MarijuanaLike Drugs May Be Effective Painkillers

Pain 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.

CONTACT: University of California, San Francisco Jeffrey Norris, 415/4762557

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