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

Participants completed a 5-day, within-subject, double-blind, placebo-controlled, randomized, human laboratory abuse potential trial. Healthy individuals were admitted to a residential research unit for 5 consecutive days. Blood samples were drawn for genome wide analyses using the Global Screening Array on day 1. Participants were administered an oral dose of the opioid hydromorphone (4mg) on day 2 of the study. Persons who did not evidence strong agonist effects then proceeded into the randomized period wherein they received 0mg, 2mg, and 8mg of oral hydromorphone on the remaining three study days. The order of dosing was randomized, with only 1 dose administered per day and all participants receiving 1 exposure to each dose. Outcomes were standard human abuse potential metrics, including self-reported drug effects and feeling high. Data were analyzed as a function of the A118SNP on the OPRM1 gene that codes for the mu opioid receptor. The overall aim was to determine whether signal for abuse potential among persons with no history of opioid misuse was associated with genotype.

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)

Adverse events collected for 6 hours post each drug administration session. Only adverse events (AEs) judged to be possibly, probably, or definitely related to study participation are reported.

AEs were documented the end of each session or in response to spontaneous reporting from participants, as a function of dose but not allele status, during the session. AEs were queried by asking "are you experiencing any side effects of the study medication?" The 4mg hydromorphone dose was the safety test dose and all individuals who had strong agonist responses (e.g., vomiting) in response to that dose were discontinued; therefore more individuals received 4mg than did other doses.

Neither participants nor staff were informed of the class of drugs under investigation. Strict blinding was maintained.