Dosing Medical Marijuana: Rational Guidelines on Trial in Washington State
Posted 09/11/2007

Sunil K. Aggarwal, MS III, PhC, BS, BA; Muraco Kyashna-Tocha, PhD; Gregory T. Carter, MD, MS

Author Information

Introduction
The medicinal value of cannabis is well documented in the medical literature.[1,2] Cannabinoids, the active ingredients, are found in the resin-producing pistillate inflorescences of the Cannabis sativa plant.[3] Since the early 1900s, cannabis has been referred to as mari(h/j)uana, a pejorative term derived from Mexican Spanish-Portuguese colloquial slang. Cannabinoids have many distinct pharmacologic properties. These include analgesic, antiemetic, antioxidative, neuroprotective, and anti-inflammatory activity, as well as modulation of glial cells and tumor growth regulation.[1] We now know that there is an endogenous molecular signaling system in our bodies that is run by cannabinoids. The discovery of this endogenous cannabinoid system with specific receptors and ligands has led to the progression of our understanding of the therapeutic actions of cannabis from folklore to valid science.[4] It now appears that the cannabinoid system evolved with our species and is intricately involved in normal human physiology, specifically in the control of movement, pain, appetite, memory, immunity, and inflammation, among others. The detection of widespread cannabinoid receptors in the brain and peripheral tissues suggests that the cannabinoid system represents a previously unrecognized, ubiquitous network in the nervous system. On that basis, exogenous cannabinoids appear to have tremendous potential in treating neurodegenerative disorders.[5,6] For example, in amyotrophic lateral sclerosis (ALS), there is animal model evidence that exogenous cannabinoids have disease-modifying potential.[7-12] Further, in a large survey, ALS patients reported that marijuana relieved the major symptoms of the disease better than prescription medications.[13] The most common reason cited by ALS patients for not considering using cannabis to treat their symptoms was lack of access.[13]

Dense cannabinoid receptor concentrations have been found in the cerebellum, basal ganglia, and hippocampus, accounting for the effects of cannabis on motor tone, coordination, and mood state.[4] Low concentrations are found in the brainstem, accounting for the remarkably low toxicity of cannabis. Of note, lethal doses for cannabis in humans have not been described. So far, we know of at least 2 molecular receptor proteins (CB1 and CB2) and 2 endogenously produced lipid cannabinoids (anandamide and 2-acylglycerol) found in numerous tissues throughout the body, including neural and immune tissues, which comprise the endogenous cannabinoid system.[1,3,4] The cannabinoid system helps regulate the function of other systems in the body, making it an integral part of the central homeostatic modulatory system -- the check-and-balance molecular signaling network in our bodies that keeps us at a healthy "98.6." Despite all of the advances in understanding the physiology and pharmacology of cannabis and cannabinoids, there remains a strong need for developing rational guidelines for dosing cannabis. We (Gregory T. Carter [GTC] and Muraco Kyashna-Tocha [MKT]) have previously attempted to address this issue, deriving a dosing scheme with the available known chemistry and pharmacology of cannabis.[14] However, it would appear that there is still considerable controversy over this issue.


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http://www.medscape.com/viewarticle/562451

Pot Compound Protective Against ‘Mad Cow’ Disease, Other Fatal Brain Disorders, Study Says
Submitted by wallah on Fri, 09/14/2007 - 00:57. cannabinoids studies CBD neurodegenerative diseases prion infection
Pot Compound Protective Against ‘Mad Cow’ Disease, Other Fatal Brain Disorders, Study Says

September 13, 2007 - Valbonne, France

Valbonne, France: The administration of the nonpsychoactive cannabinoid cannabidiol (CBD) inhibits prion accumulation in the brain and protects neurons against prion toxicity, according to preclinical data published in the September 5th edition of the Journal of Neuroscience.

Prion accumulation (the accumulation of abnormal, protein-based infectious particles in the brain) is the cause of various transmissible, fatal neurodegenerative diseases in both humans and animals – including bovine spongiform encephalopathy (commonly known as ‘Mad Cow’ disease) and Creutzfeldt-Jakob disease. No therapeutic treatments for prion-diseases are currently available.

Investigators at the National Center for Scientific Research in France reported that the administration of CBD "limited the cerebral accumulation of protease-resistant prion protein and significantly increased the survival time" in a dose-dependent manner in animals infected with a strain of prion disease.

"Our results suggest that CBD may protect neurons against the multiple molecular and cellular factors involved in the different steps of the neurodegenerative process, which takes place during prion infection," authors concluded. "When combined with its ability to target the brain and its lack of toxic side effects, CBD may represent a promising new anti-prion drug."

Previous preclinical studies of CBD have shown the compound to inhibit malignant cancer cell growth and protect neurons against alcohol-induced brain damage.

Other studies have demonstrated that cannabinoids can delay disease progression in animal models of several neurodegenerative diseases, including Alzheimer’s disease, multiple sclerosis, and amyotrophic lateral sclerosis (Lou Gehrig’s disease).

For more information, please contact Paul Armentano, NORML Senior Policy Analyst, at: paul@norml.org. Full text of the study, "Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons Against Prion Toxicity," appears in the Journal of Neuroscience. Abstracts of the study are available online at: http://www.jneurosci.org/cgi/content...act/27/36/9537. Additional information on CBD is available in the NORML report, "Emerging Clinical Applications for Cannabis and Cannabinoids," available online at: http://www.jneurosci.org/cgi/content...act/27/36/9537.

http://www.trews.org/node/662