The goal of this study is to evaluate the effects of opioid antagonists on the hypothalamic-pituitary-gonadal axis in healthy subjects.

Arm 1 Assignment: Individuals will be assigned to group 1 or group 2 based on their genetic features.

Arm 2 Assignment: Each study subject will serve as their own control.

Delivery of Interventions:

• Prior to the study visit, subjects will undergo a review of their medical history and screening laboratories.

• During the study, the subjects will complete the following

  • Arm 1: Undergo frequent blood sampling for up to 12 hours

  • Arm 2:

    • Period 1: Blood sampling q10 min for up to 12 hours
    • Period 2: Blood sampling q10 min for up to 12 hours with concurrent administration of naloxone bolus followed by a naloxone infusion

Inclusion

• Age 18-45 years (women) OR 18-60 years (men)
• Genetic sequencing data available via Mass General Brigham Biobank
• All medical conditions stable and well controlled
• If applicable, willing to use birth control methods (as approved by a study medical professional) during protocol participation
• Normal blood pressure (systolic BP < 140 mm Hg, diastolic < 90 mm Hg)
• Negative urine drug screening panel
• Hemoglobin within sex-specific reference range
• For women, negative serum hCG pregnancy test

Exclusion

• Any condition (medical, mental, or behavioral) that, in the opinion of a study investigator, would likely interfere with participation in/completion of the protocol
• Current or recent use of a medication (including hormonal replacement) that, in the opinion of a study investigator, can modulate the reproductive axis and, if applicable, unwilling to complete an appropriate washout for that particular medication and its method of administration
• Current or recent use of a medication that affects the opioid pathway
• Active illicit drug use
• Excessive alcohol consumption (> 10 drinks/week)
• For women, pregnant or breastfeeding