title: Enhancement of transdermal fentanyl and buprenorphine antinociception by transdermal delta9-tetrahydrocannabinol.
abstract: Previous studies have demonstrated that delta9-tetrahydrocannabinol (THC) enhances the antinociceptive potency of many opioids administered by a variety of different routes of administration. We hypothesized that THC would enhance fentanyl or buprenorphine analgesia via the transdermal route of administration. THC was first demonstrated to enhance opioid antinociception when both drugs were administered parenterally in a hairless guinea pig model using the pin prick test. A low dose of THC (50 mg/kg, i.p.) produced no antinociception. However, THC enhanced the potency of s.c. fentanyl by 6.7-fold, and s.c. buprenorphine in a non-parallel fashion. For the transdermal studies, THC, fentanyl or buprenorphine was applied by pipette to the skin of the dorsum between the fore- and hind-flanks and covered with individual Tegederm patches. THC (400 mg/kg) produced no antinociception. However, THC enhanced fentanyl's potency by 3.7-fold at 2-h, and 5.8-fold at 4-h. Buprenophine's potency was increased 8.2-fold at 2-h and 7.2-fold at 4-h when co-administered with THC. These results indicate that the enhancement of transdermal opioids by THC could lead to the design of an effective combination analgesic patch.
authors.affiliation: Philip Morris, U.S.A., Richmond, VA 23261, United States.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Cichewicz
authors.forename: Sandra P
authors.initials: SP
authors.lastname: Welch
authors.forename: Forrest L
authors.initials: FL
authors.lastname: Smith
mesh_terms: D000279:Administration, Cutaneous; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage* / Q000494:pharmacology; D013759:Dronabinol / Q000008:administration & dosage* / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000494:pharmacology; D006168:Guinea Pigs; D010147:Pain Measurement / Q000187:drug effects*
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D002047:Buprenorphine; D013759:Dronabinol; D005283:Fentanyl