Is there a rational basis for cannabinoids research and development in ocular pain therapy? A systematic review of preclinical evidence
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D Scuteri1, L Rombolà2, K Hamamura3
1Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy; Regional Center for Serious Brain Injuries, S. Anna Institute, 88900 Crotone, Italy.
Background:
Purpose of the present systematic review is to investigate preclinical evidence in favor of the working hypothesis of efficacy of cannabinoids in ocular pain treatment.
Methods:
Literature search includes the most relevant repositories for medical scientific literature from inception until November, 24 2021. Data collection and selection of retrieved records adhere to PRISMA criteria.
Results:
In agreement with a priori established protocol the search retrieved 2471 records leaving 479 results after duplicates removal. Eleven records result from title and abstract screening to meet the inclusion criteria; only 4 results are eligible for inclusion in the qualitative synthesis impeding meta-analysis. The qualitative analysis highlights the antinociceptive and anti-inflammatory efficacy of Δ8-tetrahydrocannabinol, cannabidiol and its derivative HU-308 and of new racemic CB1 allosteric ligand GAT211 and its enantiomers GAT228 and GAT229. Moreover, CB2R agonists RO6871304 and RO6871085 and CB2R ligand HU910 provide evidence of anti-inflammatory efficacy. CB2 agonist HU308 reduces of 241% uveitis-induced leukocyte adhesion and changes lipidome profile. Methodological and design issues raise concern of risk of bias and the amount of studies is too small for generalization. Furthermore, the ocular pain model used can resemble only inflammatory but not neuropathic pain.
Conclusions:
The role of the endocannabinoid system in ocular pain is underinvestigated, since only two studies assessing the effects of cannabinoid receptors modulators on pain behavior and other two on pain-related inflammatory processes are found. Preclinical studies investigating the efficacy of cannabinoids in ocular inflammatory and neuropathic pain models are needed to pave the way for clinical translation.
Insights
Cannabinoids show preclinical promise for treating ocular pain, with some compounds demonstrating anti-inflammatory and pain-relieving effects. However, more research is needed to confirm their efficacy and safety for clinical use.
Area of Science:
- Pharmacology
- Ophthalmology
- Neuroscience
Background:
- The endocannabinoid system's role in ocular pain is not well understood.
- Preclinical evidence suggests cannabinoids may be effective in treating ocular pain.
Purpose of the Study:
- To systematically review preclinical evidence on the efficacy of cannabinoids in ocular pain treatment.
Main Methods:
- A comprehensive literature search was conducted across major medical repositories up to November 24, 2021.
- Data collection and selection followed PRISMA guidelines, resulting in 4 eligible studies for qualitative synthesis.
Main Results:
- Several cannabinoids, including delta-8-tetrahydrocannabinol and cannabidiol derivatives, demonstrated antinociceptive and anti-inflammatory effects in preclinical models.
- Specific CB2 receptor agonists showed anti-inflammatory efficacy, with one reducing uveitis-induced leukocyte adhesion.
- Methodological limitations and small study numbers restrict generalization, and current models primarily address inflammatory, not neuropathic, ocular pain.
Conclusions:
- The endocannabinoid system's involvement in ocular pain requires further investigation.
- More preclinical studies are necessary to explore cannabinoid efficacy in both inflammatory and neuropathic ocular pain models.
- Such research is crucial for advancing the clinical application of cannabinoids in ophthalmology.
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