The NMDA antagonist memantine attenuates the expression of opioid physical dependence in humans.

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 (30 mg PO qid). Subsequently, they received a series of challenges with naloxone (0.4 mg, IM) and the severity of opioid withdrawal was monitored. Either placebo or memantine (60 mg PO) was given 6 h 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 attenuated the severity of opioid withdrawal as assessed with the Clinical Institute for Narcotic Withdrawal Scale scale. Withdrawal was significantly reduced when naloxone was administered at 6 and 52 h after memantine, but not when administered 126 h (5 days) after memantine. Medication effects, assessed 5 h after memantine administration and before naloxone administration, included significant increases in ratings of "strong" and "good" drug effect, and "I feel sedated", "mellow", and "high". CONCLUSIONS: Memantine attenuated the expression of opioid physical dependence in humans, indicating that glutamatergic neurotransmission at the NMDA receptor site contributes to the maintenance of opioid dependence. This finding suggests that memantine may be a useful adjunct in the treatment of opioid dependence.

The economic costs of heroin addiction in the United States.

This study documents the costs of heroin addiction in the United States, both to the addict and society at large. Using a cost-of-illness approach, costs were estimated in four broad areas: medical care, lost productivity, crime, and social welfare. We estimate that the cost of heroin addiction in the United States was US$21.9 billion in 1996. Of these costs, productivity losses accounted for approximately US$11.5 billion (53%), criminal activities US$5.2 billion (24%), medical care US$5.0 billion (23%), and social welfare US$0.1 billion (0.5%). The large economic burden resulting from heroin addiction highlights the importance of investment in prevention and treatment.

Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation.

The effects of drug dependence on social systems has helped shape the generally held view that drug dependence is primarily a social problem, not a health problem. In turn, medical approaches to prevention and treatment are lacking. We examined evidence that drug (including alcohol) dependence is a chronic medical illness. A literature review compared the diagnoses, heritability, etiology (genetic and environmental factors), pathophysiology, and response to treatments (adherence and relapse) of drug dependence vs type 2 diabetes mellitus, hypertension, and asthma. Genetic heritability, personal choice, and environmental factors are comparably involved in the etiology and course of all of these disorders. Drug dependence produces significant and lasting changes in brain chemistry and function. Effective medications are available for treating nicotine, alcohol, and opiate dependence but not stimulant or marijuana dependence. Medication adherence and relapse rates are similar across these illnesses. Drug dependence generally has been treated as if it were an acute illness. Review results suggest that long-term care strategies of medication management and continued monitoring produce lasting benefits. Drug dependence should be insured, treated, and evaluated like other chronic illnesses. JAMA. 2000;284:1689-1695.

The co-occurrence of smoking and binge drinking in adolescence.

The present work sought to determine adolescent rates of smoking and binge-drinking co-occurrence. Secondary analyses were conducted on the interview responses of more than 4,000 adolescents between the ages of 13 and 18 who took part in the 1995 National Household Survey on Drug Abuse. Results revealed that not only are adolescent smokers likely to be binge drinkers, but adolescent binge drinkers are also likely to be smokers. Conversely, those who abstain from involvement with one of these substances generally abstain from the other as well. The discussion highlighted race/ethnic and gender differences in co-occurrence rates as well as prevention and intervention implications.

The relationship between adolescent smoking and drinking and likelihood estimates of illicit drug use.

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.

Age-related differences in adolescent smokers' and nonsmokers' assessments of the relative addictiveness and health harmfulness of cigarettes, alcohol, and marijuana.

The present work was undertaken to determine how general beliefs about various substances and substance use behaviors change during adolescence. Secondary analyses were carried out on the telephone interview responses of 1,200 adolescent smokers and nonsmokers between the ages of 12 and 17. The specific beliefs regarding which substances were hardest to stop using and which were the most harmful to one's health by smoking status and age were compared using Chi-squared analyses for univariate comparisons, and polytomous logistic regression for multivariate analyses. Results revealed that the youngest cohort believed that marijuana was the substance most difficult to stop using while the oldest cohort believed that cigarettes were the hardest to stop using. A similar pattern was observed regarding which substance was the most harmful to one's health. While smokers believed that cigarettes were both the hardest to stop using and the most harmful, nonsmokers were divided between cigarettes and marijuana as the hardest to stop using, and indicated that marijuana, rather than cigarettes, were most harmful. Results are discussed in terms of their implications for substance abuse prevention and the development of relative risk assessments.

Cigarettes, alcohol, marijuana, other risk behaviors, and American youth.

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.

Developing a national addiction treatment information system. An introduction to the Drug Evaluation Network System.

The purpose of this article is to test the applicability and utility of the Drug Evaluation Network Study (DENS), a timely electronic information system that tracks trends in substance abuse treatment. This article examines existing large-scale data collection efforts, discusses the rationale and design of the DENS system, and presents results of the DENS pilot phase. Clinical staff from more than 40 service delivery units in five cities were trained to conduct intake assessments on laptop computers with the computerized Addiction Severity Index (ASI). The DENS computer system also included an automatic data transfer protocol to allow regular transmission of ASIs and other data to a central server at Treatment Research Institute. Descriptive information and discharge status were also collected. Several problems were encountered during the early stages of the pilot phase, including obtaining consecutive cases from treatment programs, computerization and software application, treatment staff turnover, and assuring quality of data. Data is presented on 4,300 adults entering drug and/or alcohol treatment at the nonrandomly selected DENS pilot programs between June 1996, and April 6, 1998. Various examples of how DENS data can be used are presented.

Making sense of medical marijuana.

The case for marijuana's medical use is primarily from anecdotal clinical reports, human studies of delta-9-tetrahydrocannabinol, and animal studies on constituent compounds. The authors believe that while a key policy issue is to keep marijuana out of the hands of children, its use for medicinal purposes should be resolved by scientific research and Food and Drug Administration (FDA) review. Weighed against possible benefits are increased risks such as cancer, pulmonary problems, damage to the immune system, and unacceptable psychological effects. More study is needed to determine the efficacy of marijuana as an antiemetic for cancer patients, as an appetite stimulant for AIDS and cancer patients, as a treatment for neuropathic pain, and as an antispasmodic for multiple sclerosis patients. If this new research shows marijuana to have important medical uses, FDA approval could be sought. However, the better response is accelerated development of delivery systems other than smoking for key ingredients, as well as the identification of targeted molecules that deliver beneficial effects without intoxicating effects. If the National Institutes of Health conducts research on marijuana, we would propose parallel trials on those indications under careful controls making marijuana available to appropriate patients who fail to benefit from standard existing treatments. This effort would begin after efficacy trials and sunset no later than 5 years. If this open-trial mechanism is adopted, the compassion that Americans feel for seriously ill individuals would have an appropriate medical/scientific outlet and not need to rely on referenda that can confuse adolescents by disseminating misleading information about marijuana effects.

Prevalence of adult attention-deficit hyperactivity disorder among cocaine abusers seeking treatment.

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.

Flupenthixol treatment for cocaine abusers with schizophrenia: a pilot study.

Cocaine use is common among individuals with schizophrenia and schizoaffective illness, with a prevalence ranging from 15-60% of patient samples. It is hypothesized that some schizophrenic cocaine abusers may use cocaine as an attempt to improve anhedonic symptoms or combat neuroleptic side-effects. Flupenthixol (FLX) has the distinct advantage of being both a neuroleptic medication and a potential treatment for cocaine abuse. We evaluated the efficacy of FLX in this dually diagnosed population in an open pilot study consisting of a 4-week inpatient phase and a 6-week outpatient phase. Eight individuals were initially cross-tapered off their neuroleptic medication and were given FLX in a dose of 40 mg of the decanoate every 2 weeks. Psychiatric symptomatology was assessed weekly, using the Positive and Negative Symptom Scale (PANSS) and the Beck Depression Inventory (BDI). Medication side-effects were monitored weekly, using the Simpson Neurological Rating Scale and the Abnormal Involuntary Movement Scale (AIMS). Substantial improvement in psychiatric symptomatology was noted when preadmission scores were compared to scores obtained during the last week of study enrollment. On the PANSS, positive symptom scores and negative symptom scores decreased by 31% and 29%, respectively. Similarly, BDI scores decreased by 57%. Comparing preadmission urine results to those for the last 6 weeks of enrollment in the study showed that cocaine-positive urines decreased by 28%, although most of the patients had a reduction of >75%. Missed clinic visits decreased by 26%. Thus, FLX was well-tolerated by schizophrenic cocaine abusers, suggesting that FLX may be useful for the treatment of this dually diagnosed population.

Methylphenidate treatment for cocaine abusers with adult attention-deficit/hyperactivity disorder: a pilot study.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Rationale and design of the Cocaine Alternative Treatments Study (CATS): a randomized, controlled trial of acupuncture.

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.

Methodological investigations for a multisite trial of auricular acupuncture for cocaine addiction: a study of active and control auricular zones.

We evaluated objective criteria for defining points for needle insertion prior to conducting a multisite clinical trial of auricular acupuncture for cocaine addiction. Thirty-four cocaine-abusing subjects participated in a study in which the trial's active zones (Shenmen, Liver, Lung, and Sympathetic) and control zones (located on the ear helix) were divided into quadrants and assessed along four dimensions: electrical resistance, skin discoloration, skin topography, and tenderness. Acute effects of needles inserted into points of low electrical resistance in one ear and high electrical resistance in the other were also assessed. Results showed that the active zones had lower overall electrical resistance and more subcutaneous ridges than control zones. Zones did not possess significant variability along any single dimension. Acute effects of needling high and low resistance points were similar, differing only for "fullness." Based on these findings, and in view of the difficulty of accurately measuring electrical resistance at ear points, we do not recommend the use of electrical devices for point determination in the multisite study. At present, there seems to be little scientific basis for the preselection of specific points for needle insertion within auricular zones. Needle placement should be based upon clinical judgement.