3. Umbruch 4.4..2005 - Online Pot

158 S.M. Huang and J.M. Walker
doses of cannabinoids enhance opioid analgesia, inactive doses of opioids can
also enhance cannabinoid analgesia [120, 121].
The synergistic pain-suppressive effects of cannabinoid and opioid agonists
observed in the animal studies may provide the basis for a promising approach
in clinical pain management. The synergism would allow lower doses of opioids
and cannabinoids to be administered for attainment of a given degree of
pain suppression. As moderate to high doses of most cannabinoid or opioid
agonists alone often cause unpleasant psychotropic or physiologic side effects
in humans, the use of lower doses of these drugs may improve their clinical
utility in patients. Additionally, the reduced exposure to these drugs may slow
the development of tolerance. It is also possible that the inclusion of a cannabinoid
agonist in the regime could prevent the development of opioid tolerance,
as the results of an animal study by Cichewicz and Welch [122] seemed to
indicate. As opioids are emetic substances and cannabinoids are anti-emetic,
the combination may improve the side-effect profile of both drugs. Hence it
appears that the use of carefully titrated doses of a combination of cannabinoid
and opioid agonists may provide a better quality of pain management for many
conditions.
Summary and conclusions
A large body of literature from numerous preclinical studies as well as some
clinical studies has demonstrated the ability of cannabinoids to suppress pain.
The realization of the clinical potential of cannabinoids still requires more
work in the areas of target refinement, drug selectivity and drug delivery.
Promising approaches include development of CB 1 or CB 2 agonists, inhibitors
of endocannabinoid degradation or transport mechanisms, combination dosing
of cannabinoids with other analgesics such as opioids, and new delivery systems
such as transdermal patches. Highly potent and selective pharmacological
agents that focus on normalization of pain threshold and sensitivity without
causing psychotropic side effects in humans are much desired. Along with
drug development, further characterization of the cannabinoid system is
important in providing insights that are integral to identifying potential therapeutic
approaches.
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