Cannabichromene (CBC)

Cannabichromene (CBC), the 2H-chromene phytocannabinoid first isolated from Cannabis sativa hashish resin by Gaoni and Mechoulam in 1966 and independently by Claussen, Von Spulak, and Korte in the same year, is the third or fourth most abundant cannabinoid in many cannabis chemotypes and one of the six principal phytocannabinoids of pharmacological interest. Unlike delta-9-tetrahydrocannabinol (THC), CBC does not produce psychoactive effects in behavioral assays or in human experience, a property attributable to its negligible functional activity at the CB1 cannabinoid receptor despite measurable binding affinity (Ki approximately 713 nM). The compound is pharmacologically distinguished from the other non-psychoactive cannabinoids (cannabidiol, cannabigerol, cannabinol) by its potent and selective agonism at the transient receptor potential ankyrin 1 (TRPA1) channel (EC50 approximately 90 nM), making it the most potent TRPA1 agonist among the naturally occurring phytocannabinoids characterized to date. Additional molecular targets include the CB2 cannabinoid receptor (Ki approximately 100 to 256 nM, functional agonist), TRPV3 (EC50 approximately 1.9 micromolar), TRPV4 (EC50 approximately 0.6 micromolar), TRPV1 (EC50 approximately 24.2 micromolar), and the endocannabinoid reuptake and degradation machinery, where CBC acts as a weak inhibitor of monoacylglycerol lipase and of anandamide cellular reuptake. The composite pharmacological profile supports the preclinical activity observed across anti-inflammatory, analgesic, anticonvulsant, proneurogenic, antimicrobial, and antidepressant-like endpoints. In murine models of inflammation, CBC reduces edema in carrageenan and lipopolysaccharide paw injection models, inhibits nitric oxide production and proinflammatory cytokine release (interleukin-1 beta, interleukin-6, tumor necrosis factor alpha) in activated macrophages, and ameliorates dinitrobenzene sulfonic acid-induced colitis through a TRPA1-dependent mechanism. Analgesic activity has been demonstrated in tail-flick, formalin, and cisplatin-induced peripheral neuropathy models at doses of 20 mg/kg in mice, with the descending antinociceptive pathway in the ventrolateral periaqueductal gray identified as a central site of action involving CB1, TRPA1, and adenosine A1 receptor mechanisms. Anticonvulsant efficacy comparable to cannabidiol has been demonstrated in the Scn1a-mutant mouse model of Dravet syndrome, and CBC reduced pentylenetetrazol-induced seizures in zebrafish at lower concentrations than cannabidiol or cannabinol. Proneurogenic activity has been characterized in mouse adult neural stem and progenitor cells, where CBC augments cell viability during differentiation while inhibiting astroglial commitment, a profile consistent with adult hippocampal neurogenesis enhancement. Human pharmacokinetic data, first reported by Peters et al. in 2022, demonstrate oral absorption with a time to peak plasma concentration of approximately 3.3 hours, dose-proportional exposure increases, apparent preferential absorption relative to co-administered cannabidiol, and metabolism principally by CYP2C9 to 8-prime-hydroxy-CBC and 6-prime,7-prime-epoxy-CBC as the major metabolites. No formal human efficacy trials of isolated CBC have been completed; a Phase 1 safety trial in rheumatoid arthritis (NCT07087938) is registered. The compound is available as a research-grade isolate from multiple chemical suppliers at greater than 95 percent purity and is supplied in plant-derived cannabis extracts at variable concentrations depending on chemotype. This monograph reviews the chemistry, biosynthesis, and stereochemistry of cannabichromene; the multi-target receptor pharmacology across cannabinoid receptors, TRP channels, and endocannabinoid system enzymes; the human and animal pharmacokinetic record; the preclinical pharmacology across anti-inflammatory, analgesic, anticonvulsant, proneurogenic, antimicrobial, anticancer, and antidepressant-like endpoints; sourcing and quality verification; reconstitution and handling; stack-interaction considerations; adverse-event signal; and a comparative assessment of five non-psychoactive cannabinoid and cannabis-derived compounds (cannabidiol, cannabigerol, cannabinol, cannabidivarin, beta-caryophyllene) against cannabichromene on five competency standards. The compound is not approved as a medicine by any regulatory authority. It is a research compound; investigators should obtain analytical confirmation of identity and purity on every lot.