In this study, a novel human laboratory model will be evaluated. Acute opioid-induced neuroimmune responses will be quantified among healthy volunteers (Specific Aim). To measure the neuroimmune system, we will use [11C]PBR28 positron emission tomography (PET) imaging to quantify 18kDa translocator protein (TSPO) levels. TSPO is an imaging marker of the neuroimmune system thought to reflect microglia levels. Up to twenty healthy volunteers will complete two 120-minute [11C]PBR28 PET scans. One scan will take place prior to a single morphine administration (0.07 mg/kg i.m.) and the second scan will be will start approximately 2-hours post-injection. Specific Aim: To determine whether an acute morphine injection increases TSPO availability in healthy volunteers. Hypothesis: Relative to baseline, morphine will significantly increase whole-brain TSPO availability, consistent with a neuroimmune response.
Name: Intramuscular MorphineDescription: See arm description.Type: Drug
Acute morphine challenge
Description: The percentage change in 18kDa translocator protein (TSPO) availability will be measured via 2 PET [11C]PBR28 scansMeasure: Morphine-induced Change in TSPO availability Time: One 120-minute PET [11C]PBR28 scan before and the other ~2 hours after morphine challenge
Description: The percentage change in Cogstate memory performance will be calculatedMeasure: Morphine-induced Change in Memory Proficiency Time: The Cogstate Battery will be administered twice: once before and once ~4 hours after the morphine challenge
Single Group Assignment
There is one SNP
Exclusion Criteria: - 1) Any Axis 1 DSM-5 diagnosis (SCID-5), including substance dependence for any drug of abuse; - 2) Psychotropic medication use; - 3) Recent (past 6 months) medical opioid use; - 4) Prior medical use of opioids for >5 consecutive days; - 5) Prior non-medical, i.e. recreational, opioid use; - 6) Positive urine drug screen (UDS) result (excluding marijuana); - 7) Current/past chronic pain (>6 months of continuous pain); - 8) 'Low affinity binding' individuals based on rs6971 polymorphism (<10% population) who exhibit negligible [11C]PBR28 binding; - 9) For females, pregnancy (urine or blood test); - 10) Current use of non-steroidal anti-inflammatory medications or statins; - 11) CYP2D6 genotype indicative of 'poor' or 'ultra-rapid' morphine metabolizer which is associated with greater side effect risk; - 12) First-degree relative with history of opioid- or alcohol-use disorder; - 13) MRI contraindications; - 14) Subjects who would exceed annual radiation dose limits (5 rem/12 months) if he/she participated in this study; - 15) Allergy to morphine; - 16) Medical contraindication to receive up to 0.1 mg/kg intramuscular morphine administration (as determined by Study Physician) or medical conditions that, in the opinion of the Study Physician, would increase the risk of side effects from morphine administration, such as asthma, will be excluded.