Use of Cannabis and Cannabinoids for Treatment of Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Role of Endocannabinoids in the Human Body
2.1. Mechanism of Action—Ligand/Receptor
2.2. Role in the Control of Cell Division and Cell Proliferation
2.3. Changes in the ECS with Age
3. ECS and Cancer
3.1. Changes in ECS in Cancer
3.1.1. Changes in Expression Pattern of Cannabinoid Receptors in Cancer
CB1R and CB2R
GPR55
3.1.2. Changes in Cannabinoid Receptor Endogenous Ligands in Cancer
3.1.3. Changes in the Expression Pattern of Endocannabinoid Hydrolytic Enzymes in Cancer
3.2. Changes of ECS Signaling Pathways in Cancer—Potential Molecular Targets
3.2.1. Receptor-Dependent Signaling and Changes in Response to Cannabinoids
3.2.2. Receptor-Independent Signaling and Changes in Response to Cannabinoids
3.2.3. Signaling When the Receptor Status Is Unknown
4. Effect of Cannabinoids on Various Hallmarks of Cancer
4.1. Induction of Autophagy and Apoptosis
4.2. Reduction of Inflammation and Inhibition of Proliferation
4.3. Inhibition of Angiogenesis, Tumor Invasiveness, and Metastasis
5. Effect of Terpenes and Flavonoids
6. Preclinical and Clinical Use of Cannabinoids
6.1. Cannabis and Cannabinoids for Primary Care—Tumor Shrinkage
6.1.1. Data on Humans Are Limited
6.1.2. Combination of Cannabinoids with Other Drugs—There Is Potential Benefit, but Caution Is to Be Exercised
6.2. Cannabis for Palliative Care
6.2.1. Cannabis for Pain
6.2.2. Reducing Nausea and Vomiting
6.2.3. Improving Appetite
6.2.4. Reducing Anxiety and Improving Sleep
7. Adverse, Unexpected, and Unintended Effects of Cannabinoids
8. Sex-Specific Differences in ECS, Ethical Considerations of Cannabis Use and Equal Access to Cannabis
8.1. Sex-Specific Difference in Cancer and Use of Cannabis
8.2. Effect of Cannabis as a Function of Age
8.3. Equal Access to Cannabis for Everyone
9. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Tissues/Organs | Endocannabinoids | Receptors | Metabolizing Enzymes |
---|---|---|---|
Skin | No reliable data | ↓ in CB1 expression [13] | FAAH tends to ↓ with age [45] |
Lung | 2-AG ↓ and AEA ↑ in mice [46] | No reliable data | No reliable data |
Brain | From no change [40] to a ↓ in AEA [47] ↓ in 2-AG levels in mice [48] | From ↑ in humans [41] to no change [39] to a ↓ [38,49] in mice/rats in CB1 expression, brain area-specific | ↓ FAAH activity in rats [50] ↑ in MAGL levels in mice [48] |
Blood | Small ↑ in 2-AG and AEA in mice [46] | No reliable data | No reliable data |
Tissues/Organs | Endocannabinoids | Receptors | Metabolizing Enzymes |
---|---|---|---|
Skin | Decreased AEA and increased 2-AG in melanoma [51] | ↑ CB2 in melanoma [52] | ↑ MAGL [53], and ↑ FAAH in melanoma [45] |
Intestine (colorectal) | ↑ AEA and 2-AG [54,55] ↑ LPI [55,56] | ↓ CB1 [57,58], ↑ GPR55 [57,59], ↑ CB2 and ↓ CB1 [58] | ↑ MAGL [54], ↑ FAAH [45] |
Lung | ↑ CB1 and CB2 [60,61] | ↑ FAAH [62], ↑ FAAH [45] | |
Breast | ↑ LPI [63] | ↑ CB1 and CB2 [64,65,66,67], ↑ GPR55 [68,69] | ↑ FAAH [45] |
Brain | ↑ AEA and 2-AG in many cancers [70,71,72,73,74] | ↑ CNR1, ↑ CNR2, ↑ CB1 and CB2 in glioma [75,76,77,78], ↓ CB1 in glioma [79] | ↓ FAAH [80] in glioma, ↑ FAAH in glioma [45] |
Cannabis Drugs Used | Cancer Types/Preclinical Models of Diseases | Experimental Models | Effects in Cancer | Citation |
---|---|---|---|---|
Delta-9-THC | Hepatic adenomas, hepatocellular carcinoma, decreased incidence in adenomas and papillomas in mammary glands, uterus, pituitary gland, testicles, pancreas | In vivo, in vitro | Cancer prevention | [191] |
Delta-9-THC, delta-8-THC, Selective CB2 agonist JWH-133, Co-administration of CBD and THC | Lewis lung adenocarcinoma, glioblastoma multiforme | In vivo, in vitro | Reduced tumor growth | [70,75,144,145] |
Delta-9-THC, HU-210, anandamide, CB2 agonist JWH-015 | Malignant lymphoblastic diseases | In vivo, in vitro | Reduced tumor growth | [271] |
CB1/CB2 agonist WIN-55,212-2, CB2 agonist JWH-133 | Non-melanoma skin tumors | In vivo, in vitro | Reduced tumor growth | [92] |
Delta-9-THC, CB2 agonist JWH-015 | Hepatocellular carcinoma | In vitro, in vivo | Reduced tumor growth | [195] |
Delta-9-THC, WIN55,212-2, JWH-015 | Non-small cell lung carcinoma | In vitro, in vivo (immunodeficient mice) | Reduced tumor growth | [61,272] |
CBD, THC, JWH-015 | Breast cancer | In vitro, in vivo | Reduced tumor growth | [67,151,273] |
CBD | Colorectal cancer | In vitro, in vivo | Reduced tumor growth | [218,219] |
Delta-9-THC | Non-small cell lung carcinoma, breast cancer | In vitro, in vivo (immunocompetent mice) | Increased tumor growth | [274,275] |
Delta-9-THC, CP-55,940, WIN55,212-2, CBD | Animal model of emesis | In vivo | Antiemetic effect, inhibition of chemotherapy-induced nausea and vomiting | [276,277,278] |
Anandamide, Delta-9-THC | Changes in appetite in animals | In vivo | Increased food intake | [279,280] |
WIN55,212-2, arachidonylcyclopropylamide, AM1241 | Animal models of pain induction | In vivo | Analgetic effect | [281,282,283] |
CBD, WIN55,212-2 | Animal models of chemotherapy-induced neuropathic pain | In vivo | Analgetic effect | [284,285] |
CBD | Animal models of stress, recording sleep-walking cycles in rats | In vivo | Reduction of anxiety and improvement of sleep | [286,287] |
Drugs Used | Cancer Types/Participant Groups | Primary/Anticancer Effects | Palliative Care | Adverse Effects | Citation/Clinical Trial # |
---|---|---|---|---|---|
Delta-9-THC | Intra-tumoral injection in patients with recurrent glioblastoma multiforme | No significant clinical benefit | - | - | [200,288] |
Sativex and Temozolomide | Glioblastoma multiforme | Increased 1-year survival rate in 39% | - | - | NCT01812603; NCT01812616 [289] |
Dexanabinol | Solid tumors | Progression-free survival increased | - | - | NCT01489826 |
CBD | Acute leukemia and myelodysplastic syndrome | Lower incidence rate of acute graft-versus-host disease after allogenic hematopoietic stem cell transplantation | - | - | NCT01385124 NCT01596075 [290] |
Government-issued Cannabis | Cancer patients | - | Improvement of symptoms related to nausea and vomiting, sleep disorders, restlessness, anxiety and depression, pruritus, headaches | - | [291] |
Cannabis use | Breast cancer patients | - | Relief symptoms: of pain, insomnia, anxiety, stress, nausea, and vomiting | - | [292] |
Dronabinol, Nabilone * | Patients with different cancers | - | Treatment of chemotherapy-induced nausea and vomiting | - | [293,294,295,296] |
Delta-9-THC | Patients with advanced cancers | - | Appetite stimulation | - | [296,297,298] |
Delta-9-THC, THC:CBD extracts, Nabilone | Patients with different cancers | - | Analgetic effect | - | [299,300,301,302] |
Cannabis | Patients with chemotherapy-induced peripheral neuropathy | - | Analgetic effect | - | [303] |
Delta-9-THC, Dronabinol * | Patients with different cancers | - | Anxiolytic effect, increased quality of sleep | - | [296,302] |
Cannabis use | Patients with head and neck cancers | - | Decreased anxiety and depression scores | - | [304] |
Marijuana | Chronic marijuana smokers | - | - | Increased risk for testicular germ cell tumors in “Heavy” Cannabis users | [305] |
Smoking Cannabis | Healthy subjects and Cannabis users | - | - | Cannabis use was associated with 45% reduction in bladder cancer incidence | [306] |
Smoking Cannabis | Healthy individuals, lung cancer patients | - | - | Smoking cannabis is not associated with lung cancer or head and neck cancers | [307,308,309] |
Cannabis use during nivolumab immunotherapy | Patients with advanced melanoma, non-small cell lung carcinoma, renal cell carcinoma | - | - | Cannabis use reduced the response rate to immunotherapy by 21.25%. Cannabis use was correlated with poor clinical outcome | [310,311] |
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Cherkasova, V.; Wang, B.; Gerasymchuk, M.; Fiselier, A.; Kovalchuk, O.; Kovalchuk, I. Use of Cannabis and Cannabinoids for Treatment of Cancer. Cancers 2022, 14, 5142. https://doi.org/10.3390/cancers14205142
Cherkasova V, Wang B, Gerasymchuk M, Fiselier A, Kovalchuk O, Kovalchuk I. Use of Cannabis and Cannabinoids for Treatment of Cancer. Cancers. 2022; 14(20):5142. https://doi.org/10.3390/cancers14205142
Chicago/Turabian StyleCherkasova, Viktoriia, Bo Wang, Marta Gerasymchuk, Anna Fiselier, Olga Kovalchuk, and Igor Kovalchuk. 2022. "Use of Cannabis and Cannabinoids for Treatment of Cancer" Cancers 14, no. 20: 5142. https://doi.org/10.3390/cancers14205142