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Embargoed until 2pm EST March 1, 2000
_____ Research Advocate Staff Liaison
_____ Chapter President
_____ I & R staff and volunteers
MARIJUANA DERIVATIVES IMPROVE SPASTICITY AND TREMOR IN MICE
WITH MS-LIKE DISEASE
Summary: Investigators in the United Kingdom and United States tested the ability of two
derivatives of marijuana (called cannabinoids) and three synthetic cannabinoids to control
spasiticity and tremor symptoms of the MS-like disease, EAE, in mice.
•The results, published in the March 2, 2000 issue of Nature, suggest that four different
cannabinoids could temporarily relieve spasticity and/or tremor.
•While this has not been tested in individuals with spasiticity or tremor associated with
MS, the study suggests that similar derivatives of marijuana might be developed for human
use, and for use in MS.
•It remains to be seen whether the psychoactive effects of these cannabinoids can be
minimized enough to make feasible the development of cannabinoids as a treatment.
Details: A research study by an international group of investigators suggests that specific
chemical derivatives of marijuana (called cannabinoids) or synthetic cannabinoids may
control spasticity and tremor in laboratory mice that have an MS-like disease known as
EAE. The study results were published in the March 2, 2000 issue of the journal Nature.
Background: The sometimes debilitating symptoms of spasticity (increased tone of
muscles causing stiff and awkward movements) and tremor (involuntary trembling or
quivering) can be difficult to control even with approved medications. Over the years there
have been claims that marijuana or its derivative THC (tetrahydrocannabinol) could help
control spasticity in multiple sclerosis but clinical studies have been small, generally not
properly controlled and their results difficult to interpret and controversial.
The fact that marijuana is psychoactive (can alter a person’s perceptions) complicates
efforts to determine this drug’s effects on spasticity, and creates side effects that can be
problematic. Therefore, scientists have hoped to isolate chemical components of marijuana
(cannabinoids) that may be beneficial, determine where individual components might act
in the body, and find ways to minimize the drug’s unwanted side effects.
A recent U.S. Institute of Medicine report on possible medical uses of marijuana focused on
the possible toxicity of smoked marijuana (claimed to be more toxic than cigarette
smoke), and urged the development of marijuana derivatives that might be more safely used and
which might show objective benefit for a wide range of medical problems, including
spasticity and tremor.
Marijuana exerts its effects on the body when its cannabinoid molecules interact with
docking proteins (called receptors) on the surface of cells. Many of these receptors are on
cells in the central nervous system, where they may relate to control of motor function as
well as cognition and affect.
Details of this Study: Investigators from the University College London and other
institutions in the United Kingdom and the United States performed a series of experiments
to determine if cannabinoids have the capacity to control tremor and spasticity in a mouse
disease similar to multiple sclerosis (EAE), and if so, how they might exert their effects.
The researchers tested five different cannabinoids, and found that intravenous infusions of
four of these could temporarily relieve spasticity and/or tremor in mice with EAE, depending
on the specific cannabinoid receptors with which these compounds dock. Reinforcing these
findings, the investigators also found evidence that chemicals capable of blocking specific
cannabinoid receptors could actually make spasticity and tremor in these mice worse.
What do these findings mean? This is the first study to test chemical derivatives of
marijuana on specific MS-like symptoms in mice. While this has not been tested in
individuals with spasiticity or tremor associated with MS, the study suggests that similar
derivatives of marijuana or synthetic cannabinoids might be developed for human use, and
for use in MS. It remains to be seen whether the psychoactive effects of these cannabinoids
can be minimized enough to make feasible the development of cannabinoids as a treatment.
Other research: This Nature paper underscores the fact that our bodies produce natural
cannabinoids and that our body cells have cannabinoid receptors designed to dock with these
natural substances. The investigators speculate that in the future it may be possible to
increase the amount of natural cannabinoids that the body produces to treat spasticity and
tremor, perhaps avoiding the need to provide cannabinoids through marijuana or any other
outside source. The National MS Society is currently supporting a pilot research project
Daniele Piomelli, University of California at Irvine) to investigate whether there is an
abnormality in the levels of natural cannabinoids in people with multiple sclerosis.
A large, placebo-controlled clinical trial involving 660 people with different forms of MS
has just begun in Britain to determine whether taking capsules of extracts of marijuana and
its component THC can help control spasticity.
From: Research Programs Department