“Cannabichromene (CBC: C₂₁H₃O₂, M.W.: 314.46 g) is a non-psychotropic phytocannabinoid derived from Cannabis sativa (hemp), and its potential therapeutic properties have attracted increasing attention. Specifically, it has demonstrated strong anti-inflammatory effects in animal models of edema through non-CB receptor mechanisms; however, further pharmacological studies based on cancer models are required.

In this study, we investigated the molecular mechanisms underlying the anti-cancer activity of CBC in human pancreatic cancer cells.

Through mRNA-seq analysis, the expression levels of many genes involved in cell death pathways were upregulated or downregulated after CBC treatment, and these included ferroptosis-related genes, such as HMOX1. We further confirmed the functional validity of apoptosis and ferroptosis induction after CBC treatment using various molecular assays. In addition, CBC preferentially increased the expression of TRPV1 and CB2.

Accordingly, the effects on cell death were reversed after treatment with TRPV1 and CB2 inhibitors, suggesting that receptor expression is necessary for the induction of apoptotic cell death. Finally, we confirmed the consistent regulation of apoptosis, ferroptosis, and endocannabinoid receptors during tumor growth inhibition after CBC treatment using in vivo xenograft models.

Therefore, we propose that CBC exhibits pharmacological activity via the integrative modulation of multiple cell death pathways, which can be exploited for pancreatic cancer therapy.”

https://pubmed.ncbi.nlm.nih.gov/40790027/

“Cannabinoids extracted from Cannabis sativa exert their effects by binding to specific receptors that play a role in tissue development and homeostasis maintenance in the human body.”

“CBC treatment induces apoptotic cell death in pancreatic cancer cells”

“Our current study demonstrates that CBC modulates multiple forms of cell death by regulating the expression of proteins involved in both apoptotic and ferroptotic pathways. Although CBC-induced apoptosis was dependent on TRPV1 and CB2 receptors, the ferroptotic pathway appeared to be independent of these receptors.

Accordingly, we propose that CBC exerts its pharmacological effects through the integrative modulation of multiple cell death pathways, which could offer therapeutic benefits for pancreatic cancer treatment.

These results enhance our understanding of how CBC induces diverse cell death mechanisms via ECS receptors, not only in pancreatic cancer but also in other cancer models.

This study provides a promising foundation for the development of cannabinoid-based anti-cancer drugs, offering a new strategy for targeting various types of cancer through the modulation of apoptosis and ferroptosis.”

https://www.nature.com/articles/s41420-025-02674-8

“Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive metastasis and poor response to chemotherapy, largely driven by epithelial-mesenchymal transition (EMT) and chemokine signaling.

Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has shown anticancer potential, yet its mechanisms in EMT regulation remain underexplored in PDAC.

In this study, we demonstrate that CBD significantly suppresses the expression of CXCR4/CXCR7 and matrix metalloproteinases (MMP-2/9), leading to reduced migration and invasion of MIA PaCa-2, PANC-1, and AsPC-1 cells. Moreover, CBD reversed CXCL12-induced EMT by downregulating mesenchymal markers and restoring epithelial markers. Mechanistically, CBD inhibited the expression of the long non-coding RNA MALAT1, a known EMT regulator, and antagonized its pro-invasive effects. Overexpression of MALAT1 activated the PI3K/Akt/mTOR pathway and enhanced EMT-related protein expression, all of which were effectively reversed by CBD. Furthermore, the combination of CBD and gemcitabine exhibited synergistic inhibition of MALAT1, EMT markers, and PI3K/Akt/mTOR signaling without inducing cytotoxicity, suggesting a therapeutic advantage.

Collectively, these findings reveal a novel mechanism through which CBD impedes PDAC metastasis and underscore its promise as a complementary agent in chemotherapy regimens.”

https://pubmed.ncbi.nlm.nih.gov/40767250/

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has garnered considerable interest in oncology for its anti-inflammatory, pro-apoptotic, and anti-metastatic properties.”

“CBD has garnered increasing interest in oncology due to its multifaceted anticancer properties.”

https://iubmb.onlinelibrary.wiley.com/doi/10.1002/iub.70042

“A new, canniprene B (4), along with five known (1–3 and 5–6) dihydrostilbenes were isolated from the leaves of Cannabis sativa collected at CSIR – IIIM, Jammu, India. Structures of all isolated compounds were elucidated by spectroscopic data analysis, including 1D and 2D NMR, and HR-ESI-MS. Canniprene B is a new prenylated dihydrostilbenes, a positional isomer of the known compound canniprene (5). The cytotoxic activities of these compounds (1–6) were evaluated using the SRB assay against a panel of five human cancer cell lines. Notably, canniprene B (4) exhibited varying levels of cytotoxicity with IC₅₀ values ranging from 2.5 to 33.52 μM, demonstrating the most potent activity against pancreatic cancer cells.”

https://pubmed.ncbi.nlm.nih.gov/38989798/

https://www.tandfonline.com/doi/full/10.1080/14786419.2024.2376348

“Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies with a median 5 year-survival rate of 12%.

Cannabidiol (CBD) has been found to exhibit antineoplastic potential and may potentiate the anticancer effects of cytotoxic’s such as gemcitabine.

CBD therapy has been linked to de novo synthesis of ceramide. The sphingolipid ceramide is a potent tumour suppressor lipid with roles in apoptosis and autophagy. One of the key players involved is ceramide synthase, an enzyme with six isoforms (CerS1-CerS6), reported to have disease prognostic value. Quantitative real time PCR was used to determine mRNA expression levels of ceramide synthase isoforms, GRP78, ATF4 and CHOP. Western blotting was used to analyze protein expression of these markers and knockdown of CerS1 and GRP78 were applied via an siRNA and confirmed by the two mentioned methods. Mice with PDAC xenografts were injected via intraperitoneal method with drugs and tumours were analysed with flow cytometry and processed using H&E and IHC staining. siRNA knockdown of ceramide synthase 1 (CerS1) and analysis point to evidence of a putative CerS1 dependent pathway driven by CBD in activating endoplasmic reticulum (ER) stress target; GRP78.

Upon CBD treatment, CerS1 was upregulated and downstream this led to the GRP78/ATF4/CHOP arm of the unfolded protein response (UPR) pathway being activated. In an in vivo model of PDAC in which CerS1 was not upregulated on IHC, there was no observed improvement in survival of animals, however a reduction in tumour growth was observed in combination chemotherapy and CBD group, indicating further investigations in vivo.

These findings provide evidence of a potential ceramide induced cytotoxic mechanism of action of CBD in pancreatic ductal adenocarcinoma.”

https://pubmed.ncbi.nlm.nih.gov/38720356/

“The findings presented in this work, indicate dose-dependent and time-dependent cytotoxic effects of CBD in both human and murine pancreatic cancer cells.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-024-00227-x

“Pancreatic ductal adenocarcinoma (PDAC) is the most frequent infiltrating type of pancreatic cancer. The poor prognosis associated with this cancer is due to the absence of specific biomarkers, aggressiveness, and treatment resistance. PDAC is a deadly malignancy bearing distinct genetic alterations, the most common being those that result in cancer-causing versions of the KRAS gene.

Cannabigerol (CBG) is a non-psychomimetic cannabinoid with anti-inflammatory properties.

Regarding the anticancer effect of CBG, up to now, there is only limited evidence in human cancers. To fill this gap, we investigated the effects of CBG on the PDAC cell lines, PANC-1 and MIAPaCa-2. The effect of CBG activity on cell viability, cell death, and EGFR-RAS-associated signaling was investigated. Moreover, the potential synergistic effect of CBG in combination with gemcitabine (GEM) and paclitaxel (PTX) was investigated. MTT was applied to investigate the effect of CBG on PDAC cell line viabilities. Annexin-V and Acridine orange staining, followed by cytofluorimetric analysis and Western blotting, were used to evaluate CBG’s effect on cell death. The modulation of EGFR-RAS-associated pathways was determined by Western blot analysis and a Milliplex multiplex assay. Moreover, by employing the MTT data and SynergyFinder Plus software analysis, the effect of the combination of CBG and chemotherapeutic drugs was determined.”

https://pubmed.ncbi.nlm.nih.gov/38396679/

“In conclusion, our results showed that CBG, a non-psychomimetic cannabinoid from Cannabis Sativa L., can induce an anticancer effect in two human PDAC cell lines, supporting the ability of cannabinoids to interfere with several pro-tumoral pathways.”

https://www.mdpi.com/1422-0067/25/4/2001