Opioid and Cannabinoid Pharmacokinetic Interactions

• ClinicalTrials.gov Identifier: NCT00308555
• Recruitment Status: Completed
• First Posted: March 29, 2006
• Results First Posted: July 22, 2013
• Last Update Posted: December 9, 2016
• Sponsor: University of California, San Francisco
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): University of California, San Francisco

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pain	Drug: Cannabis	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Opioid and Cannabinoid Pharmacokinetic Interactions: A Pilot Study
• Study Start Date: May 2006
• Actual Primary Completion Date: March 2009
• Actual Study Completion Date: March 2009

Arms and Interventions

Arm	Intervention/treatment
Cannabis	Drug: Cannabis

Outcome Measures

Primary Outcome Measures :

1. Disposition Kinetics of Morphine and Oxycodone Before and After Cannabis Use [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

Community Consortium

San Francisco, California, United States, 94110

Sponsors and Collaborators

University of California, San Francisco

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Donald I Abrams, M.D.; University of California, San Francisco

More Information

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00308555 History of Changes
• Other Study ID Numbers: CC # 064; 1R21DA020831-01 ( U.S. NIH Grant/Contract )
• First Posted: March 29, 2006
• Results First Posted: July 22, 2013
• Last Update Posted: December 9, 2016
• Last Verified: October 2016

Keywords provided by University of California, San Francisco:

Cannabis; Morphine; Oxycodone; Marijuana; chronic pain