Research Interests:
Research Interests:
Rationale: Preclinical observations suggest that NMDA receptor-mediated glutamatergic neurotransmission is involved in the expression and maintenance of opioid dependence. Objective: The present study evaluated whether memantine, the... more
Rationale: Preclinical observations suggest that NMDA receptor-mediated glutamatergic neurotransmission is involved in the expression and maintenance of opioid dependence. Objective: The present study evaluated whether memantine, the clinically available non-competitive NMDA receptor antagonist, decreases naloxone-precipitated withdrawal in morphine-dependent humans. Methods: Eight heroin-dependent, non-treatment seeking, inpatient participants were stabilized on a fixed dose of morphine (30mg PO qid). Subsequently, they received a series of challenges with naloxone (0.4mg, IM) and the severity of opioid withdrawal was monitored. Either placebo or memantine (60mg PO) was given 6h before each naloxone challenge. A modified multiple baseline, across-participants design was used to evaluate the effects of memantine on the severity of naloxone-precipitated opioid withdrawal. Results: Naloxone increased ratings and produced physical changes consistent with opioid withdrawal. Memantine at...
Research Interests:
Treatment of opiate dependence with naltrexone has been limited by poor compliance. Behavioral Naltrexone Therapy (BNT) was developed to promote adherence to naltrexone and lifestyle changes supportive of abstinence, by incorporating... more
Treatment of opiate dependence with naltrexone has been limited by poor compliance. Behavioral Naltrexone Therapy (BNT) was developed to promote adherence to naltrexone and lifestyle changes supportive of abstinence, by incorporating components from empirically validated treatments, including Network Therapy with a significant other to monitor medication compliance, the Community Reinforcement Approach, and voucher incentives. An overview is presented of the BNT treatment manual. In an uncontrolled Stage I trial (N = 47), 19% completed the 6-month course of treatment. Retention was especially poor in the subsample of patients who were using methadone at baseline (N = 18; 39% completed 1 month, none completed 6 months), and more encouraging among heroin-dependent patients (N = 29; 65% completed 1 month, 31% completed 6 months). Thus, attrition continues to be a serious problem for naltrexone maintenance, although further efforts to develop interventions such as BNT are warranted.
Research Interests:
To examine demographic differences in alcohol telescoping-the rate of self-reported movement from regular alcohol consumption to the onset of regular heavy drinking-as well as differences in ages of initiation of regular alcohol use and... more
To examine demographic differences in alcohol telescoping-the rate of self-reported movement from regular alcohol consumption to the onset of regular heavy drinking-as well as differences in ages of initiation of regular alcohol use and alcohol use to intoxication. The present study compared the retrospective reports of 2037 clients (1252 males, 785 females) enrolled in substance user treatment facilities around the country in 1998 and 1999. Overall, the findings support previous research, indicating that women generally move more rapidly than men from initiation of regular alcohol use to problem use (telescoping). The findings also indicate that African-Americans generally begin regular alcohol use later than their Anglo counterparts and move more rapidly from initiation of regular alcohol use to problem use (telescoping). Examining the sample by older vs. younger age groups demonstrates that gender and racial/ethnic differences in the age of initiation of regular alcohol use and i...
Research Interests:
Research Interests: Psychology, Community-Based Mental Health Services, Financial management, Quality of Mental Health Care, Substance Abuse Treatment, and 8 moreInformation Services, Humans, Substance Abuse, United States, Addiction Treatment, Personnel Management, Public health systems and services research, and Substance-Related Disorders
Research Interests: Terrorism, Depression, Anxiety, Humans, New York City, and 5 moreUnited States, Female, Alcohol Drinking, Male, and ANXIETY
Treatment of opiate dependence with naltrexone has been limited by poor compliance. Behavioral Naltrexone Therapy (BNT) was developed to promote adherence to naltrexone and lifestyle changes supportive of abstinence, by incorporating... more
Treatment of opiate dependence with naltrexone has been limited by poor compliance. Behavioral Naltrexone Therapy (BNT) was developed to promote adherence to naltrexone and lifestyle changes supportive of abstinence, by incorporating components from empirically validated treatments, including Network Therapy with a significant other to monitor medication compliance, the Community Reinforcement Approach, and voucher incentives. An overview is presented of the BNT treatment manual. In an uncontrolled Stage I trial (N = 47), 19% completed the 6-month course of treatment. Retention was especially poor in the subsample of patients who were using methadone at baseline (N = 18; 39% completed 1 month, none completed 6 months), and more encouraging among heroin-dependent patients (N = 29; 65% completed 1 month, 31% completed 6 months). Thus, attrition continues to be a serious problem for naltrexone maintenance, although further efforts to develop interventions such as BNT are warranted.
Research Interests:
Research Interests: Pharmacology, Genetics, Long Term Care, Social Problems, Medication Adherence, and 24 moreTreatment, Asthma, Pharmacovigilance, Health insurance, Public Health, Health Policy, Chronic illness, Comparative Study, Literature Review, Humans, Hypertension, Questionnaire, Chronic Disease, United States, Insurance, Ethanol, Substance Dependence, Alcohol dependence, Social System, Health Problems, Type 2 Diabetes Mellitus, Drug Dependence, Substance-Related Disorders, and JAMA
Research Interests:
Research Interests:
Research Interests:
Many studies have documented the safety, efficacy, and effectiveness of long-acting opioids (L-AOs), such as methadone and buprenorphine, in the treatment of heroin addiction. This article reviews the pharmacological differences between... more
Many studies have documented the safety, efficacy, and effectiveness of long-acting opioids (L-AOs), such as methadone and buprenorphine, in the treatment of heroin addiction. This article reviews the pharmacological differences between L-AO medications and short-acting opioids (heroin) in terms of reinforcing properties, pharmacokinetics, effects on the endocrine and immune systems. Given their specific pharmacological profile, L-AOs contribute to control addictive behavior, reduce craving, and restore the balance of disrupted endocrine function. The use of the term "substitution," referring to the fact that methadone or buprenorphine replace heroin in binding to brain opioid receptors, has been generalized to consider L-AOs as simple replacement of street drugs, thus contributing to the widespread misunderstanding of this treatment approach.
Research Interests:
This study compares the clinical characteristics of and treatment implications for five demographic groups of addicts: Black and White males and females and Hispanic males evaluated in Spanish. Among the 522 addicts, the 60 Puerto Rican... more
This study compares the clinical characteristics of and treatment implications for five demographic groups of addicts: Black and White males and females and Hispanic males evaluated in Spanish. Among the 522 addicts, the 60 Puerto Rican males had the most frequent unemployment, the least education, the most polydrug abuse and violent crimes, the highest rate of schizophrenic or anxiety disorders, and more neurotic and depressive symptoms than the other male addicts. These addicts seem to have the greatest liabilities of any group and may need residential treatment. The 126 female addicts had frequent unemployment, high rates of depression and anxiety disorders, and more severe medical problems than men. This suggested that they have some treatment needs that are different than those of male addicts, including care for dependent children. Some differences between Black and White males in drug use were also found between Black and White females. White males (177) had a high rate of antisocial personality and polydrug abuse but had fairly good economic functioning. A structured treatment program to deal with their common illicit activities may be necessary for these addicts. The 159 Black males had poor occupational functioning but relatively little psychopathology. Vocational rehabilitation may be needed for them.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Naltrexone, an opioid antagonist, is currently approved as a treatment for heroin dependence. However, naltrexone is generally not well accepted by patients, and medication non-compliance is a difficult obstacle to treatment. A... more
Naltrexone, an opioid antagonist, is currently approved as a treatment for heroin dependence. However, naltrexone is generally not well accepted by patients, and medication non-compliance is a difficult obstacle to treatment. A sustained-release form of naltrexone may improve compliance. The present study was designed to evaluate the time course, safety, and effectiveness of a depot formulation of naltrexone (Depotrex). Twelve heroin-dependent individuals participated in an 8-week inpatient study. After a 1-week detoxification period, six participants received 192 mg naltrexone base and six participants received 384 mg naltrexone base. For safety, the low dose of depot naltrexone was tested before the high dose. The effects of heroin (0, 6.25, 12.5, 18.75, 25 mg, i.v.) were evaluated for the next 6 weeks. One dose of heroin was tested per day on Mondays through Fridays, and the entire dose range was tested each week. Active heroin doses were administered in ascending order during the week, while placebo could be administered on any day. Subjective, performance, and physiological effects were measured both before and after heroin administration. The hypotheses were that depot naltrexone would antagonize the effects of heroin, and that the high dose of depot naltrexone would produce a more effective and longer-lasting antagonism than the low dose. The low and high doses of depot naltrexone antagonized heroin-induced subjective ratings for 3 and 5 weeks, respectively. Plasma levels of naltrexone remained above 1 ng/ml for approximately 3 and 4 weeks after administration of 192 mg and 384 mg naltrexone. Other than the initial discomfort associated with the injection of depot naltrexone, there were no untoward side-effects. These results suggest that this depot formulation of naltrexone provides a safe, effective, long-lasting antagonism of the effects of heroin.
Research Interests:
Clonidine hydrochloride, an alpha 2-adrenergic agonists, was used to treat seven infants who were passively addicted to narcotics because of maternal methadone maintenance. In six of seven infants, the major symptoms of narcotic... more
Clonidine hydrochloride, an alpha 2-adrenergic agonists, was used to treat seven infants who were passively addicted to narcotics because of maternal methadone maintenance. In six of seven infants, the major symptoms of narcotic withdrawal were ameliorated after a total daily oral dose of 3-4 micrograms/kg/day was achieved. One infant failed to respond. No toxic side effects of clonidine were observed at the dosage level used. The results of this pilot study suggest that clonidine may be a safe therapeutic agent for the treatment of neonatal narcotic abstinence syndrome (NNAS). Clonidine treatment of NNAS remains strictly investigational at this time. The relative efficacy and safety of clonidine versus other currently used drug regimens for NNAS also remains to be determined.
Research Interests:
Research Interests:
Buprenorphine and buprenorphine/naloxone (BUP) are newly approved for office-based treatment of opioid dependence. Federal and non-federal regulatory and monitoring agencies, national and international researchers, national professional... more
Buprenorphine and buprenorphine/naloxone (BUP) are newly approved for office-based treatment of opioid dependence. Federal and non-federal regulatory and monitoring agencies, national and international researchers, national professional organizations, researchers involved in monitoring, opioid treatment programs and the pharmaceutical industry met to synthesize and disseminate practical information to guide training, practice, monitoring, regulation and evaluation efforts with these medications. We performed a review of the literature, training curricula and practice guidelines and commissioned manuscripts describing recently completed, or still in progress, studies or field experiences with BUP treatment. A consensus process generated fifteen statements: (1) The federal government should collect baseline data on opioid-related deaths and morbidity to assess the effect of BUP on public health, (2) the patient limit for group practices should apply to individual physicians rather than group practices, (3 and 4) telephone and Internet-based physician and pharmacist support is needed, (5) clinicians who provide psychosocial services to opioid dependent patients should be informed of the role of BUP, (6) opioid-dependent patients should be instructed to present for induction in mild withdrawal, (7) the existing Center for Substance Abuse Treatment guidelines provide a reasonable induction protocol, (8) physicians should be prepared to use ancillary medications with BUP induction, (9) a physician or nurse must be available to the patient during the induction period, (10) concurrent counseling and support services are necessary, (11) detoxification without appropriate followup addiction treatment leads to rapid relapse and is not as effective as maintenance, (12) pregnant opioid-dependent women should be treated using good clinical practice including specialist addiction care and prenatal care, (13) BUP induction and withdrawal treatment may benefit from different designations for payment, (14) take-home medication options should be tailored to patients' needs, (15) there is a need for clinical and policy research in unique patient populations.
Research Interests: Psychology, Public Health, Substance Abuse Treatment, Pharmaceutical industry, Humans, and 14 moreFederal Government, United States, Addiction Treatment, Buprenorphine, Field Experiment, Detoxification, Heroin Dependence, Mental health services, Substance, Opioid Dependence, Public health systems and services research, Good Clinical Practice in Clinical Trials, Prenatal Care, and Ambulatory Care
Research Interests: Psychology, Substance Abuse Treatment, Humans, United States, Female, and 14 moreMale, Service Delivery, Addiction Treatment, Data Collection, Registries, Data transfer, Adult, Public health systems and services research, Computer communication networks, Large Scale, Pilot Projects, Substance-Related Disorders, Quality of data, and Information System
Research Interests:
Research Interests:
The differential diagnosis of psychiatric comorbidity in substance abusers is important in order to provide effective pharmacological and psychotherapeutic treatments for the comorbid psychiatric disorders. Differential diagnosis of an... more
The differential diagnosis of psychiatric comorbidity in substance abusers is important in order to provide effective pharmacological and psychotherapeutic treatments for the comorbid psychiatric disorders. Differential diagnosis of an underlying psychiatric disorder depends on the type of drug abused and the phase of abuse, ranging from acute intoxication to withdrawal. This review derives guidelines for differential diagnosis based on multiple examples of interactions between major psychiatric disorders and various abused drugs.
Research Interests:
The authors report on three cases of cocaine dependence treated with methylphenidate. All patients treated showed marked to dramatic improvement with regard to toxic/abstinence signs and symptoms, craving behavior and other behavioral... more
The authors report on three cases of cocaine dependence treated with methylphenidate. All patients treated showed marked to dramatic improvement with regard to toxic/abstinence signs and symptoms, craving behavior and other behavioral disturbances associated with heavy and chronic cocaine abuse. The authors explore the possibility that cocaine dependence is associated with pre-existing or resulting psychopathology, particularly mood disturbances. Emphasis is also placed on a predisposing or de novo attention deficit disorder (ADD) as possibly contributing to heavy or continued reliance on cocaine.
Research Interests:
During a 2.5-year follow-up of opioid addicts, we examined psychosocial antecedents and consequences of the onset and remission of cocaine abuse. Patients who never used cocaine were compared with those whose use increased or decreased... more
During a 2.5-year follow-up of opioid addicts, we examined psychosocial antecedents and consequences of the onset and remission of cocaine abuse. Patients who never used cocaine were compared with those whose use increased or decreased along several dimensions of treatment outcome including drug abuse, legal, employment, family, social, psychological, and medical problems. Cocaine abuse had a marked impact on almost every outcome area except medical problems. Patients whose cocaine use increased during follow-up had more severe problems than either those whose use decreased or those who never used cocaine. Furthermore, the attainment of cocaine abstinence among abusers was associated with improved psychosocial functioning, whereas the onset of cocaine abuse was associated with increased problem severity. Compared with drug-free and detoxification alone treatments, methadone maintenance may minimize legal complications of cocaine abuse, but otherwise it did not significantly reduce psychosocial morbidity from increasing cocaine abuse. These findings suggest that treatment-seeking opioid addicts are vulnerable to wide-ranging deterioration when they become increasingly involved with cocaine but that with the attainment of abstinence many problem areas improve.
Research Interests:
... 2 Printed in USA A Comparison of the SADS/RDC and the DSM-III Diagnosing Drug Abusers BRUCE J. ROUNSAVILLE, MD,1 PATRICIA ROSENBERGER, BA,- CHARLES WILBER, Ed.M.,2 MYRNA M. WEISSMAN, Ph.D.,' and HERBERT D. KLEBER,... more
... 2 Printed in USA A Comparison of the SADS/RDC and the DSM-III Diagnosing Drug Abusers BRUCE J. ROUNSAVILLE, MD,1 PATRICIA ROSENBERGER, BA,- CHARLES WILBER, Ed.M.,2 MYRNA M. WEISSMAN, Ph.D.,' and HERBERT D. KLEBER, MD' Two methods were ...
Research Interests:
Attention-deficit/hyperactivity disorder (ADHD) is common among cocaine abusers seeking treatment. This open trial was carried out to assess the efficacy of sustained-release methylphenidate for the treatment of cocaine abuse among... more
Attention-deficit/hyperactivity disorder (ADHD) is common among cocaine abusers seeking treatment. This open trial was carried out to assess the efficacy of sustained-release methylphenidate for the treatment of cocaine abuse among individuals with ADHD. Twelve patients who met DSM-IV diagnostic criteria for adult ADHD and cocaine dependence were entered into a 12-week trial of divided daily doses of sustained-release methylphenidate ranging from 40 to 80 mg. In addition to the pharmacotherapy, patients also received individual weekly relapse prevention therapy. Individuals were assessed weekly for ADHD symptoms; vital signs and urine toxicologies were obtained 3 times a week. Of the 12 patients entered, 10 completed at least 8 weeks of the study and 8 completed the entire study. Using both a semistructured clinical interview and a self-report assessment, patients reported reductions in attention difficulties, hyperactivity, and impulsivity. Self-reported cocaine use and craving decreased significantly. More importantly, cocaine use, confirmed by urine toxicologies, also decreased significantly. These preliminary data suggest that under close supervision, the combined intervention of sustained-release methylphenidate and relapse prevention therapy may be effective in treating individuals with both adult ADHD and cocaine dependence.
Research Interests:
Acupuncture has been incorporated as a treatment component in numerous addiction treatment programs in the United States; however, its efficacy has not been demonstrated in large-scale, controlled clinical trials. In this article we... more
Acupuncture has been incorporated as a treatment component in numerous addiction treatment programs in the United States; however, its efficacy has not been demonstrated in large-scale, controlled clinical trials. In this article we discuss the background and design of the Cocaine Alternative Treatments Study (CATS), a randomized, controlled, multisite study of acupuncture that will enroll 500 cocaine-dependent individuals at 6 sites across the country, and that constitutes the largest controlled trial for the treatment of cocaine addiction undertaken to date. After presenting the background of the study, we discuss the approach taken to address several critical issues, including the choice of appropriate control conditions, point location for needle insertion, degree of blinding, and bias checks. Complementary therapies are used by a significant number of individuals, and the need to evaluate them in controlled clinical trials is an ongoing and urgent issue.
Research Interests:
Research Interests:
Using data from a recent national survey of adolescent substance use, the present work examined whether adolescents with different patterns of alcohol and cigarette use differed in their estimates of the likelihood they would use an... more
Using data from a recent national survey of adolescent substance use, the present work examined whether adolescents with different patterns of alcohol and cigarette use differed in their estimates of the likelihood they would use an illegal drug in the future. While nonusers of either substance were the most likely to indicate that they would never use drugs in the future, users of both substances were the most likely to indicate that they would use drugs. In addition, while users of both were most likely to indicate that they were likely to use illegal substances, only-smokers were more likely than only-drinkers to indicate that they were likely to use such substances in the future. Results are discussed in terms of the gateway theory of drug sequencing and cognitive precursors of experimentation with illegal substances.
Research Interests:
Research Interests: Pharmacology, Genetics, Long Term Care, Social Problems, Medication Adherence, and 24 moreTreatment, Asthma, Pharmacovigilance, Health insurance, Public Health, Health Policy, Chronic illness, Comparative Study, Literature Review, Humans, Hypertension, Questionnaire, Chronic Disease, United States, Insurance, Ethanol, Substance Dependence, Alcohol dependence, Social System, Health Problems, Type 2 Diabetes Mellitus, Drug Dependence, Substance-Related Disorders, and JAMA
Research Interests:
Research Interests: Psychology, Clinical Trial, Social Support, Treatment Outcome, Comorbidity, and 22 moreSubstance Abuse Treatment, Humans, Substance Abuse, Female, Cocaine, Male, Statistical Significance, Sample Size, Substance, Urinalysis, Middle Aged, Active site, Methadone, Adult, Public health systems and services research, Randomized Controlled Trial, Hiv seropositivity, Controlled Clinical Trial, Large Scale, Substance-Related Disorders, JAMA, and Relaxation Therapy
... GEORGE L. COHN, JOYCE A. CRAMER, WILLIAM MCBRIDE,~ RONALD C. BROWN,^ AND HERBERT D. KLEBER Department of Psychiatry, Yale ... OH: alpha globulin, fraction IV-1; beta globulin, fraction 111; beta lipoprotein, frac-tion 111-0.... more
... GEORGE L. COHN, JOYCE A. CRAMER, WILLIAM MCBRIDE,~ RONALD C. BROWN,^ AND HERBERT D. KLEBER Department of Psychiatry, Yale ... OH: alpha globulin, fraction IV-1; beta globulin, fraction 111; beta lipoprotein, frac-tion 111-0. Schwarz/Mann, Orangeburg, NY ...
Research Interests:
ABSTRACT Radioactive heroin was injected into rats treated with (cold) heroin (HA), nontreated control rats, and previously treated “withdrawn” rats (HW). The animals were sacrificed between 0–20 min postinjection. Brain, liver, kidneys... more
ABSTRACT Radioactive heroin was injected into rats treated with (cold) heroin (HA), nontreated control rats, and previously treated “withdrawn” rats (HW). The animals were sacrificed between 0–20 min postinjection. Brain, liver, kidneys and plasma were removed and assayed for the presence of heroin in relation to MAM and morphine.
Research Interests:
Research Interests: Economics, Biology, Treatment, Economic policy, Public Health, and 17 moreHealth Policy, Medicine, Prevention, Social Welfare, Workplace, Humans, United States, Female, Male, Drug Addiction, Injecting Drug Use, Heroin Dependence, Medical Care, Prevalence, Cost Analysis, Cost of Illness, and Health Care Costs
Increases in adolescent marijuana and other drug use have created widespread concern. One theory argues that increased use of cigarettes and alcohol among younger adolescents leads to greater use of marijuana which, in turn, leads to... more
Increases in adolescent marijuana and other drug use have created widespread concern. One theory argues that increased use of cigarettes and alcohol among younger adolescents leads to greater use of marijuana which, in turn, leads to subsequent use of other drugs (e.g. cocaine, heroin, hallucinogens). Detractors of this theory claim that use of these substances is a symptom of a larger set of destructive behaviors (e.g. violence, suicide, promiscuous sex), and marijuana has no independent effect on the use of other more serious drugs. The authors examined whether, for high school seniors, early use of cigarettes, alcohol and marijuana has an independent effect on more serious drug use even when other behaviors are considered. Using the 1995 Youth Risk Behavior Survey (n = 2871) and logistic analysis, after accounting for selected other behaviors, seniors using cigarettes before age 13 were 3.3 (95% C.I. 2.3,4.6) times likelier to have used marijuana than ones who never smoked; for alcohol, the odds ratio was 4.5 (2.6,7.7). Seniors using marijuana before the age of 14 were 7.4 times (4.0,13.6) likelier to have used other drugs. Though no causal effect is demonstrated, cigarette and alcohol use was associated with the likelihood of marijuana use; marijuana use was associated with the likelihood of other drug use, even after selected other risk and protective behaviors were considered.
Research Interests:
Research Interests:
In this study, 281 cocaine abusers seeking treatment were assessed for adult attention-deficit hyperactivity disorder (ADHD). Structured assessments included the SCID for DSM-IV, a SCID-like module for ADHD, and a pattern of drug use... more
In this study, 281 cocaine abusers seeking treatment were assessed for adult attention-deficit hyperactivity disorder (ADHD). Structured assessments included the SCID for DSM-IV, a SCID-like module for ADHD, and a pattern of drug use questionnaire. The sample consisted of 82% men, 67% African-Americans, 19% Hispanics, and 14% Caucasians identified at several treatment sites. Average age was 33.7 +/- .4 years. Twelve percent (n = 34) of the sample met DSM-IV criteria for childhood ADHD. Of the entire sample, 10% (n = 27), or 79% of the patients diagnosed with childhood ADHD, had adult ADHD. A history of conduct disorder and antisocial personality disorder were prevalent among those with adult ADHD (63% and 52%, respectively). This subpopulation of cocaine abusers may be one of the most difficult-to-treat cocaine-abusing groups, particularly if the ADHD remains undetected. To provide effective treatment for cocaine abusers, clinicians may need to identify subpopulations of patients, such as those with ADHD, and target both pharmacologic and nonpharmacologic interventions for these groups.