CANNABINOID ANALGESIA EXPLAINED

Marijuana, it is claimed, relieves pain, but how? In a new study, the
analgesic effect of cannabinoids has been found to work via a part of the
brain stem also used by opioids. But, marijuana's activity is
pharmacologically dissociable from that of opioids (Nature 1998; 395:
381-83)

Researchers in Howard Fields' laboratory at the University of California,
San Francisco (CA, USA) gave rats a cannabinoid and then tested their pain
threshold with the tail-flick test--ie, how fast the rats moved their tails
away from a heat lamp. Inactivation of the rostral ventromedial medulla
(RVM) by microinjection of muscimol, which mimics an inhibitory
neurotransmitter, prevented the analgesia caused by the cannabinoid.

The activities of single neurons in the RVM were correlated with the
changes in pain thresholds caused by intravenous administration of opioid
and cannabinoid agonists and antagonists. For example, the cannabinoid
antagonist SR141716A alone induced hyperalgesia, indicating that endogenous
cannabinoids modulate pain thresholds.

"The RVM projects directly to the spinal cord, and is the final common
pathway for a lot of pain-modulating brain regions that feed into it. When
you administer cannabinoids, and record from neurons in the RVM, you see a
difference in firing correlated with the longer latency in the tail-flick
test. Then, when we injected the morphine antagonist naloxone after the
cannabinoid, it did nothing further to the tail-flick test, and nothing
further to the firing of cells in the RVM", says first author Ian Meng.

It is unclear when and why the endogenous cannabinoid system is normally
activated, but cannabinoids alone are not effective for severe pain so they
are "not going to replace morphine", says Meng. However, he adds,
"cannabinoids increase appetite, and so may help alleviate the nausea
caused by opioids."

Checked-by: Joel W. Johnson