The human trials of cannabis and 49-THC are few in number and typically small in size. These studies differ in important ways. There are marked differences between studies in dose and dose regimens, and the drug preparations differ, with some using smoked marijuana and some using49-THC by the oral or intravenous routes. Some studies used healthy volunteers whereas others used patients with clinical pain of various origins. Therefore, it is important to note that (1) some negative results may have arisen from ineffective doses; (2) the oral route of administration adds variability due to the unpredictable absorption of 49-THC; (3) smoked marijuana contains additional constituents that likely contribute to any observed effects; (4) clinical pain is very different from experimental pain due to plasticity in the neuronal circuits that mediate pain. In light of the fact that the extant materials do not permit one to reach solid conclusions about the utility of direct-acting full cannabinoid agonists as therapeutic agents in pain, it seems best to examine this literature with an eye toward uncovering whatever therapeutic potential exists.
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