Time course of the enhancement and restoration of the analgesic efficacy of codeine and morphine by delta9-tetrahydrocannabinol

Eur J Pharmacol. 2006 Jun 6;539(1-2):57-63. doi: 10.1016/j.ejphar.2006.04.003. Epub 2006 Apr 6.


Delta9-tetrahydrocannabinol (delta9-THC) synergizes with morphine and codeine by releasing endogenous opioids. These studies determined 1) the duration of enhancement of morphine and codeine by delta9-THC, 2) the effect of (delta9-THC on the time course of fully efficacious doses of the opioids, 3) restoration of efficacy of morphine and codeine by delta9-THC, and 4) duration of restoration. Sub-active combination doses of delta9-THC/morphine or delta9-THC/codeine are equivalent in duration of action and efficacy to high-dose opioids alone. Delta9-THC (20 mg/kg p.o.) significantly restores the antinociceptive effects of both high-dose morphine and codeine (100 and 200 mg/kg p.o., respectively) at later time points at which morphine or codeine was no longer active (360- and 120-min post-administration, respectively). Thus, the cannabinoid/opioid combination might be useful in therapeutics to enhance opioid activity, as well as to restore the efficacy of opioids.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics, Non-Narcotic / pharmacology*
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Codeine / pharmacology*
  • Dronabinol / pharmacology*
  • Drug Synergism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Morphine / pharmacology*


  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Morphine
  • Dronabinol
  • Codeine