Glaucoma

Scienza: Il THC diminuisce la pressione intraoculare e migliora la circolazione del sangue nell’occhio
Secondo una ricerca dell’Università di Aachen una dose orale singola di 7.5 mg di THC, applicata a 80 medici sani in un auto-esperimento ha ridotto la pressione intraoculare (IOP) e aumentato il flusso di sangue nella retina. Le misurazioni sono state fatte prima e dopo due ore dall’assunzione del THC.
Il THC ha determinato una riduzione significativa della IOP da 13.2 mm Hg a 11.8 mm Hg in media. Il tempo per il passaggio di sangue dalle arterie alle vene della retina è sceso significativamente da 1.77 secondi a 1.57 secondi in media. La pressione arteriosa sistemica e il ritmo cardiaco non sono stati significativamente alterati. I ricercatori concludono che “i cannabinoidi, già noti per la loro capacità di ridurre la IOP, possono migiorare l’emodinamica della retina. Questo può essere benefico nei disturbi circolatori dell’occhio, incluso il glaucoma.”
Abstract disponibile a: www.cannabis-med.org/studies/study.php
Fonte: Plange N, Arend KO, Kaup M, Doehmen B, Adams H, Hendricks S, Cordes A, Huth J, Sponsel WE, Remky A. Dronabinol and retinal hemodynamics in humans. Am J Ophthalmol 2007;143(1):173-4.

Cannabinoidi e glaucoma
La somministrazione attraverso la mucosa orale di estratti naturali a base di THC riduce temporaneamente l’ipertensione intra-oculare dei malati di glaucoma, secondo i risultati di uno studio pilota pubblicati sul numero di ottobre del Journal of Glaucoma.
Sei pazienti con diagnosi di ipertensione intra-oculare (IO) o glaucoma primitivo ad angolo aperto in stadio iniziale hanno partecipato in uno studio randomizzato, controllato con placebo.
I ricercatori hanno misurato l’impatto di THC, CBD (cannabidiolo) o placebo sulla pressione intra-oculare dei pazienti dopo una singola somministrazione.
La IO può causare danni al nervo ottico ed è considerata il principale fattore di rischio nel glaucoma.
“Due ore dopo la somministrazione sublinguale di 5 mg di delta 9 THC, la pressione intra-oculare era significativamente minore che dopo il placebo”, hanno trovato gli scienziati “La pressione ritornò al valore iniziale dopo 4 ore.”
Inoltre i ricercatori riferiscono che una singola dose di CBD non aveva effetto sulla IO a basse dosi (20 mg) mentre elevava la IO ad alte dosi (40 mg).
Studi clinici condotti all’Università di California a Los Angeles (UCLA) nel 1971 avevano per primi rilevato che la cannabis fumata riduceva temporaneamente la pressione dell’occhio.
Fonte: Tomida I et al.  “Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study”  Journal of Glaucoma. 2006;15(5): 349-53.

Effect of Sublingual Application of Cannabinoids on Intraocular Pressure: A Pilot Study.
Tomida I, Azuara-Blanco A, House H, Flint M, Pertwee RG, Robson PJ.
*Department of Ophthalmology, Aberdeen Royal Infirmary section signSchool of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, UK daggerCannabinoid Research Institute, Magdalen Centre, Oxford Science Park, Oxford OX4 4GA double daggerGW Pharmaceuticals plc, Ely, Cambs CB7 4ZA.
PURPOSE: The purpose of this study was to assess the effect on intraocular pressure (IOP) and the safety and tolerability of oromucosal administration of a low dose of delta-9-tetrahydrocannabinol (Delta-9-THC) and cannabidiol (CBD). PATIENTS AND METHODS: A randomized, double-masked, placebo-controlled, 4 way crossover study was conducted at a single center, using cannabis-based medicinal extract of Delta-9-THC and CBD. Six patients with ocular hypertension or early primary open angle glaucoma received a single sublingual dose at 8 AM of 5 mg Delta-9-THC, 20 mg CBD, 40 mg CBD, or placebo. Main outcome measure was IOP. Secondary outcomes included visual acuity, vital signs, and psychotropic effects. RESULTS: Two hours after sublingual administration of 5 mg Delta-9-THC, the IOP was significantly lower than after placebo (23.5 mm Hg vs. 27.3 mm Hg, P=0.026). The IOP returned to baseline level after the 4-hour IOP measurement. CBD administration did not reduce the IOP at any time. However, the higher dose of CBD (40 mg) produced a transient elevation of IOP at 4 hours after administration, from 23.2 to 25.9 mm Hg (P=0.028). Vital signs and visual acuity were not significantly changed. One patient experienced a transient and mild paniclike reaction after Delta-9-THC administration. CONCLUSIONS: A single 5 mg sublingual dose of Delta-9-THC reduced the IOP temporarily and was well tolerated by most patients. Sublingual administration of 20 mg CBD did not reduce IOP, whereas 40 mg CBD produced a transient increase IOP rise.
PMID: 16988594 [PubMed – as supplied by publisher]

Implication of Cannabinoids in Neurological Diseases
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.
Fonte: Alsasua Del Valle A.,Cell Mol Neurobiol. 2006 May 12;
Dip. Farmacologia, Facultad de Medicina, Universidad Complutense de Madrid, Avda. Complutense s/n, Madrid, 28040, Spain, aalsasua@med.ucm.es.
PMID: 16699878 [PubMed – as supplied by publisher]

Handb Exp Pharmacol. 2005;(168):719-56.
Human studies of cannabinoids and medicinal cannabis.
Robson P.
Department of Psychiatry, Oxford University, Warneford Hospital, Oxford OX3 7JX, UK. pjr@gwpharm.com
Cannabis has been known as a medicine for several thousand years across many cultures. It reached a position of prominence within Western medicine in the nineteenth century but became mired in disrepute and legal controls early in the twentieth century. Despite unremitting world-wide suppression, recreational cannabis exploded into popular culture in the 1960s and has remained easily obtainable on the black market in most countries ever since. This ready availability has allowed many thousands of patients to rediscover the apparent power of the drug to alleviate symptoms of some of the most cruel and refractory diseases known to humankind. Pioneering clinical research in the last quarter of the twentieth century has given some support to these anecdotal reports, but the methodological challenges to human research involving a pariah drug are formidable. Studies have tended to be small, imperfectly controlled, and have often incorporated unsatisfactory synthetic cannabinoid analogues or smoked herbal material of uncertain composition and irregular bioavailability. As a result, the scientific evaluation of medicinal cannabis in humans is still in its infancy. New possibilities in human research have been opened up by the discovery of the endocannabinoid system, a rapidly expanding knowledge of cannabinoid pharmacology, and a more sympathetic political environment in several countries. More and more scientists and clinicians are becoming interested in exploring the potential of cannabis-based medicines. Future targets will extend beyond symptom relief into disease modification, and already cannabinoids seem to offer particular promise in the treatment of certain inflammatory and neurodegenerative conditions. This chapter will begin with an outline of the development and current status of legal controls pertaining to cannabis, following which the existing human research will be reviewed. Some key safety issues will then be considered, and the chapter will conclude with some suggestions as to future directions for human research.
PMID: 16596794 [PubMed – indexed for MEDLINE]

J Ethnopharmacol. 2006 Apr 21;105(1-2):1-25. Epub 2006 Mar 15.
Cannabinoids in medicine: A review of their therapeutic potential.
Ben Amar M.
Substance Abuse Program, Faculties of Continuing Education and Graduate Studies, University of Montreal, C.P. 6128, succursale Centre-ville, Montreal, Que. H3C 3J7, Canada. mohamed.ben.amar@umontreal.ca
In order to assess the current knowledge on the therapeutic potential of cannabinoids, a meta-analysis was performed through Medline and PubMed up to July 1, 2005. The key words used were cannabis, marijuana, marihuana, hashish, hashich, haschich, cannabinoids, tetrahydrocannabinol, THC, dronabinol, nabilone, levonantradol, randomised, randomized, double-blind, simple blind, placebo-controlled, and human. The research also included the reports and reviews published in English, French and Spanish. For the final selection, only properly controlled clinical trials were retained, thus open-label studies were excluded. Seventy-two controlled studies evaluating the therapeutic effects of cannabinoids were identified. For each clinical trial, the country where the project was held, the number of patients assessed, the type of study and comparisons done, the products and the dosages used, their efficacy and their adverse effects are described. Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer and AIDS), analgesics, and in the treatment of multiple sclerosis, spinal cord injuries, Tourette’s syndrome, epilepsy and glaucoma.
PMID: 16540272 [PubMed – in process]

Ned Tijdschr Geneeskd. 2006 Jan 21;150(3):128-31.
The mechanism of action of cannabis and cannabinoids
Scholten WK (wk.scholten@planet.nl)
The effect ofcannabis can be explained on the basis of the function of the cannabinoid receptor system, which consists of CB receptors (CB1, CB2), endoligands to activate these receptors and an enzyme–fatty acid amidohydrolase–to metabolize the endoligands. The endoligands of the cannabinoid receptor system are arachidonic acid-like substances, and are called endocannabinoids. Indications exist that the body also contains arachidonic acid-like substances that inhibit fatty acid amido hydrolase. Various cannabinoids have diverse effects on the receptors, functioning as agonists, antagonists or partial antagonists, as well as affecting the vanilloid receptor. Many known effects ofcannabis can be explained on the basis of this mechanism of action as can the use ofcannabis in various conditions including multiple sclerosis, Parkinson’s disease, glaucoma, nausea, vomiting and rheumatoid arthritis.
PMID: 16463612 [PubMed – indexed for MEDLINE]