From: sumbuddie@sumbuddie.net

Medical Cannabis: Rational Guidelines for Dosing





Gregory T. Carter, M.D.*

Patrick Weydt, M.D.**

Muraco Kyashna-Tocha, Ph.D.+

Donald I. Abrams, M.D.++



*Department of Rehabilitation Medicine

**Department of Neurology

University of Washington School of Medicine, Seattle, WA, USA



+The Cyber Anthropology Institute, Seattle, WA, USA



++Division of Hematology/Oncology, Department of Medicine, San Francisco
General Hospital, University of California, San Francisco, CA, USA



Supported by Research and Training Center Grant HB133B980008 from the
National Institute on Disability and Rehabilitation Research, Washington,
D.C., USA.



MAILING ADDRESS FOR PROOFS/REPRINTS:

Gregory T. Carter, M.D.

1809 Cooks Hill Road

Centralia, WA 98531

USA

Phone: (360) 330-8626 FAX: (360) 330-8623

e-mail: gtcarter@u.washington.edu



The authors would like to acknowledge the following persons for their help
in preparing this manuscript: Martin Martinez, Jeffrey Steinborn, and Ethan
Russo



Abstract
The medicinal value of cannabis (marijuana) is well documented in the
medical literature. Cannabinoids, the active ingredients in cannabis, have
many distinct pharmacological properties. These include analgesic,
anti-emetic, anti-oxidative, neuroprotective, and anti-inflammatory actions,
as well as modulation of glial cells and tumor growth regulation. Concurrent
with all these advances in the understanding of physiological and
pharmacological mechanisms of cannabis, there is a strong need for
developing rational guidelines for dosing. This paper will review the known
chemistry and pharmacology of cannabis and then, on that basis, discuss
rational guidelines for dosing.
Key words: marijuana, cannabinoids, cannabis, pharmacology, dosing
1. Introduction and Brief Historical Background
Possibly the first references to the medicinal use of cannabis are found in
the Chinese pharmacopoeia of Emperor Shen-Nung, written in 2737 BC. That
document recommended cannabis for analgesia, rheumatism, beriberi, malaria,
gout and poor memory.[1] Eastern Indian documents in the Atharvaveda, dating
to about 2000 BC, also refer to the medicinal use of cannabis.[2]
Archeological evidence has been found in Israel indicating that cannabis was
used therapeutically during childbirth as an analgesic.[3] This use of
cannabis continued in the West until the mid-1880s and continues today in
parts of Asia. In ancient Greece and Rome, both the Herbal of Dioscorides
and the writings of Galen refer to the use of medicinal cannabis.[4]
The medicinal use of cannabis arrived in western medicine much later. There
is mention of it in a treatise by Culpepper written in medieval times.
British East India Company surgeon William O.Shaughnessy introduced cannabis
for medicinal purposes into the United Kingdom following his observations
while working in India in the 1840s. He used it in a tincture for a wide
range of uses, including analgesia.[5] Queen Victoria used cannabis for
relief of dysmenorrhoea in the same era.[6] In 1937, against the advice of
most of the medical community and much of the American Medical Society, the
Federal Government criminalized non-medical cannabis. Cannabis was removed
from the United States Pharmacopoeia in 1942 but up until that time
physicians could still write a prescription for cannabis.[7] The
physiological mechanisms and therapeutic value of cannabinoids continue to
be well documented in the medical literature.[6-36] However, there has been
very little written on appropriate dosing regimens for the medicinal use of
cannabis. With current and emerging laws allowing physicians in many areas
of the world to recommend the use of cannabis to treat symptoms of certain
diseases and medical conditions, there is need for medical literature
describing rational dosing guidelines. This paper will review the known
chemistry and pharmacology of cannabis and then, on that basis, discuss
rational guidelines for dosing.
2. Chemistry and Pharmacology of cannabis
Cannabis is a complex plant, with several existing phenotypes, each
containing over 400 chemicals.[14,15] Approximately 70 are chemically unique
and classified as plant cannabinoids.[11,15] There are also naturally
occurring cannabinoids produced in the human body.[8] The cannabinoids are
21 carbon terpenes, biosynthesized predominantly via a recently discovered
deoxyxylulose phosphate pathway.[16] The cannabinoids are lipophilic.
Delta-9 tetrahydrocannabinol (THC) and delta-8 THC appear to produce the
majority of the psychoactive effects of cannabis. Delta-9 THC, the active
ingredient in dronabinol (Marinol) is the most abundant cannabinoid in the
plant and this has led researchers to hypothesize that it is the main source
of the drug.s impact.[15] Dronabinol is available by prescription as a
schedule III drug.
Other major plant cannabinoids include cannabidiol and cannabinol, both of
which may modify the pharmacology of THC and have distinct effects of their
own. Cannabidiol is the second most prevalent of cannabis.s active
ingredients and may produce most of its effects at moderate, mid range
doses. Cannabidiol becomes THC as the plant matures and this THC over time
breaks down into cannabinol. Up to 40% of the cannabis resin in some strains
is cannabidiol.[15] The amount varies according to plant. Some varieties of
Cannabis sativa have been found to have no cannabidiol.[6] Since cannabidiol
may help reduce anxiety symptoms, cannabis strains without cannabidiol may
produce more panic or anxiety side effects. Cannabidiol may exaggerate some
of the THC.s effects, including increasing THC-induced euphoria, while
attenuating others. Cannabidiol slows THC metabolism in the liver.
Consequently, a dose of THC combined with cannabidiol will create more
psychoactive metabolites than the same dose of THC alone.[14,15] In mice,
pretreatment with cannabidiol increased brain levels of THC nearly 3-fold
and there is strong evidence that cannabinoids can increase the brain
concentration and pharmacological actions of other drugs.[16,17] Some
researchers have proposed that many of the negative side effects of
dronabinol could be reduced by combining it with cannabidiol or possibly
other non-psychoactive cannabinoids.[8]
Cannabidiol breaks down to cannabinol as the plant matures.[15] Much less is
known about cannabinol, although it appears to have distinct pharmacological
properties that are quite different from cannabidiol. Cannabinol has
significant anticonvulsant, sedative, and other pharmacological activities
likely to interact with the effects of THC.[14] Cannabinol may induce sleep
and may provide some protection against seizures for epileptics.[15,16,17]
Two physiologically occurring lipids, anandamide (AEA) and

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