Synthetic cannabinoids (SCs) containing a 1-pentyl-1-H substituted indole or indazole are abused around the world and are associated with an array of serious side effects. These compounds undergo extensive phase 1 metabolism after ingestion with little understanding whether these metabolites are contributing to the cannabimimetic activity of the drugs. This work presents the synthesis and pharmacological characterization of the major metabolites of two high concern SCs; APICA and ADB-PINACA. In a fluorometric assay of membrane potential, all metabolites that did not contain a carboxylic acid functionality retained potent activity at both the CB1 (EC50 = 14-787 nM) and CB2 (EC50 = 5.5-291 nM) receptors regardless of heterocyclic core or 3-carboxamide substituent. Of note were the 5-hydroxypentyl and 4-pentanone metabolites which showed significant increases in CB2 functional selectivity. These results suggest that the metabolites of SCs potentially contribute to the overall pharmacological profile of these drugs.