Intervention: Morphine
Trial phase: Phase 2
ATC code: A07DA52 | N02AA01 | N02AA51 | N02AG01
SMILES: [H][C@@]12C=C[C@H](O)[C@]3([H])Oc4c(O)ccc5c4[C@]13CCN(C)[C@]2([H])C5
Sex: Male
Age groups: Adult
Healthy volunteers: No
Participants at risk: 10
Group description: All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline over 20-30 s
Eligibility criteria:
INCLUSION CRITERIA:

Male participants between 21-55 years of age.
Good health as determined by medical history, physical exam, EKG and lab tests.
Current non-smokers or light smokers or e-cigarette users (<20 cig/week) who can easily abstain from smoking or using e-cigarettes for 1-2 days/week.
Current non-drinkers or social drinkers who do not meet past or current DSM IV criteria for alcohol abuse or alcohol dependence.
An equal number of final participants will be of OPRM1 118 A/A vs. 118A/G or 118G/G genotype. This means that after the first group (n40) is complete then only participants with the required genotype for the other group will be included.
Prior opiate use, at least one experience with one of the opiates listed in Appendix 1 of the protocol.
Comprehension/fluency with English Language.

EXCLUSION CRITERIA:<TAB>

Current or prior history of any significant disease, including cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders, or a positive hepatitis or HIV test at screening, disorders that could make administration of an opiate more risky (e.g., asthma, COPD, sleep apnea, or other breathing disorders; liver or kidney disease; thyroid disorder; trouble swallowing, or a blockage in the digestive tract (stomach or intestines); neurologic disorders (e.g., a history of head injury or brain tumor, epilepsy or other seizure disorder, CVA, migraine in treatment, etc.); low blood pressure; hypertension; neuromuscular disorder; gallbladder disease; Addison's disease or other adrenal gland disorders; enlarged prostate, urination problems)
Current Axis-I psychiatric illness as determined by the Structured Clinical Interview for DSM IV disorders (SCID).
Current or prior history of any alcohol or drug dependence as determined by the Structured Clinical Interview for DSM IV disorders (SCID).
Positive result on urine screen for illicit drugs.

Medication Use:

Current chronic prescription or over the counter medications or use of prescription or OTC medications known to interact with dopamine receptors within 2 weeks of the study
Drugs known to inhibit or induce enzymes that metabolize opiates should not be used for 4 weeks prior to the study. These include chlorzoxazone, isoniazid, metronidazole and disulfiram.
Cough-and-cold preparations that contain anti-histamines or opiate pain medicines will be withheld for at least 72 hours prior to each study session.
Drugs that may interfere with the BOLD MRI signal within 2 weeks of the study. These include, but may not be limited to: muscle relaxants or respiratory, cardiovascular or anticonvulsant medications
Morbid obesity (BMI >40 kg/m2)
Previous negative effects of opioid administration
Presence of certain implanted devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia. Justification: Implanted devices may increase the risk of MRI scanning and/or adversely affect the quality of the data; body morphology may prevent optimal positioning in the scanner and thus affect the quality of the data; participants with claustrophobia may find the MRI scan too unpleasant and may exhibit excess movement that will adversely affect the quality of the data. Assessment tool(s): Prospective participants will fill out an MRI screening questionnaire and undergo an interview with an MR technologist. Questions concerning suitability for scanning will be referred to the Medical Advisory Investigator. Prospective participants will be questioned about symptoms of claustrophobia and placed in the mock scanner during their first visit to assess for possible difficulty tolerating the confinement of the scanner and for ability to fit into the scanner.
Conditions restricting participant's ability to lie flat for up to two hours (such as coagulopathies, superficial or deep vein thrombosis, or musculoskeletal abnormalities). Justification: PET scanning sessions require participants to lie flat on their backs and remain perfectly still for approximately two hours. Therefore, conditions that would make that difficult (e.g., chronic back pain, significant scoliosis) or dangerous (e.g., familial hypercoagulability syndrome, history of thrombosis) will be exclusionary. Assessment tool(s): History and physical examination by a qualified IRP clinician, supplemented with a trial of lying in the mock scanner to assess comfort.
Head trauma leading to loss of consciousness for more than 5 min or hospitalization
Exposure to ionizing radiation from research studies that, in combination with the study tracer, would result in cumulative exposure of >5 rem within the previous 12 month period
Self-reported and/or observed signs, symptoms, or diagnosis of Raynaud's or Buerger's disease (e.g., pain in hands or feet at times of rest, during/following cold exposure or stress, any significant color changes in hands or toes). Additionally, medical staff will be present to watch for these symptoms during the actual cold pressor test.