Pain
Conditions
Keywords
Cannabis, Morphine, Oxycodone, Marijuana, chronic pain
Brief summary
We are conducting a study to assess whether smoking marijuana affects the safety of prescribed opioids in patients treated for chronic pain. This study will assess whether smoking cannabis affects the absorption, distribution, metabolism and excretion of widely used opioid analgesics. We propose to do this by investigating the effects of smoked cannabis in subjects prescribed morphine or oxycodone for chronic pain. We will also assess the clinical safety of cannabinoids and these opioids by monitoring the short-term side effects associated with combined therapy.
Detailed description
Chronic pain conditions remain problematic, especially in patients with cancer. Although opioids are effective analgesics, dose-limiting side effects in the form of sedation, nausea and vomiting, and fear of dependence often limit their use at higher - and possibly more effective - doses. Of particular interest, however, is the potential for greater than additive analgesic effect of cannabinoids and opioids in combination that would allow for opioid analgesic effect to be achieved at lower dosages than are necessary alone, which could overcome problems with both tolerance and side effects for both drug classes. Unfortunately, safety data on the combination in humans does not exist at this time and needs to be obtained. As increasing numbers of patients with chronic pain may turn to cannabis to augment the effects of their opioid analgesics, data on potential pharmacokinetic interactions and clinical safety of the combinations should be evaluated in a controlled clinical research setting.
Interventions
DRUGCannabis
Sponsors
National Institute on Drug Abuse (NIDA)
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ongoing analgesic therapy with either oxycodone hydrochloride (OxyContin) or morphine sulfate (MS Contin) every 12 hours for chronic pain. 2. Eligible subjects will be ≥ 18 years of age with a diagnosis of chronic pain and an estimated survival of greater than six months. 3. Subjects must be on a stable dose of opioid medication for at least 2 weeks before enrollment. 4. Current other analgesic medications will be maintained during the study. The subject must have been on a stable medication regimen for at least 2 weeks. 5. The following laboratory parameters documented within 45 days prior to study entry: * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 X upper limit of normal (ULN) * Total bilirubin ≤ 2 X ULN * Creatinine ≤ 2.0 mg/dL (177 µmol/L) 6. All men and women in this study must agree to use adequate birth control during this study. Acceptable barrier birth control methods are a male condom, female condom, diaphragm, or intra-uterine (IUD). 7. All women of reproductive potential (who have not reached menopause or undergone hysterectomy, oophorectomy, or tubal ligation) must have a negative urine b-HCG pregnancy test performed before initiating the protocol-specified medication. 8. Prior history of use of marijuana. Subjects must have smoked marijuana on at least 6 occasions in their lifetime prior to enrollment. 9. Able to understand and follow the instructions of the investigator, including completing the pain intensity rating scales. 10. Karnofsky Performance Score \>60. 11. Able and willing to provide informed consent.
Exclusion criteria
1. Severe coronary artery disease, uncontrolled hypertension, cardiac ventricular conduction abnormalities, or orthostatic mean blood pressure drop greater than 24 mmHg, severe chronic obstructive pulmonary disease. 2. History of renal or hepatic failure. 3. Evidence of hepatic, hematological or renal dysfunction based on judgment of physician. 4. Active substance abuse (e.g., alcohol or injection drugs). 5. Use of smoked marijuana within 30 days of enrollment verified with a urine THC level. 6. Neurologic dysfunction or psychiatric disorder severe enough to interfere with assessment of pain or sensory systems. 7. Current use of smoked tobacco products or a confirmed cotinine level. 8. Women who are pregnant or breast-feeding may not take part in this study. 9. Unable to read or speak English.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disposition Kinetics of Morphine and Oxycodone Before and After Cannabis Use | Day 1, Day 5 | Pharmacokinetics are measured on Day 1, prior to cannabis use, and again on Day 5, following cannabis use on Days 2, 3, and 4. |
Countries
United States
Participant flow
Recruitment details
315 participants were screened, via phone and e-mail, between January 2007 and February 2009. 24 subjects were enrolled, 13 taking morphine and 11 taking oxycodone.
Participants by arm
| Arm | Count |
|---|---|
| MS Contin Patients using morphine sulfate (MS Contin) every 12 hours for chronic pain | 13 |
| Oxycontin Patients using oxycodone hydrochloride (OxyContin)every 12 hours for chronic pain | 11 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | MS Contin | Oxycontin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 11 Participants | 24 Participants |
| Age, Continuous | 42.9 years STANDARD_DEVIATION 7.4 | 47.1 years STANDARD_DEVIATION 11.8 | 45.1 years STANDARD_DEVIATION 10 |
| Gender Female | 6 Participants | 6 Participants | 12 Participants |
| Gender Male | 7 Participants | 5 Participants | 12 Participants |
| Mean opioid dose, twice daily | 62 mg | 53 mg | 58 mg |
| Region of Enrollment United States | 13 participants | 11 participants | 24 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 13 | 0 / 11 |
| serious Total, serious adverse events | 0 / 13 | 0 / 11 |
Outcome results
Primary
Disposition Kinetics of Morphine and Oxycodone Before and After Cannabis Use
Pharmacokinetics are measured on Day 1, prior to cannabis use, and again on Day 5, following cannabis use on Days 2, 3, and 4.
Time frame: Day 1, Day 5
Population: The number was determined by the number of participants completing both Day 1 and Day 5 procedures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MS Contin | Disposition Kinetics of Morphine and Oxycodone Before and After Cannabis Use | Time to maximum concentration (Tmax) | 1.64 Geometric Mean Ratio |
| MS Contin | Disposition Kinetics of Morphine and Oxycodone Before and After Cannabis Use | Maximum concentration (Cmax) | 0.9 Geometric Mean Ratio |
| MS Contin | Disposition Kinetics of Morphine and Oxycodone Before and After Cannabis Use | Area under plasma concentration-time curve (AUC) | 0.95 Geometric Mean Ratio |
| Oxycodone | Disposition Kinetics of Morphine and Oxycodone Before and After Cannabis Use | Time to maximum concentration (Tmax) | -1.11 Geometric Mean Ratio |
| Oxycodone | Disposition Kinetics of Morphine and Oxycodone Before and After Cannabis Use | Maximum concentration (Cmax) | 0.99 Geometric Mean Ratio |
| Oxycodone | Disposition Kinetics of Morphine and Oxycodone Before and After Cannabis Use | Area under plasma concentration-time curve (AUC) | 0.94 Geometric Mean Ratio |