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Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification.
J Pharmacol Exp Ther. 1999 May; 289(2):859-67.JP

Abstract

The antinociceptive effects of various mu opioids given p.o. alone and in combination with Delta-9-tetrahydrocannabinol (Delta9-THC) were evaluated using the tail-flick test. Morphine preceded by Delta9-THC treatment (20 mg/kg) was significantly more potent than morphine alone, with an ED50 shift from 28.8 to 13.1 mg/kg. Codeine showed the greatest shift in ED50 value when administered after Delta9-THC (139.9 to 5.9 mg/kg). The dose-response curves for oxymorphone and hydromorphone were shifted 5- and 12.6-fold, respectively. Methadone was enhanced 4-fold, whereas its derivative, l-alpha-acetylmethadol, was enhanced 3-fold. The potency ratios after pretreatment with Delta9-THC for heroin and meperidine indicated significant enhancement (4.1 and 8.9, respectively). Pentazocine did not show a parallel shift in its dose-response curve with Delta9-THC. Naloxone administration (1 mg/kg s.c.) completely blocked the antinociceptive effects of morphine p.o. and codeine p.o. The Delta9-THC-induced enhancement of morphine and codeine was also significantly decreased by naloxone administration. Naltrindole (2 mg/kg s.c.) did not affect morphine or codeine antinociception but did block the enhancement of these two opioids by Delta9-THC. No effect was seen when nor-binaltorphimine was administered 2 mg/kg s.c. before morphine or codeine. Furthermore, the enhancements of morphine and codeine were not blocked by nor-binaltorphimine. We find that many mu opioids are enhanced by an inactive dose of Delta9-THC p.o. The exact nature of this enhancement is unknown. We show evidence of involvement of mu and possibly delta opioid receptors as a portion of this signaling pathway that leads to a decrease in pain perception.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond, Virginia, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10215664

Citation

Cichewicz, D L., et al. "Enhancement Mu Opioid Antinociception By Oral Delta9-tetrahydrocannabinol: Dose-response Analysis and Receptor Identification." The Journal of Pharmacology and Experimental Therapeutics, vol. 289, no. 2, 1999, pp. 859-67.
Cichewicz DL, Martin ZL, Smith FL, et al. Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification. J Pharmacol Exp Ther. 1999;289(2):859-67.
Cichewicz, D. L., Martin, Z. L., Smith, F. L., & Welch, S. P. (1999). Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification. The Journal of Pharmacology and Experimental Therapeutics, 289(2), 859-67.
Cichewicz DL, et al. Enhancement Mu Opioid Antinociception By Oral Delta9-tetrahydrocannabinol: Dose-response Analysis and Receptor Identification. J Pharmacol Exp Ther. 1999;289(2):859-67. PubMed PMID: 10215664.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification. AU - Cichewicz,D L, AU - Martin,Z L, AU - Smith,F L, AU - Welch,S P, PY - 1999/4/24/pubmed PY - 1999/4/24/medline PY - 1999/4/24/entrez SP - 859 EP - 67 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 289 IS - 2 N2 - The antinociceptive effects of various mu opioids given p.o. alone and in combination with Delta-9-tetrahydrocannabinol (Delta9-THC) were evaluated using the tail-flick test. Morphine preceded by Delta9-THC treatment (20 mg/kg) was significantly more potent than morphine alone, with an ED50 shift from 28.8 to 13.1 mg/kg. Codeine showed the greatest shift in ED50 value when administered after Delta9-THC (139.9 to 5.9 mg/kg). The dose-response curves for oxymorphone and hydromorphone were shifted 5- and 12.6-fold, respectively. Methadone was enhanced 4-fold, whereas its derivative, l-alpha-acetylmethadol, was enhanced 3-fold. The potency ratios after pretreatment with Delta9-THC for heroin and meperidine indicated significant enhancement (4.1 and 8.9, respectively). Pentazocine did not show a parallel shift in its dose-response curve with Delta9-THC. Naloxone administration (1 mg/kg s.c.) completely blocked the antinociceptive effects of morphine p.o. and codeine p.o. The Delta9-THC-induced enhancement of morphine and codeine was also significantly decreased by naloxone administration. Naltrindole (2 mg/kg s.c.) did not affect morphine or codeine antinociception but did block the enhancement of these two opioids by Delta9-THC. No effect was seen when nor-binaltorphimine was administered 2 mg/kg s.c. before morphine or codeine. Furthermore, the enhancements of morphine and codeine were not blocked by nor-binaltorphimine. We find that many mu opioids are enhanced by an inactive dose of Delta9-THC p.o. The exact nature of this enhancement is unknown. We show evidence of involvement of mu and possibly delta opioid receptors as a portion of this signaling pathway that leads to a decrease in pain perception. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10215664/Enhancement_mu_opioid_antinociception_by_oral_delta9_tetrahydrocannabinol:_dose_response_analysis_and_receptor_identification_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10215664 DB - PRIME DP - Unbound Medicine ER -