James W. Cornish

Naltrexone pharmacotherapy for opioid dependent federal probationers

Federal probationers or parolees with a history of opioid addiction were referred by themselves or their probation/parole officer for a naltrexone treatment study. Participation was voluntary and subjects could drop out of the study at any time without adverse consequences. Following orientation and informed consent, 51 volunteers were randomly assigned in a 2:1 ratio to a 6-month program of probation plus naltrexone and brief drug counseling, or probation plus counseling alone. Naltrexone subjects received medication and counseling twice a week; controls received counseling at similar intervals. All therapy and medication were administered in an office located adjacent to the federal probation department. Fifty-two percent of subjects in the naltrexone group continued for 6 months and 33% remained in the control group. Opioid use was significantly lower in the naltrexone group. The overall mean percent of opioid positive urine tests among the naltrexone subjects was 8%, versus 30% for control subjects (p < .05). Fifty-six percent of the controls and 26% of the naltrexone group (p < .05) had their probation status revoked within the 6-month study period and returned to prison. Treatment with naltrexone and brief drug counseling can be integrated into the Federal Probation/Parole system with favorable results on both opioid use and re-arrest rates.

Modafinil and cocaine: a double-blind, placebo-controlled drug interaction study

Modafinil is a novel compound that is approved for the treatment of narcolepsy. It is now being studied as a potential treatment for cocaine dependence. Cocaine withdrawal symptoms are associated with poor clinical outcome and are likely to be reversed by modafinil. In addition, the neurotransmitter actions of modafinil are opposite to cocaine-induced neuroadaptations affecting dopamine and glutamate reward circuits. Since cocaine-dependent subjects might use cocaine during a clinical trial with modafinil, this study tested the safety of intravenous cocaine (30 mg) in combination with modafinil. Each of seven subjects received a baseline (open-label) cocaine infusion. Three subsequent cocaine infusions were administered after subjects received 4 days of low dose modafinil (200 mg/day), high dose modafinil (400 mg/day), or placebo in randomized double-blind sequences. One subject received placebo prior to all infusions. Our results indicate that co-administering modafinil and a single dose of intravenous cocaine is not associated with medical risk in terms of blood pressure, pulse, temperature, or electrocardiogram measures. Furthermore, pretreatment with modafinil did not intensify cocaine euphoria or cocaine-induced craving. In fact, cocaine euphoria was significantly blunted (P=0.02) in one of our subjective measures.

A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients.

We conducted a multi-site, placebo-controlled, randomized double-blind clinical trial comparing bupropion HCL (300 mg/day) to placebo for the treatment of cocaine dependence in methadone-maintained subjects. A total of 149 subjects at three sites participated in a 12-week study. Outcome measures included cocaine use, level of depression, and psychosocial functioning. Results showed no significant differences between placebo and bupropion. Exploratory analyses suggested a medication effect for the subset of subjects depressed at study entry. The need to target subgroups of cocaine abusers in future pharmacotherapy trials and the possible role of treatment readiness are discussed.

Effectiveness of propranolol for cocaine dependence treatment may depend on cocaine withdrawal symptom severity

Propranolol may reduce symptoms of autonomic arousal associated with early cocaine abstinence and improve treatment outcome. This trial was an 8-week, double-blind, placebo-controlled trial of propranolol in 108 cocaine dependent subjects. The primary outcome measure was quantitative urinary benzoylecgonine levels. Secondary outcome measures included treatment retention, addiction severity index results, cocaine craving, mood and anxiety symptoms, cocaine withdrawal symptoms, and adverse events. Propranolol treated subjects had lower cocaine withdrawal symptom severity but otherwise did not differ from placebo treated subjects in any outcome measure. However, in a secondary, exploratory analysis, subjects with more severe cocaine withdrawal symptoms responded better to propranolol in comparison to placebo. In these subjects, propranolol treatment was associated with better treatment retention and lower urinary benzoylecgonine levels as compared with the placebo treatment. Propranolol may be useful only for the treatment of cocaine dependent patients with severe cocaine withdrawal symptoms.

Effectiveness and costs of inpatient versus day hospital cocaine rehabilitation

We compared the effectiveness and costs of day hospital (DH) versus inpatient (INP) rehabilitation for cocaine dependence. The research subjects were 111 inner city, lower socioeconomic, primarily African-American male veterans who qualified for a diagnosis of cocaine dependence and presented no acute medical or psychiatric conditions requiring inpatient treatment. Fifty-six men were randomly assigned to 1 month of DH rehabilitation (27 hours of weekday treatment weekly), and 55 were assigned to 1-month INP rehabilitation (48 hours of scheduled treatment weekly). Treatment outcome was evaluated 7 months after admission into treatment (92% of the subjects), and a cost analysis was performed. A significantly greater proportion of INP subjects (89.1%) completed treatment than did DH subjects (53.6%). Significant improvements in substance use, psychosocial functioning, and health status were found 7 months postadmission for both groups, but there was little evidence of differential improvement between groups. Urine toxicology findings were consistent with the self-report data in showing improvement from baseline, but no group differences in cocaine use. The groups did not differ significantly in postrehabilitation aftercare participation or in relapse to additional treatment. DH treatment costs were 40% to 60% of INP treatment costs, depending upon the measure used.

Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders

BACKGROUND Extended-release naltrexone, a sustained-release monthly injectable formulation of the full mu-opioid receptor antagonist, is effective for the prevention of relapse to opioid dependence. Data supporting its effectiveness in U.S. criminal justice populations are limited. METHODS In this five-site, open-label, randomized trial, we compared a 24-week course of extended-release naltrexone (Vivitrol) with usual treatment, consisting of brief counseling and referrals for community treatment programs, for the prevention of opioid relapse among adult criminal justice offenders (i.e., persons involved in the U.S. criminal justice system) who had a history of opioid dependence and a preference for opioid-free rather than opioid maintenance treatments and who were abstinent from opioids at the time of randomization. The primary outcome was the time to an opioid-relapse event, which was defined as 10 or more days of opioid use in a 28-day period as assessed by self-report or by testing of urine samples obtained every 2 weeks; a positive or missing sample was computed as 5 days of opioid use. Post-treatment follow-up occurred at weeks 27, 52, and 78. RESULTS A total of 153 participants were assigned to extended-release naltrexone and 155 to usual treatment. During the 24-week treatment phase, participants assigned to extended-release naltrexone had a longer median time to relapse than did those assigned to usual treatment (10.5 vs. 5.0 weeks, P<0.001; hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.68), a lower rate of relapse (43% vs. 64% of participants, P<0.001; odds ratio, 0.43; 95% CI, 0.28 to 0.65), and a higher rate of opioid-negative urine samples (74% vs. 56%, P<0.001; odds ratio, 2.30; 95% CI, 1.48 to 3.54). At week 78 (approximately 1 year after the end of the treatment phase), rates of opioid-negative urine samples were equal (46% in each group, P=0.91). The rates of other prespecified secondary outcome measures--self-reported cocaine, alcohol, and intravenous drug use, unsafe sex, and reincarceration--were not significantly lower with extended-release naltrexone than with usual treatment. Over the total 78 weeks observed, there were no overdose events in the extended-release naltrexone group and seven in the usual-treatment group (P=0.02). CONCLUSIONS In this trial involving criminal justice offenders, extended-release naltrexone was associated with a rate of opioid relapse that was lower than that with usual treatment. Opioid-use prevention effects waned after treatment discontinuation. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00781898.).

Amantadine in the early treatment of cocaine dependence: a double-blind, placebo-controlled trial

A 4-week, double-blind, placebo-controlled trial of amantadine was conducted in 61 cocaine dependent outpatients. Subjects received 100 mg of amantadine 3 times daily. A follow-up visit was conducted at week 8. There were no significant differences between groups in treatment retention, or in the number of benzoylecgonine positive urine samples. Self-reported drug and alcohol use declined in both groups. At week 8 follow-up, self-reported drug use was significantly lower in the placebo group. Amantadine was not effective, and discontinuation of it may have been associated with an increase in cocaine use.

Amantadine may facilitate detoxification of cocaine addicts

The effectiveness of amantadine hydrochloride was evaluated in a double-blind placebo controlled drug trial. The subjects were 42 cocaine dependent men enrolled in a day hospital program. Twenty-one patients were prescribed 100 mg/bid of amantadine to be taken over 10.5 days and 21 were prescribed an equivalent amount of placebo. The primary outcome measures were the Addiction Severity Index at 1 month after study entry and urines during the drug trial (end of weeks 1 and 2) and 1 month after study entry. Urines obtained at the end of the drug trial (2 weeks) indicated that the subjects receiving amantadine (93%) were more likely (P = 0.040) to be free of cocaine than the placebo (60%) subjects. Urine toxicology data at 1-month follow-up again indicated that more of the amantadine subjects (83%) were free of cocaine than the placebo (53%) subjects (p = 0.049); although no differences were found in self-reports of cocaine or other substance use in the past 30 days. The urine findings provided preliminary indication that amantadine may have some effectiveness in reducing cocaine use in cocaine dependent patients.

Mood state and recent cocaine use are not associated with levels of cocaine cue reactivity

Eighty-one cocaine-dependent outpatients were assessed for their reactions to cocaine-related cues in a laboratory setting. All subjects contributed a urine sample prior to the session. Compared with non-drug control cues, the cocaine stimuli produced increases in physiological arousal, self-reports of high, craving, and withdrawal, and self-reports of negative mood. Subjects who tested cocaine-positive on the day of testing differed only in skin resistance responding from those who tested cocaine-negative. Changes in cue-induced physiological and self-report measures were also not associated with between-subject variations in mood as measured by the Profile of Mood States (POMS) questionnaire administered prior to cue assessment. Thus, variations in baseline mood and recent cocaine use history do not introduce an additional source of variability in cue reactivity measurements. However, negative mood states at the start of a session were associated with higher levels of self-reported craving, high, and withdrawal both before and after cue exposure.

Failure of ritanserin to block cocaine cue reactivity in humans

As part of a double-blind placebo-controlled study of the effects of ritanserin on cocaine use and craving, reactivity to cocaine-related events was assessed both before and during medication. Twenty-two patients receiving ritanserin and 23 receiving placebo were exposed to cocaine cues while continuous measures of heart rate, skin temperature, and skin resistance were taken. Self-reports of high, withdrawal, and craving were also collected. The cues produced significant physiological responding as well as significant increases in high and craving during both sessions. Ritanserin reduced cue-elicited decreases in skin temperature, but had no effect on heart rate and skin resistance or on cue-induced high and craving. The results demonstrate that cue reactivity is a robust phenomenon across two assessment sessions but fail to support the use of ritanserin as a means of reducing cue-elicited drug states.