Significance The significance of the results reported is in two areas. ( i ) Because the cannabinoid receptor type 2 (CB2) agonists seem to be general protective agents, HU-433, a new specific CB2 agonist, may be of major therapeutic importance. ( ii ) Enantiomers usually have different activity profiles. We report now that HU-433 and its enantiomer HU-308 are both specific CB2 agonists, but whereas HU-433 is much more potent than HU-308 in the rescue of ovariectomy-induced bone loss and ear inflammation, its binding to the CB2 receptor (through which the activity of both enantiomers takes place) is substantially lower compared with HU-308. This situation questions the usefulness of universal radioligands for comparative binding studies.