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Modulation of oral morphine antinociceptive tolerance and naloxone-precipitated withdrawal signs by oral Delta 9-tetrahydrocannabinol.
J Pharmacol Exp Ther. 2003 Jun; 305(3):812-7.JP

Abstract

Previous studies have demonstrated a functional interaction between cannabinoid and opioid systems in the development and expression of morphine tolerance and dependence. In these experiments, we examined the effect of a low oral dose of Delta 9-tetrahydrocannabinol (Delta 9-THC) on the development of oral morphine tolerance and the expression of naloxone-precipitated morphine withdrawal signs of jumping and diarrhea in ICR mice. Chronic treatment with high-dose oral morphine produced a 3.12-fold antinociceptive tolerance. Tolerance to morphine was prevented in groups receiving a daily cotreatment with a nonanalgetic dose (20 mg/kg p.o.) of Delta 9-THC, except when challenged with a very high dose of morphine. The chronic coadministration of low-dose Delta 9-THC also reduced naloxone-precipitated (1 mg/kg s.c.) platform jumping by 50% but did not reduce diarrhea. In separate experiments, mice treated chronically with high-dose morphine p.o. were not cross-tolerant to Delta 9-THC; in fact, these morphine-tolerant mice were more sensitive to the acute antinociceptive effects of Delta 9-THC. Delta 9-THC (20 mg/kg p.o.) also reduced naloxone-precipitated jumping but not diarrhea when administered acutely to morphine-tolerant mice. These results represent the first evidence that oral morphine tolerance and dependence can be circumvented by coadministration of a nonanalgetic dose of Delta 9-THC p.o. In summary, cotreatment with a combination of morphine and Delta 9-THC may prove clinically beneficial in that long-term morphine efficacy is maintained.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

12606610

Citation

Cichewicz, Diana L., and Sandra P. Welch. "Modulation of Oral Morphine Antinociceptive Tolerance and Naloxone-precipitated Withdrawal Signs By Oral Delta 9-tetrahydrocannabinol." The Journal of Pharmacology and Experimental Therapeutics, vol. 305, no. 3, 2003, pp. 812-7.
Cichewicz DL, Welch SP. Modulation of oral morphine antinociceptive tolerance and naloxone-precipitated withdrawal signs by oral Delta 9-tetrahydrocannabinol. J Pharmacol Exp Ther. 2003;305(3):812-7.
Cichewicz, D. L., & Welch, S. P. (2003). Modulation of oral morphine antinociceptive tolerance and naloxone-precipitated withdrawal signs by oral Delta 9-tetrahydrocannabinol. The Journal of Pharmacology and Experimental Therapeutics, 305(3), 812-7.
Cichewicz DL, Welch SP. Modulation of Oral Morphine Antinociceptive Tolerance and Naloxone-precipitated Withdrawal Signs By Oral Delta 9-tetrahydrocannabinol. J Pharmacol Exp Ther. 2003;305(3):812-7. PubMed PMID: 12606610.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of oral morphine antinociceptive tolerance and naloxone-precipitated withdrawal signs by oral Delta 9-tetrahydrocannabinol. AU - Cichewicz,Diana L, AU - Welch,Sandra P, Y1 - 2003/02/11/ PY - 2003/2/28/pubmed PY - 2003/7/8/medline PY - 2003/2/28/entrez SP - 812 EP - 7 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 305 IS - 3 N2 - Previous studies have demonstrated a functional interaction between cannabinoid and opioid systems in the development and expression of morphine tolerance and dependence. In these experiments, we examined the effect of a low oral dose of Delta 9-tetrahydrocannabinol (Delta 9-THC) on the development of oral morphine tolerance and the expression of naloxone-precipitated morphine withdrawal signs of jumping and diarrhea in ICR mice. Chronic treatment with high-dose oral morphine produced a 3.12-fold antinociceptive tolerance. Tolerance to morphine was prevented in groups receiving a daily cotreatment with a nonanalgetic dose (20 mg/kg p.o.) of Delta 9-THC, except when challenged with a very high dose of morphine. The chronic coadministration of low-dose Delta 9-THC also reduced naloxone-precipitated (1 mg/kg s.c.) platform jumping by 50% but did not reduce diarrhea. In separate experiments, mice treated chronically with high-dose morphine p.o. were not cross-tolerant to Delta 9-THC; in fact, these morphine-tolerant mice were more sensitive to the acute antinociceptive effects of Delta 9-THC. Delta 9-THC (20 mg/kg p.o.) also reduced naloxone-precipitated jumping but not diarrhea when administered acutely to morphine-tolerant mice. These results represent the first evidence that oral morphine tolerance and dependence can be circumvented by coadministration of a nonanalgetic dose of Delta 9-THC p.o. In summary, cotreatment with a combination of morphine and Delta 9-THC may prove clinically beneficial in that long-term morphine efficacy is maintained. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/12606610/Modulation_of_oral_morphine_antinociceptive_tolerance_and_naloxone_precipitated_withdrawal_signs_by_oral_Delta_9_tetrahydrocannabinol_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12606610 DB - PRIME DP - Unbound Medicine ER -