Spurred by a growing interest in cannabidiolquinone (CBDQ, HU-313, <b>2</b>) as a degradation marker and alledged hepatotoxic metabolite of cannabidiol (CBD, <b>1</b>), we performed a systematic study on the oxidation of CBD (<b>1</b>) to CBDQ (<b>2</b>) under a variety of experimental conditions (base-catalyzed aerobic oxidation, oxidation with metals, oxidation with hypervalent iodine reagents). The best results in terms of reproducibility and scalability were obtained with λ<sup>5</sup>-periodinanes (Dess-Martin periodinane, 1-hydroxy-1λ<sup>5</sup>,2-benziodoxole-1,3-dione (IBX), and SIBX, a stabilized, nonexplosive version of IBX). With these reagents, the oxidative dimerization that plagues the reaction under basic aerobic conditions was completely suppressed. A different reaction course was observed with the copper(II) chloride-hydroxylamine complex (Takehira reagent), which afforded a mixture of the hydroxyiminodienone <b>11</b> and the halogenated resorcinol <b>12</b>. The λ<sup>5</sup>-periodinane oxidation was general for phytocannabinoids, turning cannabigerol (CBG, <b>18</b>), cannabichromene (CBC, <b>10</b>), and cannabinol (CBN, <b>19</b>) into their corresponding hydroxyquinones (<b>20</b>, <b>21</b>, and <b>22</b>, respectively). All cannabinoquinoids modulated to a various extent peroxisome proliferator-activated receptor gamma (PPAR-γ) activity, outperforming their parent resorcinols in terms of potency, but the iminoquinone <b>11</b>, the quinone dimers <b>3</b> and <b>23</b>, and the haloresorcinol <b>12</b> were inactive, suggesting a specific role for the monomeric hydroxyquinone moiety in the interaction with PPAR-γ.