Morphine is an opioid drug used to treat acute and chronic pain. Morphine can be administered together with cannabinoids to treat some types of pain with a synergistic interaction effect. The interaction can also reduce the tolerance of pain treatment by using a low dose combination of both drugs. More research is needed to optimize the clinical use of this drug combination.
Morphine shows enhanced potency when is combined with THC in animal models (Smith et al., 1998; Tham et al., 2005).
This synergy effect is shown to be useful to avoid tolerance when both THC and morphine are administered together in low doses (Cichewicz and McCarthy, 2003; Smith et al., 2007).
CBD shows a synergistic interaction with morphine only in the acetic acid-stimulated stretching assay (Neelakantan et al., 2015).
Cichewicz, D.L., and McCarthy, E.A. (2003). Antinociceptive Synergy between Δ9-Tetrahydrocannabinol and Opioids after Oral Administration. J. Pharmacol. Exp. Ther. 304, 1010–1015.
Neelakantan, H., Tallarida, R.J., Reichenbach, Z.W., Tuma, R.F., Ward, S.J., and Walker, E.A. (2015). Distinct interactions of cannabidiol and morphine in three nociceptive behavioral models in mice: Behav. Pharmacol. 26, 304–314.
Smith, F.L., Cichewicz, D., Martin, Z.L., and Welch, S.P. (1998). The Enhancement of Morphine Antinociception in Mice by Δ9-Tetrahydrocannabinol. Pharmacol. Biochem. Behav. 60, 559–566.
Smith, P.A., Selley, D.E., Sim-Selley, L.J., and Welch, S.P. (2007). Low dose combination of morphine and Δ9-tetrahydrocannabinol circumvents antinociceptive tolerance and apparent desensitization of receptors. Eur. J. Pharmacol. 571, 129–137.
Tham, S.M., Angus, J.A., Tudor, E.M., and Wright, C.E. (2005). Synergistic and additive interactions of the cannabinoid agonist CP55,940 with μ opioid receptor and α2-adrenoceptor agonists in acute pain models in mice. Br. J. Pharmacol. 144, 875–884.
There are some analgesic effects when combining THC with morphine, but more research is needed to find the best dose combination and to improve the time and route of administration depending on the pharmacokinetics of both drugs (Naef et al., 2003). THC shown synergic effects in combination with morphine only in the affective component of pain (Roberts et al., 2006).
Naef, M., Curatolo, M., Petersen-Felix, S., Arendt-Nielsen, L., Zbinden, A., and Brenneisen, R. (2003). The analgesic effect of oral delta-9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions: pain 105, 79–88.
Roberts, J.D., Gennings, C., and Shih, M. (2006). Synergistic affective analgesic interaction between delta-9-tetrahydrocannabinol and morphine. Eur. J. Pharmacol. 530, 54–58.