In mice THC can lower intra-ocular pressure by 28% for up to 8 hours via activation of CB1 and GPR18. CBD has opposing effects on intra-ocular pressure and can oppose the pressure lowering effects of THC (Miller et al., 2018a).
In cats and rats THC and CBG were found to reduce intra-ocular pressure. This was accompanied/caused by an increase aqueous humor outflow while aqueous humor formation was unaltered (Colasanti, 1990).
In mice, 2OG was found to bind to GPR119 and to lower intra-ocular pressure providing new potential targets for the treatment of glaucoma (Miller et al., 2017).
Similarly, elevating 2AG via inhibition of MAGL, also lowered intra-ocular pressure but in a CB1-dependent way (Alapafuja et al., 2018; Miller et al., 2016).
In rat eyes, CB1 is highly expressed in the ciliary body, offering mechanistic insight for the therapeutic actions of cannabis in the treatment of glaucoma (Porcella et al., 1998).
In mice, stimulating CB1 lowered intra-ocular pressure by 30% (Miller et al., 2018b).
In rabbits several synthetic variants of THC were used to reduce intra-ocular pressure (Adelli et al., 2017).
In rabbits, THC, Δ8THC and 11-OH-THC were found to have a comparable effect in lowering intra-ocular pressure. In this study CBD, CBC and CBG were ineffective. CBN was about half as effective as THC. In rhesus monkeys neither THC nor CBG had any effect on intra-ocular pressure suggesting species differences in cannabinoid effects (Green et al., 1982).
In cats topical CBN and CBG lowered intra-ocular pressure. Chronic administration achieved larger effects than single administrations. Contrary to cannabis, THC and CBN, there was no sign of neurotoxicity after CBG administration (Colasanti et al., 1984).
Adelli, G.R., Bhagav, P., Taskar, P., Hingorani, T., Pettaway, S., Gul, W., ElSohly, M.A., Repka, M.A., and Majumdar, S. (2017). Development of a Δ9-Tetrahydrocannabinol Amino Acid-Dicarboxylate Prodrug With Improved Ocular Bioavailability. Invest. Ophthalmol. Vis. Sci. 58, 2167–2179.
Alapafuja, S.O., Malamas, M.S., Shukla, V., Zvonok, A., Miller, S., Daily, L., Rajarshi, G., Miyabe, C.Y., Chandrashekhar, H., Wood, J., et al. (2018). Synthesis and evaluation of potent and selective MGL inhibitors as a glaucoma treatment. Bioorg. Med. Chem.
Colasanti, B.K. (1990). A comparison of the ocular and central effects of delta 9-tetrahydrocannabinol and cannabigerol. J. Ocul. Pharmacol. 6, 259–269.
Colasanti, B.K., Craig, C.R., and Allara, R.D. (1984). Intraocular pressure, ocular toxicity and neurotoxicity after administration of cannabinol or cannabigerol. Exp. Eye Res. 39, 251–259.
Green, K., Symonds, C.M., Oliver, N.W., and Elijah, R.D. (1982). Intraocular pressure following systemic administration of cannabinoids. Curr. Eye Res. 2, 247–253.
Miller, S., Leishman, E., Hu, S.S., Elghouche, A., Daily, L., Murataeva, N., Bradshaw, H., and Straiker, A. (2016). Harnessing the endocannabinoid 2-Arachidonoylglycerol to Lower Intraocular Pressure in a Murine Model. Invest. Ophthalmol. Vis. Sci. 57, 3287–3296.
Miller, S., Hu, S.S.-J., Leishman, E., Morgan, D., Wager-Miller, J., Mackie, K., Bradshaw, H.B., and Straiker, A. (2017). A GPR119 Signaling System in the Murine Eye Regulates Intraocular Pressure in a Sex-Dependent Manner. Invest. Ophthalmol. Vis. Sci. 58, 2930–2938.
Miller, S., Daily, L., Leishman, E., Bradshaw, H., and Straiker, A. (2018a). Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 59, 5904–5911.
Miller, S., Kulkarni, S., Ciesielski, A., Nikas, S.P., Mackie, K., Makriyannis, A., and Straiker, A. (2018b). Controlled-Deactivation CB1 Receptor Ligands as a Novel Strategy to Lower Intraocular Pressure. Pharm. Basel Switz. 11.
Porcella, A., Casellas, P., Gessa, G.L., and Pani, L. (1998). cannabinoid receptor CB1 mRNA is highly expressed in the rat ciliary body: implications for the antiglaucoma properties of marihuana. Brain Res. Mol. Brain Res. 58, 240–245.