Skip to main content

Advertisement

Log in

Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

Ag2:

Angiopoietin-2

AKT:

Protein kinase B

ATF-4:

Activating transcription factor 4

BAD:

Bcl2-associated agonist of cell death protein

BAX:

Bcl2-associated X protein

CACS:

Cancer anorexia-cachexia syndrome

CB1:

Cannabinoid receptor type1

CB2:

Cannabinoid receptor type2

CBC:

Cannabichromene

CBD:

Cannabidiol

CBN:

Cannabinol

CBDA:

Cannabidiolic acid

CBG:

Cannabigerol

CD147:

Cluster of differentiation 147

CD31:

Cluster of differentiation 31

CD45:

Cluster of differentiation 45

Cdc2:

Cell division cycle protein 2

CDH1:

Gene encoded E-cadherin

CDH2:

Gene encoded N-cadherin

Cdk4/2:

Cyclin-dependent kinase 4/2

CHOP:

C/EBP homologous protein

COX2:

Cyclooxygenase 2

CP55940:

Synthetic cannabinoid

CRC:

Colorectal cancer

CXCR4:

C-X-C chemokine receptor type 4

DRAM:

DNA damage-regulated autophagy modulator

ECS:

Endocannabinoid systems

EGF:

Epidermal growth factor

EMT:

Epithelial-mesenchymal transition

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulated kinase

GBM:

Glioblastoma multiforme

GPCR:

G protein-coupled receptor

GRP78:

Glucose-regulated protein

GSH:

Glutathione

H2AX:

H2A histone family member X

HER2:

Human epidermal growth factor receptor 2

5-HT3:

5-hydroxytryptamine 3

ICAM-1:

Intercellular adhesion molecule 1

IL-10:

Interleukin 10

IL-4:

Interleukin 4

JNK:

c-Jun N-terminal kinase

JunD:

AP-1 transcription factor

LAK-1:

Lymphokine-activated killer-1

MAPK:

Mitogen-activated protein kinases

MM:

Multiple myeloma

MMP2:

Matrix metalloproteinase-2

MMP2/9:

Matrix metalloproteinase-2/9

MMP9:

Matrix metalloproteinase-9

mTOR:

Mammalian target of rapamycin

NOXA:

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

NSCLC:

Non-small-cell lung cancer

p21:

Cyclin-dependent kinase inhibitor 1

p27:

Cyclin-dependent kinase inhibitor 1B

p38-MAPK:

p38 mitogen-activated protein kinase

p42/44:

Mitogen-activated protein kinase;

PAK1:

p-21 activated kinase 1

Parkin:

Cytosolic E3 ubiquitin ligase

PC:

Pancreatic cancer

PD-1:

Programmed cell death protein-1

PD-L1:

Programmed cell death ligand-1

PI3K:

Phosphatidylinositol-3 kinase

PINK1:

PTEN-induced putative kinase 1

PPARγ:

Peroxisome proliferator-activated receptor γ

pRb:

Phosphoretinoblastoma protein

PSC:

Pancreatic stellate cells

PUMA:

p53 upregulated modulator of apoptosis

QOL:

Quality of life

RAD51:

Gene encode a DNA repair protein

RAS:

Rat sarcoma virus

TGF-β:

Transforming growth factor

THC:

Tetrahydrocannabinol

TIMP1:

Tissue inhibitors of metalloproteinases1

Tes:

Testin

TME:

Tumor microenvironment

TMZ:

Temozolomide

TRB3:

Tribbles-like protein 3

TRPV1:

Transient receptor potential vanilloid-1

VEGF:

Vascular endothelial growth factors

VEGFR:

Vascular endothelial growth factor receptor

VIM:

Vimentin

References

  1. Suchopár, J., Laštůvka, Z., Mašková, S., Alblová, M., & Pařízek, A. (2021). Endocannabinoids. Ceska Gynekol, 86(6), 414–420. https://doi.org/10.48095/cccg2021414

    Article  PubMed  Google Scholar 

  2. Guggisberg, J., Schumacher, M., Gilmore, G., & Zylla, D. M. (2022). Cannabis as an anticancer agent: A review of clinical data and assessment of case reports. Cannabis and Cannabinoid Research, 7(1), 24–33. https://doi.org/10.1089/can.2021.0045

    Article  PubMed  PubMed Central  Google Scholar 

  3. Maccarrone, M. (2017). Metabolism of the endocannabinoid anandamide: Open questions after 25 years. Frontiers in Molecular Neuroscience, 10:166. https://doi.org/10.3389/fnmol.2017.00166

  4. Guzman, M. (2003). Cannabinoids: Potential anticancer agents. Nature Reviews Cancer, 3(10), 745–755. https://doi.org/10.1038/nrc1188

    Article  CAS  PubMed  Google Scholar 

  5. Hosami, F., Ghadimkhah, M. H., Salimi, V., Ghorbanhosseini, S. S., & Tavakoli-Yaraki, M. (2021). The strengths and limits of cannabinoids and their receptors in cancer: Insights into the role of tumorigenesis-underlying mechanisms and therapeutic aspects. Biomedicine & Pharmacotherapy, 144, 112279. https://doi.org/10.1016/J.Biopha.2021.112279

    Article  CAS  Google Scholar 

  6. Sledzinski, P., Zeyland, J., Slomski, R., & Nowak, A. (2018). The current state and future perspectives of cannabinoids in cancer biology. Cancer Medicine, 7(3), 765–775. https://doi.org/10.1002/cam4.1312

    Article  PubMed  PubMed Central  Google Scholar 

  7. Braile, M., Marcella, S., Marone, G., Galdiero, M. R., Varricchi, G., & Loffredo, S. (2021). The interplay between the immune and the endocannabinoid systems in cancer. Cells, 10(6), 1282. https://doi.org/10.3390/Cells10061282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Arif, Y., Singh, P., Bajguz, A., & Hayat, S. (2021). Phytocannabinoids biosynthesis in angiosperms, fungi, and liverworts and their versatile role. Plants-Basel, 10(7), 1307. https://doi.org/10.3390/Plants10071307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. O'Reilly, E. M., Cosgrave, J. M., Gallagher, W. M., & Perry, A. S. (2022). Plant-derived cannabinoids as anticancer agents. Trends in Cancer, 8(5), 350–357. https://doi.org/10.1016/j.trecan.2022.01.017

    Article  CAS  PubMed  Google Scholar 

  10. Hinz, B., & Ramer, R. (2022). Cannabinoids as anticancer drugs: Current status of preclinical research. British Journal of Cancer, 127(1), 1–13. https://doi.org/10.1038/s41416-022-01727-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Daris, B., Verboten, M. T., Knez, Z., & Ferk, P. (2019). Cannabinoids in cancer treatment: Therapeutic potential and legislation. Bosnian Journal of Basic Medical Sciences, 19(1), 14–23. https://doi.org/10.17305/bjbms.2018.3532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kovalchuk, O., & Kovalchuk, I. (2020). Cannabinoids as anticancer therapeutic agents. Cell Cycle, 19(9), 961–989. https://doi.org/10.1080/15384101.2020.1742952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pagano, C., Navarra, G., Coppola, L., Bifulco, M., & Laezza, C. (2021). Molecular mechanism of cannabinoids in cancer progression. International Journal of Molecular Sciences, 22(7), 3680. https://doi.org/10.3390/Ijms22073680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Abrams, D. I. (2022). Cannabis, cannabinoids and cannabis-based medicines in cancer care comment. Integrative Cancer Therapies, 21, 153473542210817. https://doi.org/10.1177/15347354221081772

    Article  CAS  Google Scholar 

  15. Abuhasira, R., Shbiro, L., & Landschaft, Y. (2018). Medical use of cannabis and cannabinoids containing products - Regulations in Europe and North America. European Journal of Internal Medicine, 49, 2–6. https://doi.org/10.1016/j.ejim.2018.01.001

    Article  PubMed  Google Scholar 

  16. Janatova, A., Frankova, A., Tlustos, P., Hamouz, K., Bozik, M., & Kloucek, P. (2018). Yield and cannabinoids contents in different cannabis (Cannabis sativa L.) genotypes for medical use. Industrial Crops and Products, 112, 363–367. https://doi.org/10.1016/j.indcrop.2017.12.006

    Article  CAS  Google Scholar 

  17. Velasco, G., Hernandez-Tiedra, S., Davila, D., & Lorente, M. (2016). The use of cannabinoids as anticancer agents. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 64, 259–266. https://doi.org/10.1016/j.pnpbp.2015.05.010

    Article  CAS  Google Scholar 

  18. Velasco, G., Sanchez, C., & Guzman, M. (2016). Anticancer mechanisms of cannabinoids. Current Oncology, 23, S23–S32. https://doi.org/10.3747/co.23.3080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bouca-Machado, R., Rosario, M., Alarcao, J., Correia-Guedes, L., Abreu, D., & Ferreira, J. J. (2017). Clinical trials in palliative care: A systematic review of their methodological characteristics and of the quality of their reporting. BMC Palliative Care, 16, 10. https://doi.org/10.1186/s12904-016-0181-9

    Article  PubMed  PubMed Central  Google Scholar 

  20. Ferrell, B., Borneman, T., Williams, A., Scardina, A., Fischer, P., & Smith, T. (2020). Integrating palliative care for patients on clinical trials: Opportunities for oncology nurses. Asia-Pacific Journal of Oncology Nursing, 7(3), 243–249. https://doi.org/10.4103/apjon.apjon_2_20

    Article  PubMed  PubMed Central  Google Scholar 

  21. Singh, B. N., Shankar, S., & Srivastava, R. K. (2011). Green tea catechin, epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and clinical applications. Biochemical Pharmacology, 82(12), 1807–1821. https://doi.org/10.1016/j.bcp.2011.07.093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Singh, B. N., Prateeksha, Rawat, A. K. S., Bhagat, R. M., & Singh, B. R. (2017). Black tea: Phytochemicals, cancer chemoprevention, and clinical studies. Critical Reviews in Food Science and Nutrition, 57(7), 1394–1410. https://doi.org/10.1080/10408398.2014.994700

    Article  CAS  PubMed  Google Scholar 

  23. Singh, B. N., Singh, H. B., Singh, A., Naqvi, A. H., & Singh, B. R. (2014). Dietary phytochemicals alter epigenetic events and signaling pathways for inhibition of metastasis cascade. Cancer and Metastasis Reviews, 33(1), 41–85. https://doi.org/10.1007/s10555-013-9457-1

    Article  CAS  PubMed  Google Scholar 

  24. Singh, B. R., Singh, B. N., Khan, W., Singh, H. B., & Naqvi, A. H. (2012). ROS-mediated apoptotic cell death in prostate cancer LNCaP cells induced by biosurfactant stabilized CdS quantum dots. Biomaterials, 33(23), 5753–5767. https://doi.org/10.1016/j.biomaterials.2012.04.045

    Article  CAS  PubMed  Google Scholar 

  25. Singh, B. N., Fu, J. S., Srivastava, R. K., & Shankar, S. (2011). Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: Molecular mechanisms. Plos One, 6(11), e27306. https://doi.org/10.1371/journal.pone.0027306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bakshi, H. A., Faruck, H. L., Ravesh, Z., Ansari, P., Hannan, J. M. A., Hashimoto, R., Takayama, K., Farzand, R., Nasef, M. M., Mensah, A., Aljabali, A. A. A., Mishra, V., Charbe, N. B., Goyal, R., Negi, P., Serrano-Aroca, Á., Bahar, B., El-Tanani, M., Courtenay, A. J., et al. (2022). Therapeutic potential of cannabinoids on tumor microenvironment: A molecular switch in neoplasia transformation. Integrative Cancer Therapies, 21, 15347354221096766. https://doi.org/10.1177/15347354221096766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Guzman, M., Galve-Roperh, I., & Sanchez, C. (2001). Ceramide: A new second messenger of cannabinoid action. Trends in Pharmacological Sciences, 22(1), 19–22. https://doi.org/10.1016/S0165-6147(00)01586-8

    Article  CAS  PubMed  Google Scholar 

  28. Mc Allister, S. D., Chan, C., Taft, R. J., Luu, T., Abood, M. E., Moore, D. H., Aldape, K., & Yount, G. (2005). Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells. Journal of Neuro-Oncology, 74(1), 31–40. https://doi.org/10.1007/s11060-004-5950-2

    Article  CAS  PubMed  Google Scholar 

  29. Galve-Roperh, I., Sanchez, C., Cortes, M. L., del Pulgar, T. G., Izquierdo, M., & Guzman, M. (2000). Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nature Medicine, 6(3), 313–319. https://doi.org/10.1038/73171

    Article  CAS  PubMed  Google Scholar 

  30. Carracedo, A., Gironella, M., Lorente, M., Garcia, S., Guzman, M., Velasco, G., & Iovanna, J. L. (2006). Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. Cancer Research, 66(13), 6748–6755. https://doi.org/10.1158/0008-5472.CAN-06-0169

    Article  CAS  PubMed  Google Scholar 

  31. Caffarel, M. M., Sarrió, D., Palacios, J., Guzmán, M., & Sánchez, C. (2006). Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Research, 66(13), 6615–6621. https://doi.org/10.1158/0008-5472.can-05-4566

    Article  CAS  PubMed  Google Scholar 

  32. Greenhough, A., Patsos, H. A., Williams, A. C., & Paraskeva, C. (2007). The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. Internation Journal of Cancer, 121(10), 2172–2180. https://doi.org/10.1002/ijc.22917

    Article  CAS  Google Scholar 

  33. Powles, T., te Poele, R., Shamash, J., Chaplin, T., Propper, D., Joel, S., et al. (2005). Cannabis-induced cytotoxicity in leukemic cell lines: The role of the cannabinoid receptors and the MAPK pathway. Blood, 105(3), 1214–1221. https://doi.org/10.1182/blood-2004-03-1182

    Article  CAS  PubMed  Google Scholar 

  34. Tomko, A., Whynot, E., & Dupré, D. (2021). Anti-cancer properties of cannabidiol and Δ9-tetrahydrocannabinol and potential synergistic effects with gemcitabine, cisplatin and other cannabinoids in bladder cancer. Journal of Cannabis Research, 4(1), 41. https://doi.org/10.1186/s42238-022-00151-y

    Article  Google Scholar 

  35. Sanchez, C., Galve-Roperh, I., Canova, C., Brachet, P., & Guzman, M. (1998). Delta(9)-tetrahydrocannabinol induces apoptosis in C6 glioma cells. FEBS Letters, 436(1), 6–10. https://doi.org/10.1016/S0014-5793(98)01085-0

    Article  CAS  PubMed  Google Scholar 

  36. Semlali, A., Beji, S., Ajala, I., & Rouabhia, M. (2021). Effects of tetrahydrocannabinols on human oral cancer cell proliferation, apoptosis, autophagy, oxidative stress, and DNA damage. Archives of Oral Biology, 129, 105200. https://doi.org/10.1016/j.archoralbio.2021.105200

    Article  CAS  PubMed  Google Scholar 

  37. Galanti, G., Fisher, T., Kventsel, I., Shoham, J., Gallily, R., Mechoulam, R., Lavie, G., Amariglio, N., Rechavi, G., & Toren, A. (2008). Delta 9-tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells. Acta Oncologica, 47(6), 1062–1070. https://doi.org/10.1080/02841860701678787

    Article  CAS  PubMed  Google Scholar 

  38. Śledziński, P., Nowak-Terpiłowska, A., & Zeyland, J. (2020). Cannabinoids in medicine: Cancer, immunity, and microbial diseases. International Journal of Molecular Sciences, 22(1), 263. https://doi.org/10.3390/ijms22010263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Preet, A., Ganju, R. K., & Groopman, J. E. (2008). Delta(9)-tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene, 27(3), 339–346. https://doi.org/10.1038/sj.onc.1210641

    Article  CAS  PubMed  Google Scholar 

  40. Anis, O., Vinayaka, A. C., Shalev, N., Namdar, D., Nadarajan, S., Anil, S. M., Cohen, O., Belausov, E., Ramon, J., Gati, E. M., & Koltai, H. (2021). Cannabis-derived compounds cannabichromene and Δ9-tetrahydrocannabinol interact and exhibit cytotoxic activity against urothelial cell carcinoma correlated with inhibition of cell migration and cytoskeleton organization. Molecules, 26(2), 465. https://doi.org/10.3390/molecules26020465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mechta-Grigoriou, F., Gerald, D., & Yaniv, M. (2001). The mammalian Jun proteins: Redundancy and specificity. Oncogene, 20(19), 2378–2389. https://doi.org/10.1038/sj.onc.1204381

    Article  CAS  PubMed  Google Scholar 

  42. Eferl, R., & Wagner, E. F. (2003). AP-1: A double-edged sword in tumorigenesis. Nature Reviews Cancer, 3(11), 859–868. https://doi.org/10.1038/nrc1209

    Article  CAS  PubMed  Google Scholar 

  43. Caffarel, M. M., Moreno-Bueno, G., Cerutti, C., Palacios, J., Guzman, M., Mechta-Grigoriou, F., et al. (2008). JunD is involved in the antiproliferative effect of delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene, 27(37), 5033–5044. https://doi.org/10.1038/onc.2008.145

    Article  CAS  PubMed  Google Scholar 

  44. Zhang, Y. Z., Zheng, W., Shen, K. W., & Shen, W. W. (2018). Delta 9-tetrahydrocannabinol inhibits epithelial-mesenchymal transition and metastasis by targeting matrix metalloproteinase-9 in endometrial cancer. Oncology Letters, 15(6), 8527–8535. https://doi.org/10.3892/ol.2018.8407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Carracedo, A., Lorente, M., Egia, A., Blázquez, C., García, S., Giroux, V., Malicet, C., Villuendas, R., Gironella, M., González-Feria, L., Piris, M. Á., Iovanna, J. L., Guzmán, M., & Velasco, G. (2006). The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell, 9(4), 301–312. https://doi.org/10.1016/j.ccr.2006.03.005

    Article  CAS  PubMed  Google Scholar 

  46. Peeri, H., & Koltai, H. (2022). Cannabis biomolecule effects on cancer cells and cancer stem cells: Cytotoxic, anti-proliferative, and anti-migratory activities. Biomolecules, 12(4), 491. https://doi.org/10.3390/Biom12040491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ramer, R., Schwarz, R., & Hinz, B. (2019). Modulation of the endocannabinoid system as a potential anticancer strategy. Frontiers in Pharmacology, 10:430. https://doi.org/10.3389/Fphar.2019.00430

  48. Haustein, M., Ramer, R., Linnebacher, M., Manda, K., & Hinz, B. (2014). Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1. Biochemical Pharmacology, 92(2), 312–325. https://doi.org/10.1016/j.bcp.2014.07.014

    Article  CAS  PubMed  Google Scholar 

  49. Schoeman, R., de la Harpe, A., Beukes, N., & Frost, C. L. (2022). Cannabis with breast cancer treatment: Propitious or pernicious? 3 Biotech, 12(2):54. https://doi.org/10.1007/S13205-021-03102-1

  50. Liu, W. M., Scott, K. A., Shamash, J., Joel, S., & Powles, T. B. (2008). Enhancing the in vitro cytotoxic activity of delta9-tetrahydrocannabinol in leukemic cells through a combinatorial approach. Leuk Lymphoma, 49(9), 1800–1809. https://doi.org/10.1080/10428190802239188

    Article  CAS  PubMed  Google Scholar 

  51. Oesch, S., & Gertsch, J. (2009). Cannabinoid receptor ligands as potential anticancer agents - High hopes for new therapies? Journal of Pharmacy and Pharmacology, 61(7), 839–853. https://doi.org/10.1211/jpp/61.07.0002

    Article  CAS  PubMed  Google Scholar 

  52. Torres, S., Lorente, M., Rodríguez-Fornés, F., Hernández-Tiedra, S., Salazar, M., García-Taboada, E., Barcia, J., Guzmán, M., & Velasco, G. (2011). A combined preclinical therapy of cannabinoids and temozolomide against glioma. Molecular Cancer Therapeutics, 10(1), 90–103. https://doi.org/10.1158/1535-7163.MCT-10-0688

    Article  CAS  PubMed  Google Scholar 

  53. Yang, Y., Huynh, N., Dumesny, C., Wang, K., He, H., & Nikfarjam, M. (2020). Cannabinoids inhibited pancreatic cancer via P-21 activated kinase 1 mediated pathway. International Journal of Molecular Sciences, 21(21), 8035. https://doi.org/10.3390/Ijms21218035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. McKallip, R. J., Nagarkatti, M., & Nagarkatti, P. S. (2005). Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. Journal of Immunology, 174(6), 3281–3289. https://doi.org/10.4049/jimmunol.174.6.3281

    Article  CAS  Google Scholar 

  55. Luo, C. K., Chou, P. H., Ng, S. K., Lin, W. Y., & Wei, T. T. (2022). Cannabinoids orchestrate cross-talk between cancer cells and endothelial cells in colorectal cancer. Cancer Gene Therapy, 29(5), 597–611. https://doi.org/10.1038/s41417-021-00346-0

    Article  CAS  PubMed  Google Scholar 

  56. Tucci, S. A., Rogers, E. K., Korbonits, M., & Kirkham, T. C. (2004). The cannabinoid CB1 receptor antagonist SR141716 blocks the orexigenic effects of intrahypothalamic ghrelin. British Journal of Pharmacology, 143(5), 520–523. https://doi.org/10.1038/sj.bjp.0705968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Vasquez, N. A., & Nielsen, D. E. (2022). The Endocannabinoid system and eating behaviours: A review of the current state of the evidence. Current Nutrition Reports, 11(4), 665–674. https://doi.org/10.1007/s13668-022-00436-x

    Article  CAS  Google Scholar 

  58. Nelson, K., Walsh, D., Deeter, P., & Sheehan, F. (1994). A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. Journal of Palliative Care, 10(1), 14–18.

    Article  CAS  PubMed  Google Scholar 

  59. Strasser, F., Luftner, D., Possinger, K., Ernst, G., Ruhstaller, T., Meissner, W., Ko, Y.-D., Schnelle, M., Reif, M., & Cerny, T. (2006). Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: A multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the cannabis-in-cachexia-study-group. Journal of Clinical Oncology, 24(21), 3394–3400. https://doi.org/10.1200/Jco.2005.05.1847

    Article  CAS  PubMed  Google Scholar 

  60. Zutt, M., Hanssle, H., Emmert, S., Neumann, C., & Kretschmer, L. (2006). Dronabinol for supportive therapy in patients with malignant melanoma and liver metastases. Hautarzt, 57(5), 423–427. https://doi.org/10.1007/s00105-005-1063-x

    Article  CAS  PubMed  Google Scholar 

  61. Jatoi, A., Windschitl, H. E., Loprinzi, C. L., Sloan, J. A., Dakhil, S. R., Mailliard, J. A., Pundaleeka, S., Kardinal, C. G., Fitch, T. R., Krook, J. E., Novotny, P. J., & Christensen, B. (2002). Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: A north central cancer treatment group study. Journal of Clinical Oncology, 20(2), 567–573. https://doi.org/10.1200/jco.2002.20.2.567

    Article  CAS  PubMed  Google Scholar 

  62. Turcott, J., Guillen- Núñez, M. D. R., Flores, D., Oñate, L., Zatarain-Barrón, Z., Barrón, F., & Arrieta, O. (2018). The effect of Nabilone on appetite, nutritional status, and quality of life in lung cancer patients: A randomized, double-blind clinical trial. Journal of Thoracic Oncology, 13(10), S360–S361. https://doi.org/10.1016/j.jtho.2018.08.328

    Article  Google Scholar 

  63. Brisbois, T. D., de Kock, I. H., Watanabe, S. M., Mirhosseini, M., Lamoureux, D. C., Chasen, M., MacDonald, N., Baracos, V. E., & Wismer, W. V. (2011). Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: Results of a randomized, double-blind, placebo-controlled pilot trial. Annals of Oncology, 22(9), 2086–2093. https://doi.org/10.1093/annonc/mdq727

    Article  CAS  PubMed  Google Scholar 

  64. Costa, B. (2007). On the pharmacological properties of delta9-tetrahydrocannabinol (THC). Chemistry & Biodiversity, 4(8), 1664–1677. https://doi.org/10.1002/cbdv.200790146

    Article  CAS  Google Scholar 

  65. Mlost, J., Bryk, M., & Starowicz, K. (2020). Cannabidiol for pain treatment: Focus on pharmacology and mechanism of action. International Journal of Molecular Sciences, 21(22), 8870. https://doi.org/10.3390/Ijms21228870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Mitchell, V. A., Harley, J., Casey, S. L., Vaughan, A. C., Winters, B. L., & Vaughan, C. W. (2021). Oral efficacy of delta(9)-tetrahydrocannabinol and cannabidiol in a mouse neuropathic pain model. Neuropharmacology, 189, 108529. https://doi.org/10.1016/j.neuropharm.2021.108529

    Article  CAS  PubMed  Google Scholar 

  67. Noyes Jr., R., Brunk, S. F., Avery, D. A., & Canter, A. C. (1975). The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clinical Pharmacology and Therapy, 18(1), 84–89. https://doi.org/10.1002/cpt197518184

    Article  Google Scholar 

  68. Johnson, J. R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E. D., Potts, R., & Fallon, M. T. (2010). Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and thc extract in patients with intractable cancer-related pain. Journal of Pain and Symptom Management, 39(2), 167–179. https://doi.org/10.1016/j.jpainsymman.2009.06.008

    Article  PubMed  Google Scholar 

  69. Portenoy, R. K., Ganae-Motan, E. D., Allende, S., Yanagihara, R., Shaiova, L., Weinstein, S., McQuade, R., Wright, S., & Fallon, M. T. (2012). Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: A randomized, placebo-controlled, graded-dose trial. Journal of Pain, 13(5), 438–449. https://doi.org/10.1016/j.jpain.2012.01.003

    Article  CAS  PubMed  Google Scholar 

  70. Johnson, J. R., Lossignol, D., Burnell-Nugent, M., & Fallon, M. T. (2013). An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal thc spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. Journal of Pain and Symptom Management, 46(2), 207–218. https://doi.org/10.1016/j.jpainsymman.2012.07.014

    Article  CAS  PubMed  Google Scholar 

  71. Lynch, M. E., Cesar-Rittenberg, P., & Hohmann, A. G. (2014). A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. Journal of Pain and Symptom Management, 47(1), 166–173. https://doi.org/10.1016/j.jpainsymman.2013.02.018

    Article  PubMed  Google Scholar 

  72. Fallon, M. T., Lux, E. A., McQuade, R., Rossetti, S., Sanchez, R., Sun, W., Wright, S., Lichtman, A. H., & Kornyeyeva, E. (2017). Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: Two double-blind, randomized, placebo-controlled phase 3 studies. British Journal of Pain, 11(3), 119–133. https://doi.org/10.1177/2049463717710042

    Article  PubMed  PubMed Central  Google Scholar 

  73. Staquet, M., Gantt, C., & Machin, D. (1978). Effect of a nitrogen analog of tetrahydrocannabinol on cancer pain. Clinical Pharmacology and Therapy, 23(4), 397–401. https://doi.org/10.1002/cpt1978234397

    Article  CAS  Google Scholar 

  74. Benredjem, B., & Pineyro, G. (2021). Are (THC:CBD) ratios good descriptors of the analgesic potential of cannabinoids? Canadian Journal of Physiology and Pharmacology, 99(11), S2–S2.

    Google Scholar 

  75. Janelsins, M. C., Kesler, S. R., Ahles, T. A., & Morrow, G. R. (2014). Prevalence, mechanisms, and management of cancer-related cognitive impairment. International Review of Psychiatry, 26(1), 102–113. https://doi.org/10.3109/09540261.2013.864260

    Article  PubMed  Google Scholar 

  76. Darmani, N. A. (2001). Delta(9)-tetrahydrocannabinol and synthetic cannabinoids prevent emesis produced by the cannabinoid CB1 receptor antagonist/inverse agonist SR 141716A. Neuropsychopharmacology, 24(2), 198–203. https://doi.org/10.1016/S0893-133x(00)00197-4

    Article  CAS  PubMed  Google Scholar 

  77. Meiri, E., Jhangiani, H., Vredenburgh, J. J., Barbato, L. M., Carter, F. J., Yang, H.-M., & Baranowski, V. (2007). Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Current Medical Research and Opinion, 23(3), 533–543. https://doi.org/10.1185/030079907X167525

    Article  CAS  PubMed  Google Scholar 

  78. Machado Rocha, F. C., Stéfano, S. C., De Cássia Haiek, R., Rosa Oliveira, L. M., & Da Silveira, D. X. (2008). Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: Systematic review and meta-analysis. European Journal of Cancer Care (Engl), 17(5), 431–443. https://doi.org/10.1111/j.1365-2354.2008.00917.x

    Article  CAS  Google Scholar 

  79. Kesner, A. J., & Lovinger, D. M. (2020). Cannabinoids, endocannabinoids and sleep. Frontiers in Molecular Neuroscience, 13, 125. https://doi.org/10.3389/Fnmol.2020.00125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kaul, M., Zee, P. C., & Sahni, A. S. (2021). Effects of cannabinoids on sleep and their therapeutic potential for sleep disorders. Neurotherapeutics, 18(1), 217–227. https://doi.org/10.1007/s13311-021-01013-w

    Article  PubMed  PubMed Central  Google Scholar 

  81. Martin-Willett, R., Master, A., Bidwell, L. C., & Sznitman, S. R. (2021). Cannabis use and sleep. In V. B. Patel & V. R. Preedy (Eds.), Handbook of substance misuse and addictions: from biology to public health (pp. 1–30). Springer International Publishing.

    Google Scholar 

  82. Guzmán, M., Duarte, M. J., Blázquez, C., Ravina, J., Rosa, M. C., Galve-Roperh, I., Sánchez, C., Velasco, G., & González-Feria, L. (2006). A pilot clinical study of delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. British Journal of Cancer, 95(2), 197–203. https://doi.org/10.1038/sj.bjc.6603236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Cote, M., Trudel, M., Wang, C. S., & Fortin, A. (2016). Improving quality of life with nabilone during radiotherapy treatments for head and neck cancers: A randomized double-blind placebo-controlled trial. Annals of Otology Rhinology and Laryngology, 125(4), 317–324. https://doi.org/10.1177/0003489415612801

    Article  PubMed  Google Scholar 

  84. Fabre, L. F., & Mclendon, D. (1981). The efficacy and safety of nabilone (a synthetic cannabinoid) in the treatment of anxiety. Journal of Clinical Pharmacology, 21(8-9), S377–S382. https://doi.org/10.1002/j.1552-4604.1981.tb02617.x.

    Article  Google Scholar 

  85. Shannon, S., Lewis, N., Lee, H., & Hughes, S. (2019). Cannabidiol in anxiety and sleep: A large case series. The Permanente Journal, 23, 18–041. https://doi.org/10.7812/TPP/18-041

    Article  PubMed  PubMed Central  Google Scholar 

  86. Scott, K. A., Dalgleish, A. G., & Liu, W. M. (2017). Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration. International Journal of Oncology, 51(1), 369–377. https://doi.org/10.3892/ijo.2017.4022

    Article  CAS  PubMed  Google Scholar 

  87. Nabissi, M., Morelli, M. B., Offidani, M., Amantini, C., Gentili, S., Soriani, A., Cardinali, C., Leoni, P., & Santoni, G. (2016). Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration. Oncotarget, 7(47), 77543–77557. https://doi.org/10.18632/oncotarget.12721

    Article  PubMed  PubMed Central  Google Scholar 

  88. Soto-Mercado, V., Mendivil-Perez, M., Jimenez-Del-Rio, M., Fox, J. E., & Velez-Pardo, C. (2020). Cannabinoid CP55940 selectively induces apoptosis in Jurkat cells and in ex vivo T-cell acute lymphoblastic leukemia through H2O2 signaling mechanism. Leukemia Research, 95, 106389. https://doi.org/10.1016/j.leukres.2020.106389

    Article  CAS  PubMed  Google Scholar 

  89. Munson, A. E., Harris, L. S., Friedman, M. A., Dewey, W. L., & Carchman, R. A. (1975). Antineoplastic activity of cannabinoids. The Journal of the National Cancer Institute, 55(3), 597–602. https://doi.org/10.1093/jnci/55.3.597

    Article  CAS  PubMed  Google Scholar 

  90. Zhu, L. X., Sharma, S., Stolina, M., Gardner, B., Roth, M. D., Tashkin, D. P., et al. (2000). Delta-9-tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. Journal of Immunology, 165(1), 373–380. https://doi.org/10.4049/jimmunol.165.1.373

    Article  CAS  Google Scholar 

  91. Müller, L., Radtke, A., Decker, J., Koch, M., & Belge, G. (2017). The synthetic cannabinoid WIN 55,212-2 elicits death in human cancer cell lines. Anticancer Research, 37, 6341–6345. https://doi.org/10.21873/anticanres.12086

    Article  CAS  PubMed  Google Scholar 

  92. Milian, L., Mata, M., Alcacer, J., Oliver, M., Sancho-Tello, M., de Llano, J. J. M., Camps, C., Galbis, J., Carretero, J., & Carda, C. (2020). Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro. Plos One, 15(2), e0228909. https://doi.org/10.1371/journal.pone.0228909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Milián, L., Monleón-Guinot, I., Sancho-Tello, M., Galbis, J. M., Cremades, A., Almenar-Ordaz, M., Peñaroja-Martinez, J., Farras, R., de Llano, J. J. M., Carda, C., & Mata, M. (2022). In vitro effect of Δ9-tetrahydrocannabinol and cannabidiol on cancer-associated fibroblasts isolated from lung cancer. International Journal of Molecular Sciences, 23(12), 6766. https://doi.org/10.3390/ijms23126766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Blasco-Benito, S., Moreno, E., Seijo-Vila, M., Tundidor, I., Andradas, C., Caffarel, M. M., et al. (2019). Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer (vol 116, pg 3863, 2019). Proceedings of the National Academy of Sciences of the United States of America, 116(13), 6505–6505. https://doi.org/10.1073/pnas.1903209116

    Article  CAS  Google Scholar 

  95. Marcu, J. P., Christian, R. T., Lau, D., Zielinski, A. J., Horowitz, M. P., Lee, J., Pakdel, A., Allison, J., Limbad, C., Moore, D. H., Yount, G. L., Desprez, P.-Y., & McAllister, S. D. (2010). Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Molecular Cancer Therapeutics, 9(1), 180–189. https://doi.org/10.1158/1535-7163.mct-09-0407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ellert-Miklaszewska, C., & I. A., & Kaminska, B. (2021). Synthetic cannabinoids induce autophagy and mitochondrial apoptotic pathways in human glioblastoma cells independently of deficiency in TP53 or PTEN tumor suppressors. Cancers, 13(3). https://doi.org/10.3390/cancers13030419

  97. Blázquez, C., Casanova, M. L., Planas, A., del Pulgar, T. G., Villanueva, C., Fernández‐Aceñero, M. J., Aragonés, J., Huffman, J. W., Jorcano, J. L., & Guzmán, M. (2003). Inhibition of tumor angiogenesis by cannabinoids. FASEB Journal, 17(3), 1–16. https://doi.org/10.1096/fj.02-0795fje

    Article  CAS  Google Scholar 

  98. López-Valero, I., Saiz-Ladera, C., Torres, S., Hernández-Tiedra, S., García-Taboada, E., Rodríguez-Fornés, F., Barba, M., Dávila, D., Salvador-Tormo, N., Guzmán, M., Sepúlveda, J. M., Sánchez-Gómez, P., Lorente, M., & Velasco, G. (2018). Targeting glioma initiating cells with a combined therapy of cannabinoids and temozolomide. Biochemical Pharmacology, 157, 266–274. https://doi.org/10.1016/j.bcp.2018.09.007

    Article  CAS  PubMed  Google Scholar 

  99. Soroceanu, L., Singer, E., Dighe, P., Sidorov, M., Limbad, C., Rodriquez-Brotons, A., Rix, P., Woo, R. W. L., Dickinson, L., Desprez, P.-Y., & McAllister, S. D. (2022). Cannabidiol inhibits RAD51 and sensitizes glioblastoma to temozolomide in multiple orthotopic tumor models. Neurooncology. Neuro-Oncology Advances, 4(1):vdac019. https://doi.org/10.1093/noajnl/vdac019

  100. Wasik, A. M., Almestrand, S., Wang, X., Hultenby, K., Dackland, Å.-L., Andersson, P., Kimby, E., Christensson, B., & Sander, B. (2011). WIN55,212-2 induces cytoplasmic vacuolation in apoptosis-resistant MCL cells. Cell Death & Disease, 2, e225. https://doi.org/10.1038/cddis.2011.106

    Article  CAS  Google Scholar 

  101. Fisher, T., Golan, H., Schiby, G., PriChen, S., Smoum, R., Moshe, I., Peshes-Yaloz, N., Castiel, A., Waldman, D., Gallily, R., Mechoulam, R., & Toren, A. (2016). In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma. Current Oncology, 23(2), 15–22. https://doi.org/10.3747/co.23.2893

    Article  Google Scholar 

  102. Ruiz, L., Miguel, A., & Diaz-Laviada, I. (1999). Delta(9)-tetrahydrocannabinol induces apoptosis in human prostate PC-3 cells via a receptor-independent mechanism. FEBS Letters, 458(3), 400–404. https://doi.org/10.1016/S0014-5793(99)01073-X

    Article  CAS  PubMed  Google Scholar 

  103. Morell, C., Bort, A., Vara, D., Ramos-Torres, A., Rodriguez-Henche, N., & Diaz-Laviada, I. (2016). The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells. Prostate Cancer and Prostatic Diseases, 19(3), 248–257. https://doi.org/10.1038/pcan.2016.19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Armstrong, J. L., Hill, D. S., McKee, C. S., Hernandez-Tiedra, S., Lorente, M., Lopez-Valero, I., Anagnostou, M. E., Babatunde, F., Corazzari, M., Redfern, C. P. F., Velasco, G., & Lovat, P. E. (2015). Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death. Journal of Investigative Dermatology, 135(6), 1629–1637. https://doi.org/10.1038/jid.2015.45

    Article  CAS  PubMed  Google Scholar 

  105. Glodde, N., Jakobs, M., Bald, T., Tuting, T., & Gaffal, E. (2015). Differential role of cannabinoids in the pathogenesis of skin cancer. Life Sciences, 138, 35–40. https://doi.org/10.1016/j.lfs.2015.04.003

    Article  CAS  PubMed  Google Scholar 

  106. Whyte, D. A., Al-Hammadi, S., Balhaj, G., Brown, O. M., Penefsky, H. S., & Souid, A. K. (2010). Cannabinoids inhibit cellular respiration of human oral cancer cells. Pharmacology, 85(6), 328–335. https://doi.org/10.1159/000312686

    Article  CAS  PubMed  Google Scholar 

  107. Lichtman, A. H., Lux, E. A., McQuade, R., Rossetti, S., Sanchez, R., Sun, W., Wright, S., Kornyeyeva, E., & Fallon, M. T. (2018). Results of a double-blind, randomized, placebo-controlled study of nabiximols oromucosal spray as an adjunctive therapy in advanced cancer patients with chronic uncontrolled pain. Journal of Pain and Symptom Management, 55(2), 179–188.e1. https://doi.org/10.1016/j.jpainsymman.2017.09.001

    Article  PubMed  Google Scholar 

  108. Maida, V., Ennis, M., Irani, S., Corbo, M., & Dolzhykov, M. (2008). Adjunctive nabilone in cancer pain and symptom management: A prospective observational study using propensity scoring. The Journal of Supportive Oncology, 6(3), 119–124.

    CAS  PubMed  Google Scholar 

  109. Walsh, D., Kirkova, J., & Davis, M. P. (2005). The efficacy and tolerability of long-term use of dronabinol in cancer-related anorexia: A case series. Journal of Pain and Symptom Management, 30(6), 493–495. https://doi.org/10.1016/j.jpainsymman.2005.11.007

    Article  PubMed  Google Scholar 

  110. Ofir, R., Bar-Sela, G., Ben-Arush, M. W., & Postovsky, S. (2019). Medical marijuana use for pediatric oncology patients: Single institution experience. Pediatric Hematology and Oncology, 36(5), 225–266.

    Article  Google Scholar 

  111. Duran, M., Pérez, E., Abanades, S., Vidal, X., Saura, C., Majem, M., Arriola, E., Rabanal, M., Pastor, A., Farré, M., Rams, N., Laporte, J.-R., & Capellà, D. (2010). Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. British Journal of Clinical Pharmacology, 70(5), 656–663. https://doi.org/10.1111/j.1365-2125.2010.03743.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Chang, A. E., Shiling, D. J., Stillman, R. C., Goldberg, N. H., Seipp, C. A., Barofsky, I., et al. (1979). Delata-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. A prospective, randomized evaluation. Annals of Internal Medicine, 91(6), 819–824. https://doi.org/10.7326/0003-4819-91-6-819

    Article  CAS  PubMed  Google Scholar 

  113. Sallan, S. E., Cronin, C., Zelen, M., & Zinberg, N. E. (1980). Antiemetics in patients receiving chemotherapy for cancer: A randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. The New England Journal of Medicine, 302(3), 135–138. https://doi.org/10.1056/nejm198001173020302

    Article  CAS  PubMed  Google Scholar 

  114. Shiling, D. J., Stillman, R. C., Chang, A. E., Goldberg, N. H., Seipp, C. A., Barofsky, I., & Rosenberg, S. A. (1981). A prospective evaluation of delta-9-tetrahydrocannabinol as an antiemetic in patients receiving adriamycin and cytoxan chemotherapy. Cancer, 47(7), 1746–1751. https://doi.org/10.1002/1097-0142(19810401)47:7<1746::aid-cncr2820470704>3.0.co;2-4

    Article  PubMed  Google Scholar 

  115. Sallan, S. E., Zinberg, N. E., & Frei 3rd, E. (1975). Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. The New England Journal of Medicine, 293(16), 795–797. https://doi.org/10.1056/nejm197510162931603

    Article  CAS  PubMed  Google Scholar 

  116. Twelves, C., Short, S., & Wright, S. (2017). A two-part safety and exploratory efficacy randomized double-blind, placebo-controlled study of a 1:1 ratio of the cannabinoids cannabidiol and delta-9-tetrahydrocannabinol (CBD:THC) plus dose-intense temozolomide in patients with recurrent glioblastoma multiforme (GBM). Journal of Clinical Oncology, 35. https://doi.org/10.1200/Jco.2017.35.15_Suppl.2046

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Brahma N. Singh.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Prateeksha, P., Sharma, V.K., Singh, S.M. et al. Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy. Cancer Metastasis Rev 42, 823–845 (2023). https://doi.org/10.1007/s10555-023-10078-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-023-10078-2

Keywords

Navigation