Valenti, Denise A, OD

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University of the Incarnate Word

Optometric Clinical Practice Volume 7 Issue 1 April 2025 Marijuana and Intrinsically Photosensitive Retinal Ganglion Cells Denise A. Valenti OD IMMAD LLC, denisavalenti@gmail.com Follow this and additional works at: https://athenaeum.uiw.edu/optometric_clinical_practice  Part of the Health and Physical Education Commons, Optometry Commons, and the Other Medicine and Health Sciences Commons The Athenaeum provides a publication platform for fully open access journals, which means that all articles are available on the Internet to all users immediately upon publication. However, the opinions and sentiments expressed by the authors of articles published in our journal does not necessarily indicate the endorsement or reflect the views of the University of the Incarnate Word and its employees. The authors are solely responsible for the content of their work. Please address questions to athenaeum@uiwtx.edu. Recommended Citation Valenti DA. Marijuana and Intrinsically Photosensitive Retinal Ganglion Cells. Optometric Clinical Practice. 2025; 7(1):6. https://doi.org/10.37685/uiwlibraries.2575-7717.7.1.1033 This Expanding the Box is brought to you for free and open access by The Athenaeum. It has been accepted for inclusion in Optometric Clinical Practice by an authorized editor of The Athenaeum. For more information, please contact athenaeum@uiwtx.edu. Marijuana and Intrinsically Photosensitive Retinal Ganglion Cells Abstract Expanding the Box Keywords Cannabinoid system, contrast sensitivity, marijuana use, retinal dysfunciton, visual processing Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 International License. Cover Page Footnote This work was supported by Award No. 15PNIJ-22-GG-04417-RESS awarded by the National Institute of Justice, Office of Justice Programs, U.S. Department of Justice. The opinions, findings, and conclusions or recommendations expressed in this paper are those of the author and do not necessarily reflect those of the Department of Justice. This expanding the box is available in Optometric Clinical Practice: https://athenaeum.uiw.edu/optometric_clinical_practice/vol7/iss1/3  Historically, research assessments of the visual system have demonstrated dysfunction of visual processing with acute inhaled cannabis use. With the advancement of technology, as well as discovery of the intrinsically photosensitive retinal ganglion cells (ipRGC), there has been improved understanding of disruptions in visual neuroprocessing of retinal function with the use of marijuana/cannabis and these disruptions are becoming better understood. Given the substantial change in marijuana policy with over 50% of the United States, all of Canada, much of Europe, all of Germany,1 and portions of South America now having legal adult use of recreational marijuana,2 clinicians need to be proactive in identifying the visual functions impacted by acute and chronic marijuana use. Optometry researchers were pioneers in the study of cannabis/marijuana and published a series of impressive peer reviewed papers in the mid-1970s. The work was of incredible quality, superior to much of the research undertaken at the time, and certainly better than the majority of the research since then. The optometric research utilized controlled National Institutes of Health approved cannabis product3 and had Institutional Review Board (IRB) approved placebo, double-blind dose-controlled studies. The topics covered: Alcohol and Marijuana effects on static visual acuity,4 Marijuana smoking and reduced pressure in human eyes: drug action or epiphenomenon?,5 Alcohol and marijuana effects on ocular tracking,6 Pupil size after use of marijuana and alcohol,7 Marijuana, alcohol, and combined drug effects on the time course of glare recovery,8 and Evidence for acute effects of alcohol and marijuana on color discrimination.9 More recently, researchers have identified disruptions in visual processing including dysfunctions such as reduced contrast, poor binocular function, and glare disability.10  The cannabinoid system within the retina is complex, with every layer of the retina having cannabinoid receptors.11,12 Acute use of marijuana depletes the retina of dopamine13 and reductions in dopamine result in disruptions and dysfunction of retinal processing, particularly in the magnocellular visual pathway. A study of cannabis users found that the frequency of marijuana use correlated significantly to poorer ability to detect the contrast of stripes, both static and dynamic/temporal.14 Based on functional measures of retina response to temporal striped squares of variable contrast similar to the frequency doubling technology (FDT) 10-degree visual field used clinically, the regional dysfunction identified after acute marijuana use shows a relationship to the retinal location of a subclass of retinal ganglion cells known as melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGC).15  These cells contribute to vision related functions such as contrast sensitivity, depth perception, and motion perception. Within the human retina there are hypothesized to be six major categories of ipRGC, M1-6 within the inner portion of the inner plexiform layer. Of these, two categories M1 and M2 have been layered within the outer portion of the inner 6Valenti: Marijuana and Intrinsically Photosensitive Retinal Ganglion CellsPublished by The Athenaeum, 2025 plexiform layer. Outer stratifying ipRGC have inputs from bipolar cells and dopaminergic amacrine cells. There is input from diffuse bipolar cell axon terminals to the inner stratifying ipRGC. Inner and outer cells have feedback to the brain lateral geniculate nucleus (LGN).16 The LGN pathway contributes to the visual functions of contrast sensitivity, motion perception and depth perception.  The ipRGC cells have projections to other brain nuclei, particularly those modulating circadian and pupil functions, including the suprachiasmatic nucleus.16 The ipRGCs are responsible for the post illumination pupil response (PIPR). The PIPR is the sustained constriction of the pupil when pupil responses are considered normal. A dysfunction in the sustained constriction is part of the standard Drug Enforcement Expert (DRE) evaluation performed roadside when marijuana is suspected to be causing impairment to drive.17 The dysfunction in sustained pupil constriction is referred to as rebound dilation. The pupil initially constricts with direct illumination but then has a partial dilation with continued direct illumination. The ipRGCs are temporarily dysfunctional with acute marijuana use and are the contributing factors in the observation of rebound dilation.15 Blue light is the primary driver of both direct and consensual PIPR response under normal circumstances, absent of THC.18,19 The observation of the cannabis induced dysfunction of rebound dilation is chromatically driven. It is observed with illumination sources having blue in the wavelength spectrum. Red wavelengths will illicit the response, but lesser so. Under normal circumstances (i.e., when there is no marijuana) the normal pupil response is a consensual maintenance of constriction in response to the red stimuli.20 Other wavelengths are processed by other cell categories. A smaller population category, M5, processes ultraviolet wavelengths of light21 which projects to the LGN. Given that the LGN processes visual signals, one has to wonder how much the use of marijuana influenced the visual effect of black light/UV posters from the 60s and 70s. We are gaining insight into the retinal neuroprocessing with acute marijuana use, but variables related to age at onset of use and chronic use require further study. There is indication that the visual system is permanently remodeled if use occurred prior to full development of the visual system. Adolescent use results in poor response to visual facial emotion.22 Daily, chronic marijuana users react differently to visual spatial driving tasks than occasional users24 and that there is a difference in the visual system is supported by retinal optical coherence tomography imaging.23,24 In conclusion, the visual system is an effective biomarker of brain and neuroprocessing. Evaluations of function and structure can offer extensive information and insight into how alterations of the neuroprocessing pathways are 7Optometric Clinical Practice, Vol. 7, Iss. 1 [2025], Art. 3https://athenaeum.uiw.edu/optometric_clinical_practice/vol7/iss1/3DOI: 10.37685/uiwlibraries.2575-7717.7.1.1033 impacted and become dysfunctional with acute use of cannabis. Marijuana/cannabis use as a recreational and medicinal drug is growing worldwide. Primary care clinicians need to understand the dysfunctions in the visual system that can contribute further to the understanding of the short term and long-term consequences of marijuana use.   REFERENCES 1. McGuinness D. Germany legalises cannabis, but makes it hard to buy. BBC. February 23, 2024. https://www.bbc.com/news/world-europe-68378807. Accessed February 23, 2025. 2. Breen K. Where Recreational Weed is Legal. CBS News. May 17, 2024. https://www.cbsnews.com/news/legal-weed-map-states. Accessed February 23, 2025. 3. National Institute on Drug Abuse. NIDA's Role in Providing Cannabis for Research. National Institute on Drug Abuse website. March 27, 2020. https://nida.nih.gov/research/resources-grants-contracts/nidas-role-in-providing-cannabis-research. Accessed February 26, 2025. 4. Adams AJ, Brown B, Flom MC, Jones RT, Jampolsky A. Alcohol and marijuana effects on static visual acuity. Am J Optom Physiol Opt 1975;52:729-735. doi: 10.1097/00006324-197511000-00001  5. Flom MC, Adams AJ, Jones RT. Marijuana smoking and reduced pressure in human eyes: drug action or epiphenomenon? Invest Ophthalmol 1975;14:52-55. 6. Flom MC, Brown B, Adams AJ, Jones RT. Alcohol and marijuana effects on ocular tracking. Am J Optom Physiol Opt 1976;53:764-773. doi:  10.1097/00006324-197612000-00003 7. Brown B, Adams AJ, Haegerstrom-Portnoy G, Jones RT, Flom MC. Pupil size after use of marijuana and alcohol. Am J Ophthalmol 1977;83:350-354. doi: 10.1016/0002-9394(77)90732-2 8. Adams AJ, Brown B, Haegerstrom-Portnoy G, Flom MC, Jones RT. Marijuana, alcohol, and combined drug effects on the time course of glare recovery. Psychopharmacology (Berl) 1978;56:81-86. doi:  10.1007/BF00571413 9. Adams AJ, Brown B, Haegerstrom-Portnoy G, Flom MC, Jones RT. Evidence for acute effects of alcohol and marijuana on color discrimination. Percept Psychophys 1976;20:119–124. doi: 10.3758/BF03199442 10. Ortiz-Peregrina S, Ortiz C, Casares-López M, Jiménez JR, Anera RG. Effects of cannabis on visual function and self-perceived visual quality. Sci Rep 2021;11:1655. doi: 10.1038/s41598-021-81070-5  8Valenti: Marijuana and Intrinsically Photosensitive Retinal Ganglion CellsPublished by The Athenaeum, 2025 11. Straiker AJ, Maguire G, Mackie K, Lindsey J. Localization of cannabinoid CB1 receptors in the human anterior eye and retina. Invest Ophthalmol Vis Sci 1999;40:2442-2448. 12. Miller S, Daily L, Leishman E, Bradshaw H, Straiker A. Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure. Invest Ophthalmol Vis Sci 2018;59:5904-5911. doi:  10.1167/iovs.18-24838 13. Polli L, Schwan R, Albuisson E, et al. Oscillatory potentials abnormalities in regular cannabis users: Amacrine cells dysfunction as a marker of central dopaminergic modulation. Prog Neuropsychopharmacol Biol Psychiatry 2021;108:110083. doi: 10.1016/j.pnpbp.2020.110083 14. Mikulskaya E, Martin FH. Contrast sensitivity and motion discrimination in cannabis users. Psychopharmacology (Berl) 2018;235:2459-2469. doi: 10.1007/s00213-018-4944-2 15. Kaiher H, Valenti DA, Koppy T. Drug Recognition Expert: Rebound Dilation Response of Intrinsically Photosensitive Retinal Ganglion Cells. Proc Northeast Assoc Forensic Sci October 2024:4. 16. Beier C, Zhang Z, Yurgel M, Hattar S. Projections of ipRGCs and conventional RGCs to retinorecipient brain nuclei. J Comp Neurol 2021;529:1863-1875. doi: 10.1002/cne.25061 17. Hartman RL, Richman JE, Hayes CE, Huestis MA. Drug Recognition Expert (DRE) examination characteristics of cannabis impairment. Accid Anal Prev 2016;92:219-229. doi: 10.1016/j.aap.2016.04.012 18. Chakraborty R, Collins MJ, Kricancic H, et al. The intrinsically photosensitive retinal ganglion cell (ipRGC) mediated pupil response in young adult humans with refractive errors. J Optom 2022;15:112-121. doi:  10.1016/j.optom.2020.12.001 19. Kankipati L, Girkin CA, Gamlin PD. Post-illumination pupil response in subjects without ocular disease. Invest Ophthalmol Vis Sci 2010;51:2764-2769. doi: 10.1167/iovs.09-4717 20. Traustason S, Brondsted AE, Sander B, Lund-Andersen H. Pupillary response to direct and consensual chromatic light stimuli. Acta Ophthalmol 2016;94:65-69. doi: 10.1111/aos.12894 21. Stabio ME, Sabbah S, Quattrochi LE, et al. The M5 Cell: A Color-Opponent Intrinsically Photosensitive Retinal Ganglion Cell. Neuron 2018;97:150-163. doi: 10.1016/j.neuron.2017.11.030 22. Spechler PA, Orr CA, Chaarani B, et al. Cannabis use in early adolescence: Evidence of amygdala hypersensitivity to signals of threat. Dev Cogn Neurosci 2015;16:63-70. doi: 10.1016/j.dcn.2015.08.007  9Optometric Clinical Practice, Vol. 7, Iss. 1 [2025], Art. 3https://athenaeum.uiw.edu/optometric_clinical_practice/vol7/iss1/3DOI: 10.37685/uiwlibraries.2575-7717.7.1.1033 23. Kalenderoglu A, Orum MH, Karadag AS, et al. Increases in retinal nerve fiber layer thickness may represent the neuroprotective effect of cannabis: an optical coherence tomography study. J Addict Dis 2020;38:280-290. doi: 10.1080/10550887.2020.1754109 24. Dayi A, Dayi Ö, Kurt E, Yorguner N. Kannabis Kullanan Olgularda Optik Koherens Tomografi Bulgulari [Optical Coherence Tomography Findings in Cannabis Users]. Turk Psikiyatri Derg 2020;31:239-243. doi: 10.5080/u25205  10Valenti: Marijuana and Intrinsically Photosensitive Retinal Ganglion CellsPublished by The Athenaeum, 2025

Marijuana and Intrinsically Photosensitive Retinal Ganglion Cells

https://athenaeum.uiw.edu/cgi/viewcontent.cgi?article=1157&context=optometric_clinical_practice

Marijuana and Intrinsically Photosensitive Retinal Ganglion Cells

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