NEW ORLEANS(BW HealthWire)Oct. 26, 1997Pain relief may be provided by
marijuanalike drugs that exert their influence on brain cells in the same
way as the active component of the illegal weed, according to researchers
from the University of California San Francisco.

Ian Meng, PhD, and Barton Manning, PhD, both postdoctoral fellows, and
Howard Fields, MD, PhD, a professor of neurology with the Keck Center for
Integrative Neurosciences at UCSF, report that a synthetic marijuanalike
drug called WIN 55212 enhances the brain's ability to suppress pain in
rats, and probably in humans as well.

WIN 55212 dulls pain by acting on the same painsuppressing nerve circuits
as morphine and other opioid drugs, the most powerful painkillers known,
the researchers say, and such drugs may one day be used in combination with
opioids or other painkillers to provide better treatment for certain kinds
of pain.

Meng discussed the findings today at the Society for Neuroscience annual
meeting in New Orleans, during a press conference. Researchers from
several universities briefed reporters on studies of the painkilling
properties of cannabinoids. Cannabinoids are a class of chemicals that
includes tetrahydrocannabinol (THC), the component of marijuana responsible
for the "high" sought by recreational users.

The brain circuits affected include a key paincontrolling center called
the rostral ventromedial medulla. Fields has studied the transmission of
pain signals through this network for more than 15 years, identifying many
key cellular mechanisms of pain suppression by investigating the actions of
opioid drugs on this circuitry.

Now, in studies conducted on rats, Meng has determined that cannabinoids
and opioids produce similar changes within cells in the rostral
ventromedial medulla. Meng also monitored pain suppression by measuring
how long it took the rodents to remove their tails from an uncomfortable
heat source.

He found that drugs which block the painkilling effects of morphine do not
eliminate the pain relief provided by WIN 55212. Furthermore,
cannabinoidblocking chemicals do not reduce the effectiveness of morphine.

"The results indicate that the two classes of pain relievers act through
different biochemical mechanisms, even though they affect the electrical
transmission of pain impulses in the cells in the same way," according to
Meng.

Just as the study of morphine's effects enabled Fields and other
researchers to pioneer explorations of the rostral ventral medulla, the
study of cannabinoids will enable scientists to gain new insights into the
brain's mechanisms for suppressing or enhancing pain, Meng says.

Despite their unrivaled painkilling potency, opioids can have significant
side effects. These include the development of drug tolerance, whereby a
patient requires everhigher doses to experience pain relief, and drug
dependence, which causes a patient to become temporarily sick when opioid
treatment is withdrawn. Other side effects may include confusion, nausea
and constipation.

The cannabinoid THC, in addition to enhancing mood in some users, is
believed to reduce nausea, which may offer a significant advantage over
morphine. However it also impairs mental functioning in a variety of ways.

While it may not be possible to eliminate the side effects of opioids or
cannabinoids used to treat pain, combining them may enhance pain relief,
permitting the use of lower doses of each, and thereby alleviating the side
effects, Meng suggests.

In recent years scientists have identified the natural cannabinoid receptor
to which THC attaches, as well as naturally occurring cannabinoids, such as
anandamide, that act on this cannabinoid receptor. These discoveries and
the development of synthetic cannabinoids that act more preferentially on
the receptor, such as WIN 55212, should now lead to more rapid advances in
understanding the function of cannabinoids in the brain, according to Meng
and Fields.

It is not clear why natural opioids, called endorphins, and their
cannabinoid counterparts should act on many of the same nerve circuits.
However, Fields speculates that the rostral ventromedial medulla nerve
cells arose early in animal evolution, and may have properties similar to
the primitive endocrine system.

The endocrine system releases hormones that promote the survival of the
animal in specific circumstances. The hormone acts upon a certain group of
nerve cells that generate behavior appropriate to the situation, a fight or
a flight in response to danger, for instance.

In the same way, Fields suggests, natural brain cannabinoids might activate
specific ensembles of nerve cells that produce behavior appropriate to
particular situations. Suppression of pain through the rostral
ventromedial medulla in response to cannabinoids may be one aspect of an
overall behavior, such as feeding when hungry, he proposes.

Even though endorphins suppress pain by acting on the same nerve cells
within the brain, they may be released to perform their painkilling duties
under different circumstances, such as during a freezing response to fear,
Fields suggests.