Marijuana has recently become legalized both for recreational and medicinal use, and its prevalence is on the rise ¹. Medical marijuana has been approved by the FDA for treating chemotherapy-induced nausea and vomiting ^2,3. Although the effects of cannabinoids have been investigated in multiple cancer types, there are controversial results regarding its effect on tumor growth. Several publications reported the anti-cancer effects of Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the active ingredient in cannabis plants and medical marijuana ^4,5. Those studies often used extremely high-dosing range of cannabinoids, which exceed the binding constants between cannabinoids and cannabinoid receptors. On the contrary, many publications reported that Δ⁹-THC with physiological doses enhanced tumor growth and metastasis ^6-9. Recent systematic review and meta-analysis study showed an increase in certain cancers with marijuana use ¹⁰, however, the association between cannabinoids and tumor growth remains unclear. 

In the present study, researchers at National Taiwan University College of Medicine demonstrated the oncogenic role of cannabinoid receptors in colorectal cancer (CRC) by disclosing increased expressions of CB1 and CB2 receptors in patients with colorectal adenocarcinoma at National Taiwan University Hospital and in mouse models. Δ⁹-THC with a physiological dose promoted CRC tumor growth and angiogenesis in mouse models. Using human induced pluripotent stem cell (iPSC) and in vivo angiogenesis models, we discovered that Δ⁹-THC increased the secretion of five growth factors from CRC cells through the nuclear translocation of STAT1 transcription factor. Pharmacological treatment with STAT1 antagonist or abrogation of STAT1 with CRISPR/Cas9-based strategy rescued the adverse effects of Δ⁹-THC in CRC.  

We are reporting for the first time that Δ⁹-THC promotes CRC tumor growth and angiogenesis via a STAT1-dependent manner. We hypothesize that clinical co-treatment with STAT1 antagonist and Δ⁹-THC would allow for beneficial effects of Δ⁹-THC such as appetite stimulant and sedation while protecting from adverse effects on tumor cells and tumor microenvironment in patients with CRC. 

For further information, the original article is available at

https://www.nature.com/articles/s41417-021-00346-0

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