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Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy


Tetrahydrocannabinols (THCs) antagonize the CB1 and CB2 cannabinoid receptors, whose signaling to the endocannabinoid system is essential for controlling cell survival and proliferation as well as psychoactive effects. Most tumor cells express a much higher level of CB1 and CB2; THCs have been investigated as potential cancer therapeutic due to their cannabimimetic properties. To date, THCs have been prescribed as palliative medicine to cancer patients but not as an anticancer modality. Growing evidence of preclinical research demonstrates that THCs reduce tumor progression by stimulating apoptosis and autophagy and inhibiting two significant hallmarks of cancer pathogenesis: metastasis and angiogenesis. However, the degree of their anticancer effects depends on the origin of the tumor site, the expression of cannabinoid receptors on tumor cells, and the dosages and types of THC. This review summarizes the current state of knowledge on the molecular processes that THCs target for their anticancer effects. It also emphasizes the substantial knowledge gaps that should be of concern in future studies. We also discuss the therapeutic effects of THCs and the problems that will need to be addressed in the future. Clarifying unanswered queries is a prerequisite to translating the THCs into an effective anticancer regime.

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Fig. 1





Protein kinase B


Activating transcription factor 4


Bcl2-associated agonist of cell death protein


Bcl2-associated X protein


Cancer anorexia-cachexia syndrome


Cannabinoid receptor type1


Cannabinoid receptor type2








Cannabidiolic acid




Cluster of differentiation 147


Cluster of differentiation 31


Cluster of differentiation 45


Cell division cycle protein 2


Gene encoded E-cadherin


Gene encoded N-cadherin


Cyclin-dependent kinase 4/2


C/EBP homologous protein


Cyclooxygenase 2


Synthetic cannabinoid


Colorectal cancer


C-X-C chemokine receptor type 4


DNA damage-regulated autophagy modulator


Endocannabinoid systems


Epidermal growth factor


Epithelial-mesenchymal transition


Endoplasmic reticulum


Extracellular signal-regulated kinase


Glioblastoma multiforme


G protein-coupled receptor


Glucose-regulated protein




H2A histone family member X


Human epidermal growth factor receptor 2


5-hydroxytryptamine 3


Intercellular adhesion molecule 1


Interleukin 10


Interleukin 4


c-Jun N-terminal kinase


AP-1 transcription factor


Lymphokine-activated killer-1


Mitogen-activated protein kinases


Multiple myeloma


Matrix metalloproteinase-2


Matrix metalloproteinase-2/9


Matrix metalloproteinase-9


Mammalian target of rapamycin


A proapoptotic member of BH3-only Bcl-2 family proteins


Non-small-cell lung cancer


Cyclin-dependent kinase inhibitor 1


Cyclin-dependent kinase inhibitor 1B


p38 mitogen-activated protein kinase


Mitogen-activated protein kinase;


p-21 activated kinase 1


Cytosolic E3 ubiquitin ligase


Pancreatic cancer


Programmed cell death protein-1


Programmed cell death ligand-1


Phosphatidylinositol-3 kinase


PTEN-induced putative kinase 1


Peroxisome proliferator-activated receptor γ


Phosphoretinoblastoma protein


Pancreatic stellate cells


p53 upregulated modulator of apoptosis


Quality of life


Gene encode a DNA repair protein


Rat sarcoma virus


Transforming growth factor




Tissue inhibitors of metalloproteinases1




Tumor microenvironment




Tribbles-like protein 3


Transient receptor potential vanilloid-1


Vascular endothelial growth factors


Vascular endothelial growth factor receptor




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The authors would like to acknowledge the Council of Scientific and Industrial Research, India (OLP-0106). The institutional manuscript number is CSIR-NBRI_MS/2022/09/02.

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Prateeksha, P., Sharma, V.K., Singh, S.M. et al. Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy. Cancer Metastasis Rev (2023).

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  • Tetrahydrocannabinols
  • Cannabis
  • Cannabinoid receptors
  • Cannabimimetic properties
  • Metastasis
  • Angiogenesis
  • Antitumor