Age and sex effects levels of choline compounds in the anterior cingulate cortex of adolescent methamphetamine users

Background

Methamphetamine can be neurotoxic to the adult brain; however, many individuals first use methamphetamine during adolescence, and the drug's impact on this period of brain development is unknown. Therefore, we evaluated young methamphetamine users for possible abnormalities in brain metabolite concentrations.

Methods

Anterior cingulate cortex (ACC), frontal white matter (FWM), basal ganglia, and thalamus were studied with localized proton magnetic resonance spectroscopy in 54 periadolescent (ages 13-23 years) methamphetamine users and 53 comparison subjects. The concentrations of major brain metabolites and their associations with age, sex and cognition were assessed.

Results

FWM total-creatine correlated with age in methamphetamine-using males and comparison females, but not comparison males or methamphetamine-using females, leading to a drug by sex by age interaction (p = 0.003) and ACC choline-containing compounds (CHO) correlated with age only in comparison males leading to a drug by sex by age interaction (p = 0.03). Higher ACC CHO was associated with faster performance on the Stroop Interference task in the control males. Male methamphetamine users had slowest performance on the Stroop Interference task and did not show age-appropriate levels of ACC CHO.

Conclusions

The altered age-appropriate levels of ACC CHO and poorer executive function in male methamphetamine users suggest methamphetamine abuse may interfere with brain maturation. These periadolescents did not have the abnormal neuronal markers previously reported in adult methamphetamine users, suggesting that neuronal abnormalities may be the result of long-term use or interference in normal cortical maturation, emphasizing the need for early intervention for young methamphetamine users.     

Use of gelatine capsules for application of methamphetamine: a new harm reduction approach

Background

In order to reduce injecting drug use, low-threshold facilities in the Czech Republic have started to distribute empty gelatine capsules as an oral alternative of drug application for those injecting methamphetamine. This report reviews implementation of this intervention and its possible benefits and limitations.

Methods

Between December 2008 and January 2009, 109 low-threshold facilities were asked to complete a questionnaire about the capsule programmes. Two focus groups were conducted, one with professionals involved in distribution and one with peer outreach workers who were interviewed on their experience of using the capsules.

Results

A total of 50 facilities (46%) responded to the questionnaire; 16 (32%) distributed the capsules regularly and 19 (38%) were planning to introduce this practice. The main target groups were injecting users of methamphetamine whose veins had been damaged, and methamphetamine users wishing to reduce injecting. The advantages of capsules, as perceived by service staff and peer outreach workers, were their easy use and the satisfactory effect of the oral application; health risks related to the oral use of methamphetamine were considered drawbacks.

Conclusion

Capsule distribution is a promising harm reduction approach for injectors of methamphetamine or other stimulants; nonetheless its benefits and limitations should be further analysed in an in-depth longitudinal study.     

Physiological and subjective effects of acute intranasal methamphetamine during atomoxetine maintenance

Rationale

Methamphetamine abuse and dependence are significant public-health concerns. Behavioral therapies are effective for reducing methamphetamine use. However, many patients enrolled in behavioral therapies are unable to achieve significant periods of abstinence suggesting other strategies like pharmacotherapy are needed.

Objectives

This experiment determined the physiological and subjective effects of acutely administered intranasal methamphetamine during atomoxetine maintenance in seven non-treatment seeking stimulant-dependent participants. Atomoxetine was chosen for study because it blocks reuptake at the norepinephrine transporter and increases extracellular dopamine levels in the prefrontal cortex. In this way, atomoxetine might function as an agonist replacement therapy for stimulant-dependent patients.

Methods

After at least 7 days of maintenance on atomoxetine (0 and 80 mg/day), participants were administered ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) across two experimental sessions. Intranasal methamphetamine doses were separated by 90 min.

Results

Intranasal methamphetamine produced prototypical physiological and subjective effects (e.g., increased heart rate, blood pressure, temperature and subjective ratings of Good Effects). Atomoxetine maintenance augmented the heart rate-increasing effects of methamphetamine, but attenuated the pressor effects. The subjective effects of intranasal methamphetamine were similar during atomoxetine and placebo maintenance.

Conclusions

These results suggest that methamphetamine can be safely administered to participants maintained on atomoxetine, but whether it might be an effective pharmacotherapy for methamphetamine dependence remains to be determined.     

Use of anabolic androgenic steroids in substance abusers arrested for crime

Background

Use of anabolic androgenic steroids (AASs) has been associated with both violent crime and the use of illicit drugs. The scientific literature on polysubstance abuse as a confounder for AAS-related violence is sparse and ambiguous. With the intent of further investigating this issue, we have gathered data concerning drug abuse and AAS experience among substance abusers who have been arrested for a variety of crimes.

Methods

Data were collected from structured interviews with substance abusers (n = 3597) apprehended at two remand prisons in Sweden from 2002 through 2008. Analyses concerned type of criminal act, primary drug used during the past year, and experience of AAS use.

Results

Those stating AAS experience (n = 924, 20 women and 904 men) were more often apprehended for violent crimes (OR = 1.65). This association remained significant after controlling for age and sex (OR = 1.28). AAS users and non-users claimed similar primary substances of use during the past year, with the exception of benzodiazepine use, which was more common in the AAS group (OR = 2.30), although this did not affect the frequency of violent crime. Among AAS-experienced participants, there was no difference in violent crime incidence between current users and former users.

Conclusions

Study results suggest that AASs do not function as a proximal trigger for violence but still involve an increased risk for violence in users of illicit drugs. These findings also suggest that AAS use is highly overrepresented in women who commit crimes.     

The relationship between social network factors, HIV, and Hepatitis C among injection drug users in Chennai, India

Objective

The purpose of this study was to examine whether social network factors predict HIV and Hepatitis C (HCV) serostatus after controlling for individual-level factors at baseline among a cohort of male injection drug users in Chennai, India.

Methods

The sample, which was recruited through street outreach, consists of 1078 males who reported having injected drugs in the last 6 months.

Results

The participants reported 3936 social support and risk network members. HIV and HCV positive serostatus were negatively associated with network member providing emotional support, and positively associated with network member providing material support. In addition, HCV positivity was associated with network member being an active drug user known for more than 10 years and network member being male kin networks, even after adjusting for individual demographic factors and risk behaviors.

Conclusions

These findings suggest that social network factors are significantly linked to HIV and HCV status among IDUs in Southern India and highlight the mixed effects of social capital on health. Future HIV/HCV prevention efforts should incorporate IDU peers to alter drug network injection risk norms. For drug users who have minimal network support, support groups and other informal and formal support mechanisms may be need to help them with health care and psychological support needs for dealing with HIV/HCV.     

Malnutrition in a population of HIV-positive and HIV-negative drug users living in Chennai, South India

Background

Malnutrition is a strong predictor of poor outcomes in people living with HIV (PLHIV). Drug users are at increased risk of malnutrition regardless of whether or not they are infected with HIV. Little data exists on the nutritional status of drug users (with or without HIV infection) in India.

Methods

We describe and compare the nutrition and metabolic status of 107 HIV-positive and 193 HIV-negative male clients of a community-based drop-in center for injection drug users in Chennai, India. Measures of nutrition and metabolic status include body composition, dietary intake, food insecurity, and serum lipid levels.

Results

We found poor overall nutritional status in both the HIV-positive and HIV-negative clients, with HIV-positive men faring worse on some parameters. Both groups had extremely low percent body fat, but levels in HIV-positive participants were significantly lower (6.5% versus 7.9%, p = .01). HIV-positive men also had significantly lower total caloric and fat intakes compared to HIV-negative men. A considerable proportion (70%) of both HIV-positive and HIV-negative drug users were food insecure. HDL cholesterol levels were significantly lower and below normal range in the HIV-positive compared to HIV-negative men.

Conclusions

The high levels of food insecurity and poor nutritional status in this population, regardless of HIV status, indicates critical need for intervention. Improving nutritional status in those who are infected with HIV prior to initiation of antiretroviral treatment may help patients to reap the full benefits of therapy.     

Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance

Background

Medications development for methamphetamine dependence is ongoing, but no widely accepted, effective pharmacotherapy has been identified. Previous studies have demonstrated neurobiological perturbations to central GABA_A activity following chronic stimulant use, and that positive modulation of GABA_A receptors attenuates the neurochemical and behavioral response to stimulant drugs such as methamphetamine. Therefore, GABA_A modulators could be useful as pharmacotherapies for stimulant-use disorders.

Methods

This study tested the hypothesis that intranasal methamphetamine would be safe and well tolerated during maintenance on extended-release alprazolam (XR), and that the effects of methamphetamine would be attenuated. Eight non-treatment-seeking, stimulant-dependent individuals completed an inpatient experiment in which ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) were administered after four days of alprazolam XR maintenance (0 and 1 mg/day).

Results

Intranasal methamphetamine produced prototypical effects (e.g., increased positive subjective ratings and elevated cardiovascular signs). The combination of intranasal methamphetamine and alprazolam XR was safe and well tolerated. Alprazolam XR produced small, but orderly, reductions in some of the subjective effects of methamphetamine, and performance impairment.

Conclusions

The present results demonstrate that methamphetamine use during alprazolam XR treatment would not pose a significant safety risk. Given the potential of GABA_A positive modulators to manage certain aspects of stimulant abuse and dependence (i.e., drug-induced seizures, anxiety and stress), but the relatively small impact on the acute abuse-related effects of methamphetamine observed here, additional research with GABA_A positive modulators is warranted, but should consider their use as an adjunct component of combination behavioral and/or drug treatment.     

Estimated effect of prenatal cocaine exposure on examiner-rated behavior at age 7 years

Prenatal cocaine exposure has been linked to increased child behavior difficulties in some studies but not others.

Objective

The primary aim was to estimate the relationship between in utero cocaine exposure and child behavioral functioning at age 7 years with ratings made by blinded examiners during a structured testing session. A second aim was to examine whether caregiver drug use and psychological problems might mediate suspected relationships between prenatal cocaine exposure and aspects of examiner-rated behavior.

Methods

407 children (212 cocaine-exposed, 195 non-exposed) participating in the longitudinal Miami Prenatal Cocaine Study (MPCS) were rated with regard to their behavior during a neuropsychological assessment conducted at age 7 years. Raters were trained research psychometricians blinded to drug exposure status. Individual behavioral items were summarized and the cocaine-behavior relationship was estimated within the context of latent variable modeling, using Mplus software.

Results

Two latent variables, Behavioral Regulation and Sociability, were derived via exploratory latent structure analysis with promax rotation. Prenatal cocaine exposure, statistically controlling for child sex, test age, and prenatal exposure to alcohol, tobacco, and marijuana, was associated with Behavioral Regulation (estimated slope ß = − 0.25; 95% CI = − 0.48, − 0.02; p = 0.04) but not Sociability (estimated slope ß = − 0.03; 95% CI = − 0.26, 0.20; p = 0.79). Neither postnatal drug use by caregivers nor the severity of their psychological problems at age 5 follow-up predicted levels of child Behavioral Regulation or Sociability at age 7 years (p > 0.10).

Conclusions

Examiner ratings of child behavior at age 7 revealed less optimal behavioral regulation for prenatally cocaine-exposed compared to non-exposed children, in contrast with what had been previously found from parent-report data. This evidence highlights the potential value of trained observers in assessing behavioral outcomes of children exposed in utero to drugs and other toxicants.     

Serotonin 6 receptor gene is associated with methamphetamine-induced psychosis in a Japanese population

Background

Altered serotonergic neural transmission is hypothesized to be a susceptibility factor for psychotic disorders such as schizophrenia. The serotonin 6 (5-HT6) receptor is therapeutically targeted by several second generation antipsychotics, such as clozapine and olanzapine, and d-amphetamine-induced hyperactivity in rats is corrected with the use of a selective 5-HT6 receptor antagonist. In addition, the disrupted prepulse inhibition induced by d-amphetamine or phencyclidine was restored by 5-HT6 receptor antagonist in an animal study using rats. These animal models were considered to reflect the positive symptoms of schizophrenia, and the above evidence suggests that altered 5-HT6 receptors are involved in the pathophysiology of psychotic disorders. The symptoms of methamphetamine (METH)-induced psychosis are similar to those of paranoid type schizophrenia. Therefore, we conducted an analysis of the association of the 5-HT6 gene (HTR6) with METH-induced psychosis.

Method

Using five tagging SNPs (rs6693503, rs1805054, rs4912138, rs3790757 and rs9659997), we conducted a genetic association analysis of case-control samples (197 METH-induced psychosis patients and 337 controls) in the Japanese population. The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients.

Results

rs6693503 was associated with METH-induced psychosis patients in the allele/genotype-wise analysis. Moreover, this association remained significant after Bonferroni correction. In the haplotype-wise analysis, we detected an association between two markers (rs6693503 and rs1805054) and three markers (rs6693503, rs1805054 and rs4912138) in HTR6 and METH-induced psychosis patients, respectively.

Conclusion

HTR6 may play an important role in the pathophysiology of METH-induced psychosis in the Japanese population.     

A web-based survey on mephedrone

Background

This study sought to collect information on the former legal-high ‘mephedrone’ using a web-based survey targeted at mephedrone users.

Methods

The survey was advertised on websites frequented by drug users. Individuals were invited to complete the survey if they had taken mephedrone on at least one occasion in the past.

Results

One thousand and six completed forms were received from declared users, making this the largest survey on mephedrone to date.

Conclusion

Results showed that mephedrone users consider its effects to compare best with those of MDMA, and while MDMA was considered marginally safer and its effects more pleasurable, mephedrone's appeal lay in its availability, low price and reliable purity.     

The relationship between injection and noninjection drug use and HIV disease progression

Background

Injection drug use is associated with poor HIV outcomes even among persons receiving highly active antiretroviral therapy (HAART), but there are limited data on the relationship between noninjection drug use and HIV disease progression.

Methods

We conducted an observational study of HIV-infected persons entering care between January 1, 1999, and December 31, 2004, with follow-up through December 31, 2005.

Results

There were 1,712 persons in the study cohort: 262 with a history of injection drug use, 785 with a history of noninjection drug use, and 665 with no history of drug use; 56% were White, and 24% were females. Median follow-up was 2.1 years, 33% had HAART prior to first visit, 40% initiated first HAART during the study period, and 306 (17.9%) had an AIDS-defining event or died. Adjusting for gender, age, race, prior antiretroviral use, CD4 cell count, and HIV-1 RNA, patients with a history of injection drug use were more likely to advance to AIDS or death than nonusers (adjusted hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.43-2.70, p < .01). There was no statistically significant difference of disease progression between noninjection drug users and nonusers (HR = 1.19, 95% CI = 0.92-1.56, p = .19). An analysis among the subgroup who initiated their first HAART during the study period (n = 687) showed a similar pattern (injection drug users: HR = 1.83, 95% CI = 1.09-3.06, p = .02; noninjection drug users: HR = 1.21, 95% CI = 0.81-1.80, p = .35). Seventy-four patients had active injection drug use during the study period, 768 active noninjection drug use, and 870 no substance use. Analyses based on active drug use during the study period did not substantially differ from those based on history of drug use.

Conclusions

This study shows no relationship between noninjection drug use and HIV disease progression. This study is limited by using history of drug use and combining different types of drugs. Further studies ascertaining specific type and extent of noninjection drug use prospectively, and with longer follow-up, are needed.     

Chronic hepatitis C virus infection and increases in viral load in a prospective cohort of young, HIV-uninfected injection drug users

Background

Chronic hepatitis C (HCV) infection, defined as persistent RNA (viral load) for at least 6 months, accounts for up to 50% of all cirrhosis, end-stage liver disease and liver cancer cases. Moreover, elevated HCV viral load is consistently associated with high infectivity and poor therapy response. This study aims to identify modifiable behavioral correlates both chronic HCV infection and increases in viral load over time among injection drug users (IDUs).

Methods

Cross-sectional and longitudinal analyses were performed using self-interview and serological data from a prospective cohort study (2002-2006) among young (age 18-35), HIV-negative, HCV therapy-naïve IDUs (n = 113) from metropolitan Chicago, Illinois, USA.

Results

After adjustment for age, gender and race/ethnicity, using drugs measured or mixed in someone else's syringe (odds ratio = 2.7, 95% confidence interval: 1.1, 6.7) was associated with chronic (n = 75, 66%) versus resolved (n = 38, 34%) HCV infection status. Among chronically-infected IDUs, injecting with a new, sterile syringe infrequently (<1/2 half the time when injecting) compared to frequently (1/2 the time or more when injecting) was associated with increases in viral load over time after adjusting for age, gender, race/ethnicity and time effects.

Conclusions

Reductions in risky injection-related practices among young IDUs may ameliorate both the burden of chronic HCV infection-related liver disease and elevated viral load-related poor treatment response.     

Studying up harm reduction policy: the office as an assemblage

Background

By recounting the making of the office that contributed to the implementation of the harm reduction policy in Taiwan, this paper aims to answer two questions: Who and what assembled to make this policy possible? Which conceptual tool works best to understand what this policy-making was all about?

Methods

The research was designed as a multi-sited qualitative study whose materials were collected through archival research, in-depth interviews, and direct field observation. The data were analysed on the basis of the constructivist version of grounded theory.

Result

Formulating the office as an assemblage with heterogeneous components and shifting territories, the present work endeavours to show how it was constituted by way of guanxi, or webs of social relationship that blur the boundary between the private and the public, the governmental and the social.

Conclusion

This “studying up” approach is hoped to elicit more research on the office in which harm reduction policies are made into the backdrop of drug users on the street.     

Evaluation of the hydrolytic activity of a long-acting mutant bacterial cocaine in the presence of commonly co-administered drugs

Background

Cocaine toxicity is a prevalent problem in the Unites States for which there is currently no FDA-approved pharmacotherapy. We have developed a bacterial cocaine esterase (CocE) towards this indication. A thermostabilized mutant of CocE (DM-CocE) retains the hydrolytic activity of the wild-type esterase, rapidly hydrolyzing cocaine into the inactive metabolites ecgonine methyl ester and benzoic acid, and can prevent cocaine toxicities in rodent and non-human primate models. To advance DM-CocE towards clinical use, we examine here how the hydrolytic activity of DM-CocE is altered by some drugs commonly co-administered with cocaine.

Methods

We employed a spectrophotometric cocaine hydrolysis assay to evaluate whether pharmacologically relevant doses of alcohol, nicotine, morphine, phencyclidine, ketamine, methamphetamine, naltrexone, naloxone, or midazolam would alter the Michaelis-Menten kinetics of DM-CocE for cocaine. Mass spectrometry was used to evaluate interaction with diazepam as this drug interferes with the absorbance spectra of cocaine critical for the spectrophotometric assay.

Results

Alcohol, nicotine, morphine, phencyclidine, ketamine, methamphetamine, naltrexone, naloxone, and midazolam did not alter cocaine hydrolysis by DM-CocE. However, diazepam significantly slowed DM-CocE cocaine hydrolysis at very high concentrations, most likely through interaction of the phenyl ring of the benzodiazepine with the active site of DM-CocE.

Conclusions

DM-CocE does not display significant drug interactions, with the exception of diazepam, which may warrant further study as DM-CocE progresses towards a clinically used pharmacotherapy for cocaine toxicity. Alternate benzodiazepines, e.g., midazolam could be used to avoid this potential interaction.     

Psychosocial treatments for cocaine dependence: the role of depressive symptoms

Background

The association between cocaine use and depression has been frequently observed. However, less is known about the significance of depression in the treatment of cocaine use disorders. This study examined possible interrelations between drug use and depression severity among cocaine-dependent patients in psychosocial treatments for cocaine dependence.

Methods

Monthly assessed drug use and depression severity scores of N = 487 patients during 6-month psychosocial treatments for cocaine dependence were analyzed using hybrid latent growth models.

Results

Results indicated a moderate but statistically significant (z = 3.13, p < .01) influence of depression severity on increased drug use in the upcoming month, whereas drug use did not affect future depression severity.

Conclusions

Findings suggest that depression symptoms are an important predictor of drug use outcomes during psychosocial treatments for cocaine dependence and, hence, underline the importance of adequately addressing depression symptoms to improve treatment outcomes.     

BZP-party pills: a review of research on benzylpiperazine as a recreational drug

Background

BZP-party pills are yet another ‘designer drug’ which mimics the stimulant qualities of amphetamines and MDMA/Ecstasy. As legal markets for the substance have developed in the last decade (especially amongst young people) so has public and governmental concern.

Methods

This article provides a summary of the available international research on benzylpiperazine (BZP) and its popular use in the compound form known as ‘party pills’. Through performing an analysis of the available medical and social scientific literature, the review outlines current knowledge on the compound, the prevalence of usage of BZP-party pills, as well as the associated harms, risks and rationales for use of the drug.

Results

Despite moves towards legislative control of BZP-party pills, the evidence presented suggests limited social and health harms associated with the drug, although research on long term effects is a significant gap in the literature. It also remains inconclusive as to whether BZP-party pills act as a ‘gateway’ to illegal drugs or, conversely, play a role in harm reduction with illegal drug users turning to legal alternatives; there is some evidence for both positions.

Conclusion

With increasing controls of BZP-party pills, and with the increasing numbers of ‘legal highs’ and new designer drugs on the market, we conclude that new legal alternatives will continue to surface to replace the drug in the future. Considering a harm reduction approach to drug taking, it is suggested that policy makers consider the creation of a legal holding category which restricts and regulates the market in legal highs whilst the social and health harms associated with each drug can be thoroughly investigated.