Midbrain functional connectivity and ventral striatal dopamine D2-type receptors: link to impulsivity in methamphetamine users.

Stimulant use disorders are associated with deficits in striatal dopamine receptor availability, abnormalities in mesocorticolimbic resting-state functional connectivity (RSFC) and impulsivity. In methamphetamine-dependent research participants, impulsivity is correlated negatively with striatal D2-type receptor availability, and mesocorticolimbic RSFC is stronger than that in controls. The extent to which these features of methamphetamine dependence are interrelated, however, is unknown. This question was addressed in two studies. In Study 1, 19 methamphetamine-dependent and 26 healthy control subjects underwent [18F]fallypride positron emission tomography to measure ventral striatal dopamine D2-type receptor availability, indexed by binding potential (BPND), and functional magnetic resonance imaging (fMRI) to assess mesocorticolimbic RSFC, using a midbrain seed. In Study 2, an independent sample of 20 methamphetamine-dependent and 18 control subjects completed the Barratt Impulsiveness Scale in addition to fMRI. Study 1 showed a significant group by ventral striatal BPND interaction effect on RSFC, reflecting a negative relationship between ventral striatal BPND and RSFC between the midbrain and striatum, orbitofrontal cortex and insula in methamphetamine-dependent participants, but a positive relationship in the control group. In Study 2, an interaction of the group with RSFC on impulsivity was observed. Methamphetamine-dependent users exhibited a positive relationship of midbrain RSFC to the left ventral striatum with cognitive impulsivity, whereas a negative relationship was observed in healthy controls. The results indicate that ventral striatal D2-type receptor signaling may affect the system-level activity within the mesocorticolimbic system, providing a functional link that may help explain high impulsivity in methamphetamine-dependent individuals.

Reinforcement of competing behavior during extinction.

Conditioned behavior declines in frequency when reinforcement is discontinued. In two experiments this extinction process was facilitated when competing behavior was reinforced as the original response was extinguished. When reinforcement for competing behavior was withdrawn, however, rats resumed their original behavior and there were no overall savings in total responses to extinction.

Control of their environment reduces emotionality in rats.

Rats reared from birth in a "contingent environment" in which they controlled lighting conditions and the delivery of food and water were compared as adults to rats reared in an environment in which they received the same food, water, and lighting conditions, but without control over their occurrence. Rats reared in the contingent environment were less emotional, as judged by activity and defecation scores in open-field testing.

Outpatient treatment of prescription opioid dependence: comparison of two methods.

Twenty-one patients dependent on prescription opioids were treated by 21-day detoxification followed by psychotherapeutic counseling (D/C), and 21 patients were detoxified 21 days and provided opioid maintenance if detoxification was unsuccessful (D/M). Only five of 21 (23.8%) patients in the D/C group compared with 20 of 21 (95.2%) in the D/M group completed three weeks of treatment. No patient initially perceived that chronic pain due to a medical condition would be an impediment to withdrawal from opioids, but pain that was masked by opioid dependency and that emerged during detoxification proved to be an insurmountable barrier to total withdrawal in the majority of patients. Treatment of outpatients with dependence on prescription opioids is best provided by opioid maintenance therapy and adjunctive pain therapy.

Clinical experience with naltrexone in suburban opioid addicts.

In a study of 160 patients (including 114 active heroin addicts and 42 former heroin addicts maintained on methadone, propoxyphene napsylate, or LAAM), subjects were retained on treatment with naltrexone for a mean of 50.7 days (range, 1-635). Clonidine or guanabenz acetate was used to detoxify subjects who received naltrexone within 10 days of their last dose of opioid. Because of the number of subjects dropping out of treatment after only a few days, it is recommended that there be an opioid-free period of 5 or more days for heroin-dependent subjects and 10 or more days for those on medical maintenance. A naloxone challenge should be administered at a dosage of 0.8 mg. Use of naltrexone combined with psychotherapy appears to promote long periods of opioid abstinence but does not prevent relapse after treatment. Trained clinicians utilizing an appropriate induction protocol can effectively treat volunteer opioid addicts with naltrexone.

Localization of neurochemical effects of cocaine and other stimulants in the human brain.

The cocaine epidemic is a complex problem that has defied conventional medical, psychological, and legal interventions. A better understanding of the brain mechanisms that lead to cocaine's unsurpassed euphoric and reinforcing effects, as well as to associated physical brain damage, will be needed to develop new treatment strategies. Although much work has been done on cocaine's effects in the brains of animals, most techniques used have not been safe for human subjects. Positron emission tomography (PET) offers a unique opportunity for studying the cerebral biochemistry of cocaine abuse in humans. The authors present preliminary data from their ongoing studies of the effects of cocaine and related psychostimulants on the brain's energy requirements and on catecholamine neurotransmitter systems.

A 3-year progress report on the implementation of LAAM in the United States.

AIMS: LAAM, a long-acting opioid agonist, was approved by the US Food and Drug Administration in 1993 for use in licensed narcotic treatment programs. These programs have the exclusive authority in the United States to dispense methadone and LAAM for the treatment of opiate dependence. The purpose of this report is to describe the course of LAAM's implementation and to document some of the factors that have influenced the time course and extent of this process. DESIGN: Narcotic treatment programs approved for LAAM use were contacted by telephone at three timepoints following the FDA approval of LAAM in 1993. FINDINGS: Regulatory hurdles have been the most significant factor in slowing the use of LAAM. Some clinics have enthusiastically moved LAAM into mainstream use with great success. At other clinics LAAM implementation has been impeded by staff resistance and management reluctance. Some specific clinical practices, such as provision of adequate dose levels and flexible dosing practices, appear to be associated with superior clinical response, but issues of staff and organizational attitude toward the new medication are probably the most important impediments to a more positive response. CONCLUSIONS: The tasks involved with introducing a new opiate agonist treatment into mainstream use in the United States are numerous and complex. Clinical policies, fiscal issues and regulatory factors must all be addressed. The introduction of LAAM into the treatment system provides some useful lessons as other new addiction pharmacotherapies are moved into mainstream use.

Propoxyphene napsylate maintenance treatment for narcotic dependence: a non-methadone model.

One hundred and seventy eight heroin addicts entered propoxyphene napsylate (PN) maintenance. Patients attended a general medical clinic twice each week and took home a three- to four-day supply of PN, to be taken in doses of 300 to 400 mg three or four times per day. Over a 21-month period, subjects entered and re-entered PN treatment 266 times (1.5 times per patient) and remained in treatment a mean of 10.6 weeks. When compared with a group of methadone maintenance patients, similar characteristics in employment and heroin use were found. The ability to take PN, attend a clinic less often than daily and discontinue and re-enter treatment on a discretionary basis is a preferred treatment approach for some narcotic addicts.

Efficacy of psychotherapeutic counselling during 21-day ambulatory heroin detoxification.

Structured, psychotherapeutic counselling during 21-day heroin detoxification was evaluated by randomly assigning a group of 25 heroin addicts to a detoxification treatment regimen with mandatory counselling by a therapist and 25 to a control group who received only standard detoxification without counselling. There was no significant difference between groups in the number who successfully detoxified as measured by conversion of morphine positive urine to morphine negative urine. The counselling intervention group did, however, improve the attendance of subjects while in detoxification treatment, and significantly more patients entered long-term treatment following detoxification. Maximal use of a counselor during 21-day heroin detoxification may best be realized by directing therapy toward engaging patients in long-term care.

Characteristics of 68 chronic phencyclidine abusers who sought treatment.

An analysis of 68 phencyclidine (PCP) users who sought treatment reveals that chronic compulsive, daily use occurs and that intravenous use is relatively common. Twenty-five (37%) subjects considered themselves to be addicted to PCP and 19 (29%) desired medication to assist withdrawal. Unwanted behaviors under the influence of PCP were common and primarily related to memory loss, or acts which resulted from loss of impulse control.

Overdose, suicide attempts and death among a cohort of naltrexone-treated opioid addicts.

In a study evaluating naltrexone with either an intensive psychosocial protocol or standard community treatment for opioid dependence, 13 of 81 subjects overdosed within a 12-month period of study participation. There were four fatalities, one of which was a suicide. Among the nine nonfatal overdoses, there were four suicide attempts. Characteristics of subjects and naltrexone-taking are described.

Cocaine abuse counseling as HIV prevention.

The current study evaluated the efficacy of cocaine abuse counseling alone as a strategy to reduce HIV-related sexual risk behaviors. Participants were 232 cocaine-abusing or dependent individuals who received up to 26 weeks of Matrix counseling but no formal HIV-prevention interventions. One hundred fifty-seven (67.6%) participants completed assessments at admission, during treatment, and at 6 months following admission. Participants located for follow-up were significantly more likely to be Caucasian, to be better educated, and to complete longer treatment episodes than those not located. Main study findings indicated a statistically significant association between safer sex behavior and completion of a cocaine abuse counseling episode (chi 2 (2, n = 157) = 6.25, p < .05). Participants who completed counseling were more likely to change to safer sex or maintain safer sex over the 6-month period than participants who terminated counseling prematurely. The primary method for reducing sexual risk involved overall decreases in reported numbers of partners (Partners-baseline = 5.32, SD = 6.25; Partners6 Months = 2.47, SD = 2.62; F(1, 132) = 36.32, p < .001) among this group of mostly heterosexual (89.9%), Caucasian (69.0%), crack cocaine users (65.6%). We concluded that cocaine abuse counseling is a powerful intervention for reducing HIV-related sexual behaviors in this group at high risk for exposure to HIV. Study findings suggested that efforts to evaluate HIV prevention programs must also account for the effect of drug counseling.

Burnout in substance abuse counselors. Impact of environment, attitudes, and clients with HIV.

Due to associations between acquired immunodeficiency sydnrome (AIDS) and substance abuse, many substance abuse treatment counselors have clients with human immunodeficiency virus (HIV)/AIDS. We assess the contribution of various hypothesized predictors of burnout among 134 substance abuse counselors working with clients with HIV/AIDS. Counselors reported practice-related variables, including support from coworkers and supervisors, caseload, percentage of HIV-positive clients, and whether they worked at a methadone clinic, and personal characteristics of job efficacy and education. The three burnout dimensions were emotional exhaustion, depersonalization, and personal accomplishment. Emotional exhaustion was significantly predicted by less support, less efficacy, and working in a methadone clinic. Depersonalization was predicted by less efficacy, less support, and working in a methadone clinic. Personal accomplishment was predicted by having a lower percentage of clients with HIV/AIDS, and more efficacy, support, and education. We present empirically based suggestions for interventions that can prevent or limit burnout.

Sexual HIV risk among gay and bisexual male methamphetamine abusers.

The current report examined HIV-related high risk sexual behaviors among a small sample of gay and bisexual male methamphetamine abusers in Los Angeles. Participants were 16 methamphetamine-abusing or -dependent gay or bisexual males who participated in a treatment demonstration project between 1989 and 1993. All participants completed the NIDA/WAVE survey, a detailed inventory of HIV-related risk behaviors. Findings indicate a strong connection between methamphetamine abuse and high-risk sexual behavior. For the 12 months prior to treatment 62.5% of participants reported having anal insertive sex without a condom, and 56.3% reported having sex with someone who had HIV. Drug use before or during sex, measured on a 5-point Likert scale, was frequent (M = 4.27, SD = 0.7). Implications for treatment of gay and bisexual male methamphetamine abusers and prevention of HIV among this population are discussed.

Clinical experiences with 959 opioid-dependent patients treated with levo-alpha-acetylmethadol (LAAM).

Levo-alpha-acetylmethadol (LAAM) is an orphan drug that will soon be generally available to treatment facilities. We have recently treated 959 opioid addicts with LAAM for periods up to 36 consecutive months. Three times per week dosing of LAAM proved to be a safe and effective treatment agent for the majority of subjects. During LAAM induction there is a delay in opioid activity as LAAM forms its long-acting metabolites, therefore, symptomatic withdrawal medication must usually be administered during the first 96 hours of treatment to adequately suppress opioid withdrawal symptoms and prevent self-administration of drugs by the patient. No long-term hepatic toxicity or tumor formation could be demonstrated by liver function studies and liver-spleen imaging in a subgroup of patients. Some opioid addicts report that they prefer LAAM over methadone, but the reverse was reported by about 40% of our patients which suggests that both drugs are needed for adequate maintenance treatment of the opioid-addicted population.

An intensive outpatient approach for cocaine abuse treatment. The Matrix model.

The Matrix model of outpatient treatment was developed during the 1980s in response to an overwhelming demand for cocaine abuse treatment services. The model was constructed using components based upon empirically supported findings from the substance abuse research field. Over the course of development, data were collected on the treatment model and the model was modified based upon empirical evaluation. A pilot study comparing the Matrix outpatient model with an inpatient hospital treatment program produced preliminary support for the clinical utility of the model. An open trial comparing publicly and privately funded patients demonstrated that patients with fewer resources were more difficult to engage and retain in this model of outpatient treatment. In a controlled trial, a clear positive relationship was documented between duration and amount of treatment involvement in the Matrix model and positive outcome at 1 year. Due to a variety of methodological issues, the study was not able to answer definitively the question of clinical efficacy. In all of these studies, patients treated with the Matrix model demonstrated statistically significant reductions in drug and alcohol use and improvements in psychological indicators. This body of work, along with the public acceptance the model has received in the treatment community, support the usefulness of this intensive outpatient approach for cocaine abuse. Further research is underway to provide additional controlled information on the value of this treatment approach.

Cocaine and methamphetamine: differential addiction rates.

Clients admitted to treatment centers for stimulant addiction were categorized as either regular users of cocaine or of methamphetamine based on an algorithm involving 5 specific criteria. A subsample consisting of 90 regular users of cocaine and nonusers of methamphetamine, and 39 regular users of methamphetamine and nonusers of cocaine, was selected for comparison. Analyses showed that, when compared with cocaine users, the methamphetamine users exhibited a shorter period of time from 1st use to regular use (period of initial use) and from 1st use to treatment entry (period of pretreatment use). Relative to cocaine use, the use of methamphetamine appears to induce a faster rate of progression toward regular use and subsequent need for treatment.

Contingency management for tobacco smoking in methadone-maintained opiate addicts.

Seventeen methadone-maintained cigarette smokers received 4 weeks of contingency management (CM) as a stop-smoking intervention. Results indicated that CM patients significantly reduced breath CO levels from baseline to completion of treatment and that 23.4% of patients maintained 1 week or more of continued smoking abstinence. Results indicated a link between smoking abstinence and reduced cocaine use, although not reduced opiate use, which raised questions about possible shared biological and psychological mechanisms for tobacco and cocaine use.

Alternative response training, differential reinforcement of other behavior, and extinction in squirrel monkeys (Saimiri sciureus).

In Experiment I, (a) extinction, (b) extinction plus reinforcement of a discrete alternative response, and (c) differential reinforcement of other behavior were each correlated with a different stimulus in a three-component multiple schedule. The alternative-response procedure more rapidly and completely suppressed behavior than did differential reinforcement of other behavior. Differential reinforcement of other behavior was slightly more effective than extinction alone. In Experiment II, reinforcement of specific alternative behavior during extinction and differential reinforcement of other behavior were used in two components, while one component continued to provide reinforcement for the original response. Once again, the alternative-response procedure was most effective in reducing responding as long as it remained in effect. However, the responding partially recovered when reinforcement for competing behavior was discontinued. In general, responding was less readily reduced by differential reinforcement of other behavior than by the specific alternative-response procedure.

Psychological approaches for the treatment of cocaine dependence--a neurobehavioral approach.

A variety of psychological approaches have been utilized for the treatment of cocaine dependence. Most information has been presented in case report format. However, several investigations have established integrated outpatient approaches which are currently being systematically evaluated. One of these approaches, the neurobehavioral model of cocaine dependency treatment establishes a clear timetable for cocaine recovery and focusses attention on four discreet areas of functioning. Strategies for addressing these areas of functioning include relapse prevention methods as well as individual therapy procedures, family systems materials, educational information, 12 step involvement and urine testing. The model constructs a comprehensive framework for facilitating involvement in recovery activities which promote positive behavior change. Use of this standardized treatment format allows for the evaluation of the treatment model. In an open trial with 486 cocaine users, a majority of subjects were retained in treatment for a clinically significant period of time and while in treatment provided urine samples indicating substantial periods of cocaine abstinence. Current research is underway to evaluate: (1) subject factors which appear to be related to successful outcome with this treatment model; (2) a controlled clinical trial to evaluate the treatment model with cocaine users using random assignment; (3) a double-blind evaluation of desipramine versus placebo and versus no medication as an adjunct to the support provided by the model.