The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases
Abstract
:1. Introduction
The Physiology of Aging
2. Chronic Inflammation and Immunosenescence in Aging
2.1. Cannabinoids in Chronic Inflammation
2.2. Immunosenescence and Cannabinoid System
Changes of Cannabinoid System in Immune Dysregulation Associated with an Increased Risk of Infections in Elderly Patients
3. The Interplay between Cannabinoid System and Age-Related Diseases
3.1. Cannabinoids Potential in Age-Related Neurodegenerative Diseases: Alzheimer’s Disease
The Link between the Cannabinoid Systems and Alzheimer’s Disease through Its Effects on Inflammation, on the Immune System and on Oxidative Stress
3.2. Cannabinoids Potential in Age-Related Neurodegenerative Diseases: Parkinson’s Disease
3.3. Cannabinoids Potential in Age-Related Neurodegenerative Diseases: Multiple Sclerosis
4. The Endocannabinoid System and Aging-Related Musculoskeletal Changes
4.1. The Endocannabinoid System and Bone Changes
4.2. The Endocannabinoid System and Osteoarthritis
4.3. The Endocannabinoid System and Skeletal Muscle Changes
5. Cannabinoid Implications in Age-Related Oncological Diseases
5.1. The Relationship between the Endocannabinoid System, Carcinogenesis, and Tumor Progression
5.2. Cannabinoid Usage for the Management of Pain-Associated Cancer
5.3. Cannabinoid Usage to Ameliorate Chemotherapy-Induced Nausea and Vomiting
5.4. Cannabinoid Usage to Ameliorate Cancer—Associated Cachexia and Anorexia
5.5. Cannabinoid Usage to Ameliorate Cancer—Associated Anxiety and Depression
6. Cardiovascular Aging and Cannabinoid System
6.1. The Endocannabinoid System and Aging—Associated Hypertension
6.2. The ECS and Aging—Associated Atherosclerosis
7. Study Limitations
8. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Cannabinoids | Cannabinoid Origin | Mechanism of Action on Cannabinoids Receptors | Experimental Model | Main Findings | Ref. |
---|---|---|---|---|---|
CP 55.940 |
|
|
|
| [14,15] |
Rimonabant (SR-141716A) |
|
|
|
| [16,17] |
AM251 |
|
|
|
| [18,19,20] |
WIN 55212-2 |
|
|
|
| [21,22,23,24,25] |
Δ9-THC (Δ9-tetrahydrocannabinol) |
|
|
|
| [26,27] |
CBD (cannabidiol) |
|
|
|
| [28,29,30,31] |
JWH-015 |
|
|
|
| [32,33,34] |
JWH-133 |
|
|
|
| [35,36] |
Cannabinoid | Specific Cannabinoid Studied | Disease | Number of Patients Enrolled | Inclusion Criteria | Main Findings | Ref. |
---|---|---|---|---|---|---|
Synthetic Δ9-tetrahydrocannabinol | Dronabinol | Multiple Sclerosis | 240 |
|
| [62] |
Synthetic Δ9-tetrahydrocannabinol | ECP002A (oral formulation of Δ9- tetrahydrocannabinol) | Multiple Sclerosis | 24 |
|
| [63] |
Synthetic Tetrahydrocannabinol:Cannabidiol spray | Nabiximols | Multiple Sclerosis | 106 |
|
| [64] |
Synthetic Cannabidiol | ZYN002 (transdermal synthetic cannabidiol gel) | Osteoarthritis | 320 |
|
| [65] |
Synthetic Δ9-tetrahydrocannabinol | Nabilone | Alzheimer disease | 38 |
|
| [66] |
Synthetic Δ9-tetrahydrocannabinol | Donabinol | Pancreatic cancer | 104 estimated |
|
|
Compound and Endocannabinoid System Targets | Experimental Model | Main Findings |
---|---|---|
Cannabidiol mixed rCB1 and CB2 agonist |
|
|
|
| |
|
| |
|
| |
|
| |
ACEA rCB1 agonist |
|
|
THC mixed rCB1 and CB2 agonist |
|
|
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
WIN 55,212-2 mixed rCB1 and CB2 agonist |
|
|
|
| |
HU210 mixed rCB1 and CB2 agonist |
|
|
JWH-133 selective rCB2 agonist |
|
|
|
|
Cancer Type | Receptor Expression | Effects | Ref. |
---|---|---|---|
Colorectal cancer | ↑ CB2 ↑ CB1 | ↓ disease-free survival, ↓ overall survival, ↑ tumor growth ↓ disease outcome | [344,345] |
Prostate cancer | ↑ CB1 | ↑ Gleason score, ↑ incidence of metastases at diagnosis, ↑ tumor size, ↑ rate of proliferation, ↓ disease-specific survival | [340,341] |
Pancreatic cancer | ↓ CB1 | ↓ survival | [343] |
Head and neck squamos cell carcinoma | ↑ CB2 | ↓ survival | [346] |
Hepatocellular carcinoma | ↑ CB1 ↑ CB2 | ↑ disease-free survival | [337] |
Glioma | ↑ CB2 | ↑ tumor aggressivity | [338] |
Glioblastoma | ↑ CB2 | ↑ histologic grade | [347] |
Non-small cell lung cancer | ↑ CB1, ↑ CB2 | ↑ survival | [339] |
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Tudorancea, I.M.; Ciorpac, M.; Stanciu, G.D.; Caratașu, C.; Săcărescu, A.; Ignat, B.; Burlui, A.; Rezuș, E.; Creangă, I.; Alexa-Stratulat, T.; et al. The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases. Biomedicines 2022, 10, 2492. https://doi.org/10.3390/biomedicines10102492
Tudorancea IM, Ciorpac M, Stanciu GD, Caratașu C, Săcărescu A, Ignat B, Burlui A, Rezuș E, Creangă I, Alexa-Stratulat T, et al. The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases. Biomedicines. 2022; 10(10):2492. https://doi.org/10.3390/biomedicines10102492
Chicago/Turabian StyleTudorancea, Ivona Maria, Mitică Ciorpac, Gabriela Dumitrița Stanciu, Cătălin Caratașu, Alina Săcărescu, Bogdan Ignat, Alexandra Burlui, Elena Rezuș, Ioana Creangă, Teodora Alexa-Stratulat, and et al. 2022. "The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases" Biomedicines 10, no. 10: 2492. https://doi.org/10.3390/biomedicines10102492