Browsing by Subject "Amphetamine-Related Disorders"
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Item Open Access Bupropion and Naltrexone in Methamphetamine Use Disorder.(The New England journal of medicine, 2021-01) Trivedi, Madhukar H; Walker, Robrina; Ling, Walter; Dela Cruz, Adriane; Sharma, Gaurav; Carmody, Thomas; Ghitza, Udi E; Wahle, Aimee; Kim, Mora; Shores-Wilson, Kathy; Sparenborg, Steven; Coffin, Phillip; Schmitz, Joy; Wiest, Katharina; Bart, Gavin; Sonne, Susan C; Wakhlu, Sidarth; Rush, A John; Nunes, Edward V; Shoptaw, StevenBackground
The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied.Methods
We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses.Results
A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial.Conclusions
Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).Item Open Access Depressive symptoms, substance use, and HIV-related high-risk behaviors among opioid-dependent individuals: results from the Clinical Trials Network.(Substance use & misuse, 2011-01) Pilowsky, Daniel J; Wu, Li-Tzy; Burchett, Bruce; Blazer, Dan G; Ling, WalterThe sample included 343 opioid-dependent adults enrolled in two national multisite studies of the National Drug Abuse Treatment Clinical Trials Network (CTN001-002). Opioid-dependent individuals were recruited from 12 sites across the United States from January 2001 to July 2002. We examined associations between depressive symptoms, co-occurring substance use (i.e., the use of substances other than opioids), and HIV-related sexual and injection risk behaviors. Data were collected using the Addiction Severity Index and the HIV Risk Behavior Scale, and analyzed using linear regression. Depressive symptoms were associated with an increased level of injection risk behaviors but were not associated with risky sexual behaviors. The co-occurring use of amphetamines also increased the likelihood of risky sexual behaviors. The study limitations and clinical implications are noted. The study was funded by the U.S. National Institute on Drug Abuse.Item Open Access Evaluating brief screeners to discriminate between drug use disorders in a sample of treatment-seeking adults.(General hospital psychiatry, 2013-01) Wu, Li-Tzy; Swartz, Marvin S; Pan, Jeng-Jong; Burchett, Bruce; Mannelli, Paolo; Yang, Chongming; Blazer, Dan GOBJECTIVE:The objective was to identify a potential core set of brief screeners for the detection of individuals with a substance use disorder (SUD) in medical settings. METHOD:Data were from two multisite studies that evaluated stimulant use outcomes of an abstinence-based contingency management intervention as an addition to usual care (National Drug Abuse Treatment Clinical Trials Network trials 006-007). The sample comprised 847 substance-using adults who were recruited from 12 outpatient substance abuse treatment settings across the United States. Alcohol and drug use disorders were assessed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Checklist. Data were analyzed by factor analysis, item response theory (IRT), sensitivity and specificity procedures. RESULTS:Comparatively prevalent symptoms of dependence, especially inability to cut down for all substances, showed high sensitivity for detecting an SUD (low rate of false negative). IRT-defined severe (infrequent) and low discriminative items, especially withdrawal for alcohol, cannabis and cocaine, had low sensitivity in identifying cases of an SUD. IRT-defined less severe (frequent) and high discriminative items, including inability to cut down or taking larger amounts than intended for all substances and withdrawal for amphetamines and opioids, showed good-to-high values of area under the receiver operating characteristic curve in classifying cases and noncases of an SUD. CONCLUSION:Findings suggest the feasibility of identifying psychometrically reliable substance dependence symptoms to develop a two-item screen for alcohol and drug disorders.Item Open Access Heterogeneity of stimulant dependence: a national drug abuse treatment clinical trials network study.(The American journal on addictions, 2009-05) Wu, Li-Tzy; Blazer, Dan G; Patkar, Ashwin A; Stitzer, Maxine L; Wakim, Paul G; Brooner, Robert KWe investigated the presence of DSM-IV subtyping for dependence on cocaine and amphetamines (with versus without physical dependence) among outpatient stimulant users enrolled in a multisite study of the Clinical Trials Network (CTN). Three mutually exclusive groups were identified: primary cocaine users (n = 287), primary amphetamine users (n = 99), and dual users (cocaine and amphetamines; n = 29). Distinct subtypes were examined with latent class and logistic regression procedures. Cocaine users were distinct from amphetamine users in age and race/ethnicity. There were four distinct classes of primary cocaine users: non-dependence (15%), compulsive use (14%), tolerance and compulsive use (15%), and physiological dependence (tolerance, withdrawal, and compulsive use; 56%). Three distinct classes of primary amphetamine users were identified: non-dependence (11%), intermediate physiological dependence (31%), and physiological dependence (58%). Regardless of stimulants used, most female users were in the most severe or the physiological dependence group. These results lend support for subtyping dependence in the emerging DSM-V.Item Open Access Infrequent illicit methadone use among stimulant-using patients in methadone maintenance treatment programs: a national drug abuse treatment clinical trials network study.(The American journal on addictions, 2008-07) Wu, Li-Tzy; Blazer, Dan G; Stitzer, Maxine L; Patkar, Ashwin A; Blaine, Jack DWe sought to determine the prevalence, patterns, and correlates of past-month illicit methadone use and history of regular illicit use among stimulant-using methadone maintenance treatment patients. We obtained self-reported information on illicit methadone use from 383 participants recruited from six community-based methadone maintenance programs. Overall, 1.6% of participants reported illicit use in the past month, and 4.7% reported a history of regular use. Younger age and history of outpatient psychological treatment were associated with increased odds of past-month illicit use. Illicit methadone use among patients in maintenance programs is infrequent; however, a number of factors may increase risk of illicit use.Item Open Access Misuse of methamphetamine and prescription stimulants among youths and young adults in the community.(Drug and alcohol dependence, 2007-07) Wu, Li-Tzy; Pilowsky, Daniel J; Schlenger, William E; Galvin, Deborah MGender differences in the prevalence and characteristics of misuse of methamphetamine (meth) and prescription stimulants were examined in a representative US sample of youths and young adults aged 16-25 (N=24,409).Stimulant misusers were categorized into three mutually exclusive subgroups: meth users only, meth and prescription stimulant users, and prescription stimulant users only (e.g., Benzedrine, Ritalin, or Dexedrine). Multinominal logistic regression analyses identified the characteristics associated with misuse of meth and prescription stimulants.About 1 in 10 youths reported any misuse of stimulants in their lifetime. Prescription stimulant misuse occurred earlier and was more frequent than meth misuse. About 47% of meth misusers also reported prescription stimulant misuse. Among misusers of meth and prescription stimulants, males were more likely than females to misuse methylphenidate (82% versus 65%) but were less likely to misuse diet pills or amphetamines (37% versus 49%). Multinominal logistic regression analyses indicated that all subgroups of lifetime stimulant misuse were associated with past year substance abuse. The characteristics of meth misusers differed slightly from prescription stimulants misusers.Multidrug use is common among stimulant misusers. Parents should be informed about the risk of prescription stimulant misuse by their youths.Item Open Access The high prevalence of substance use disorders among recent MDMA users compared with other drug users: Implications for intervention.(Addictive behaviors, 2009-08) Wu, Li-Tzy; Parrott, Andy C; Ringwalt, Christopher L; Patkar, Ashwin A; Mannelli, Paolo; Blazer, Dan GIn light of the resurgence in MDMA use and its association with polysubstance use, we investigated the 12-month prevalence of substance use disorders (SUDs) among adult MDMA users to determine whether they are at risk of other drug-related problems that would call for targeted interventions.Data were drawn from the 2006 National Survey on Drug Use and Health. Past-year adult drug users were grouped into three mutually exclusive categories: 1) recent MDMA users, who had used the drug within the past year; 2) former MDMA users, who had a history of using this drug but had not done so within the past year; and 3) other drug users, who had never used MDMA. Logistic regression procedures were used to estimate the association between respondents' SUDs and MDMA use while adjusting for their socioeconomic status, mental health, age of first use, and history of polydrug use.Approximately 14% of adults reported drug use in the past year, and 24% of those past-year drug users reported a history of MDMA use. Recent MDMA users exhibited the highest prevalence of disorders related to alcohol (41%), marijuana (30%), cocaine (10%), pain reliever/opioid (8%), and tranquilizer (3%) use. Adjusted logistic regression analyses revealed that, relative to other drug users, those who had recently used MDMA were twice as likely to meet criteria for marijuana and pain reliever/opioid use disorders. They were also about twice as likely as former MDMA users to meet criteria for marijuana, cocaine, and tranquilizer use disorders.Seven out of ten recent MDMA users report experiencing an SUD in the past year. Adults who have recently used MDMA should be screened for possible SUDs to ensure early detection and treatment.Item Open Access α4β2 Nicotinic receptor desensitizing compounds can decrease self-administration of cocaine and methamphetamine in rats.(European journal of pharmacology, 2019-02) Levin, Edward D; Rezvani, Amir H; Wells, Corinne; Slade, Susan; Yenugonda, Venkata M; Liu, Yong; Brown, Milton L; Xiao, Yingxian; Kellar, Kenneth JSazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a selective α4β2 nicotinic receptor desensitizing agent and partial agonist. Sazetidine-A has been shown in our previous studies to significantly reduce nicotine and alcohol self-administration in rats. The question arises whether sazetidine-A would reduce self-administration of other addictive drugs as well. Nicotinic receptors on the dopaminergic neurons in the ventral tegmental area play an important role in controlling the activity of these neurons and release of dopamine in the nucleus accumbens, which is critical mechanism for reinforcing value of drugs of abuse. Previously, we showed that the nonspecific nicotinic antagonist mecamylamine significantly reduces cocaine self-administration in rats. In this study, we acutely administered systemically sazetidine-A and two other selective α4β2 nicotinic receptor-desensitizing agents, VMY-2-95 and YL-2-203, to young adult female Sprague-Dawley rats and determined their effects on IV self-administration of cocaine and methamphetamine. Cocaine self-administration was significantly reduced by 0.3 mg/kg of sazetidine-A. In another set of rats, sazetidine-A (3 mg/kg) significantly reduced methamphetamine self-administration. VMY-2-95 significantly reduced both cocaine and methamphetamine self-administration with threshold effective doses of 3 and 0.3 mg/kg, respectively. In contrast, YL-2-203 did not significantly reduce cocaine self-administration at the same dose range and actually significantly increased cocaine self-administration at the 1 mg/kg dose. YL-2-203 (3 mg/kg) did significantly decrease methamphetamine self-administration. Sazetidine-A and VMY-2-95 are promising candidates to develop as new treatments to help addicts successfully overcome a variety of addictions including tobacco, alcohol as well as the stimulant drugs cocaine and methamphetamine.