Our primary objective is to assess whether smoking cannabis affects the safety of prescribed opioids in patients treated for cancer-related pain. We propose to do this by conducting a study to investigate the effects of smoked cannabis on the pharmacokinetics and metabolism of widely used opioid analgesics. The trial will be conducted among experienced marijuana users prescribed opiates for cancer-related pain. The study will enroll 10 patients prescribed oral controlled-released morphine (MS Contin(r)) and 10 patients prescribed oral controlled-released oxycodone (OxyContin(r)) to assess the effect of smoking cannabis on the 12-hour plasma area-under-the-curve of these opioid analgesics. A secondary aim will be to assess the clinical safety of the concomitant use of cannabinoids and opioids by monitoring side effects associated with combined therapy. The study will be conducted in the General Clinical Research Center (GCRC) at San Francisco General Hospital (SFGH). The inpatient setting permits measurement of plasma opioid and THC levels over time and rigorous assessment of safety by way of closely observed nurse monitoring for potential side effects. The study will be comprised of a 5-day intervention period in the GCRC. On Day 1, subjects undergo 12 hours of blood sampling to define their stable concentration over time curve for their opioid analgesic. At 8pm on day 1, participants will smoke approximately one 3.5% THC cigarette. On Days 2 through 4 subjects will smoke one cigarette at 8am, 2pm and 8pm. On Day 5 subjects will smoke one cigarette at 8am. On Day 5, opioid pharmacokinetic specimens will be obtained over 12 hours and THC plasma levels will be obtained over 1 hour to determine the effect of smoked marijuana on the disposition of morphine, and oxycodone. Objective cardiovascular affects and subjective psycho-behavioral affects of opioids and cannabis will be assessed prior to and during the 12-hour period after morning administration of opioid analgesics during each study day. In addition, subjective psycho-behavioral affects will be assessed by GCRC nursing staff every 8 hours during the study period. Nausea and vomiting will be assessed daily via self-report. The study will be conducted over a 2-year period. ? ? ?
| Abrams, D I; Couey, P; Shade, S B et al. (2011) Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther 90:844-51 |
