Pre-clinical research implicates dopaminergic neurotransmission as critical in producing the effects of stimulants. Previous stimulant challenge studies using volunteers treated with dopaminergic antagonists have generally failed to... more
Pre-clinical research implicates dopaminergic neurotransmission as critical in producing the effects of stimulants. Previous stimulant challenge studies using volunteers treated with dopaminergic antagonists have generally failed to demonstrate reduction of subjective effects. We ...
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This study evaluated the association between negative affective symptoms during initial abstinence and euphorigenic response to experimentally administered cocaine. Cocaine-dependent individuals achieved 5 days of abstinence in a hospital... more
This study evaluated the association between negative affective symptoms during initial abstinence and euphorigenic response to experimentally administered cocaine. Cocaine-dependent individuals achieved 5 days of abstinence in a hospital setting. Forty milligrams of cocaine was given intravenously on the fifth day of abstinence, and participants were asked to rate the subjective effects produced by the drug. The associations between irritability, self-reported depression, and the subjective "high" produced by cocaine were evaluated. Increased levels of irritability and depression both correlated positively and statistically significantly with heightened response to experimentally administered cocaine as indexed by self-reported subjective "high." The positive association between irritability and subjective "high" remained after controlling for self-reported depressive symptoms. The opponent process model predicts that increased levels of negative affect should be associated with diminished euphoric response to cocaine; however, the opposite was observed. If these findings are replicated in a larger sample, then it may be necessary to reconsider the applicability of the opponent process model to cocaine addiction in humans.
Research Interests: Psychology, Depression, Medicine, Humans, Negative Affect, and 15 moreCocaine, Addictive Behaviours, Mechanism, Depressive Disorder, Abstinence, Middle Aged, Adult, Addictive Behaviors, Depressive Symptoms, Indexation, Process Model, Irritability, Euphoria, Cocaine dependence, and Substance Withdrawal Syndrome
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Bupropion hydrochloride is a dopamine and norepinephrine reuptake inhibitor which may be an effective treatment for cocaine dependence due to its ability to reverse deficits in dopaminergic functioning that occur in chronic cocaine users.... more
Bupropion hydrochloride is a dopamine and norepinephrine reuptake inhibitor which may be an effective treatment for cocaine dependence due to its ability to reverse deficits in dopaminergic functioning that occur in chronic cocaine users. We performed a randomized, double-blind, placebo controlled trial comparing outpatient treatment with bupropion (N = 37) and placebo (N = 33) in combination with standard cognitive behavioral therapy. There were no statistically significant differences between bupropion and placebo in treatment outcomes, including aggregate measures of urine drug screen results (Joint Probability Index at 16 weeks: 0.43 for bupropion and 0.38 for placebo), treatment retention, cocaine craving ratings, and assessments of depressive symptoms. The failure to find an effect for bupropion relative to placebo, when combined with standard cognitive behavioral therapy, dampens enthusiasm for future development of bupropion as a cocaine pharmacotherapy.
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Cocaine-induced craving has been implicated in the maintenance of ongoing cocaine use and is presumed to be mediated by enhanced synaptic availability of monoamines, including dopamine. Apathy is a neuropsychiatric syndrome that is... more
Cocaine-induced craving has been implicated in the maintenance of ongoing cocaine use and is presumed to be mediated by enhanced synaptic availability of monoamines, including dopamine. Apathy is a neuropsychiatric syndrome that is associated with hypodopaminergic functioning and is neurobiologically distinct from depression. Apathy has been observed to be prevalent during the initial phases of abstinence in cocaine-dependent individuals. In the current report, we sought to investigate the relationship between apathy, depression, and craving in response to an acute intravenous administration of cocaine. To this end, sixteen non-treatment seeking volunteers were evaluated. Following acute administration of cocaine (40 mg, IV), patients with low apathy scores exhibited increased craving, whereas patients with high apathy scores exhibited decreased craving. In addition, patients with high apathy scores exhibited increased ratings of the subjective measure of "High", suggesting that high apathy predicts a greater hedonic response in dependence. Self-reported ratings of depression did not account for the observed differences. The data reveal that cocaine-induced craving is not ubiquitous, and may not play a critical role in the maintenance of cocaine dependence. Overall, the findings suggest that apathy predicts hedonic but not craving response to cocaine.
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Research Interests: Clinical Psychology, Chemistry, Addiction, Clinical Trial, Item Response Theory, and 15 moreCausality, Comorbidity, Human, Humans, Female, Drug Addiction, AIDS, Dependence, Human immunodeficiency virus, Adult, Latent Class Analysis, Clinical Assessment, Clinical Trials Network, Latent class model, and HIV infections
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Research Interests: Psychology, Demography, Depression, Public Health, Medicine, and 15 moreHumans, Impulse Control Disorders, Project evaluation, Placebo, Female, Methamphetamine, Male, Contingency Management, Drug abuse, Length of Stay, Questionnaires, Adult, Continuity of Patient Care, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Demography, Addiction Medicine, Treatment Outcome, Medicine, Humans, and 15 moreUnited States, Female, Male, Buprenorphine, Craving, Middle Aged, Adult, Public health systems and services research, Randomized Controlled Trial, Narcotics, Opioid, Heroin, Substance-Related Disorders, Opiate substitution treatment, and Medical prescription
Research Interests: Psychology, Design, Effectiveness, Evidence Based Medicine, Clinical Trial, and 15 moreHindsight bias, Experimental Design, Medicine, Humans, Drug abuse, Information Dissemination, Health Problems, Public health systems and services research, Comparative Effectiveness Research, Randomized Clinical Trial, Community Based Mental Health Services, Effectiveness Trial, Randomized Controlled Trials as Topic, Community health services, and clinical study design
Objectives: This article describes how smartphones were used to monitor and encourage medication adherence in a pilot study evaluating the potential efficacy of a combination pharmacotherapy for methamphetamine use disorder. We examine... more
Objectives: This article describes how smartphones were used to monitor and encourage medication adherence in a pilot study evaluating the potential efficacy of a combination pharmacotherapy for methamphetamine use disorder. We examine the feasibility, utility, and acceptability of using smartphones to capture dosing videos from the perspectives of participants and staff. Methods: The study was an 8-week, open-label evaluation of extended-release injectable naltrexone combined with once-daily oral extended-release bupropion (BRP, Welbutrin XL, 450 mg/day). Participants attended visits twice-weekly for observed BRP dosing, assessments, and medical management. BRP was dispensed once weekly for dosing on nonclinic days. Medication adherence was assessed objectively (by observation in the clinic and smartphone videos for dosing at home) and subjectively (self-reports of dosing). Surveys assessing the smartphone component were completed by participants and study staff. Results: Participa...
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ABSTRACT
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Research Interests: Pharmacogenomics, Medicine, Humans, Internal Medicine, Pharmacogenetics, and 11 moreFemale, Buprenorphine, Methadone, Genotype, Single Nucleotide Polymorphism, European Continental Ancestry Group, Genetic variation, Opioid, Confidence Interval, Opiate substitution treatment, and Pharmacology and pharmaceutical sciences
Although there are increasing reports of methamphetamine use, studies examining the cognitive consequences of methamphetamine have not been performed on a population currently using the drug. To characterize this population, 65 people... more
Although there are increasing reports of methamphetamine use, studies examining the cognitive consequences of methamphetamine have not been performed on a population currently using the drug. To characterize this population, 65 people currently using MA regularly and 65 non‐users were given a battery of cognitive tests. The battery included recall, recognition, Digit Symbol, Trail Making A & B, Stroop, Wisconsin Card Sort, backward digit span, and the FAS test of verbal fluency. The methamphetamine users were significantly more impaired on recall tasks, digit symbol, Stroop color words, and Trail Making B, but scores fell within the normal ranges on the other measures.
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To evaluate the impact on outcome of a simple educational intervention in schizophrenic patients at risk of relapse. At discharge, 114 schizophrenic patients with at least one previous episode were assigned randomly to a simple... more
To evaluate the impact on outcome of a simple educational intervention in schizophrenic patients at risk of relapse. At discharge, 114 schizophrenic patients with at least one previous episode were assigned randomly to a simple educational intervention which had no resource implications, or standard care. The intervention failed to improve outcome. While insight and treatment attitudes improved, suicidal ideation increased. Systematic management of treatment-emergent adverse effects offered no benefits, although incapacitation from extrapyramidal side-effects at discharge predicted relapse. There are limits to which psychoeducational interventions can be simplified without loss of effectiveness in terms of relapse prevention in schizophrenia. Enhanced insight may be associated with increased suicidal ideation.
Research Interests: Psychology, Psychiatry, Psychotherapy, Mental Health, Depression, and 15 moreAdolescent, Medicine, Humans, Female, Male, Psychological Intervention, Middle Aged, Adult, Brief Intervention, Ambulatory Care, Psychiatric Status Rating Scales, attitude to health, Antipsychotic agents, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Addiction, Survival Analysis, Medicine, Humans, Smoking Cessation, and 15 morePlacebo, Female, Methamphetamine, Male, Placebos, Randomised Controlled Trial, Adult, Randomized Controlled Trial, Randomized Clinical Trial, Depressive Symptoms, bupropion, Psychology and Cognitive Sciences, Central nervous system stimulants, Medical and Health Sciences, and Cigarette Smoke
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Research Interests: Psychology, Treatment Outcome, Adolescent, Medicine, Counseling, and 15 moreHumans, Smoking, Female, Methamphetamine, Cognitive Therapy, Male, Young Adult, Patient Compliance, Depressive Disorder, Adult, Socioeconomic Factors, Psychiatric Status Rating Scales, Psychology and Cognitive Sciences, Central nervous system stimulants, and Medical and Health Sciences
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Once-monthly intramuscular extended-release naltrexone (XR-NTX) has demonstrated efficacy for the prevention of relapse in opioid dependence, providing an alternative to agonist or partial agonist maintenance (ie, methadone and... more
Once-monthly intramuscular extended-release naltrexone (XR-NTX) has demonstrated efficacy for the prevention of relapse in opioid dependence, providing an alternative to agonist or partial agonist maintenance (ie, methadone and buprenorphine). The question remains, for whom is this unique treatment most efficacious and can patient-treatment matching factors be identified? A moderator analysis was conducted on a previously reported 24-week, placebo-controlled, multisite, randomized controlled trial of XR-NTX (n = 126) versus placebo (n = 124) among recently detoxified opioid-dependent adults in Russia, which showed XR-NTX superior to placebo in proportion of opioid abstinent weeks. The moderator analysis examined a dichotomous indicator of good clinical response-achieving at least 90% of weeks abstinent over the 24-week trial. A series of logistic regression models were fit for this outcome as functions of treatment (XR-NTX vs placebo), each baseline moderator variable, and their int...
Research Interests: Addiction Medicine, Treatment Outcome, Medicine, Humans, Internal Medicine, and 15 moreSubstance Abuse, Placebo, Female, Male, Young Adult, Buprenorphine, Abstinence, Middle Aged, Methadone, Adult, Opioid Dependence, Public health systems and services research, Naltrexone, Predictors, and Injections
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LAAM and methadone are both full mu opiate agonists and have been shown to reduce dependence on heroin when given continuously under supervised dosing conditions. LAAM has a long duration of action requiring dosing every two or three days... more
LAAM and methadone are both full mu opiate agonists and have been shown to reduce dependence on heroin when given continuously under supervised dosing conditions. LAAM has a long duration of action requiring dosing every two or three days compared to methadone which requires daily dosing. LAAM is not as widely available internationally as methadone, and may be withdrawn from the market following ten cases of life-threatening cardiac arrhythmias and an association with QT prolongation. To compare the efficacy and acceptability of LAAM maintenance with methadone maintenance in the treatment of heroin dependence. We searched MEDLINE (January 1966 to August 2000), PsycINFO (1887 to August 2000), EMBASE (January 1985 to August 2000), and the Cochrane Controlled Trials Register (Issue 2 2000). In addition we hand searched NIDA monographs until August 2000 and searched reference lists of articles. All randomised controlled trials, controlled clinical trials and controlled prospective studies comparing LAAM and methadone maintenance for the treatment of heroin dependence and measuring outcomes of efficacy or acceptability were included. Data on retention in treatment, heroin use, side-effects and mortality were collected by two reviewers independently. A meta-analysis was performed using RevMan. Discrepancies were resolved by consensus. Eighteen studies, (15 RCTs, 3 Controlled prospective studies) met the inclusion criteria for the review. Three were excluded from the meta-analysis due to lack of data on retention, heroin use or mortality. Cessation of allocated medication (11 studies, 1473 participants) was greater with LAAM than with methadone, (RR 1.36, 95%CI 1.07-1.73, p=0.001, NNT=7.7 (or 8)). Non-abstinence was less with LAAM (5 studies, 983 participants; RR 0.81, 95%CI 0.72-0.91, p=0.0003, NNT=9.1 (or 10)). In 10 studies (1441 participants) there were 6 deaths from a range of causes, 5 in participants assigned to LAAM (RR 2.28 (95%CI 0.59-8.9, p=0.2). other relevant outcomes, such as quality of life and criminal activity could not be analysed because of lack of information in the primary studies. LAAM appears more effective than methadone at reducing heroin use. More LAAM patients than methadone ceased their allocated medication during the studies, but many transferred to methadone and so the significance of this is unclear. There was no difference in safety observed, although there was not enough evidence to comment on uncommon adverse events.
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The purpose of this study was to investigate the blood levels of methadone in participants receiving methadone for the treatment of opioid dependence. After stabilization on methadone for four weeks, blood samples from 95 participants... more
The purpose of this study was to investigate the blood levels of methadone in participants receiving methadone for the treatment of opioid dependence. After stabilization on methadone for four weeks, blood samples from 95 participants were collected between treatment weeks 4 and 12, before and after receiving doses of methadone, and its blood levels were measured. A multiple linear regression model was used to examine the association between methadone blood levels and the outcomes of methadone maintenance treatment (MMT). Outcome differences between participants who had high (≥2) or low (<2) peak-to-trough ratios were also compared using an independent sample t-test. The blood level of methadone was not correlated with the clinical outcome of MMT with the moderate range of doses given. However, the retention of patients who had a free peak-to-trough ratio >2 was significantly poorer than those whose ratio was <2. Thus, monitoring plasma methadone levels is unlikely to be ef...
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For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays.Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification.Methadone,... more
For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays.Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification.Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized.This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies. The National Institute on Drug Abuse's Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients.Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX. The primary outcome...
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Despite the growing prevalence of opioid use among offenders, pharmacotherapy remains an underused treatment approach in correctional settings. The aim of this 4-year trial is to assess the clinical utility, effectiveness, and cost... more
Despite the growing prevalence of opioid use among offenders, pharmacotherapy remains an underused treatment approach in correctional settings. The aim of this 4-year trial is to assess the clinical utility, effectiveness, and cost implications of extended-release naltrexone (XR-NTX, Vivitrol®; Alkermes Inc.) alone and in conjunction with patient navigation for jail inmates with opioid use disorder (OUD). Opioid-dependent inmates will be randomly assigned to one of three treatment conditions before being released to the community to include: 1) XR-NTX only; 2) XR-NTX plus patient navigation (PN), and 3) enhanced treatment-as-usual (ETAU) with drug education and a community treatment referral. Before release from jail, participants in the XR-NTX and XR-NTX plus PN conditions will receive their first XR-NTX injection. Those in the XR-NTX plus PN condition also will meet with a patient navigator. Participants in both XR-NTX conditions will be scheduled for medical management sessions t...
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To examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone®) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) to reduce cocaine use in... more
To examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone®) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. This multi-centered, double-blind, placebo-controlled study, conducted under the auspices of the National Drug Abuse Treatment Clinical Trials Network, randomly assigned 302 participants at sites in California, Oregon, Washington, Colorado, Texas, Georgia, Ohio, New York, and Washington D.C., USA to 1 of 3 conditions provided with XR-NTX: 4 mg/day BUP (BUP4, n = 100), 16 mg/day BUP (BUP16, n = 100), or no buprenorphine (placebo; PLB, n = 102). Participants received pharmacotherapy for 8 weeks, with 3 clinic visits per week. Cognitive Behavioral Therapy was provided weekly. Follow-up assessments occurred at 1 and 3 months post-intervention. The planned pr...