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Biomedical subjects

Charles R Schuster

Publications and source records attributed to Charles R Schuster.

15 recordsLinked to original sources
PubMed2006

Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers.

OBJECTIVE: Preclinical investigations have established that methamphetamine (MA) produces long-term changes in dopamine (DA) neurons in the striatum. Human studies have suggested similar effects and correlated motor and cognitive deficits. The present study was designed to further our understanding of changes in brain function in humans that might result from chronic high dose use of MA after at least 3 months of abstinence. METHOD: Brain function in abstinent users was compared to controls using neuroimaging of monoamine transporters and cognitive assessment. Striatal levels of DA transporter (DAT) and vesicular monoamine transporter type-2 (VMAT2) were determined using [11C]methylphenidate and [11C]dihydrotetrabenazine positron emission tomography, respectively. Cognitive function was evaluated using tests of motor function, memory, learning, attention, and executive function. RESULTS: Striatal DAT was approximately 15% lower and VMAT2 was 10% lower in MA abusers across striatal subregions. The MA abusers performed within the normal range but performed more poorly compared to controls on three of the 12 tasks. CONCLUSIONS: Failure to find more substantial changes in transporter levels and neurocognitive function may be attributed to the length of time that MA users were abstinent (ranging from 3 months to more than 10 years, mean 3 years), although there were no correlations with length of abstinence. Persistent VMAT2 reductions support the animal literature indicating a toxic effect of MA on nigrostriatal nerve terminals. However, the magnitude of the MA effects on nigrostriatal projection integrity is sufficiently small that it is questionable whether clinical signs of DA deficiency are likely to develop.

Adolescent↗
PubMed2006

History and current perspectives on the use of drug formulations to decrease the abuse of prescription drugs.

This article is part of a supplemental issue of the journal devoted entirely to papers on how abuse liability of medications is affected by their formulation for medical use. This article reviews the history of abuse and addiction to medications in the United States and the legislation designed to control these problems. The provisions in legislation related specifically to formulations of medications designed to decrease their abuse potential will be noted. In addition, the role of the College on Problems of Drug Dependence (CPDD) as an organization initially founded to develop analgesic medications with less abuse potential than morphine is briefly reviewed. Examples of current approaches to the development of formulations of medications to decrease their abuse potential discussed in detail in the articles to follow are outlined. Finally, the use of behavioral economic analyses to better delineate the relative abuse potential of new medication formulations is discussed.

Chemistry, Pharmaceutical↗
PubMed2006

Characteristics of U.S. substance abuse treatment facilities adopting buprenorphine in its initial stage of availability.

This study examined the adoption of buprenorphine for the treatment of opiate dependence among U.S. substance abuse treatment facilities and their characteristics at the time of the initial availability of the medication. Data come from a 2003 national survey of all substance abuse treatment facilities in the U.S. Out of our sample of 13,060 facilities, 5.5% of facilities reported they offered buprenorphine. Not unexpectedly, the prevalence was higher in certified opioid treatment programs (11.3%) compared to other facilities (4.6%). For opioid treatment programs, offering Naltrexone (OR=8.34, 95% CI=5.53, 12.58) and offering medically supervised withdrawal (OR=2.76, 95% CI=1.38, 5.52) were independent and robust predictors of offering buprenorphine. These same variables were independent predictors for the non-opioid treatment programs as well (Naltrexone, OR=14.32, 95% CI=7.85, 26.10; and medically supervised withdrawal services, OR=4.42, 95% CI=3.01, 6.49). Our results suggest that the adoption of buprenorphine soon after the Food and Drug Administration approved its use for treatment of opioid dependence and the shipping of the medication commenced was associated with facilities already offering pharmacotherapies such as Naltrexone and medically assisted withdrawal. These findings provide baseline data to track the adoption of buprenorphine by substance abuse treatment programs in future years.

Buprenorphine↗
PubMed2005

Effect of rate of administration on subjective and physiological effects of intravenous cocaine in humans.

The rate hypothesis of psychoactive drug action holds that the faster a drug reaches the brain and starts to act, the greater its reinforcing effects and abuse liability. A previous human study using a single cocaine dose confirmed the rate hypothesis for subjective responses, but found no rate effect on cardiovascular responses. We evaluated the rate hypothesis in 17 experienced cocaine users (7 [all men] provided complete data; 6 participated in only 1-2 sessions) by administering IV cocaine at each of three doses (10, 25, 50 mg) and injection durations (10, 30, 60 s) in a double-blind, placebo-controlled, escalating dose design. Heart rate, blood pressure, and positive (e.g., rush, high) and negative (e.g., feel bad, anxious) subjective effects (100-mm visual analogue scales) were measured for 1h after dosing. Peak change from baseline, time to peak, and area under the time-response curve were evaluated with repeated measures mixed linear regression analyses, allowing use of data from all sessions for all subjects, including non-completers. Both dose (mg) and infusion rate (mg/s) significantly influenced most subjective and cardiovascular variables. Analysis of the interaction suggested that dose had a stronger impact than rate. Rate had a stronger influence on positive subjective effects than on negative subjective effects or cardiovascular variables. These findings provide support for the rate hypothesis as it applies to both subjective and cardiovascular effects of IV cocaine administration in humans.

Adult↗
PubMed2005

Computer-based brief motivational intervention for perinatal drug use.

Computer-based brief motivational interventions may be able to reach a high proportion of at-risk individuals and thus have potential for significant population impact. The present studies were conducted to determine the acceptability and preliminary efficacy of a computer-based brief motivational intervention (the motivation enhancement system, or MES). In Study 1, quantitative and qualitative feedback from 30 postpartum women and 17 women in treatment for drug use were used to modify the software. In Study 2, 50 urban postpartum women who reported drug use in the month before pregnancy completed the intervention and provided repeated within-session ratings of state motivation. In Study 3, 30 women were randomly assigned to intervention or control conditions with 1-month follow-up. Overall, women rated the MES as highly acceptable and easy to use and reported significant increases in state motivation at postintervention and at 1-month follow-up (d = .49). These preliminary results are encouraging and suggest that further work in this area is warranted.

Adult↗
PubMed2003

Postmarketing surveillance of abuse liability of sibutramine.

The abuse liability of medications is a growing concern as the number of newly approved psychoactive medications increases. Postmarketing surveillance can assist in determining abuse liability, but strategies are not well-defined for medications believed to be at low abuse risk. Using a newly approved medication (sibutramine--an anorectic drug), a novel approach to postmarketing abuse surveillance was introduced. A one-page anonymous questionnaire covering sibutramine, a scheduled anorectic drug (phentermine), and a fabricated name was added to the intake process of 58 treatment programs. From the 8780 completed questionnaires, 8.8% had heard of sibutramine and phentermine. For continued use to get high (a proxy for abuse), the rate for sibutramine was lower than for phentermine (0.6 vs. 2.2%, McNemar's chi(2) = 110.45, P < 0.001) but was higher than for the fabricated name (0.6 vs. 0.3%, McNemar's chi(2) = 11.86, P < 0.001). These results suggest the risk of abuse associated with sibutramine was lower than that associated with a known abused drug, one that itself is considered low risk despite decades of population exposure. The relatively high rate of hearing of sibutramine may be due to the direct-to-consumer advertisement. This approach is only one indicator in a surveillance framework but appears promising and validates findings from laboratory-based abuse liability studies that also indicate low abuse liability for sibutramine.

Adult↗
PubMed2003

Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers.

The clinical effectiveness of opioid maintenance for heroin dependence is believed to result from a medication's ability to decrease mu-opioid receptor (muOR) availability thereby replacing agonist effects, alleviating withdrawal symptoms and attenuating heroin effects. We empirically tested this hypothesis in five heroin-dependent volunteers who were successively maintained on 32, 16, 2, and 0 mg daily buprenorphine (BUP) tablet doses. We predicted and confirmed that higher BUP doses would decrease in vivo muOR availability (measured with PET and [(11)C]carfentanil), increase plasma levels of BUP and its metabolite nor-BUP, and decrease withdrawal symptoms and hydromorphone (HYD) responses. Relative to placebo, BUP significantly decreased mean (+/-SEM) whole-brain muOR availability 41+/-8, 80+/-2, and 84+/-2% at 2, 16, and 32 mg, respectively. Regions of interest (ROIs) (prefrontal cortex, anterior cingulate, thalamus, amygdala, nucleus accumbens, caudate) showed similar dose-dependent effects. Changes in muOR availability varied across ROIs (prefrontal cortex, 47% vs amygdala, 27%) at BUP 2 mg, but were more homogeneous across ROIs at BUP 32 mg (94-98%; except thalamus, 88%). Relative to placebo (0 ng/ml), peak plasma levels of BUP and nor-BUP were comparable and dose-dependent (0.5-1, 5-6, and 13-14 ng/ml at 2, 16, and 32 mg, respectively). muOR availability decreases were negatively correlated with BUP plasma level and positively correlated with questionnaire-based opioid withdrawal symptoms and attenuation of HYD symptoms. These findings suggest that high-dose BUP maintenance produces near-maximal muOR occupation, muOR availability correlates well with plasma levels, and BUP-related opioid symptoms and antagonist blockade exhibit concentration-effect relationships.

Adult↗
PubMed2003

Improving on-time counseling attendance in a methadone treatment program: a contingency management approach.

Two studies were conducted to investigate the effectiveness of contingency management techniques in promoting punctual counseling attendance among methadone maintenance patients. In Study 1, 50 participants were recruited from an inner-city methadone maintenance program. Study 1 used an A-B-A design with baseline, intervention, and return-to-baseline phases. On-time attendance was reinforced during the intervention phase with a voucher that was redeemable for a draw out of a box containing 100 tokens with values varying from 0.00 dollars to 100.00 dollars. Methadone maintenance patients who exhibited poor attendance during baseline showed a significant positive response during the contingency management intervention phase. Study 2 used the same design as Study 1 except that the 52 participants were randomized into reinforcement groups that received either the variable rate of reinforcement as in Study 1 or a fixed value reinforcer of 3.25 dollars. As in Study 1, Poor Attenders significantly improved counseling attendance during the intervention. There were no differences between the variable and fixed reinforcement groups. Overall, results suggest that targeting Poor Attenders with contingency management techniques may be a cost-effective method of improving counseling attendance. Targeting Poor Attenders early in treatment may be especially important for improving treatment outcomes.

Adult↗
PubMed2002

Effects of buprenorphine sublingual tablet maintenance on opioid drug-seeking behavior by humans.

RATIONALE: Buprenorphine can decrease opioid self-administration by humans and animals, but its ability to decrease drug-seeking behavior and craving (i.e. motivational measures) among outpatient volunteers using clinically relevant dosing schedules has not been extensively studied. OBJECTIVES: We investigated whether daily versus alternating-day administration of high versus low buprenorphine doses influenced choice of, and operant responding for, hydromorphone versus money. METHODS: Fourteen heroin-dependent outpatients were maintained under four buprenorphine sublingual tablet (double blind) dose conditions using a within-subject, randomized crossover design. All participants received, for 2 weeks each, buprenorphine doses of 2 mg daily, 4 mg/placebo on alternating days, 16 mg daily, and 32 mg/placebo on alternating days. In each laboratory test session, participants chose between money ($2/choice) and drug (1/8 of total hydromorphone, 4 or 24 mg IM in different sessions) alternatives using an eight-trial non-independent progressive ratio schedule (FR 100, 200,.12,800). The drug dose and money amount earned was delivered after the end of the 2.5-h work period. RESULTS: Hydromorphone 24 mg was more reinforcing than 4 mg. Higher versus lower average buprenorphine doses (regardless of daily versus alternate-day schedule) significantly decreased hydromorphone 24 mg choice and increased money choice. Baseline heroin craving questionnaire scores predicted drug choice, and craving scores were significantly decreased by high-dose buprenorphine. CONCLUSIONS: High-dose buprenorphine attenuated opioid drug-seeking behavior, heroin craving self-reports and increased sensitivity to alternative reinforcement. These beneficial effects were retained when high-dose buprenorphine was administered on alternate days.

Administration, Sublingual↗
PubMed2002

Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence.

In this 12-week double-blind placebo-controlled trial of methylphenidate (MTP) versus placebo in 48 cocaine-dependent attention-deficit/hyperactivity disorder (ADHD) adults, the authors sought to determine whether MTP would be safe, control ADHD symptoms, and affect cocaine use. Efficacy indexes revealed significantly greater ADHD symptom relief in the MTP group. There were no group differences in self-reported cocaine use, urinalysis results, or cocaine craving. Because of the relatively small sample size, the results are preliminary. However, we found that MTP improved subjective reports of ADHD symptoms and did not worsen cocaine use while participants were in treatment.

Adolescent↗
PubMedDate not supplied

Women are less likely to be admitted to substance abuse treatment within 30 days of assessment.

The information gathered in a centralized intake unit (CIU) allows payers and administrators to examine if there are access issues for their population. For this study, the authors examined whether there were gender differences in the rate at which people are admitted to treatment within 30 days of assessment. Of the 5,004 individuals seeking publicly-funded substance abuse treatment in Detroit for the years 1996-97, 50.3% of those assessed at the CIU actually entered treatment. Women (31% of the people assessed) had a lower rate of admission (45% for women versus 53% for men) a difference that was maintained even after controlling for known risk factors. Women who were given priority for admission (i.e., those who were pregnant, had children, or injected drugs) had a higher rate of admission than other women (73% versus 39%), but only 17% of the women presenting were included in the priority groups. Men who were injecting drugs (a priority group) also had a higher rate of admission than other men (83% versus 49%). In multivariate analysis controlling for priority groups and known risk factors, women were still less likely to be admitted to treatment within 30 days of admission than men. Establishing priorities improves the rate of admission within 30 days of assessment for those groups, but more needs to be done to improve the admission rate for women. These results demonstrate that a CIU allows administrators to monitor for access issues.

Adult↗
PubMedDate not supplied

Interaction effects of treatment setting and client characteristics on retention and completion.

Client-treatment matching assumes treatment outcome will be improved if characteristics of clients are matched to specific elements of treatment. Few empirical studies, however, have examined matching across different types of treatment settings. The present research examined differences in demographics and substance-related problems in populations admitted to three substance abuse treatment settings--outpatient (n = 1132), intensive outpatient (n = 1190), and residential (n = 149)--and tested whether interactions between client characteristics and type of setting predicted rates of 30-day retention and treatment completion. In addition, three specific hypotheses based on prior theoretical and empirical investigations were tested. Client characteristics included demographic information (e.g., sex, age, race) and Addiction Severity Index (ASI) composite scores. Client-setting interactions were found for both retention and completion. All three hypotheses received at least partial support. Implications for client assignment and future research are discussed.

Adult↗
PubMedDate not supplied

Double-blind placebo-controlled trial of fluoxetine in smoking cessation treatment including nicotine patch and cognitive-behavioral group therapy.

Smoking cessation attempts are often complicated by dysphoria/depression, weight gain, craving, and other nicotine withdrawal symptoms. Fluoxetine's antidepressant and anorectant properties, along with its capacity to attenuate compulsive behavior, suggest that this medication might facilitate smoking cessation treatment. We examined the effect of fluoxetine on smoking cessation in the context of a program that included group cognitive-behavioral therapy (six weeks) and transdermal nicotine patch(ten weeks). In a double-blind randomized trial of fluoxetine for smoking cessation, 150 daily smokers were assigned to placebo (n=48), 20 mg (n=51), or 40 mg fluoxetine (n=51). Fluoxetine did not significantly improve smoking cessation rates, either for those with or without major depressive disorder(MDD)histories or elevated current depression. Our results suggest that fluoxetine may moderate withdrawal symptoms, even if that was not manifested in improved smoking cessation rates. Our results, however, clearly favor the use of fluoxetine if weight gain is a major clinical obstacle to smoking cessation.

Administration, Cutaneous↗