On the basis of the murine results, the efficacy of the 5-HT3 receptor antagonist ondansetron was tested in human volunteers using an experimental protocol for inducing opioid withdrawal [30]. Eight healthy male volunteers were pretreated with placebo or ondansetron (8 mg) before i.v. administration of morphine and subsequent naloxone-precipitated withdrawal. The effect of the pretreatment drug was assessed using well-established objective (OOWS, primary outcome) and subjective (SOWS) measures of opioid withdrawal [5]. Ondansetron pretreatment caused a substantial (76.4%±22.6) and statistically significant (P=0.0313) decrease in mean OOWS score (Fig. 9). Seven of the eight volunteers developed objective signs of opioid withdrawal, and ondansetron pretreatment reduced these signs in all seven affected individuals. The OOWS score is a composite measure of 13 physically observable signs. The volunteers manifested 12 of the 13 measured signs, and ondansetron pretreatment decreased all 12 of these individual signs indicating a broad-spectrum effect (Fig. 9). In contrast, there was only a very small mean decrease in the subjective symptoms (SOWS score) that did not reach statistical significance (4.1%±62.5, P>0.05, Fig. 10).
