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Orexin's Role in Nicotine Dependence

This study is exploring how a medication called Belsomra (suvorexant), which is already approved for insomnia, might help people with nicotine dependence. Researchers believe Belsomra, by blocking a brain chemical called orexin, could reduce the desire for substances. You would receive Belsomra or a placebo (an inactive substance) in a randomized, double-blind way, meaning neither you nor the study staff would know which you're getting. The study will use fMRI (functional Magnetic Resonance Imaging) scans to see how your brain responds to cues related to nicotine. An additional group will look at Belsomra's interaction with methylphenidate on thinking skills in non-smokers. The goal is to see if Belsomra can reduce brain activity linked to substance cravings. This study is for individuals aged 18 to 60.

Study design
This is an interventional study with a planned enrollment of 140 participants. It uses a randomized, double-blind, placebo-controlled crossover design for Belsomra, and a control arm for methylphenidate.
What's involved
You would undergo a baseline scan, followed by acute drug administration scans. For the Belsomra arm, you would take either Belsomra or placebo. For the methylphenidate arm, you would have a baseline visit with two fMRI scans and four acute drug administration sessions over 6-14 days.
Compensation
Not stated in the trial record.
Follow-up
Your brain's response to cues and Belsomra's effectiveness will be measured at each scan visit.

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NCT05630781

Orexin s Role in the Neurobiology of Substance Use Disorder

Recruiting
NAAges 18–60InterventionalBasic science
National Institute on Drug Abuse (NIDA)
~140 participants
Updated 2026-08-19 on ClinicalTrials.gov
What's tested:BelsomraPlaceboMethylphenidate

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
fMRI - cue reactivity
Measured over each scan visit
+3 more outcomes measured

Conditions

Nicotine Dependence

Explore related trials

Nicotine Dependence

Where it's being run

1 sites across 1 states
Maryland1

Study leadership

  • Amy C Janes, Ph.D. · PRINCIPAL_INVESTIGATOR · National Institute on Drug Abuse (NIDA)

Who to contact

NIDA IRP Screening Team
[email protected]
(800) 535-8254
Email the study team

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Eligibility criteria

Inclusion

Participants will be volunteers between the ages of 18-60 at the time of enrollment in the study (both sexes). Justification: Many neural processes change with age, and these changes could introduce unwanted variability in both behavioral and MRI signals.
Able and willing to provide written informed consent, which includes agreement to all Lifestyle Considerations at the time of study consent.
Participants must smoke/vape a minimum of 4 times per week 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).

Exclusion

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.
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.
Participant cannot have any history of neurological disorders, including seizures, epilepsy, or cognitive impairment which may impact MRI metrics.
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 strong CYP3A inhibitor/inducer (metabolism by CYP3A is the major elimination pathway for suvorexant)
Participants cannot have any past or present significant cardiac disorders or cerebrovascular conditions such as palpitations, tachycardia, use of the cardiac medication Digoxin, arrhythmias, acute coronary syndrome, ischemic heart disease, or uncontrolled hypertension.
Participants cannot have narcolepsy.
Participants cannot self-report complex sleep behaviors such as sleep driving, preparing and eating food or making phone calls.
Participants with Major Depressive Disorder who are using medication must be stable on medication for 3 months.
Subjects with suicidal ideation where outpatient treatment is determined unsafe.
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.
Contraindication to MRI as determined by MRI Safety Screening form.
Participants cannot self-report compromised respiratory function such as severe obstructive sleep apnea or severe chronic obstructive pulmonary disease.
Participants cannot meet DSM-5 criteria for moderate or severe ADHD.
May not have used any nicotine product more than once per week in the past year. Must have an expired carbon monoxide level of less than or equal to 5 ppm.
Must not have a history of excessive substance use that may impact reward function, as evaluated by the PI, MAI, and/or designee.
Current pharmacological treatment for opioid use disorder (i.e., use of methadone)
May not have (or currently be treated/medicated for) any diagnoses/conditions contraindicated for use of methylphenidate.
Participants may not have a diagnosis of moderate or severe ADHD (irrespective of medication use) or present with undiagnosed ADHD during screening.

What this trial measures

  • fMRI - cue reactivityeach scan visit

    Test whether acute and/or chronic suvorexant reduces smoking/vaping cue reactivity

  • cue reactivity and suvorexant effectivenesseach scan visit

    Determine whether baseline variance in cue reactivity contributes to suvorexant s effectiveness

  • task based fMRIeach scan visit

    Determine whether suvorexant blunts reward sensitivity

  • fMRIeach scan visit

    to assess not only whether there is an interaction between acute methylphenidate and suvorexant on brain function and reward/cognition, but also whether any sex differences within this interaction exist