Variations in the oral microbiome and metabolome of methamphetamine users.

Drug addiction can seriously damage human physical and mental health, while detoxification is a long and difficult process. Although studies have reported changes in the oral microbiome of methamphetamine (METH) users, the role that the microbiome plays in the process of drug addiction is still unknown. This study aims to explore the function of the microbiome based on analysis of the variations in the oral microbiome and metabolome of METH users. We performed the 16S rRNA sequencing analysis based on the oral saliva samples collected from 278 METH users and 105 healthy controls (CTL). In addition, the untargeted metabolomic profiling was conducted based on 220 samples. Compared to the CTL group, alpha diversity was reduced in the group of METH users and the relative abundances of Peptostreptococcus and Gemella were significantly increased, while the relative abundances of Campylobacter and Aggregatibacter were significantly decreased. Variations were also detected in oral metabolic pathways, including enhanced tryptophan metabolism, lysine biosynthesis, purine metabolism, and steroid biosynthesis. Conversely, the metabolic pathways of porphyrin metabolism, glutathione metabolism, and pentose phosphate were significantly reduced. It was speculated that four key microbial taxa, i.e., Peptostreptococcus, Gemella, Campylobacter, and Aggregatibacter, could be involved in the toxicity and addiction mechanisms of METH by affecting the above metabolic pathways. It was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders was gradually increased. Our study provides novel insights into exploring the toxic damage and addiction mechanisms underlying the METH addiction.IMPORTANCEIt was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders gradually increased. The prediction models based on oral microbiome and metabolome could effectively predict the methamphetamine (METH) smoking. Our study provides novel insights into the exploration of the molecular mechanisms regulating the toxic damage and addiction of METH as well as new ideas for early prevention and treatment strategies of METH addiction.

A rare case of renal infarction due to heroin and amphetamine abuse: case report.

BACKGROUND: Renal infarctions as a result of recreational drug use are rare and are commonly associated with cocaine use. Although amphetamines have a similar mechanism of action as cocaine, there are few reports linking them to ischemic events, and only one to renal infarction. Similarly, few reports link heroin use with infarcts, but never in the kidney. Although uncommon, several mechanisms have been implicated in heroin and amphetamine-induced infarction, including vasculopathy, vasculitis and the activation of the coagulation cascade. CASE PRESENTATION: 47-year-old female with a past medical history of non-intravenous heroin and amphetamine abuse, chronic obstructive pulmonary disease, hypertension, hyperlipidemia presented with right lower extremity swelling and rash, which was diagnosed as cellulitis and treated appropriately. Incidentally, the patient was found to have an acute kidney injury and further workup identified multiple renal infarcts in the right kidney. The patient had no past medical history of clotting disorders. Blood culture and urine cultures were sterile; autoimmune and hypercoagulable workup were negative. Urinalysis was unremarkable. Urine toxicology was only positive for opiates and amphetamines, which were thought to be the most likely cause of the renal infarct. Patient was lost to outpatient follow up due to noncompliance, but returned to the hospital for re-emergence of her cellulitis, during which no new infarcts were discovered, and the previous renal infarct had scarred over. CONCLUSION: There are very few reports of heroin and amphetamine-induced infarctions. This case report describes a rare but important complication of heroin/amphetamine abuse that could be easily overlooked.

Leukocyte telomere length is not shortened in methamphetamine dependence or methamphetamine-induced psychosis but is increased following traumatic events.

OBJECTIVE: This study aims to examine the effects of methamphetamine (MA) use and dependence and MA withdrawal symptoms on the telomere length and whether shortening of the latter is associated with MA-induced psychosis (MIP). METHODS: This study included 185 MA-abuse, 118 MA-dependent, and 67 MIP patients, diagnosed using DSM-IV criteria. The Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA) questionnaire was employed to collect MA-related data. MIP was confirmed using the Methamphetamine Experience Questionnaire (MEQ). The leukocyte telomere length was measured using real-time polymerase chain reaction measuring the Telomere/Single gene ratio (T/S ratio). Data were analysed using multivariate statistical analyses. RESULTS: There were no significant associations between the T/S ratio and severity of MA-use, MIP, and MA withdrawal symptoms. MIP was significantly predicted by alcohol dependence, antisocial personality disorder, and MA-use severity. There were significantly positive associations between the T/S ratio and previous traumatic and life-threatening events. The T/S ratio was not affected by alcohol and nicotine dependence. Alcohol and nicotine dependence, antisocial personality disorder, and severity of MA use increased risk of MA withdrawal symptoms. CONCLUSION: MIP and MA-use severity are not associated with leukocyte telomere length, but previous traumatic and life-threatening events are associated with increased telomere length.

Survival Probabilities and Predictors of Major Depressive Episode Incidence Among Individuals With Various Types of Substance Use Disorders.

Objective: This study aimed to estimate the survival probabilities related to the occurrence of major depressive episodes (MDEs) after the onset of substance use disorders (SUDs) using data from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III.Methods: The Alcohol Use Disorder and Associated Disabilities Interview Schedule-5 was used to diagnose SUD, and psychiatric diagnoses were based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Individuals with incidents of various SUDs with no prior history of MDEs (n = 5,987 with alcohol use disorder [AUD], 1,353 with cannabis use disorder [CUD], 351 with opioid use disorder [OUD], 827 with stimulant use disorder [STUD], and 5,363 with nicotine use disorder [NUD]) were included. The survival probabilities of these groups were compared to those of a control group without an SUD (n = 20,034). Outcome measures included the number of years from the age at SUD onset until MDE occurrence or the time of the interview.Results: The probabilities of experiencing MDEs after 1 year were 3.56%, 4.80%, 7.78%, 8.46%, and 5.31% for AUD, CUD, OUD, STUD, and NUD, respectively. The groups differed statistically significantly from each other and from the control group (P < .0001). Individuals with AUD and STUD, respectively, had a lower and higher probability of having an MDE compared to those with other SUDs. Young age, family history of depression, anxiety disorder presence, and failure to achieve full remission consistently predicted an MDE for all substances.Conclusions: The findings highlight that users of all studied substances have an increased probability of having an MDE over the lifespan.

The rising tide of methamphetamine use in elderly trauma patients.

BACKGROUND: Methamphetamine (METH) is associated with an elevated risk of injury and the outcomes in the elderly remain unclear. We analyzed METH's impact in elderly trauma patients. METHODS: Retrospective analysis (2009-2018) of trauma patients at a Level I trauma center. Elderly patients were defined as age ≥55. Substance use was identified by blood alcohol test and urine drug screen. Cox proportional hazard model was used to assess patient and injury characteristics with mortality. RESULTS: Of 15,770 patient encounters with substance use testing, 5278 (34%) were elderly. Elderly METH use quadrupled over time (2%-8%; p < 0.01). Elderly METH + patients were more likely to require surgical intervention (35% vs. 17%), mechanical ventilation (15% vs. 7%), and a longer hospitalization (6.5 vs. 3.6 days) compared with elderly substance negative. Multivariate analysis showed increasing age, ventilator use, and injury severity were associated with mortality (ps < 0.01); METH was not related to mortality. CONCLUSION: Substance use in elderly trauma patients increased significantly. METH use in elderly trauma patients is a risk factor for significantly greater resource utilization.

NUPR1- CHOP experssion, autophagosome formation and apoptosis in the postmortem striatum of chronic methamphetamine user.

Methamphetamine (Meth) is a neuro-stimulator substrate which might lead to neural cell death and the activation of several interconnected cellular pathways as well. However, the precise molecular mechanisms underlying Meth-induced neural cell death remained unclear yet. The current study aimed to assess the specific relationship between long-term Meth exposure and several endoplasmic reticulum stress, autophagy, and apoptosis associated markers including C/EBP homologous protein (CHOP), Tribbles homolog 3(Trib3), Nuclear protein 1(NUPR1), and Beclin-1 expression in postmortem human striatum. Therefore, the effects of long-term Meth exposure on autophagy and apoptosis in the striatum of postmortem users were evaluated and molecular, immunehistochemical, and histological examinations were performed on 10 control and 10 Meth-addicted brains. The level of CHOP, Trib3, NUPR1, and Beclin-1, Microtubule-associated proteins 1A/1B light chain 3B(LC3), Caspase 3, and Autophagy protein 5 (ATG5) were measured by using qPCR and immunohistochemistry. Stereological neural cell counting, Hematoxylin and Eosin, Nissl and Tunel staining were also performed. Based on our findings, the expression level of CHOP, Trib3, NUPR1, and Beclin-1 in the striatum of Meth group were significantly higher than the control group. Besides, the neuronal cell death was substantially increased in the striatum based on data obtained from the Tunel assay and the stereological analysis. Long-term presence of Meth in the brain can induce ER stress and overexpression of NUPR1 which is associated with the upregulation of CHOP, a pro-apoptotic transcription factor. Moreover, an increase in Trib3 expression is implicated in CHOP-dependent autophagic cell death during Meth-induced ER stress accompanied by an increase in neuronal cell death in the striatum of the postmortem human brains. Beclin 1 expression was also upregulated which may due to the activation of autophagic mechanisms upon prolonged Meth exposure.

Assessment of demand for methamphetamine and cigarettes among individuals with methamphetamine use disorder.

Methamphetamine (MA) is a highly addictive stimulant with recent upward trends in prevalence and associated public health problems. Drug demand, as assessed by hypothetical purchasing tasks, has been useful in addictions research and may help our understanding of the factors influencing MA use. However, no studies have assessed MA demand using current models of demand. The purpose of the current study was to assess demand for MA using a hypothetical drug purchasing task. Given high rates of cigarette smoking among MA users, it was of interest also to assess and compare demand for MA relative to cigarettes. Participants consisted of non-treatment-seeking volunteers with MA use disorder (N = 18), of whom 17 reported daily smoking. Results showed the exponentiated demand model provided a good fit to consumption data. Results from Bayesian generalized linear modeling demonstrated multiple positive relationships (posterior probability ≥75%) between self-reported drug use (days MA used in the past 30 days, cigarettes smoked per day) and indices of demand for each drug (Qo, Omax, Pmax, and break point). Comparing MA to cigarettes, results from Bayesian generalized linear mixed modeling revealed greater abuse liability for MA compared to cigarettes (posterior probability ≥99%) based on α and essential value. Overall, the findings of the current study support the feasibility and validity of the exponentiated demand model for assessing demand for drugs among individuals with MA use disorder. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Impact of Childhood Emotional Abuse on Pain Interference Among People with Chronic Pain who Inject Drugs in Vancouver, Canada.

OBJECTIVE: High levels of chronic pain interference with daily activities are known to negatively impact quality of life. Although mental health conditions have been associated with pain interference and child abuse, research has been mixed regarding it acting as a mediator, with even less known among people who inject drugs. Therefore, we sought to explore childhood emotional abuse and pain interference among this population. METHODS: Data were derived from two prospective cohort studies of community-recruited people who inject drugs in Vancouver, Canada, between June 2014 and November 2016. We employed multivariable generalized estimating equations to examine the relationship between childhood emotional abuse and pain interference in the past six months. We also conducted a mediation analysis to examine whether mental health disorder diagnoses mediated this association. RESULTS: Among 822 eligible participants, 341 (41.5%) reported childhood emotional abuse. In a multivariable analysis, experiencing childhood emotional abuse remained independently associated with pain interference (adjusted odds ratio = 1.33, 95% confidence interval [CI] = 1.05-1.70) after adjusting for a range of confounders. Results from the mediation analysis yielded a statistically significant positive average causal mediation effect (ß = 0.01, 95% CI = 0.001-0.02). Approximately 12% of the effect was due to mediation. CONCLUSIONS: Our results demonstrate among people who inject drugs with chronic pain, those who experienced childhood emotional abuse were more likely to report pain interference, which was partially mediated by mental health disorder diagnosis history. These findings highlight the importance of incorporating screening and appropriate treatment for mental illness into chronic pain treatment.

Screening Of Pulmonary Hypertension in Methamphetamine Abusers (SOPHMA): rationale and design of a multicentre, cross-sectional study.

INTRODUCTION: Methamphetamine misuse is classified as a 'likely' risk factor for pulmonary arterial hypertension (PAH). Nevertheless, the actual prevalence of and a screening strategy for PAH in methamphetamine users have not been established. We plan to study the prevalence of PAH and identify its independent risk factors among methamphetamine users. METHODS AND ANALYSIS: The Screening Of Pulmonary Hypertension in Methamphetamine Abusers (SOPHMA) study will be a multicentre, cross-sectional screening study that will involve substance abuse clinics, hospitals and rehabilitation facilities in Hong Kong that cater to more than 20 methamphetamine users. A total of 400 patients who (1) are ≥18 years at enrolment; (2) report methamphetamine use in the last 2 years; (3) are diagnosed with methamphetamine use disorder; and (4) voluntarily agree to participate by providing written informed consent will be included. Patients will undergo standard echocardiography-based PAH screening procedures recommended for those with systemic sclerosis. Right heart catheterisation will be offered to participants with intermediate or high echocardiographic probability of PAH. For participants with a low echocardiographic probability of PAH, rescreening will be performed within 1 year. The primary measure will be the prevalence of PAH in methamphetamine users. The secondary measures will be the risk factors and a prediction model for PAH in methamphetamine users. ETHICS AND DISSEMINATION: The SOPHMA study has been approved by the institutional review board. The findings of this study will provide the necessary evidence to establish universal guidelines for screening of PAH in methamphetamine users. Our results will be disseminated through immediate feedback to study participants, press release to the general public, as well as presentation in medical conferences and publications in peer-reviewed journals to healthcare providers and academia worldwide.

Clinical and Socioeconomic Differences in Methamphetamine-Positive Burn Patients.

Previous research on burn patients who test positive for methamphetamines (meth) has yielded mixed results regarding whether meth-positive status leads to worse outcomes and longer hospitalizations. We hypothesized that meth-positive patients at our regional burn center would have worse outcomes. We reviewed burn admissions from January 2014 to December 2017 and compared total patients versus meth-positive, and matched meth-negative versus meth-positive for total BSA burn, length of stay (LOS), intensive care unit (ICU) days, days on ventilator, discharge status (lived/died), number of operating room (OR) visits, number of procedures, socioeconomic status, comorbidities, and discharge disposition. Of 1363 total patients, 264 (19.4%) were meth-positive on toxicology screen. We matched 193 meth-positive patients with meth-negative controls based on TBSA burn, age, and inhalation injury. In the total population comparison, meth-positive patients had larger burns (15.6% vs 12.2%; P = .004), longer LOS (17.8 vs 14.3 days; P = .041), and fewer operations/TBSA (0.12 vs 0.2; P = .04), and lower socioeconomic status. Meth-positive patients were less likely to be discharged to a skilled nursing facility, and more likely to leave against medical advice. In the matched patients, we found no significant differences in LOS or OR visits/TBSA burn. Meth-positive patients have lower socioeconomic status, larger burns, and longer LOS compared to the total burn population. Methamphetamine use, by itself, does not appear to change outcomes. Methamphetamine use leads to larger burns in a population with fewer resources than the general population.

Rates of Perioperative Complications Among Patients Undergoing Orthopedic Trauma Surgery Despite Having Positive Results for Methamphetamine.

The burden of psychosocial problems, including substance abuse, is high among trauma patients. Use of illicit substances is often noted during urine toxicology screening on admission and can delay surgery because of concerns for an interaction with anesthesia. Methamphetamine theoretically has potential to increase perioperative anesthetic risks. However, the authors are unaware of any studies documenting increased rates of cardiovascular complications in the perioperative period among orthopedic trauma patients. This study sought to determine the rate of cardiovascular complications in these patients. The authors reviewed the medical records of all patients between 2013 and 2018 who underwent orthopedic trauma surgery at two level I trauma centers in the setting of a methamphetamine-positive urine toxicology screening prior to surgery. Information on demographics, injury, type of surgical intervention, and incidence of perioperative cardiovascular and overall medical complications prior to discharge was recorded. Ninety-four patients were included in the study (mean age, 44 years; range, 16-78 years). Twenty-six (28%) patients had multiple injuries. Thirteen (14%) patients had debridement and/or provisional stabilization of an open or unstable fracture, 18 (19%) had treatment for an infection, and 63 (67%) had definitive fracture surgery. The overall rates of perioperative cardiovascular complications and perioperative medical complications were 2.1% and 3.2%, respectively. This study provides both a baseline understanding of the complication rate for methamphetamine-positive orthopedic trauma patients during general anesthesia and justification for larger multicenter studies to further investigate this topic. [Orthopedics. 2019; 42(4):192-196.].

Acute Methamphetamine-Induced Hepatic and Pancreatic Ischemia.

Methamphetamine is a central nervous system stimulant that induces arousal, a positive mood, cardiac stimulation, and an acute improvement in cognitive domains. Its illicit exploitation is rapidly growing in North America. Typically, extended use of the drug induces organ damage via vasoconstriction and subsequent ischemia. This case specifically discusses hepatic and pancreatic pathology resulting from methamphetamine overdose alongside an unusual discovery of globally necrotic von Meyenburg complexes.

Crisis under the radar: Illicit amphetamine use is reaching epidemic proportions and contributing to resource overutilization at a Level I trauma center.

INTRODUCTION: Trauma centers reported illicit amphetamine use in approximately 10% of trauma admissions in the previous decade. From experience at a trauma center located in a southwestern metropolis, our perception is that illicit amphetamine use is on the rise and that these patients utilize in-hospital resources beyond what would be expected for their injuries. The purposes of this study were to document the incidence of illicit amphetamine use among our trauma patients and to evaluate its impact on resource utilization. METHODS: We conducted a retrospective cohort study using 7 consecutive years of data (starting July 2010) from our institution's trauma registry. Toxicology screenings were used to categorize patients into one of three groups: illicit amphetamine, other drugs, or drug-free. Adjusted linear and logistic regression models were used to predict hospital cost, length of stay, intensive care unit admission, and ventilation between drug groups. Models were conducted with combined injury severity (Injury Severity Score [ISS]) and then repeated for ISS of less than 9, ISS 9 to 15, and ISS 16 or greater. RESULTS: Eight thousand five hundred eighty-nine patients were categorized into the following three toxicology groups: 1,255 (14.6%) illicit amphetamine, 2,214 (25.8%) other drugs, and 5,120 (59.6%) drug-free. Illicit amphetamine use increased threefold over the course of the study (from 7.85% to 25.0% of annual trauma admissions). Adjusted linear models demonstrated that illicit amphetamine among patients with ISS of less than 9 was associated with 4.6% increase in hospital cost (p = 0.019) and 7.4% increase in length of stay (p = 0.043). Logistic models revealed significantly increased odds of ventilation across all ISS groups and increased odds of intensive care unit admission when all ISS groups were combined (p = 0.001) and within the group with ISS of less than 9 (p = 0.002). CONCLUSIONS: Hospital resource utilization of amphetamine patients with minor injuries is significant. Trauma centers with similar epidemic growth in proportion of amphetamine patients face a potentially significant resource strain relative to other centers. LEVEL OF EVIDENCE: Prognostic/Epidemiological, level II; Therapeutic, level III.

Coronary sinus flow is reduced in methamphetamine abusers: a transthoracic echocardiographic study.

To compare the coronary sinus flow among healthy participants, methamphetamine abusers without chest pain and those with chest pain. One hundred and eight methamphetamine abusers: 53 ones without chest pain, 55 ones with chest pain, free of ascertained coronary artery disease, were enrolled in this study. A control group of 50 age-matched male healthy participants was studied for comparison. Standard 2D, flow and tissue Doppler echo with measurements of cardiac morphologic and functional indicators, coronary sinus flow, and inferior vena cava (IVC) ultrasound with measurements of the IVC dimensions and their collapsibility index were performed, respectively. Compared to healthy participants, methamphetamine abusers had higher blood pressure, greater left ventricular mass index and more impaired diastolic function, with preserved cardiac sizes, systolic function and right atrial pressure. Methamphetamine abusers with chest pain had faster heart rate than those without chest pain and healthy participants. Coronary sinus flow was significantly less in methamphetamine abusers than in healthy participants (P < 0.05), and was extremely lower in those with chest pain than in healthy participants (about one-fourth) (P < 0.01). The area under the curve (AUC) of coronary sinus flow was 0.913 (0.864-0.962), and the cutoff value with 221.65 mL/min had sensitivity of 83.4%, specificity of 87.2% and accuracy of 85.2% for differentiating methamphetamine abusers from healthy participants. While the AUC of coronary sinus flow was 0.996 (0.989-1.003), and the cutoff value with 172.59 mL/min had sensitivity of 100%, specificity of 93.3% and accuracy of 96.5% for predicting methamphetamine abusers with chest pain. Coronary sinus flow is significant reduced in methamphetamine abusers, which is maybe a good indicator for indentifying methamphetamine abusers from normal population, and for predicting methamphetamine abusers with chest pain.

A survival case of intravenous paraquat intoxication: A case report.

RATIONALE: Paraquat, an agent highly toxic to humans and animals, is a widely used herbicide and also commonly used for suicide attempts in Taiwan. The most common route of intoxication is oral ingestion, and parenteral poisoning is respectively rare. PATIENT CONCERNS: A 39-year-old illicit abuser of heroin and amphetamine injected 0.5 mL of 24% paraquat directly into his right cephalic vein due to hallucination. The patient was brought to our emergency department for management 4 hours after injection. He was fully conscious and had normal vital signs. Systemic review showed mild dyspnea, abdominal pain and right wrist pain over the injection site. The only abnormal physical finding was erythema over the injection site and epigastric tenderness. DIAGNOSIS: Laboratory investigations, including complete blood count, liver and renal function, and electrolytes initially yielded normal results. Urinalysis showed normal findings except a positive urine paraquat test (4+). The initial plasma paraquat concentration was 0.51 µg/mL. INTERVENTIONS: He was admitted to the intensive care unit and underwent one session of charcoal hemoperfusion therapy. Acute kidney injury developed on the fourth day after intoxication, with the level of serum creatinine rising rapidly from 0.96 to 4.57 mg/dL and the daily urine output decreased noticeably from > 2000 to 900 mL. The serum creatinine level improved gradually with adequate fluid supplementation. OUTCOMES: The patient was discharged 13 days later in a stable condition. LESSONS: Intravenous paraquat intoxication is rare. Patients who suffer from intravenous intoxication may not directly suffer from mucosal irritation, but the clinical onset of systemic effects is more immediate and lethal. The prognosis of paraquat poisoning is determined by the time of poisoning and the plasma paraquat concentration before treatment. Proudfoot's curve provides a simple method of predicting the survival rate. The most effective mode of management is extracorporeal therapy, and immunosuppressive or antioxidant therapies have shown insufficient evidence of benefit.

Differential effect of the DRD3 genotype on inflammatory cytokine responses during abstinence in amphetamine-dependent women.

Amphetamine exposure impacts on innate and adaptive immunity and DRD3 may modulate the effect of amphetamine on the immune response. We assessed the immune-cytokine markers in 72 female patients with amphetamine dependence (AD) at baseline and after 4-week drug abstinence and in 51 healthy women. Multiplex magnetic bead assay was used to measure the plasma cytokine expression level simultaneously in all participants and DRD3 rs6280 polymorphism was genotyped in patients. We demonstrated an increase of the T helper 1 (Th1) cytokines (IL-2), Th2 cytokines (IL-4, IL-5, IL-6 and IL-10) and other cytokines (IL-1ß) in the entire AD cohort. A similar cytokine pattern, along with a significantly decreased IL-8 and IL-10 levels was observed after 4-week abstinence. Among AD patients with DRD3 rs6280 TT genotype, the cytokine expression profile was consistent with total AD cohort at baseline and revealed a significant down-regulated plasma level of the Th1, Th2, and other cytokines except for IL-6 after 4-week abstinence. In AD group with DRD3 rs6280 C allele carrier, we found IL-2 level was significantly higher than healthy controls at baseline and remained higher, accompanied with a borderline increase in IL-4, IL-6 and IL-1ß levels after 4-week abstinence. Our results suggest that chronic use of amphetamine increased both pro- and anti-inflammatory cytokines in AD patients, indicating the immune imbalance that may persist for 4 weeks or more. Besides, DRD3 rs6280 TT genotype may be associated with favorable recovery in general inflammatory cytokines during period of abstinence.

Region-specific changes in markers of neuroplasticity revealed in HIV-1 transgenic rats by low-dose methamphetamine.

Methamphetamine abuse co-occurring with HIV infection presents neuropathology in brain regions that mediate reward and motivation. A neuronal signaling cascade altered acutely by meth and some HIV-1 proteins is the mitogen-activated protein kinase (MAPK) pathway. It remains unknown if chronic co-exposure to meth and HIV-1 proteins converge on MAPK in vivo. To make this determination, we studied young adult Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats that self-administered meth (0.02-0.04 mg/kg/0.05 ml iv infusion, 2 h/day for 21 days) and their saline-yoked controls. One day following the operant task, rats were killed. Brain regions involved in reward-motivation [i.e., nucleus accumbens (NA) and ventral pallidum (VP)], were assayed for a MAPK cascade protein, extracellular signal-regulated kinase (ERK), and a downstream transcription factor, ΔFosB. In the NA, activated (phosphorylated; p) ERK-to-ERK ratio (pERK/ERK) was increased in meth-exposed Tg rats versus saline Tg controls, and versus meth non-Tg rats. ΔFosB was increased in meth Tg rats versus saline and meth non-Tg rats. Assessment of two targets of ΔFosB-regulated transcription revealed (1) increased dopamine D1 receptor (D1R) immunoreactivity in the NA shell of Tg-meth rats versus saline Tg controls, but (2) no changes in the AMPA receptor subunit, GluA2. No changes related to genotype or meth occurred for ERK, ΔFosB or D1R protein in the VP. Results reveal a region-specific activation of ERK, and increases in ΔFosB and D1R expression induced by HIV-1 proteins and meth. Such effects may contribute to the neuronal and behavioral pathology associated with meth/HIV comorbidity.

The relationship between interleukin-6 and functional connectivity in methamphetamine users.

Methamphetamine (MA) causes an increase in pro-inflammatory cytokines in animal models and in humans. Resulting activation of microglia and neuro-inflammation could, via effects on reward networks, mediate behavioral characteristics of addiction. We examined the relationship between interleukin-6 (IL-6) and corticolimbic and striatolimbic resting-state functional connectivity (RSFC). Thirty adults diagnosed with MA dependence and 20 control subjects underwent a resting-state functional magnetic resonance imaging (fMRI) scan and gave a blood sample for determination of plasma IL-6 levels. Seed-based RSFC analyses were performed to examine the interactive effect of group and IL-6 on ventral striatal and prefrontal connectivity. Within the MA group, IL-6 levels were positively related to striatolimbic RSFC but negatively related to corticostriatal RSFC. Our findings with IL-6 support the idea that inflammation may at least partly mediate the link among MA use disorder, RSFC, and behavior, possibly via effects on mesolimbic and mesocortical dopaminergic systems.

Knowledge and possession of take-home naloxone kits among street-involved youth in a Canadian setting: a cohort study.

BACKGROUND: The distribution of take-home naloxone (THN) kits has been an important strategy in reducing overdose fatalities among people who use drugs. However, little is known about the use of THN among youth who are street-involved. The present study explores knowledge and possession of THN among street-involved youth in a Canadian setting. METHODS: Data were derived from the At-Risk Youth Study (ARYS), a prospective cohort of street-involved youth age 14-28 at enrollment in Vancouver, Canada. Participants completed a standardized questionnaire, which included items related to knowledge and possession of THN, sociodemographic characteristics, and substance use-related factors. Multivariable logistic regression models were used to identify factors independently associated with knowledge and possession of THN. RESULTS: Between December 2014 and November 2016, 177 youth were interviewed, including 68 females (38.4%). While 126 (71.2%) participants reported knowledge of THN, only 40 (22.6%) possessed a THN kit. Caucasian/white ethnicity was found to be positively associated with both knowledge and possession of THN (both p < 0.05). Public injection drug use in the last 6 months was found to be positively associated with knowledge of THN, while daily heroin use and daily methamphetamine use were associated with possession of THN (all p < 0.05). Male gender was negatively associated with possession of THN (p < 0.05). CONCLUSIONS: These findings highlight important gaps between knowledge and possession of THN among youth and the need to increase participation in THN programs among specific populations including non-white and male youth. Further research is needed to gain a better understanding of the barriers that may prevent certain youth from acquiring THN kits.