. The statistical population consisted of all recovered consumers of methamphetamine living with HIV/AIDS who were referred to the Positive Club. Fifty-seven (57) recovered consumers of methamphetamine, living with HIV/AIDS, were selected by convenience sampling method. They were randomly assigned to an experimental (saffron) group and a control (placebo) group. The experimental group received 30 ml of saffron per day for 8 weeks, whereas the control (placebo) group received placebo the same way. BDI-II was used in this study as a measurement instrument. ANCOVA models were used for statistical inference. RESULTS: The findings showed that saffron and its ingredients had been effective in reducing depression among this group (P < 0.05). CONCLUSION: In fact, saffron with its active ingredients (Crusin and Saffranal) by serotonin and dopamine secretion in the brain, help in reducing depression among recovered consumers of methamphetamine living with HIV/AIDS.

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.

Addiction and treatment experiences among active methamphetamine users recruited from a township community in Cape Town, South Africa: A mixed-methods study.

BACKGROUND: Since 2000, there has been a dramatic increase in methamphetamine use in South Africa, but little is known about the experiences of out-of-treatment users. This mixed-methods study describes the substance use histories, addiction symptoms, and treatment experiences of a community-recruited sample of methamphetamine users in Cape Town. METHODS: Using respondent driven sampling, 360 methamphetamine users (44% female) completed structured clinical interviews to assess substance abuse and treatment history and computerized surveys to assess drug-related risks. A sub-sample of 30 participants completed in-depth interviews to qualitatively explore experiences with methamphetamine use and drug treatment. RESULTS: Participants had used methamphetamine for an average of 7.06 years (SD=3.64). They reported using methamphetamine on an average of 23.49 of the past 30 days (SD=8.90); 60% used daily. The majority (90%) met ICD-10 criteria for dependence, and many reported severe social, financial, and legal consequences. While only 10% had ever received drug treatment, 90% reported that they wanted treatment. In the qualitative interviews, participants reported multiple barriers to treatment, including beliefs that treatment is ineffective and relapse is inevitable in their social context. They also identified important motivators, including desires to be drug free and improve family functioning. CONCLUSION: This study yields valuable information to more effectively respond to emerging methamphetamine epidemics in South Africa and other low- and middle-income countries. Interventions to increase uptake of evidence-based services must actively seek out drug users and build motivation for treatment, and offer continuing care services to prevent relapse. Community education campaigns are also needed.

Short-term cessation of sex work and injection drug use: evidence from a recurrent event survival analysis.

OBJECTIVE: This study quantitatively examined the prevalence and correlates of short-term sex work cessation among female sex workers who inject drugs (FSW-IDUs) and determined whether injection drug use was independently associated with cessation. METHODS: We used data from FSW-IDUs (n=467) enrolled into an intervention designed to increase condom use and decrease sharing of injection equipment but was not designed to promote sex work cessation. We applied a survival analysis that accounted for quit-re-entry patterns of sex work over 1-year stratified by city, Tijuana and Ciudad Juarez, Mexico. RESULTS: Overall, 55% of participants stopped sex work at least once during follow-up. Controlling for other characteristics and intervention assignment, injection drug use was inversely associated with short-term sex work cessation in both cities. In Ciudad Juarez, women receiving drug treatment during follow-up had a 2-fold increase in the hazard of stopping sex work. In both cities, income from sources other than sex work, police interactions and healthcare access were independently and significantly associated with shorter-term cessation. CONCLUSIONS: Short-term sex work cessation was significantly affected by injection drug use. Expanded drug treatment and counseling coupled with supportive services such as relapse prevention, job training, and provision of alternate employment opportunities may promote longer-term cessation among women motivated to leave the sex industry.

Event-level relationship between methamphetamine use significantly associated with non-adherence to pharmacologic trial medications in event-level analyses.

BACKGROUND: Methamphetamine use has been previously associated with poor medication adherence, but, to date, there have been no studies that have conducted event-level analyses on correlates of medication adherence in studies of pharmacologic agents for methamphetamine dependence. METHODS: We pooled data from two previous, randomized controlled trials (using bupropion and mirtazapine, respectively) for methamphetamine dependence and used a mixed effects logistic model to examine correlates of daily opening of the medication event monitoring system (MEMS) cap as a repeated measure. We explored whether periods of observed methamphetamine use via urine testing were associated with study medication adherence based on MEMS cap openings. RESULTS: We found a significant negative association between methamphetamine-urine positivity and event-level study medication adherence as measured by MEMS cap openings (AOR: 0.69; 95% CI: 0.49-0.98). In addition, age (AOR: 1.07; 95% CI: 1.02-1.11) and depressive symptoms (AOR: 0.78; 95% CI: 0.64-0.90) were significantly associated with adherence. Finally, participants were more likely to open their study medication bottles on days when they presented for in-person urine testing. CONCLUSIONS: Our event-level analysis shows that methamphetamine use can be associated with reduced medication adherence as measured by MEMS cap openings in pharmacologic trials, which corroborates prior research. These findings may suggest that medication adherence support in pharmacologic trials among methamphetamine users may be needed to improve study compliance and could be targeted towards periods of time when there are more likely to not open their study medication pill bottles.

Characterizing longitudinal health state transitions among heroin, cocaine, and methamphetamine users.

AIMS: Characterize longitudinal patterns of drug use careers and identify determinants of drug use frequency across cohorts of primary heroin, methamphetamine (MA) and cocaine users. DESIGN: Pooled analysis of prospective cohort studies. SETTINGS: Illicit drug users recruited from community, criminal justice and drug treatment settings in California, USA. PARTICIPANTS: We used longitudinal data on from five observational cohort studies featuring primary users of heroin (N=629), cocaine (N=694) and methamphetamine (N=474). The mean duration of follow-up was 20.9 years. MEASUREMENTS: Monthly longitudinal data was arranged according to five health states (incarceration, drug treatment, abstinence, non-daily and daily use). We fitted proportional hazards (PH) frailty models to determine independent differences in successive episode durations. We then executed multi-state Markov (MSM) models to estimate probabilities of transitioning between health states, and the determinants of these transitions. FINDINGS: Across primary drug use types, PH frailty models demonstrated durations of daily use diminished in successive episodes over time. MSM models revealed primary stimulant users had more erratic longitudinal patterns of drug use, transitioning more rapidly between periods of treatment, abstinence, non-daily and daily use. MA users exhibited relatively longer durations of high-frequency use. Criminal engagement had a destabilizing effect on health state durations across drug types. Longer incarceration histories were associated with delayed transitions toward cessation. CONCLUSIONS: PH frailty and MSM modeling techniques provided complementary information on longitudinal patterns of drug abuse. This information can inform clinical practice and policy, and otherwise be used in health economic simulation models, designed to inform resource allocation decisions.

Clinical features of methamphetamine-induced paranoia and preliminary genetic association with DBH-1021C→T in a Thai treatment cohort.

AIMS: To explore the clinical features of methamphetamine-induced paranoia (MIP) and associations between MIP and a genetic polymorphism in dopamine ß-hydroxylase (DBH-1021C→T). DESIGN: Retrospective analysis of clinical presentation and genetic association by χ(2) test and logistic regression analysis. SETTING: A Thai substance abuse treatment center. PARTICIPANTS: A total of 727 methamphetamine-dependent (MD) individuals. MEASUREMENTS: Clinical: Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) and the Methamphetamine Experience Questionnaire (MEQ). Genetic: DBH-1021C→T. FINDINGS: Forty per cent of individuals (289 of 727; 39.8%) with MD had MIP. Within-binge latency to MIP onset occurred more rapidly in the most recent compared with initial MIP episode (P = 0.02), despite unchanging intake (P = 0.89). Individuals with MIP were significantly less likely to carry lower (TT/CT) compared with higher (CC) activity genotypes (34.3 versus 43.3%; χ(2) 1 = 5, P = 0.03). DBH effects were confirmed [odds ratio (OR) = 0.7, P = 0.04] after controlling for associated clinical variables (MD severity, OR = 3.4, P < 0.001; antisocial personality disorder, OR = 2.2, P < 0.001; alcohol dependence, OR = 1.4, P = 0.05; and nicotine dependence, OR = 1.4, P = 0.06). TT/CT carriers were more likely to initiate cigarette smoking (OR = 3.9, P = 0.003) and probably less likely to be dependent on alcohol (OR = 0.6, P = 0.05). CONCLUSIONS: Among methamphetamine-dependent individuals, paranoia appears to occur increasingly rapidly in the course of a session of methamphetamine use. Severity of methamphetamine dependence and antisocial personality disorder predicts methamphetamine-induced paranoia. The genetic polymorphism in dopamine ß-hydroxylase is associated with methamphetamine-induced paranoia and influences smoking initiation.

Relationship of age to impulsivity and decision making: a baseline secondary analysis of a behavioral treatment study in stimulant use disorders.

Because stimulant use disorders remain prevalent across the lifespan, cognition is an important area of clinical care and research focus among aging adults with stimulant use disorders. This secondary analysis of a National Institute on Drug Abuse Clinical Trials Network study suggests that decision making, verbal learning/memory, executive function, and set shifting are important cognitive domains to screen clinically and treat in aging adults with stimulant use disorders. Some suggestions are made on how clinical treatment providers can practically use these results. An important direction for future research is the development of cognitively remediating treatments for impaired cognitive domains in aging adults with stimulant use disorders.

Pilot randomized trial of bupropion for adolescent methamphetamine abuse/dependence.

PURPOSE: To perform a pilot clinical trial of bupropion for methamphetamine abuse/dependence among adolescents. METHODS: Nineteen adolescents with methamphetamine abuse (n = 2) or dependence (n = 17) were randomly assigned to bupropion SR 150 mg twice daily or placebo for 8 weeks with outpatient substance abuse counseling. RESULTS: Bupropion was well-tolerated except for one female in the bupropion group who was hospitalized for suicidal ideation during a methamphetamine relapse. Adolescents receiving bupropion and females provided significantly fewer methamphetamine-free urine tests compared to participants receiving placebo (p = .043) and males (p = .005) respectively. CONCLUSIONS: Results do not support the feasibility of additional trials of bupropion for adolescent methamphetamine abuse/dependence. Future studies should investigate the influence of gender on adolescent methamphetamine abuse and treatment outcomes.

Methamphetamine use parameters do not predict neuropsychological impairment in currently abstinent dependent adults.

Methamphetamine (meth) abuse is increasingly of public health concern and has been associated with neurocognitive dysfunction. Some previous studies have been hampered by background differences between meth users and comparison subjects, as well as unknown HIV and hepatitis C (HCV) status, which can also affect brain functioning. We compared the neurocognitive functioning of 54 meth dependent (METH+) study participants who had been abstinent for an average of 129 days, to that of 46 demographically comparable control subjects (METH-) with similar level of education and reading ability. All participants were free of HIV and HCV infection. The METH+ group exhibited higher rates of neuropsychological impairment in most areas tested. Among meth users, neuropsychologically normal (n=32) and impaired (n=22) subjects did not differ with respect to self-reported age at first use, total years of use, route of consumption, or length of abstinence. Those with motor impairment had significantly greater meth use in the past year, but impairment in cognitive domains was unrelated to meth exposure. The apparent lack of correspondence between substance use parameters and cognitive impairment suggests the need for further study of individual differences in vulnerability to the neurotoxic effects of methamphetamine.

Predicting adherence to treatment for methamphetamine dependence from neuropsychological and drug use variables.

Although some individuals who abuse methamphetamine have considerable cognitive deficits, no prior studies have examined whether neurocognitive functioning is associated with outcome of treatment for methamphetamine dependence. In an outpatient clinical trial of bupropion combined with cognitive behavioral therapy and contingency management (Shoptaw, S., Heinzerling, K.G., Rotheram-Fuller, E., Steward, T., Wang, J., Swanson, A.N., De La Garza, R., Newton, T., Ling, W., 2008. Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence. Drug Alcohol Depend 96, 222-232.), 60 methamphetamine-dependent adults completed three tests of reaction time and working memory at baseline. Other variables that were collected at baseline included measures of drug use, mood/psychiatric functioning, employment, social context, legal status, and medical status. We evaluated the relative predictive value of all baseline measures for treatment outcome using Classification and Regression Trees (CART; Breiman, L., Friedman, J.H., Olshen, R.A., Stone, C.J., 1984. Classification and Regression Trees. Wadsworth, Belmont, CA.), a nonparametric statistical technique that produces easily interpretable decision rules for classifying subjects that are particularly useful in clinical settings. Outcome measures were whether or not a participant completed the trial and whether or not most urine tests showed abstinence from methamphetamine abuse. Urine-verified methamphetamine abuse at the beginning of the study was the strongest predictor of treatment outcome; two psychosocial measures (e.g., nicotine dependence and Global Assessment of Functioning) also offered some predictive value. A few reaction time and working memory variables were related to treatment outcome, but these cognitive measures did not significantly aid prediction after adjusting for methamphetamine usage at the beginning of the study. On the basis of these findings, we recommend that research groups seeking to identify new predictors of treatment outcome compare the predictors to methamphetamine usage variables to assure that unique predictive power is attained.

Evaluating and training substance abuse counselors: a pilot study assessing standardized patients as authentic clients.

Clinician training and supervision are needed to transfer evidence-based practices to community-based treatment organizations. Standardized patients (SPs) are used for clinician training and evaluating. However, to be effective for substance abuse counselors, SPs must realistically portray substance abuse treatment clients. The current study assessed authenticity of SPs as substance abuse treatment clients. Twenty-one substance abuse counselors interviewed SP(s) with differing profiles. Counselors provided quantitative and qualitative ratings of SP authenticity. Counselor responses to the study procedures were analyzed as well. Quantitative results include high-authenticity ratings for the SPs but counselors' subjective responses varied. Counselor's rated the experience of participating in the study positively and provided constructive comments for future applications of this methodology. Results support future work on SPs as teaching and evaluation tools in substance abuse counseling. Findings also illustrate the need to refine definitions of authenticity for SPs as substance abuse clients.

Factors associated with incarceration and incident human immunodeficiency virus (HIV) infection among injection drug users participating in an HIV vaccine trial in Bangkok, Thailand, 1999-2003.

AIMS: To determine if incarceration was associated with human immunodeficiency virus (HIV) infection and identify risk factors for incarceration among injection drug users (IDUs) participating in an HIV vaccine trial in Bangkok. DESIGN: The AIDSVAX B/E HIV vaccine trial was a randomized, double-blind, placebo-controlled study. A proportional hazards model was used to evaluate demographic characteristics, risk behavior and incarceration as predictors of HIV infection and generalized estimation equation logistic regression analysis to investigate demographic characteristics and risk behaviors for predictors of incarceration. SETTING: The trial was conducted in Bangkok Metropolitan Administration drug-treatment clinics, 1999-2003. PARTICIPANTS: A total of 2546 HIV-uninfected IDUs enrolled in the trial. MEASUREMENTS: HIV testing was performed and an interviewer-administered questionnaire was used to assess risk behavior and incarceration at baseline and every 6 months for a total of 36 months. FINDINGS: HIV incidence was 3.4 per 100 person-years [95% confidence interval (CI), 3.0-3.9] and did not differ among vaccine and placebo recipients. In multivariable analysis, being in jail (P < 0.04), injecting (P < 0.0001), injecting daily (P < 0.0001) and sharing needles (P = 0.02) were associated with HIV infection and methadone maintenance was protective (P = 0.0006). Predictors of incarceration in multivariable analysis included: male sex (P = 0.04), younger age (P < 0.0001), less education (P = 0.001) and being in jail (P < 0.0001) or prison (P < 0.0001) before enrollment. CONCLUSIONS: Among IDUs in the AIDSVAX B/E trial, incarceration in jail was associated with incident HIV infection. IDUs in Thailand remain at high risk of HIV infection and additional prevention tools are needed urgently. HIV prevention services, including methadone, should be made available to IDUs.