Cannabichromene (CBC): a comprehensive review of biosynthesis, pharmacology, therapeutic potential, and translational perspectives

Cannabis sativa L. produces a chemically diverse array of over 150 phytocannabinoids, of which cannabichromene (CBC) represents the fourth most abundant constituent in many chemovars, yet remains profoundly underexplored relative to its structural congeners delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and its precursor cannabigerol (CBG). Unlike THC, CBC is non-psychoactive and lacks the intoxicating central effects associated with THC, positioning it as a particularly attractive candidate for therapeutic development. This comprehensive review critically examines the current state of knowledge on CBC, encompassing its biosynthetic origin through the polyketide and mevalonate/methylerythritol phosphate pathways, the enzymatic conversion of cannabigerolic acid (CBGA) to cannabichromenic acid (CBCA) by CBC synthase (CBCAS), and subsequent spontaneous and thermally accelerated decarboxylation. We survey the natural occurrence and distribution of CBC across Cannabis chemovars, the genetic and environmental determinants of its accumulation, and the advanced extraction, isolation, and analytical methodologies employed for its characterization. The pharmacokinetic profile of CBC, including absorption, distribution, hepatic metabolism via cytochrome P450 enzymes, and elimination, is discussed in the context of its notably low oral bioavailability. The molecular pharmacology of CBC is examined in depth, highlighting its unique receptor interaction profile: minimal direct engagement with CB1/CB2 cannabinoid receptors, potent agonism at transient receptor potential channels (TRPV1, TRPA1, TRPV3, TRPV4), and indirect modulation of endocannabinoid tone through inhibition of anandamide reuptake. We evaluate the preclinical evidence supporting its anti-inflammatory, analgesic, antimicrobial, anticancer, neuroprotective, antidepressant, and dermatological activities, and contextualize these findings within the entourage effect framework. The toxicological safety profile, drug-drug interaction potential, and regulatory landscape are critically assessed. Finally, we identify translational challenges, including formulation limitations, the absence of clinical trials, and regulatory fragmentation, and propose future research directions encompassing nanotechnology-based delivery systems, synthetic biology platforms for sustainable production, multi-omics integration, and precision medicine approaches. This review establishes CBC as a high-potential but critically understudied phytocannabinoid deserving of accelerated preclinical and clinical investigation.