The orexin (hypocretin) neuropeptide system is a target for novel therapeutics to treat cocaine use disorder with alcohol coabuse.

An estimated 50-90% of individuals with cocaine use disorder (CUD) also report using alcohol. Cocaine users report coabusing alcohol to 'self-medicate' against the negative emotional side effects of the cocaine 'crash', including the onset of anxiety. Thus, pharmaceutical strategies to treat CUD would ideally reduce the motivational properties of cocaine, alcohol, and their combination, as well as reduce the onset of anxiety during drug withdrawal. The hypothalamic orexin (hypocretin) neuropeptide system offers a promising target, as orexin neurons are critically involved in activating behavioral and physiological states to respond to both positive and negative motivators. Here, we seek to describe studies demonstrating efficacy of orexin receptor antagonists in reducing cocaine, alcohol- and stress-related behaviors, but note that these studies have largely focused on each of these phenomena in isolation. For orexin-based compounds to be viable in the clinical setting, we argue that it is imperative that their efficacy be tested in animal models that account for polysubstance use patterns. To begin to examine this, we present new data showing that rats' preferred level of cocaine intake is significantly increased following chronic homecage access to alcohol. We also report that cocaine intake and motivation are reduced by a selective orexin-1 receptor antagonist when rats have a history of cocaine + alcohol, but not a limited history of cocaine alone. In light of these proof-of-principle data, we outline what we believe to be the key priorities going forward with respect to further examining the orexin system in models of polysubstance use. This article is part of the special issue on Neurocircuitry Modulating Drug and Alcohol Abuse.

Cost-Effectiveness of Internet-Based Cognitive-Behavioral Treatment for Bulimia Nervosa: Results of a Randomized Controlled Trial.

OBJECTIVE: To evaluate the cost-effectiveness of Internet-based cognitive-behavioral therapy for bulimia nervosa (CBT-BN) compared to face-to-face delivery of CBT-BN. METHODS: This study is a planned secondary analysis of data from a randomized clinical trial. Participants were 179 adults (98% female, mean age = 28 years) meeting DSM-IV criteria for bulimia nervosa who were randomized to group face-to-face or group Internet-based CBT-BN for 16 sessions during 20 weeks. The cost-effectiveness analysis was conducted from a third-party payor perspective, and a partial societal perspective analysis was conducted to investigate cost-utility (ie, cost per gain in quality-adjusted life-years) and patient out-of-pocket travel-related costs. Net health care costs were calculated from protocol and nonprotocol health care services using third-party payor cost estimates. The primary outcome measure in the clinical trial was abstinence from binge eating and purging, and the trial start and end dates were 2008 and 2016. RESULTS: The mean cost per abstinent patient at posttreatment was $7,757 (95% confidence limit [CL], $4,515, $13,361) for face-to-face and $11,870 (95% CL, $6,486, $22,188) for Internet-based CBT-BN, and at 1-year follow-up was $16,777 (95% CL, $10,298, $27,042) for face-to-face and $14,561 (95% CL, $10,165, $21,028) for Internet-based CBT-BN. There were no statistically significant differences between treatment arms in cost-effectiveness or cost-utility at posttreatment or 1-year follow-up. Out-of-pocket patient costs were significantly higher for face-to-face (mean [95% CL] = $178 [$127, $140]) than Internet-based ($50 [$50, $50]) therapy. CONCLUSIONS: Third-party payor cost-effectiveness of Internet-based CBT-BN is comparable with that of an accepted standard. Internet-based dissemination of CBT-BN may be a viable alternative for patients geographically distant from specialist eating disorder services who have an unmet need for treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00877786​.

Cost-effectiveness of an internet-based aftercare intervention after inpatient treatment in a psychosomatic hospital.

OBJECTIVE: The implementation of new interventions into routine care requires the demonstration of both their effectiveness and cost-effectiveness. METHOD: We explored the cost-effectiveness of an Internet-based aftercare program in addition to treatment as usual (CHAT) which was compared to treatment as usual (TAU) following inpatient treatment. Incremental cost-effectiveness ratios were calculated based on cost of the intervention, cost of outpatient treatment, and remission rates within 1 year after discharge from hospital. RESULTS: Assuming a willingness-to-pay of an additional 14.87 € per treatment for every additional percent of remission, CHAT was cost-effective against TAU at a 95% level of certainty. Cost per remission equaled 2664.84 € in TAU and 1752.75 € in CHAT (34.2% savings). CONCLUSIONS: This is the first evidence that Internet-based aftercare may enhance long-term treatment outcome in a cost-effective way.

Chronic treatment with curcumin enhances methamphetamine locomotor sensitization and cue-induced reinstatement of methamphetamine self-administration.

OBJECTIVES: Curcumin, a major active component of Curcuma longa, possesses antidepressant effects that are mediated by the 5-HT system. However, little is known about the effect of curcumin on the behavioral consequences of methamphetamine (METH). METHODS: The subjects were male, adult Sprague-Dawley rats. In Experiment 1, the effects of 20 and 40 mg/kg curcumin (i.p.) on response rates and breakpoints of 0.06 mg/kg/infusion METH were evaluated. In Experiment 2, rats were self-administering METH for 10 days followed by a 14-day abstinence period. During the abstinence period, the animals were treated with DMSO, 20 or 40 mg/kg curcumin. All rats were then tested for extinction responding and cue-induced reinstatement. In Experiment 3, rats were treated with DMSO, 20, or 40 mg/kg curcumin 15 min before a METH-induced locomotor activity test for 14 consecutive days. In Experiment 4, rats were pretreated with DMSO or curcumin (20 mg/kg or 40 mg/kg) for 13 days and were subsequently tested for METH-induced locomotor activity on the 14th day. In Experiment 5, three groups were tested for locomotor activity after an injection of DMSO, 20, or 40 mg/kg curcumin. The test was repeated for 14 days. RESULTS: Curcumin produced little effect on response rates and breakpoints maintained by METH. Chronic treatment of only 40 mg/kg curcumin during the abstinence phase enhanced cue-induced reinstatement of METH self-administration. Chronic administration of curcumin increased METH-induced sensitization of locomotor activity at the lower (20 mg/kg) but not higher (40 mg/kg) dose. However pretreatment of curcumin alone showed no significant effect on acute locomotor responses to METH and locomotor responses per se. CONCLUSIONS: Curcumin enhanced, rather than inhibited the behavioral effects of METH.