Suvorexant maintenance enhances the reinforcing but not subjective and physiological effects of intravenous cocaine in humans

Stoops, William W.; Strickland, Justin C.; Hatton, Kevin; Hays, Lon R.; Rayapati, Abner O.; Lile, Joshua A.; Rush, Craig R.

doi:10.1016/j.pbb.2022.173466

Cited by 10 publications

(7 citation statements)

References 75 publications

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“…Nevertheless, the current results add to the existing preclinical literature that SUV can reduce oxycodone intake in addition to stimulants ( Simmons et al, 2017 ; Gentile et al, 2018 ) and alcohol intake ( Flores-Ramirez et al, 2022 ), supporting that SUV may be an effective treatment strategy for reducing intake of various drugs of abuse (i.e., opioids, stimulants, and alcohol). However, despite preclinical reports indicating that 10 and 30 mg/kg SUV can reduce stimulant intake in rats ( Simmons et al, 2017 ; Gentile et al, 2018 ), a recent report indicates that 10 and 20 mg/kg SUV increased cocaine intake in a clinical setting ( Stoops et al, 2022 ). It is possible that maintaining SUV levels through chronic (minimum of 3 days) administration ( Stoops et al, 2022 ) elicits different effects on drug intake and seeking compared to that of acute SUV administration utilized in preclinical studies (e.g., current study; Simmons et al, 2017 ; Gentile et al, 2018 ; Flores-Ramirez et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, despite preclinical reports indicating that 10 and 30 mg/kg SUV can reduce stimulant intake in rats ( Simmons et al, 2017 ; Gentile et al, 2018 ), a recent report indicates that 10 and 20 mg/kg SUV increased cocaine intake in a clinical setting ( Stoops et al, 2022 ). It is possible that maintaining SUV levels through chronic (minimum of 3 days) administration ( Stoops et al, 2022 ) elicits different effects on drug intake and seeking compared to that of acute SUV administration utilized in preclinical studies (e.g., current study; Simmons et al, 2017 ; Gentile et al, 2018 ; Flores-Ramirez et al, 2022 ). As such, clinical dose-response studies on the efficacy of SUV to reduce oxycodone intake and seeking under acute and chronic treatment regimens should be fully evaluated.…”

Section: Discussionmentioning

confidence: 99%

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Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats

et al. 2023

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Background: The Department of Health and Human Services reports that prescription pain reliever (e.g., oxycodone) misuse was initiated by 4,400 Americans each day in 2019. Amid the opioid crisis, effective strategies to prevent and treat prescription opioid use disorder (OUD) are pressing. In preclinical models, the orexin system is recruited by drugs of abuse, and blockade of orexin receptors (OX receptors) prevents drug-seeking behavior. The present study sought to determine whether repurposing suvorexant (SUV), a dual OX receptor antagonist marketed for the treatment of insomnia, can treat two features of prescription OUD: exaggerated consumption and relapse.Methods: Male and female Wistar rats were trained to self-administer oxycodone (0.15 mg/kg, i. v., 8 h/day) in the presence of a contextual/discriminative stimulus (SD) and the ability of SUV (0–20 mg/kg, p. o.) to decrease oxycodone self-administration was tested. After self-administration testing, the rats underwent extinction training, after which we tested the ability of SUV (0 and 20 mg/kg, p. o.) to prevent reinstatement of oxycodone seeking elicited by the SD.Results: The rats acquired oxycodone self-administration and intake was correlated with the signs of physical opioid withdrawal. Additionally, females self-administered approximately twice as much oxycodone as males. Although SUV had no overall effect on oxycodone self-administration, scrutiny of the 8-h time-course revealed that 20 mg/kg SUV decreased oxycodone self-administration during the first hour in males and females. The oxycodone SD elicited strong reinstatement of oxycodone-seeking behavior that was significantly more robust in females. Suvorexant blocked oxycodone seeking in males and reduced it in females.Conclusions: These results support the targeting of OX receptors for the treatment for prescription OUD and repurposing SUV as pharmacotherapy for OUD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats

et al. 2023

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“…Participants for this secondary analysis were enrolled in a study on the influence of suvorexant on the reinforcing, subjective and physiological effects of intravenous cocaine (see details in Stoops et al ., 2022). Eight (4 women; 2 White, 5 Black, 1 Multiethnic) nontreatment-seeking participants with cocaine use disorder were enrolled in that parent study.…”

Section: Methodsmentioning

confidence: 99%

“…Three participants met the criteria for alcohol use disorder but were not physically dependent because participants with physical dependence on alcohol were excluded from participation. Additional details on screening and participant inclusion criteria are described in the primary outcomes report (Stoops et al ., 2022). The Medical Institutional Review Board of the University of Kentucky approved this study.…”

Section: Methodsmentioning

confidence: 99%

“…The primary goal of this analysis was to use purchase task methods to determine the influence of dual orexin receptor antagonism on demand for cocaine. Data were collected in a double-blind randomized study evaluating whether maintenance on the DORA suvorexant (0, 5, 10 and 20 mg/day) affected intravenous cocaine self-administration (0, 10 and 30 mg/70 kg) in human participants with cocaine use disorder (Stoops et al ., 2022). We used a blinded commodity purchase task to measure responses for blinded cocaine doses under each suvorexant maintenance condition.…”

Section: Introductionmentioning

confidence: 99%

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Use of drug purchase tasks in medications development research: orexin system regulation of cocaine and drug demand

Strickland

Hatton

Hays

et al. 2023

Behavioural Pharmacology

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Commodity purchase tasks provide a useful method for evaluating behavioral economic demand in the human laboratory. Recent research has shown how responding to purchase tasks for blinded drug administration can be used to study abuse liability. This analysis uses data from a human laboratory study to highlight how similar procedures may be particularly useful for understanding momentary changes in drug valuation when screening novel interventions. Eight nontreatment-seeking participants with cocaine use disorder (one with partial data) were enrolled in a cross-over, double-blind, randomized inpatient study. Participants were maintained on the Food and Drug Administration-approved insomnia medication suvorexant (oral; 0, 5, 10, 20 mg/day) in randomized order with experimental sessions completed after at least 3 days of maintenance on each suvorexant dose. Experimental sessions included administration of a sample dose of 0, 10 and 30 mg/70 kg intravenous cocaine. Analyses focused on purchase tasks for the blinded sample dose as well as alcohol, cigarettes and chocolate completed 15 min after the sample dose. As expected based on abuse liability, near zero demand was observed for placebo with dose-related increases in cocaine demand. Suvorexant maintenance increased cocaine demand in a dose-related manner with the greatest increase observed for the 10 mg/kg cocaine dose. Increased demand under suvorexant maintenance was also observed for alcohol. No effect of cocaine administration was observed for alcohol, cigarette, or chocolate demand. These data support the validity of demand procedures for measuring blinded drug demand. Findings also parallel self-administration data from this study by showing increases in cocaine use motivation under suvorexant maintenance.

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A dose-ranging study of the physiological and self-reported effects of repeated, rapid infusion of remifentanil in people with opioid use disorder and physical dependence on fentanyl

Lile,

Shellenberg,

Babalonis

et al. 2024

Psychopharmacology

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Suvorexant maintenance enhances the reinforcing but not subjective and physiological effects of intravenous cocaine in humans

Cited by 10 publications

References 75 publications

Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats

Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats

Use of drug purchase tasks in medications development research: orexin system regulation of cocaine and drug demand

A dose-ranging study of the physiological and self-reported effects of repeated, rapid infusion of remifentanil in people with opioid use disorder and physical dependence on fentanyl

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