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Cannabis Research - Medical Uses - glaucoma


Authors
Green K, Zalkow LH, Deutsch HM, Yablonski ME, Oliver N, Symonds CM, Elijah RD
Title
Ocular and systemic responses to water soluble material derived from Cannabis sativa (marihuana).
Source
Current Eye Research
Date
1981
Issue
1(2)
Pages
65-75
Abstract
A water soluble material, isolated from Cannabis sativa, has been tested in albino and pigmented rabbits and rhesus monkeys for both ocular and systemic effects. Intravenous administration produced a dose-related fall in intraocular pressure in both albino and pigmented rabbits with concentrations as low as 0.005 mg/animal being effective, but no response was found in monkeys. High concentrations (0.2 to 1 mg/animal) induced a hypertensive phase in intraocular pressure prior to the ocular hypotension; higher concentrations (2 or 5 mg/animal) also induced antidiuresis and general relaxation. Tachyphylaxis was found to repeated daily injections. Alpha and beta-adrenergic antagonists caused some reduction of the hypertensive phase but had no effect on the hypotensive phase. Superior cervical ganglionectomy did not influence the time course of the intraocular pressure response. Indomethacin inhibited the hypertensive intraocular pressure phase but was ineffective against the hypotensive phase. Systemic blood pressure was unchanged following intravenous administration of 0.2 mg material/animal. Aqueous tumor protein concentration was increased at both 1 and 6 hours after intravenous administration, becoming greater at the later time. Aqueous humor turnover rate was substantially reduced reaching a minimum 8.75 hours after administration. Topical administration was ineffective in eyes when the epithelium was removed in rabbits with and without pretreatment with aspirin. Neither gastric nor suppository administration of large quantities (10 mg or greater) of material had any influence on intraocular pressure.

Authors
ElSohly MA, Harland EC, Benigni DA, Waller CW
Title
Cannabinoids in glaucoma II: the effect of different cannabinoids on intraocular pressure of the rabbit.
Source
Current Eye Research
Date
1984 Jun
Issue
3(6)
Pages
841-50
Abstract
Thirty-two different cannabinoids were tested for their ability to reduce intraocular pressure (IOP) in the rabbit. These included many of delta 9- and delta 8-THC derivatives and metabolites along with other natural and synthetic cannabinoids. In addition, some non-cannabinoid constituents of Cannabis were screened using the same model. All compounds were administered intravenously, while only a few were tested topically in mineral oil. Water soluble derivatives of delta 9- and delta 8-THC were prepared and tested topically in aqueous solution. The data revealed that certain derivatives of delta 9-and delta 8-THC were more active in lowering IOP than the parent cannabinoids. In addition, compounds other than delta 9- and delta 8-THC and their derivatives were shown to have activity.

Authors
Elsohly MA, Harland E, Murphy JC, Wirth P, Waller CW
Title
Cannabinoids in glaucoma: a primary screening procedure.
Source
Journal of Clinical Pharmacology
Date
1981 Aug-Sep
Issue
21(8-9 Suppl)
Pages
472S-478S
Abstract
A procedure was developed for screening of cannabinoids for their ability to reduce intraocular pressure (IOP) using normal rabbits. Eight animals per group were used for statistical significance of data. A negative control group was used for every screen as well as a positive control with 1.5 mg/kg delta 9-THC given intravenously (I.V.). All compounds were tested by I.V. injection and IOP measurements were taken periodically for 5 hours. Data were analyzed by a computer program which takes into account the change in IOP of the control group. Following this procedure we found that delta 8-THC, delta 9-THC, cannabinol, and nabilone were active while cannabidiol was inactive.

Authors
Merritt JC, Perry DD, Russell DN, Jones BF
Title
Topical delta 9-tetrahydrocannabinol and aqueous dynamics in glaucoma.
Source
Journal of Clinical Pharmacology
Date
1981 Aug-Sep
Issue
21(8-9 Suppl)
Pages
467S-471S
Abstract
Systemic delta 9-tetrahydrocannabinol (THC), administered either by smoking marihuana or as synthetic THC in soft gelatin capsules, lowers ocular tension in various glaucomas, but at the expense of significant decreases in systolic blood pressure. Topical THC in light mineral oil vehicles, though effective in laboratory animals, was not shown effective in 0.05 and 0.1% topical solutions when administered to six subjects with primary open-angle glaucoma in a randomized, balanced, double-masked protocol. Light mineral oil, which has an affinity for corneal epithelium, is an optimum vehicle for administering drugs whose mechanisms of action are systemic rather than local within the eye. Further glaucoma research should therefore proceed with marihuanas containing insignificant levels of THC (less than 0.4%) and with various local delivery systems of the ocular-active cannabinoid found in Cannabis sativa.

Authors
Innemee HC, Hermans AJ, van Zwieten PA
Title
The influence of delta 9-tetrahydrocannabinol on intraocular pressure in the anaesthetized cat.
Source
Documenta Ophthalmologica
Date
1980 Apr 15
Issue
48(2)
Pages
235-41
Abstract
delta 9-Tetrahydrocannabinol (delta 9-THC) was injected both intravenously and into the brain stem via the left vertebral artery. Contrary to results obtained with clonidine, neither the fall in intraocular pressure (IOP), nor the arterial hypotension induced by delta 9-THC, were enhanced after the 'central' administration of the drug. For clonidine, a central mechanism underlying the ocular hypotensive effect has recently been proposed. This suggestion is based upon the enhanced fall in IOP after 'central' administration of clonidine. The pontomedullary area is considered to be the main initial target of this drug. Obviously, the IOP-lavering mechanism of delta 9-THC is different from that of clonidine.

Authors
Colasanti BK, Craig CR, Allara RD
Title
Intraocular pressure, ocular toxicity and neurotoxicity after administration of cannabinol or cannabigerol.
Source
Experimental Eye Research
Date
1984 Sep
Issue
39(3)
Pages
251-9
Abstract
Cannabinol or cannabigerol was administered to cats topically in doses of 250, 500 and 1000 micrograms as a single drop or chronically via osmotic minipumps (20 micrograms hr-1) over a period of 9 days. While cannabinol had a modest effect on intraocular pressure after a single dose, it caused a more significant reduction in ocular tension during chronic administration. Cannabigerol had similar effects, but the magnitude of response to its chronic administration was greater. Cannabinol but not cannabigerol caused conjunctival erythema and hyperemia. After systemic administration of cannabinol (20, 40 or 80 mg kg-1) to rats, 8-13 Hz polyspike discharges appeared in the electrocorticogram during wakefulness and during rapid eye movement sleep episodes. Cannabigerol (10, 30 and 100 mg kg-1) lacked this effect. These results indicate that chronic administration of these cannabinoids lowers ocular tension considerably. Like marihuana and delta-9-tetrahydrocannabinol, cannabinol produced both ocular toxicity and neurotoxicity. As cannabigerol lacked these toxicities, it appears that the ocular hypotensive effect of this cannabinoid is somewhat dissociable from both the adverse central and ocular effects accompanying marihuana intake.

Authors
Deutsch HM, Green K, Zalkow LH
Title
Isolation of ocular hypotensive agents from Cannabis sativa.
Source
Journal of Clinical Pharmacology
Date
1981 Aug-Sep
Issue
21(8-9 Suppl)
Pages
479S-485S
Abstract
Recent work in our laboratories has shown that a hydrophilic fraction from Cannabis sativa (marihuana) has extremely potent intraocular pressure (IOP)-lowering activity as measured in albino rabbits when delivered by intravenous injection. A crude extract reduced IOP by 50-60 per cent (to the episcleral venous pressure) at dosage levels of about 500 micrograms/animal. Fractionation of this material by solvent extraction, high-performance liquid chromatography, and gel filtration chromatography has produced samples with high activity at 50 micrograms/animal. The active material has been shown to be noncannabinoid and of high molecular weight.

Id Code
75203518
Authors
Purnell WD, Gregg JM
Title
Delta(9)-tetrahydrocannabinol,, euphoria and intraocular pressure in man.
Source
Annals of Ophthalmology
Date
1975 Jul
Issue
7(7)
Pages
921-3
Abstract
Delta(9)-tetrahydrocannabinol (THC), an active narcotic principle of marijuana, was solubilized and administered intravenously to two male volunteers. Changes in intraocular pressure were recorded and compared to changes in the cortical effects of THC, as indicated by the subjects' report of degree of "high." The peak effect of THC on the central nervous system coincided well with the reduction of intraocular pressure induced by the drug; hypotony, however, outlasted euphoria. The results indicate that THC may have value as a hypotonizing ocular medicant.

Id Code
77236186
Authors
Cooler P, Gregg JM
Title
Effect of delta-9-tetrahydrocannabinol on intraocular pressure in humans.
Source
Southern Medical Journal
Date
1977 Aug
Issue
70(8)
Pages
951-4
Abstract
As early as 1971, it was noted that smoking marijuana lowered intraocular pressure. In this study one of the active components of marijuana, delta-9-tetrahydrocannabinol, was given intravenously to ten subjects with normal intraocular pressures. Two strengths were used--0.022 mg/kg of body weight and 0.044 mg/kg of body weight. Intraocular pressure was found to decrease as much as 51% of baseline normal with an average decrease of 37%. Heart rate increased in a range of 22% and 65% of the resting pulse. Respiratory rate was not affected. No analgesic properties were demonstrated by either cutaneous or periosteal stimulation. Anxiety levels were increased by delta-9-tetrahydrocannabinol over placebo and diazepam (Valium). The mechanism of action is still uncertain but it is believed by some workers to be similar to that of a beta-adrenergic stimulator.

Id Code
91268694
Authors
Colasanti BK
Title
A comparison of the ocular and central effects of delta 9-tetrahydrocannabinol and cannabigerol.
Source
Journal of Ocular Pharmacology
Date
1990 Winter
Issue
6(4)
Pages
259-69
Abstract
Both delta 9-tetrahydrocannabinol (delta 9-THC) and cannabigerol, two naturally occurring marihuana cannabinoids, produced only a modest fall in intraocular pressure after acute topical application to the eyes of cats. After chronic administration unilaterally to the cornea via Alzet osmotic minipumps and connecting extraocular cannulas, however, a considerable fall in ocular tension amounting to 4 to 7 mm Hg occurred. After systemic administration of delta 9-THC to rats, polyspike discharges appeared in the cortical electroencephalogram initially during wakefulness and behavioral depression. These polyspikes subsequently became evident within rapid eye movement sleep episodes. Cannabigerol was devoid of this effect. After removal of either sympathetic or parasympathetic input to the eyes of cats, the intraocular pressure lowering effect of delta 9-THC was not changed. Neither delta 9-THC nor cannabigerol altered the rate of formation of aqueous humor. On the other hand, both cannabinoids produced a two-to three-fold increase in aqueous outflow facility. These results suggest that cannabigerol and related cannabinoids may have therapeutic potential for the treatment of glaucoma.

Id Code
87127659
Authors
Liu JH, Dacus AC
Title
Central nervous system and peripheral mechanisms in ocular hypotensive effect of cannabinoids.
Source
Archives of Ophthalmology
Date
1987 Feb
Issue
105(2)
Pages
245-8
Abstract
Systemic administration of cannabinoids decreases intraocular pressure (IOP). To determine whether the mechanism of action originates in the central nervous system, we administered various cannabinoids into the cerebral ventricles of conscious New Zealand albino rabbits. When delta 9-tetrahydrocannabinol (delta 9-THC), delta 8-tetrahydrocannabinol, cannabinol, and cannabidiol were given intravenously, only delta 9-THC produced dose-dependent ocular hypotension and miosis. Bolus administration into the cerebral ventricles or ventriculocisternal perfusion of delta 9-THC did not change IOP or pupil size. In urethane-anesthetized rabbits, IOP and blood pressure were lowered by intravenous administration of delta 9-THC but not by bolus cerebral administration. These observations indicate that the action of cannabinoids on IOP does not originate in the central nervous system. Alteration of blood pressure may be involved in the mechanism of ocular hypotension induced by delta 9-THC.

Id Code
93026157
Authors
Muchtar S, Almog S, Torracca MT, Saettone MF, Benita S
Title
A submicron emulsion as ocular vehicle for delta-8-tetrahydrocannabinol: effect on intraocular pressure in rabbits.
Source
Ophthalmic Research
Date
1992
Issue
24(3)
Pages
142-9
Abstract
delta 8-Tetrahydrocannabinol (delta 8-THC), a known antiglaucoma lipophilic drug, was incorporated in a submicron emulsion for ocular administration. The mean droplet size of the emulsion was 130 +/- 41 nm, and no droplet was larger than 400 nm. No change in pH, particle size distribution or zeta potential was noted after sterilization by steam autoclaving or long-term storage over 9 months. An intense and long-lasting intraocular pressure (IOP)-depressant effect was observed after ocular application (50 microliters) of the THC emulsion, 0.4% (w/w), to rabbits with ocular hypertension (chymotrypsin model). Lesser effects were observed in normotensive rabbits. No irritation effect of either the emulsion vehicle or THC emulsion on the rabbit eyes was detected. These results underline the promising properties of submicron emulsions as vehicles for lipophilic ophthalmic drugs. The mechanism by which the emulsion induced the marked delta 8-THC antiglaucoma effect remains unclear. However, the possible involvement of delta 8-THC systemic absorption in the hypotensive effect induced by the emulsion cannot be excluded and will be the subject of further investigation.

Authors
- Porcella A, Casellas P, Gessa GL, Pani L
Title
- Cannabinoid receptor CB1 mRNA is highly expressed in the rat ciliary body: implications for the antiglaucoma properties of marihuana
Language
- ENG
Date
- 1998 Jul 15
Issue
- 0169-328X
Source
- Brain Res Mol Brain Res
Pages
- 240-5
Abstract
- We used RT-PCR to measure relative differences in cannabinoid receptor (CB) mRNAs in the rat eye, comparing CB1 or CB2 transcripts to that of the normalizing reference gene beta2 microglobulin (beta2m). Significantly higher levels of CB1 mRNA levels were found in the ciliary body (0.84+/-0.05% of beta2m) than in the iris, (0.34+/-0.04% of beta2m), retina (0.07+/-0.005% of beta2m) and choroid (0.06+/-0.005% of beta2m). CB2 mRNA was undetectable. This expression pattern supports a specific role for the CB1 receptor in controlling intraocular pressure, helping to explain the antiglaucoma property of cannabinoids. Copyright 1998 Elsevier Science B.V. All rights reserved.
Research Institute
- Center for Neuropharmacology, C.N.R. and "B.B. Brodie" Department of Neuroscience, University of Cagliari, via Porcell, 4, 09124-I Cagliari, Italy
Source
- Brain Res Mol Brain Res 1998 Jul 15;58(1-2):240-5