Category Archives: Glaucoma

Medicinal Uses of Marijuana and Cannabinoids

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“In the past two decades, there has been increasing interest in the therapeutic potential of cannabis and single cannabinoids, mainly cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). THC and cannabis products rich in THC exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). Since 1975, 140 controlled clinical trials using different cannabinoids or whole-plant preparations for the treatment of a large number of disorders and symptoms have been conducted. Results have led to the approval of cannabis-based medicines [dronabinol, nabilone, and the cannabis extract nabiximols (Sativex®, THC:CBD = 1:1)] as well as cannabis flowers in several countries. Controlled clinical studies provide substantial evidence for the use of cannabinoid receptor agonists in cancer chemotherapy induced nausea and vomiting, appetite loss and cachexia in cancer and HIV patients, neuropathic and chronic pain, and in spasticity in multiple sclerosis. In addition, there is also some evidence suggesting a therapeutic potential of cannabis-based medicines in other indications including Tourette syndrome, spinal cord injury, Crohn’s disease, irritable bowel syndrome, and glaucoma. In several other indications, small uncontrolled and single-case studies reporting beneficial effects are available, for example in posttraumatic stress disorder, attention deficit hyperactivity disorder, and migraine. The most common side effects of THC and cannabis-based medicines rich in THC are sedation and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. In recent years there is an increasing interest in the medical use of CBD, which exerts no intoxicating side effects and is usually well-tolerated. Preliminary data suggest promising effects in the treatment of anxiety disorders, schizophrenia, dystonia, and some forms of epilepsy. This review gives an overview on clinical studies which have been published over the past 40 years.”

http://www.tandfonline.com/doi/abs/10.1080/07352689.2016.1265360?needAccess=true&journalCode=bpts20

“Review Identifies 140 Controlled Clinical Trials Related to Cannabis”  http://blog.norml.org/2017/06/04/review-identifies-140-controlled-clinical-trials-related-to-cannabis/

Rimonabant, a selective cannabinoid1 receptor antagonist, protects against light-induced retinal degeneration in vitro and in vivo.

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“The endocannabinoid system is involved in some neurodegenerative diseases such as Alzheimer’s disease. An endogenous constellation of proteins related to cannabinoid1 receptor signaling, including free fatty acids, diacylglycerol lipase, and N-acylethanolamine-hydrolyzing acid amidase, are localized in the murine retina. Moreover, the expression levels of endogenous agonists of cannabinoid receptors are changed in the vitreous fluid.

However, the role of the endocannabinoid system in the retina, particularly in the light-induced photoreceptor degeneration, remains unknown. Therefore, we investigated involvement of the cannabinoid1 receptor in light-induced retinal degeneration using in vitro and in vivo models.

Rimonabant suppressed light-induced photoreceptor cell death. Cannabinoid1 receptor expression was upregulated by light exposure. Treatment with rimonabant improved both a- and b-wave amplitudes and the thickness of the outer nuclear layer.

These results suggest that the cannabinoid1 receptor is involved in light-induced retinal degeneration and it may represent a therapeutic target in the light-induced photoreceptor degeneration related diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/28315677

Implication of cannabinoids in neurological diseases.

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“1. Preparations from Cannabis sativa (marijuana) have been used for many centuries both medicinally and recreationally. 2. Recent advances in the knowledge of its pharmacological and chemical properties in the organism, mainly due to Delta(9)-tetrahydrocannabinol, and the physiological roles played by the endocannabinoids have opened up new strategies in the treatment of neurological and psychiatric diseases. 3. Potential therapeutic uses of cannabinoid receptor agonists include the management of spasticity and tremor in multiple sclerosis/spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, cancer, and vasodilation that accompanies advanced cirrhosis. CB(1) receptor antagonists have therapeutic potential in Parkinson’s disease. 4. Dr. Julius Axelrod also contributed in studies on the neuroprotective actions of cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/16699878

“Medical marijuana: emerging applications for the management of neurologic disorders.” https://www.ncbi.nlm.nih.gov/pubmed/15458761

Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry.

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“Cannabis has been used since ancient times to relieve neuropathic pain, to lower intraocular pressure, to increase appetite and finally to decrease nausea and vomiting.

The combination of the psychoactive cannabis alkaloid Δ9-tetrahydrocannabinol (THC) with the non-psychotropic alkaloids cannabidiol (CBD) and cannabinol (CBN) demonstrated a higher activity than THC alone.

Extraction efficiency of oil was significantly higher than that of water with respect to the different cannabinoids.

Fifteen minutes boiling was sufficient to achieve the highest concentrations of cannabinoids in the cannabis tea solutions.

As the first and most important aim of the different cannabis preparations is to guarantee therapeutic continuity in treated individuals, a strictly standardized preparation protocol is necessary to assure the availability of a homogeneous product of defined stability.”

https://www.ncbi.nlm.nih.gov/pubmed/28207408

Potential roles of (endo)cannabinoids in the treatment of glaucoma: from intraocular pressure control to neuroprotection.

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“Recent evidence shows that the endocannabinoid system is involved in the pathogenesis of numerous neurodegenerative diseases of the central nervous system. Pharmacologic modulation of cannabinoid receptors or the enzymes involved in the synthesis, transport, or breakdown of endogenous cannabinoids has proved to be a valid alternative to conventional treatment of these diseases.

In this review, we will examine recent findings that demonstrate the involvement of the endocannabinoid system in glaucoma, a major neurodegenerative disease of the eye that is a frequent cause of blindness.

Experimental findings indicate that the endocannabinoid system contributes to the control of intraocular pressure (IOP), by modulating both production and drainage of aqueous humor.

There is also a growing body of evidence of the involvement of this system in mechanisms leading to the death of retinal ganglion cells, which is the end result of glaucoma.

Molecules capable of interfering with the ocular endocannabinoid system could offer valid alternatives to the treatment of this disease, based not only on the reduction of IOP but also on neuroprotection.”

https://www.ncbi.nlm.nih.gov/pubmed/18929127

[Possibilities of applying cannabinoids’ in the treatment of glaucoma].

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“Over a period of several decades numerous scientific research has proven that, regardless of the route of administration, cannabinoids are able to decrease intraocular pressure.

What is more, these compounds are characterized by neuroprotection and vasodilatation properties, that additionally substantiate it’s therapeutic utility in conservative treatment of glaucoma.

So far, it has not been described in details what mechanism is used to lower the intraocular pressure by cannabinoids. Nevertheless, the presence of endocannabinoid receptors in structures of the eye responsible for formation and outflow of aqueous humor is an explanation for effectiveness of these compounds, when administered in topical form.

These days, with the aid of modern pharmacological technology are available significantly bigger possibilities of improving bioavailability of cannabinoids administered to the eye than in the past, as well as limitation of it’s undesired side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/19112869

Soft cannabinoid analogues as potential anti-glaucoma agents.

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“Cannabinoids have intraocular pressure (IOP) lowering effects, thus, they have a therapeutic potential in the treatment of glaucoma.

Our aim was to develop a safer, cannabinoid type anti-glaucoma agent, a topically applied soft analogue, that has local, but no systemic effect.

The lead compound chosen was a nitrogen-containing cannabinoid analogue that was shown to have IOP lowering activity.

A full library of possible soft drugs was generated and the structures were ranked based on the closeness of calculated properties to those of the lead compound.

The lead compound has been synthesized, and a preliminary pharmacological study was performed.

The structure-activity relationship and pharmacological results indicate a good possibility for the development of a safe, soft anti-glaucoma agent.”

https://www.ncbi.nlm.nih.gov/pubmed/10756540

Cannabinoids in the treatment of glaucoma.

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“The leading cause of irreversible blindness is glaucoma, a disease normally characterized by the development of ocular hypertension and consequent damage to the optic nerve at its point of retinal attachment. This results in a narrowing of the visual field, and eventually results in blindness.

A number of drugs are available to lower intraocular pressure (IOP), but, occasionally, they are ineffective or have intolerable side-effects for some patients and can lose efficacy with chronic administration.

The smoking of marijuana has decreased IOP in glaucoma patients. Cannabinoid drugs, therefore, are thought to have significant potential for pharmaceutical development.

The discovery of ocular cannabinoid receptors implied an explanation for the induction of hypotension by topical cannabinoid applications, and has stimulated a new phase of ophthalmic cannabinoid research.

Featured within these investigations is the possibility that at least some cannabinoids may ameliorate optic neuronal damage through suppression of N-methyl-D-aspartate receptor hyperexcitability, stimulation of neural microcirculation, and the suppression of both apoptosis and damaging free radical reactions, among other mechanisms.

Separation of therapeutic actions from side-effects now seems possible through a diverse array of novel chemical, pharmacological, and formulation strategies.”

 https://www.ncbi.nlm.nih.gov/pubmed/12182967

[Cannabinoid applications in glaucoma].

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“Glaucoma is a slowly progressive optic neuropathy that is one of the leading causes of legal blindness throughout the world.

Currently there is a limited group of topical drugs for the medical treatment of glaucoma is currently limited, and research needs to be focused on new therapeutic horizons, such as the potential usefulness of the cannabinoid agonists for the treatment of glaucoma.

To review the current scientific literature related to the beneficial effects derived from the different ways of administration of cannabinoids indicated for the glaucomatous optic neuropathy.

Cannabinoid receptors have shown an intense expression in ocular tissues implicated in the regulation of the intraocular pressure, as well as inner layers of the retina. Through activation of CB1 and CB1 specific receptors and through other still unknown pathways, the cannabinoid agonists have shown both a clear hypotensive, as well as an experimentally proved neuroprotective effect on retinal ganglion cells.

CONCLUSIONS:

Some cannabinoid agonists (WIN 55212-2, anandamide) have demonstrated, in experimental studies, to act as «ideal drugs» in the management of glaucoma, as they have been shown to have good tolerability after topical application, efficiently reduce intraocular pressure, and behave as neuroprotectors on retinal ganglion cells.”

https://www.ncbi.nlm.nih.gov/pubmed/21414525

The arguments for and against cannabinoids application in glaucomatous retinopathy.

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“Glaucoma represents several optic neuropathies leading to irreversible blindness through progressive retinal ganglion cell (RGC) loss. Reduction of intraocular pressure (IOP) is known as the only modifiable factor in the treatment of this disorder.

Application of exogenous cannabinoids to lower IOP has attracted attention of scientists as potential agents for the treatment of glaucoma.

Accordingly, neuroprotective effect of these agents has been recently described through modulation of endocannabinoid system in the eye.

In the present work, pertinent information regarding ocular endocannabinoid system, mechanism of exogenous cannabinoids interaction with the ocular endocannabinoid system to reduce IOP, and neuroprotection property of cannabinoids will be discussed according to current scientific literature.

In addition to experimental studies, bioavailability of cannabinoids, clinical surveys, and adverse effects of application of cannabinoids in glaucoma will be reviewed.”

https://www.ncbi.nlm.nih.gov/pubmed/28027538