An Assessment of Fentanyl Dose Requirements in Opioid-maintained Individuals

Inclusion Criteria: 1. Male or female, aged 18 to 65. 2. Maintained on any opioid with oral morphine equivalent daily dose (MEDD) of 60 mg and above. 3. Have adequate intravenous access for drug infusion. 4. Are currently abstaining from oral and intravenous recreational drug use. Exclusion Criteria: 1. Known positive for Hepatitis B, Hepatitis C or HIV 2. Contraindication to cold pain testing e.g. cardiac or vascular disease especially Raynaud's phenomenon, blood pressure problems, diabetes, epilepsy and recent serious injury. 3. Using medication which affects pupil size e.g. glaucoma 4. Visual acuity poorer than 6 / 25 corrected (so that saccadic eye movements can be performed correctly. 5. Patients with respiratory insufficiency and poor respiratory drive. The criteria will be a spirometry reading of less than 70% the predicted value and/or having resting oxygen saturation levels of less than 95% on air. 6. Subject is pregnant and/or lactating. 7. Chronic use of benzodiazepines which cannot be withheld for 5 half-lives of the benzodiazepine the patient is on. 8. Known intolerance to fentanyl or other opioids 9. Patients taking tramadol. 10. Patients taking CYP3A4 inhibitors like amiodarone, azole antifungals, cimetidine, clarithromycin, cyclosporine, diltiazem, erythromycin, fluoroquinolones, grapefruit juice, HIV protease inhibitors, metronidazole, quinine, selective serotonin reuptake inhibitors (SSRIs) and tacrolimus. 11. A positive urine test for benzodiazepines on the day of screening or testing. 12. A positive breathalyzer test on the day of testing. 13. Creatinine clearance \< 30ml/min as estimated by Cockcroft-Gault formula. 14. Patients with bradyarrythmia.