Orexin's Role in The Neurobiology of Substance Use Disorder

• Status: Not yet recruiting
• Trial end date: 2027-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Study Description:

Despite the availability of pharmacotherapy for some substance use disorders, relapse vulnerability is still a significant issue. This suggests medications with alternative mechanisms of action should be explored to address this unmet need. Substantial preclinical research indicates that orexin antagonism blunts the internally and externally triggered motivation to attain abused substances. This research project will translate these preclinical findings into the clinical domain by administering the FDA approved orexin antagonist, suvorexant, to those with a substance use disorder. Suvorexant's ability to blunt neurobiological correlates of substance misuse will be assessed. This will be assessed following acute and repeated drug administration. Baseline individual differences will be considered to determine whether neurobiological variance influences suvorexant's impact.

Objectives:

The objective is to determine the acute and chronic impact of the orexin antagonist, suvorexant, on neurobiological and behavioral factors linked with substance use disorders. Whether such effects are mediated by baseline characteristics will be tested. Given suvorexant is an FDA approved treatment for insomnia, sleep will be evaluated as well.

Endpoints:

Suvorexant's impact on brain function will be assessed several ways by evaluating: 1) resting function, 2) reactivity to drug cues, 3) reactivity to non-drug related cognitive tasks. Sleep and nicotine use will be measured throughout the study period.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute on Drug Abuse (NIDA)
• Treatments: Suvorexant

Criteria

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Participants will be male and female volunteers between the ages of 18-60. Justification: Many neural processes change with age, and these changes could introduce unwanted variability in both behavioral and MRI signals.

• Participants must be a daily smoker/vaper with a urine cotinine level corresponding to nicotine user status for the specific test being used (typically corresponding to a urine cotinine above about 200 ng/ml) and have been smoking or vaping consistently for at least the past year (excluding quit attempts).

• Female participants must have a negative pregnancy test on all study days.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Participants cannot meet DSM-5 criteria for lifetime and/or current psychotic disorders such as bipolar disorder, schizophrenia, schizoaffective disorder

• Participants cannot meet DSM-5 criteria for current substance use disorders other than nicotine and marijuana and cannot meet criteria for current moderate or severe alcohol use disorder

• Participants cannot have positive illicit drug and alcohol screen on each study visit other than for nicotine or marijuana.

• Participants must report no marijuana use within 24 hours of the study visit as confirmed by self-report.

• Medications with the potential to depress CNS function will be assessed by the MAI, PI, or a physician's assistant and participants excluded as necessary.

• Participants cannot have a history of major head trauma resulting in cognitive impairment, seizure, or other neurological disorders.

• Participants cannot be pregnant or breastfeeding. Justification: The impact of suvorexant on the developing fetus and infant.

• Individuals with severe hepatic impairment will be excluded

• Participants cannot be obese as determined by a Body Mass Index (BMI) of greater than 35.

• Participants cannot be using a CYP3A inhibitor/inducer (metabolism by CYP3A is the major elimination pathway for suvorexant)

• Participants cannot have a current cardiac disorder such as palpitations, tachycardia and/or use of the cardiac medication Digoxin

• Participants cannot have narcolepsy

• Participants cannot self-report complex sleep behaviors such as sleep driving, preparing and eating food or making phone calls

• Participants cannot self-report compromised respiratory function such as severe obstructive sleep apnea or severe chronic obstructive pulmonary disease

• Participants cannot have current major depressive disorder (within the past 6 months) and/or indorse suicidal ideation on the Beck Depression Inventory.

• Subjects that cannot speak English. Justification: To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify, given the small sample size for each experiment. Additionally, the data integrity of some of the cognitive tasks and standardized questionnaires used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing MRI procedures. The inability to effectively communicate MRI safety procedures in a language other than English could compromise the safety of non-English speaking participants.