The Bibenzyl Canniprene Inhibits the Production of Pro-Inflammatory Eicosanoids and Selectively Accumulates in Some <i>Cannabis sativa</i> Strains

Canniprene (<b>1</b>), an isoprenylated bibenzyl unique to <i>Cannabis sativa</i>, can be vaporized and therefore potentially inhaled from marijuana. Canniprene (<b>1</b>) potently inhibited the production of inflammatory eicosanoids via the 5-lipoxygenase pathway (IC₅₀ 0.4 μM) and also affected the generation of prostaglandins via the cyclooxygenase/microsomal prostaglandin E₂ synthase pathway (IC₅₀ 10 μM), while the related spiranoid bibenzyls cannabispiranol (<b>2</b>) and cannabispirenone (<b>3</b>) were almost inactive in these bioassays. The concentration of canniprene (<b>1</b>) was investigated in the leaves of 160 strains of <i>C. sativa</i>, showing wide variations, from traces to >0.2%, but no correlation was found between its accumulation and a specific phytocannabinoid profile