Study to Evaluate the Efficacy of Dronabinol (Marinol) as Add-On Therapy for Patients on Opioids for Chronic Pain

During the informed consent process subjects will be informed that Marinol (Dronabinol) is generally not used for chronic pain and there will be no provision for extended treatment with Dronabinol.

The study comprises two phases, the blinded single-dose phase and the open-label multi-dose phase. There are five visits in all; one baseline visit, three treatment visits in the single-dose phase, and then a final end-of-study visit after the multi-dose phase is over.

Subjects will be initially screened by telephone, and if eligible will present for a baseline visit. This visit will verify enrollment criteria, and will include a history and physical exam, urine pregnancy test if indicated, and baseline assessments. Subjects who meet full enrollment criteria will be randomly allocated to one of the treatment sequences of the single-dose phase.

Single-Dose Phase

The treatment sequence will be a randomized 3-treatment, 3-period crossover trial. Each subject will receive each treatment in a sequence randomly allocated by the Investigational Drug Services Department at Brigham and Women's Hospital. These visits will be scheduled a minimum of 3 days apart, and subjects will be instructed to reschedule if their pain is less than 4/10 on the morning of their visit.

On the days of the treatment visits, subjects will arrive in the Clinical Trials Center at 7-8am, without having taken their morning opioid dose. They will also be fasting, except for clear liquids. They will have a baseline blood sample drawn for level of THC, if any, in their blood. Patients will receive study drug at 8-9 am, and will be monitored for 8 hours, and subsequently discharged home. At the 4- and 8-hour mark, two more blood samples will be drawn. Total amount of blood taken for all three samples together will be less than 10 ml. Subjects who require rescue dosing during the 8-hour study period will take their customary rescue analgesic, be observed in the study center to ensure that they achieve adequate relief of their pain, and then discharged home. A "rescue assessment" will be completed at the time of rescue dosing and will be the final assessment for that treatment session. At the end of the fourth visit (the final treatment visit), prior to discharge, subjects will be offered entry into the one-month open-label extension.

Multi-Dose Phase

Subjects who choose to enter the open-label extension will be provided Marinol tablets which they will then take according to a prearranged titration table. Subjects may titrate upwards for inadequate analgesia or downwards for side effects. Subjects must be on a dose for a minimum of two days prior to upward titration, but may titrate downward at any time due to side effects. Subjects unable to tolerate any regimens will be dropped from the study. Subjects will be required to be on a stable dronabinol regimen during the last week of the study. Subjects who choose to terminate early will be encouraged to present for a termination visit.

Subjects will continue baseline analgesics, including background and rescue opioids as they had been prior to the trial. Downward titration of opioids will be allowed if clinically indicated, per judgment of patient and investigator. Subjects will be contacted weekly at the end of weeks 1, 2, and 3. Data collected during the telephone contacts will relate to pain, medication consumption (study and non-study analgesics), and side effects. Subjects will present for an end-of-study visit at the end of week 4.