Marijuana and Glaucoma

Educational Objectives

The goal of this program is to improve use of medical marijuana for patients with glaucoma. After hearing and assimilating this program, the clinician will be better able to:

1. Review studies about the effectiveness and safety of cannabis products and synthetic cannabinoids for reducing intraocular pressure.
2. Provide an update on federal policies regulating the use of medical marijuana for research and therapeutic purposes.

Summary

Components: marijuana is derived from the cannabis plant; Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the primary compounds in cannabis; only THC has psychoactive properties; marijuana refers specifically to the dried buds of cannabis varieties that contain THC in concentrations >0.3%; cannabinoid 1 receptors are expressed in the ciliary body, trabecular meshwork, and Schlemm canal, which are involved in production and drainage of aqueous humor; therefore, effects of cannabinoids on intraocular pressure (IOP) is plausible; cannabinoid receptors are expressed in the retina, and animal studies show that cannabinoids have a neuroprotective effect

Effects of THC on IOP

Inhaled formulations: Hepler and Frank (1971) described a reduction in IOP of 25% to 30% in healthy volunteers after smoking marijuana, and the effect lasted 3 to 4 hr; the IOP-lowering effect was confirmed by Merritt et al (1981); peak effect occurred at 90 min, with reduction in IOP of 20% to 25%, and effect lasted for 4 hr; Mosaed et al (2022) found that IOP-lowering effect peaked at 60 min, with decrease of 16% from baseline, in 11 healthy adults who used cannabis ≥4 times per mo; plasma levels of THC ≤20 ng/mL were correlated with reduction in IOP

Oral formulations: Flach (2002) found that the initial decrease in IOP with oral cannabinoids was not sustained in 9 patients with treatment-refractory, end-stage glaucoma; dose of THC needed to be escalated as tolerance developed; side effects were reported, and all patients elected to discontinue treatment ≤9 mo of enrollment

Sublingual formulations: Tomida et al (2006) found reduction in IOP of 14% with sublingual THC in 6 patients with ocular hypertension and primary open-angle glaucoma; peak effect occurred 2 hr after administration, and IOP returned to baseline at 4 hr

Topical formulations: Green et al (1982) found no reduction in IOP and transient conjunctival hyperemia with topical THC and vehicle; Jay and Green (1983) found that 5 of 28 individuals who received topical THC or vehicle discontinued the study because of side effects (eg, lid swelling, burning sensation), and no IOP reduction was observed in the remaining participants; Pescolido et al (2018) found that topical formulations made from therapeutic cannabis extracts containing THC and CBD did not have an IOP-lowering effect in 4 of 5 participants with uncontrolled glaucoma

Bioavailability of THC: highest with inhaled formulations (18%-50%) and lower with oral formulations (4%-20%) due to first-pass metabolism by the liver

Effects of CBD on IOP: Tomida et al (2006) found that sublingual CBD did not lower IOP in 6 patients with ocular hypertension or primary open-angle glaucoma, and IOP was higher 4 hr after administration of 40 mg CBD compared with placebo; Miller et al (2018) found elevation of IOP was the predominant effect of CBD eyedrops in mice, and CBD prevented THC from lowering IOP

Cannabinoids for treatment of glaucoma: THC is not currently a feasible option for treatment due to the short duration of action, psychotropic effects, and development of tolerance to the IOP-lowering effect; systemic risks associated with cannabis use include small risk for addiction, structural changes of the brain and decreased intelligence quotient in early users of cannabis, impaired cognitive function, and increased risk for psychotic disorders (eg, schizophrenia), chronic obstructive pulmonary disorder, and motor vehicle accidents

Regulatory issues: inclusion of glaucoma as an eligible condition for the use of medical marijuana is not based on good-quality evidence; no regulatory oversight for cannabis products exists, and lack of uniform standards of the production process leads to high variability in THC content of available products; Vandrey et al (2015) found that 17% of cannabis products were accurately labeled, and most products were overlabeled

Considerations for drug delivery: currently available routes of administration are not optimal; smoking or vaping may cause pulmonary harm, and dosing is unpredictable; oral ingestion has lower bioavailability and unpredictable absorption; topical delivery is ineffective because THC is highly lipophilic; position statement from the American Glaucoma Society (Jampel 2010) stated that the side effects and short duration of action, coupled with a lack of evidence that use alters the disease course, preclude recommending the drug in any form for glaucoma treatment; the 2014 American Academy of Ophthalmology Task Force on Complementary Therapies stated that no scientific evidence shows increased benefits or decreased risks of marijuana use to treat glaucoma compared with currently available pharmaceutical agents

Patient perception: statistics published by the Colorado Department of Public Health in 2022 showed that a small proportion of patients cited treatment of glaucoma as a reason to use medical marijuana; Belyea et al (2016) found that the intent to use marijuana was modest among patients with glaucoma; factors associated with positive intent to use include perception of legality and acceptability, perceived safety and effectiveness, false beliefs about use of marijuana for glaucoma, and relevance of treatment costs; factors associated with negative intent to use include perceptions of systemic adverse effects and satisfaction with current glaucoma management; Weldy et al (2020) found that 3% of patients reported using marijuana specifically for treatment of glaucoma, 51% of cannabis retailers recommended its use; clinicians should proactively address the topic of cannabis use for glaucoma in the context of common patient questions

Synthetic cannabinoids: reduction in IOP was observed after a single oral dose of 3 synthetic derivatives of THC (dronabinol, nabilone, BW156Y); case study of a patient with ocular hypertension found a decrease in IOP after 3 wk of oral nabilone with no significant adverse effects; Porcella et al (2001) found that WIN55212-2 reduced IOP by 15% to 23% from baseline in 8 patients with treatment-resistant glaucoma, with the peak effect occurring 1 hr after administration

Palmitoylethanolamide (PEA): postulated to prolong the effect of anandamide and does not have the systemic effect associated with THC; randomized placebo-controlled study by Gagliano et al (2011) found a mean IOP reduction of 3.5 mm Hg with PEA at 2 mo; Pescosolido et al (2011) found that the IOP increase after prophylactic iridotomy was lower when pretreated with a PEA tablet compared with pretreatment with placebo

Medical Marijuana and Cannabidiol Research Expansion Act (2022): expands the number of sites that can grow and distribute cannabis for research, speeds the issuance of government permits to scientists who want to study cannabis, and obliges the federal government to ensure an adequate supply of marijuana to scientists interested in performing research

Readings

Belyea DA, Alhabshan R, Del Rio-Gonzalez AM, et al. Marijuana use among patients with glaucoma in a city with legalized medical marijuana use. JAMA Ophthalmol. 2016;134(3):259-264. doi:10.1001/jamaophthalmol.2015.5209; Flach AJ. Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma. Trans Am Ophthalmol Soc. 2002;100:215-22; Hepler RS, Frank IR. Marihuana smoking and intraocular pressure. JAMA. 1971;217:1392; Jampel H. American glaucoma society position statement: marijuana and the treatment of glaucoma. J Glaucoma. 2010; 19:75–76; Jay WM, Green K. Multiple-drop study of topically applied 1% delta 9-tetrahydrocannabinol in human eyes. Arch Ophthalmol. 1983;101:591–593; Miller S, Daily L, Leishman E, Bradshaw H, Straiker A. Δ9-tetrahydrocannabinol and cannabidiol differentially regulate intraocular pressure. Invest Ophthalmol Vis Sci. 2018;59(15):5904-5911. doi:10.1167/iovs.18-24838; Pescosolido N, Librando A, Puzzono M, et al. Palmitoylethanolamide effects on intraocular pressure after Nd: YAG laser iridotomy: An experimental clinical study. J Ocul Pharm. 2011;27:629–635; Porcella A; Maxia C; Gessa GL, et al. The synthetic cannabinoidWIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies. Eur J Neurosci. 2001;13:409–412; Vandrey R, Raber JC, Raber ME, Douglass B, Miller C, Bonn-Miller MO. Cannabinoid dose and label accuracy in edible medical cannabis products [published correction appears in JAMA. 2015 Jul 14;314(2):188]. JAMA. 2015;313(24):2491-2493. doi:10.1001/jama.2015.6613; Weldy EW, Stanley J, Koduri VA, et al. Perceptions of marijuana use for glaucoma from patients, cannabis retailers, and glaucoma specialists. Ophthalmol Glaucoma. 2020;3:453-459.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Radhakrishnan is a consultant for Netra Systems. Members of the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Radhakrishnan was recorded exclusively for Audio Digest. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.75 CE contact hours.

Lecture ID:

OP610904

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.