A Critical Review of the Role of the Cannabinoid Compounds ?9-Tetrahydrocannabinol (?9-THC) and Cannabidiol (CBD) and their Combination in Multiple Sclerosis Treatment
Abstract
:1. Introduction
1.1. Multiple Sclerosis, Neuropathology, Treatment Avenues and Outcomes
1.2. The Endocannabinoid System and Multiple Sclerosis
2. Animal Studies
2.1. Animal Models of Multiple Sclerosis
2.1.1. Virally-Induced Demyelination
2.1.2. Toxin-Induced Demyelination
2.1.3. Experimental Autoimmune Encephalomyelitis (EAE)
2.2. Cannabidiol Slows Symptom Onset in EAE Mice
2.3. Combinations of Δ9-THC and CBD Are More Effective in Symptom Relief and Neuroinflammation Reduction
3. Human Studies
3.1. Cannabinoids Are Only Moderately Effective in Reducing MS Related Spasticity
3.2. Cannabinoids May Be Effective in Reducing Neuropathic Pain in pwMS
3.3. Cognitive Effects of Cannabinoid Treatment
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Ligand (Route) | Concentration (Time of Administration in Days Post Disease Induction) | Species (Sex) | Effect | Reference |
---|---|---|---|---|
CBD (IP) | 20 mg/kg (9–25) | C57BL/6 (f) | ↑ | [56] |
CBD (IP) | 5–10 mg/kg (0) | C57BL/6 (f) | ↑ | [57] |
10 mg/kg (0) | ||||
50 mg/kg (0) | ||||
CBD (OG) | 75 mg/kg (1) | C57BL/6 (f) | ↑ | [58] |
CBD (IP) | 5 mg/kg (19–21) | C57BL/6 (f) | ↑ | [59] |
CBD (IP) | 5 mg/kg (11–13) | C57BL/6 (f) | ↑ | [60] |
CBD:Δ9-THC (IV) | 5 mg/kg (210) | Biozzi ABH (m/f) | ↑ | [61] |
10 mg/kg (210) | ||||
CBD:Δ9-THC (SC) | 10 mg/kg (11) | C57BL/6 (f) | ↑ | [62] |
Δ9-THC (SC) | 20 mg/kg (11) | C57BL/6 (f) | ↑ | [62] |
CBD (SC) | 20 mg/kg (11) | C57BL/6 (f) | — | [62] |
CBD:Δ9-THC (SC) | 10 mg/kg (10–15) | C57BL/6 (f) | ↑ | [63] |
CBD (SC) | 20 mg/kg (10–15) | C57BL/6 (f) | — | [63] |
Δ9-THC (SC) | 20 mg/kg (10–15) | C57BL/6 (f) | ↑ | [63] |
CBD:Δ9-THC (IP) | 10 mg/kg (10–15) | C57BL/6 (f) | ↑ | [64] |
CBD:Δ9-THC oil extract (OG) | 215 mg/kg (6–18) | Lewis (f) | ↑ | [65] |
CBD oil extract (OG) | 215 mg/kg (6–18) | Lewis (f) | — | [65] |
Δ9-THC oil extract (OG) | 215 mg/kg (6–18) | Lewis (f) | — | [65] |
Adverse Event | [69] | [70] | [71] | [72] | [73] | [74] | [75] | [76] | Total |
---|---|---|---|---|---|---|---|---|---|
Dizziness | 5 | 7 | 13 | 35 | 4 | 34 | 50 | 4 | 152 |
Headache | 0 | 0 | 9 | 0 | 0 | 7 | 9 | 3 | 208 |
Somnolence | 0 | 0 | 9 | 11 | 0 | 16 | 0 | 0 | 36 |
Muscle Weakness | 3 | 2 | 5 | 0 | 0 | 1 | 0 | 3 | 14 |
Spasticity | 0 | 0 | 3 | 4 | 0 | 0 | 0 | 0 | 7 |
Paraesthesia | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 2 |
Tremor | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 1 | 4 |
Vertigo | 2 | 1 | 0 | 0 | 0 | 16 | 34 | 4 | 57 |
Tinnitus | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 2 |
Mood Disruption | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 3 |
Euphoria | 0 | 0 | 9 | 0 | 0 | 0 | 0 | 1 | 10 |
Attention | 0 | 0 | 1 | 0 | 2 | 6 | 0 | 11 | 20 |
Insomnia | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 3 |
Fatigue | 5 | 0 | 5 | 29 | 2 | 16 | 25 | 6 | 88 |
Feeling abnormal | 0 | 0 | 5 | 50 | 0 | 5 | 0 | 0 | 60 |
Feeling hot | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 3 |
Oral Discomfort | 4 | 0 | 3 | 0 | 0 | 19 | 13 | 5 | 44 |
Nausea | 2 | 0 | 1 | 0 | 0 | 12 | 17 | 2 | 34 |
Appetite | 0 | 0 | 2 | 3 | 0 | 0 | 0 | 0 | 5 |
Stomatitis | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Incontinence | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Hypertension | 0 | 1 | 0 | 0 | 0 | 8 | 0 | 0 | 9 |
Pharyngodynia | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 3 |
Vision Blurred | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 4 |
Diarrhoea | 0 | 0 | 0 | 0 | 0 | 7 | 13 | 0 | 20 |
Vomiting | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 5 |
Memory Impairment | 0 | 0 | 0 | 0 | 0 | 6 | 0 | 0 | 6 |
Psychomotor Impairment | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 5 |
Total Adverse Events | 806 | ||||||||
Total Participants | 166 | 22 | 24 | 144 | 28 | 312 | 333 | 17 |
Ligand | Chemical Name | Reference |
---|---|---|
Nabiximols (Sativex) | (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol;2-[(6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol | [77] |
Δ9-tetrahydrocannabinol (Dronabinol) | (−)-(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol | [78] |
ECP002A | (−)-(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol | [77] |
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Jones, É.; Vlachou, S. A Critical Review of the Role of the Cannabinoid Compounds ?9-Tetrahydrocannabinol (?9-THC) and Cannabidiol (CBD) and their Combination in Multiple Sclerosis Treatment. Molecules 2020, 25, 4930. https://doi.org/10.3390/molecules25214930
Jones É, Vlachou S. A Critical Review of the Role of the Cannabinoid Compounds ?9-Tetrahydrocannabinol (?9-THC) and Cannabidiol (CBD) and their Combination in Multiple Sclerosis Treatment. Molecules. 2020; 25(21):4930. https://doi.org/10.3390/molecules25214930
Chicago/Turabian StyleJones, Éamon, and Styliani Vlachou. 2020. "A Critical Review of the Role of the Cannabinoid Compounds ?9-Tetrahydrocannabinol (?9-THC) and Cannabidiol (CBD) and their Combination in Multiple Sclerosis Treatment" Molecules 25, no. 21: 4930. https://doi.org/10.3390/molecules25214930
APA StyleJones, É., & Vlachou, S. (2020). A Critical Review of the Role of the Cannabinoid Compounds ?9-Tetrahydrocannabinol (?9-THC) and Cannabidiol (CBD) and their Combination in Multiple Sclerosis Treatment. Molecules, 25(21), 4930. https://doi.org/10.3390/molecules25214930