COMMENTARY

Dosing Medical Marijuana: Rational Guidelines on Trial in Washington State

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

Disclosures

September 11, 2007

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.[7,8,9,10,11,12] 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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