A118G SNP and OPRM1 Gene Opioid-Mediated Effects in Humans
Condition: Opioid Sensitivity; Individual Difference; Abuse Opioids
MeSH terms: Hypersensitivity
Intervention: Within-subject test of blinded study medication
Intervention description: Within-subject double-blind, randomized, placebo-controlled, residential human abuse potential study. All participants received 4mg oral hydromorphone on study day 2 and a subset continued into the randomized portion for study days 3-5 wherein they received placebo, 2mg hydromorphone, and 8mg hydromorphone in randomized order. Only one dose was administered per day and following randomized all participants received each dose in random order. Outcomes were collected during 8-hour residential-based sessions and included metrics of FDA human abuse potential testing as well as secondary outcomes of laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition. Participants were genotyped for rs-1799971 status and results were analyzed as between-group comparisons based upon genotype.
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Intervention model description: Within-subject, double-blind, randomized, placebo-controlled, human laboratory design wherein each participant completed each of the study conditions (outlined below as four arms). Participants were genotyped for rs-1799971and data were analyzed using between-group designs based upon rs-1799971 status.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Neither participants nor staff were informed of the class of drugs under investigation. Strict blinding was maintained.
Enrollment: 100.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: opioid; abuse; genetic; A118G; OPRM1

Summary:

      Within-subject, double-blind, placebo-controlled examination of opioid abuse potential in
      healthy individuals as a function of A118G SNP on the OPRM1 gene.
    

Eligibility criteria:

        Inclusion Criterion:

          1. Provide a urine sample that tests negative for opioids, methadone, buprenorphine,
             oxycodone, amphetamine, cocaine, and benzodiazepines

          2. Negative ethanol breath test (0.000)

          3. Aged 21-50

          4. Deemed medically eligible to take hydromorphone

        Exclusion Criterion:

          1. Answer "yes" to question 1 of the Brief Pain Inventory (89) to assess the presence of
             chronic pain.

          2. Current use of opioids or other medications for pain

          3. Meet DSM-5 criteria for current or lifetime alcohol or drug use disorder (excluding
             nicotine)

          4. Self-report any illicit drug use in the past 7 days

          5. Self-report opioid use >5 days in the past 30

          6. Evidence of opioid physical dependence at screening or following 1st residential
             overnight (following confirmed opioid abstinence)

          7. Allergy to hydromorphone or other opioid agonists

          8. Experience an adverse event that warrants opioid antagonist treatment following 1st
             hydromorphone dose.

          9. If female, not be pregnant or breastfeeding

         10. Presence of any clinically significant medical (e.g., chronic renal insufficiency,
             history of myocardial infarction, seizure disorder) and/or psychiatric illness (e.g.,
             schizophrenia, bipolar disorder) that may interfere with study participation.

         11. BMI >30 (obese category)