Antinociceptive Effects of Cannabichromene (CBC) in Mice: Insights from von Frey, Tail-Flick, Formalin, and Acetone Tests

Abstract

Cannabis sativa contains minor cannabinoids that have potential therapeutic value in pain management. However, detailed experimental evidence for the antinociceptive effects of many of these minor cannabinoids remains lacking. Here, we employed artificial intelligence (AI) to perform compound–protein interaction estimates with cannabichromene (CBC) and receptors involved in nociceptive signaling. Based on our findings, we investigated the antinociceptive properties of CBC in naïve or neuropathic C57BL/6 male and female mice using von Frey (mechanical allodynia), tail-flick (noxious radiant heat), formalin (acute and persistent inflammatory pain), and acetone (cold thermal) tests. For von Frey assessments, CBC dose (0–20 mg/kg, i.p.) and time (0–6 h) responses were measured in male and female neuropathic mice. For tail-flick, formalin, and acetone assays, CBC (20 mg/kg, i.p.) was administered to naïve male and female mice 1 h prior to testing. The results show that CBC (10 and 20 mg/kg, i.p.) significantly reduced mechanical allodynia in neuropathic male and female mice 1–2 h after treatment. Additionally, CBC treatment caused significant reductions in nociceptive behaviors in the tail-flick assay and in both phase 1 and phase 2 of the formalin test. Finally, we found a significant interaction in neuropathic male mice in the acetone test. In conclusion, our results suggest that CBC targets receptors involved in nociceptive signaling and imparts antinociceptive properties that may benefit males and females afflicted with diverse forms of acute or chronic/persistent pain.

The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders

“…However, other cannabinoids have not been extensively studied. Future research could focus on clinical trials to investigate the therapeutic potential of these lesser-known cannabinoids and their derivatives, which have proven in vitro or in vivo biological activity, such as the following: THCV-antiepileptic activity [347], potential against Parkinson's disease [348,349], antipsychotic effects [350], CBG-anticonvulsant activity [351], counteract neuroinflammation [352], neuroprotective in Huntington's disease [202], in multiple sclerosis [353], CBG derivatives-anti-inflammatory in multiple sclerosis [354], in amyotrophic lateral sclerosis [355], neuroprotective potential in Huntington's disease [356], in Parkinson's disease [357][358][359], CBC-promotes neural stem/progenitor cells viability [360], induces neuronal differentiation in NSC-34 Cells [361], antinociceptive activity [362], anti-inflammatory [363], CBN-neuroprotective activity [167], antiseizure potential [364].…”

Effect of High-Tunnel and Open-Field Production on the Yield, Cannabinoids, and Volatile Profiles in Industrial Hemp (Cannabis sativa L.) Inflorescence

“…Among the parts of industrial hemp, the hemp flower has garnered global attention due to the plethora of bioactive compounds with superior nutraceutical and therapeutic values. For instance, cannabidiol (CBD) possesses several biological activities, including antimicrobial, antioxidant, anti-inflammatory, anticancer, and antiarthritic properties, reduces stress and anxiety, relieves pain, and promotes relaxation. , Cannabigerol (CBG) is a minor cannabinoid showing positive effect on chronic pain, depression, inflammatory bowel disease, bacterial infections, and cancer. , Similarly, cannabichromene (CBC) holds potential therapeutic benefits, such as anti-inflammatory and antinociceptive properties, and improves respiratory distress syndrome. − Furthermore, binary cannabinoid mixtures containing combinations of neutral and acidic cannabinoids (e.g., cannabidiol (CBD) together with cannabidiolic acid (CBDA)) display superior synergistic antioxidant effects compared to their potential as individual compounds . CBD, CBG, and CBC fall under nonpsychoactive cannabinoids, making them suitable for future food, pharmaceutical, and medicinal applications. , Meanwhile, industrial hemp also contains a psychoactive cannabinoid, delta-9-tetrahydrocannabinol (d9-THC).…”