Stress and drug-cue-induced craving in opioid-dependent individuals in naltrexone treatment.

BACKGROUND: Naltrexone is a nonaddictive medication that blocks the euphoric effects of opioids. However, naltrexone treatment is associated with high rates of noncompliance and opioid relapse, possibly because it does not reduce stress and protracted withdrawal symptoms during early recovery. Prior clinical and preclinical research has indicated that both stress and drug-cue-related arousal response is associated with craving and vulnerability to relapse in a range of drug-using populations. AIMS: To examine opioid craving and the subjective and cardiovascular response to stress and drug cues in naltrexone-treated opioid abusers. METHOD: Eleven men and three women engaged in naltrexone treatment for opioid dependence. They were exposed to personalized stress, drug-cue, and neutral-relaxing imagery in a single laboratory session. Subjective (craving, emotion) and cardiovascular (heart rate, systolic blood pressure, and diastolic blood pressure) measures were assessed. RESULTS: Stress and drug-cue-related imagery significantly increased opioid craving, anxiety, and negative emotions and significantly decreased positive emotions compared to neutral imagery. Selective emotional responses were greater in the stress condition than in the drug-cue condition. Only stress-related imagery was associated with an increased cardiovascular response. CONCLUSIONS: Naltrexone-treated opioid abusers demonstrate vulnerability to stress and drug-cue-induced craving and arousal responses that may contribute to the high rates of noncompliance and relapse among opioid-dependent individuals undergoing naltrexone treatment. Pharmacological and behavioral interventions that specifically target the negative affectivity that co-occurs with drug-cue and stress-induced craving could be of benefit in improving naltrexone treatment outcomes in opioid dependence.

Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings.

OBJECTIVE: A preliminary study examined whether lofexidine decreases stress-induced and cue-induced opioid craving and improves opioid abstinence in naltrexone-treated opioid-dependent individuals. MATERIALS AND METHODS: Eighteen opioid-dependent patients were stabilized for 4 weeks with naltrexone (50 mg daily) and lofexidine (2.4 mg bid) before entering a 4-week randomized, double-blind placebo-controlled discontinuation study where one group continued on lofexidine for an additional 4 weeks, while the second was tapered to placebo (Lofexidine-naltrexone vs Placebo-naltrexone). Ten patients also participated in guided imagery exposure to stress, drug cue, and neutral scenarios in a single laboratory session. RESULTS: Lofexidine-naltrexone patients had higher opioid abstinence rates and improved relapse outcomes as compared to the Placebo-naltrexone group. Furthermore, Lofexidine-naltrexone patients had significantly lower heart rates and an attenuated stress and drug cue-induced opioid craving response in the laboratory as compared to the Placebo-naltrexone group. CONCLUSIONS: Although preliminary, these findings are the first to document lofexidine's potential in addressing stress-related opioid craving and relapse outcomes in humans. The results also suggest that combination therapies that target both drug-related reinforcement (naltrexone) and stress- and cue-related aspects of drug seeking could be beneficial in addiction relapse prevention. Further development of lofexidine to address stress-related opioid craving and relapse is warranted.

The use of contingency management and motivational/skills-building therapy to treat young adults with marijuana dependence.

Marijuana-dependent young adults (N = 136), all referred by the criminal justice system, were randomized to 1 of 4 treatment conditions: a motivational/skills-building intervention (motivational enhancement therapy/cognitive-behavioral therapy; MET/CBT) plus incentives contingent on session attendance or submission of marijuana-free urine specimens (contingency management; CM), MET/CBT without CM, individual drug counseling (DC) plus CM, and DC without CM. There was a significant main effect of CM on treatment retention and marijuana-free urine specimens. Moreover, the combination of MET/CBT plus CM was significantly more effective than MET/CBT without CM or DC plus CM, which were in turn more effective than DC without CM for treatment attendance and percentage of marijuana-free urine specimens. Participants assigned to MET/CBT continued to reduce the frequency of their marijuana use through a 6-month follow-up.