heroin and lorcaserin

Lorcaserin, a high-affinity 5-HT. In this 7-week inpatient trial, 12 non-treatment-seeking volunteers (11 males) with moderate-to-severe opioid use disorder were detoxified from opioids. In a randomized cross-over fashion, participants were first stabilized on lorcaserin (10 mg BID) or placebo (0 mg BID). Participants underwent a two-week testing period during which the reinforcing and subjective effects of intranasal oxycodone were examined in verbal choice, cue-exposure, and progressive-ratio choice sessions. The two testing weeks were identical with the exception that during the first week, active oxycodone (10 mg) was available during verbal choice (self-administration) sessions, and during the second week placebo oxycodone was available. Subsequently, participants were stabilized on the other medication condition (placebo or lorcaserin) and underwent the same testing procedures again.. Lorcaserin did not alter oxycodone self-administration. However, lorcaserin had a trend to increase "wanting heroin" when oxycodone was available, and to accentuate oxycodone-induced miosis.. Under the current experimental conditions, lorcaserin at a dose of 10 mg BID did not reliably decrease the abuse liability of oxycodone, even though the study was sufficiently powered (≥80 %) to detect clinically meaningful differences in the main outcome variables between the placebo and active lorcaserin condition. Future research could explore a wider dose range of lorcaserin and oxycodone.

Topics: Administration, Intranasal; Adult; Benzazepines; Choice Behavior; Cross-Over Studies; Cues; Female; Heroin; Humans; Male; Opioid-Related Disorders; Oxycodone; Reinforcement, Psychology; Self Administration; Treatment Outcome

The opioid epidemic continues despite the availability of medications, including buprenorphine, for opioid use disorder (OUD); identifying novel and effective treatments is critical for decreasing the prevalence of OUD and ending this crisis. Buprenorphine alone does not markedly attenuate abuse-related effects of nonopioids. Treatment outcomes might be improved by combining buprenorphine with a second medication targeting substance use disorder (SUD), such as lorcaserin, a serotonin. This study investigated the effectiveness of buprenorphine/lorcaserin mixtures to decrease preference for heroin or cocaine in monkeys choosing between food and i.v. infusions.. When saline was available for self-administration, monkeys chose food; when heroin or cocaine was available, monkeys dose-dependently increased choice of infusions. Noncontingent administration of heroin, cocaine, or buprenorphine before sessions increased preference for saline over food. Daily noncontingent administration of buprenorphine increased saline choice, decreased heroin choice, and increased variability across monkeys and sessions; preference for cocaine was not altered. Adding lorcaserin to daily treatment reduced variability such that choice of saline and heroin was consistently less than 20%; choice of cocaine did not change.. Because buprenorphine/lorcaserin mixtures would not likely alter abuse of cocaine, they might not be useful for treating SUDs; nevertheless, mixtures reduced variability and decreased preference for heroin, compared with buprenorphine alone, perhaps suggesting that a different drug mixture, in which buprenorphine is combined with a second, nonopioid drug, might offer advantages over treatment with buprenorphine alone.

Topics: Animals; Benzazepines; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Heroin; Macaca mulatta; Opioid-Related Disorders; Self Administration

The current opioid crisis has reinvigorated preclinical research in the evaluation of non-opioid candidate treatments for opioid use disorder (OUD). Emerging evidence suggests 5-HT. Adult male (1) and female (6) rhesus monkeys were trained to respond under a concurrent schedule of food delivery (1 g pellets, fixed-ratio 100 schedule) and intravenous heroin injections (0-0.032 mg/kg/injection, fixed-ratio 10 schedule) during daily 2 h sessions. Heroin choice dose-effect functions were determined daily before and following 7-day saline substitution or 7-day continuous treatment with naltrexone (0.0032-0.032 mg/kg/h, IV) or lorcaserin (0.032-0.32 mg/kg/h, IV).. Under baseline conditions, increasing heroin doses maintained a dose-dependent increase in heroin choice. Both saline substitution and 7-day naltrexone treatment significantly attenuated heroin choice and produced a reciprocal increase in food choice. Continuous lorcaserin (0.32 mg/kg/h) treatment significantly increased heroin choice.. In contrast to saline substitution and naltrexone, lorcaserin treatment was ineffective to reduce heroin-vs.-food choice. These preclinical results do not support the therapeutic potential and continued evaluation of lorcaserin as a candidate OUD treatment.

Topics: Analgesics, Opioid; Animals; Benzazepines; Choice Behavior; Dose-Response Relationship, Drug; Feeding Behavior; Female; Heroin; Macaca mulatta; Male; Self Administration

Drug abuse remains a serious public health issue, underscoring the need for additional treatment options. Agonists at serotonin (5-HT)2C receptors, particularly lorcaserin, are being considered as pharmacotherapies for abuse of a variety of drugs, including cocaine and opioids. The current study compared the capacity of lorcaserin to attenuate reinstatement of extinguished responding previously maintained by either cocaine or an opioid; this type of procedure is thought to model relapse, an important aspect of drug abuse. Six rhesus monkeys responded under a fixed-ratio schedule for cocaine (0.032 mg/kg/infusion) or remifentanil (0.00032 mg/kg/infusion). Reinstatement of extinguished responding was examined following administration of noncontingent infusions of cocaine (0.32 mg/kg) or heroin (0.0032-0.1 mg/kg) combined with response-contingent presentations of the drug-associated stimuli, or heroin alone without presentation of drug-associated stimuli. When combined with drug-associated stimuli, cocaine and heroin increased extinguished responding. On average, monkeys emitted fewer reinstated responses following 0.32 mg/kg cocaine, compared with the number of responses emitted when cocaine was available for self-administration or when extinguished responding was reinstated by 0.032 mg/kg heroin. When drug-associated stimuli were not presented, heroin did not increase responding. Lorcaserin dose dependently attenuated reinstated responding, and its potency was similar regardless of whether cocaine or heroin was given before reinstatement sessions. The generality of this effect of lorcaserin across pharmacological classes of abused drugs might make it particularly useful for reducing relapse-related behaviors in polydrug abusers. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Topics: Analgesics, Opioid; Animals; Benzazepines; Cocaine; Dose-Response Relationship, Drug; Heroin; Macaca mulatta; Male; Models, Animal; Remifentanil; Self Administration; Serotonin 5-HT2 Receptor Agonists; Substance-Related Disorders

Preclinical studies indicate that lorcaserin (Belviq®), an FDA-approved serotonin 2 C receptor agonist, may be a promising medication for the treatment of stimulant addiction. However, few studies have investigated its effects on self-administration of drugs of abuse from other pharmacological classes, including opioids. Here, adult male rhesus macaques (N = 3) responded under a fixed ratio 30 schedule of food (1-g banana-flavored pellets) and IV heroin delivery. Following stable self-administration of a range of heroin doses (0.32-32 μg/kg/inj, IV), the effects of acute pretreatment with lorcaserin (0.32-1.0 mg/kg, IM) on heroin- and food-maintained responding was determined. The ability of repeated treatment with lorcaserin (1.0 mg/kg) to produce sustained decreases in heroin and/or food intake and reinforcing strength were then analyzed using behavioral economic demand procedures. Results show that self-administration of intravenous heroin was dose-dependent, with peak responding maintained, on average, by the unit dose of 3.2 μg/kg/inj. Lorcaserin pretreatment produced a dose-dependent flattening of the dose-response function for heroin self-administration in each subject. On the other hand, lorcaserin did not decrease food-maintained responding. Repeated lorcaserin treatment reduced heroin intake by selectively decreasing its reinforcing strength, as evidenced by a leftward shift in the demand curves for heroin and the absence of comparable changes in the reinforcing strength of food. These results indicate that serotonin 2 C receptor agonists, such as lorcaserin, have behaviorally selective effects on IV self-administration behavior, and deserve further consideration as candidates for the management of opioid use disorder.

Topics: Animals; Behavior, Animal; Benzazepines; Dose-Response Relationship, Drug; Eating; Food; Heroin; Macaca mulatta; Male; Receptor, Serotonin, 5-HT2C; Reinforcement, Psychology

Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction.

Topics: Adrenergic alpha-2 Receptor Agonists; Animals; Behavior, Animal; Benzazepines; Central Nervous System Stimulants; Clonidine; Heroin; Male; Mice; Motor Activity; Naloxone; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT2 Receptor Agonists; Substance Withdrawal Syndrome