Pubdate: Sat, 7 Nov 1998
Source: Lancet, The (UK)
Volume: 352, Number 9139
Contact:  http://www.thelancet.com/ 
Author: Rachelle H B Fishman

CANNABINOID IS NEUROPROTECTIVE IN HEAD TRAUMA

The leading cause of death among young men in the western
world--sequelae of severe head trauma--has no approved treatment.

But clinical results from Israel indicate that dexanabinol (HU-211), a
non-psychotropic cannabinoid analogue, may be "the most promising
neuroprotective agent seen to date", says Lawrence Marshall
(University of California, San Diego, CA, USA), an authority on head
trauma.

Phase II clinical trials provide strong evidence that the analogue can
reduce intracranial pressure and significantly improve outcome in
severe head injury, he adds. Other treatments, in phase III clinical
trials, are yet to show definitive human benefit.

Dexanabinol is "distinguished from earlier failed drugs by its triple
mechanism of action", explains neuropharmcologist Anat Biegon
(Pharmos, Rehovot, Israel). Dexanabinol's neuroinhibitory effect on
NMDA receptors was discovered 10 years ago by Tel Aviv University
biochemists Mordechai Sokolovsky and Yoel Kloog. Pharmos licensed
dexanabinol in 1991 for development as a drug. Biegon then directed
work in Israel and the USA that revealed dexanabinol's potent
anti-inflammatory and antioxidant activities.

2 years ago, Pharmos began phase II double-blind, randomised,
placebo-controlled clinical trials in six Israeli trauma centres
(Lancet 1996, 348: 1436). Of 67 unconscious patients, mostly young men
injured in road accidents, 30 were given dexanabinol and 37 received
placebo intravenously within 6 hours of injury (mean time 5 hours).

"The significant reduction in intracranial pressure below the 'damage
threshold' of 25 mm Hg--a key predictor of neurological
outcome--without jeopardising blood pressure was quite impressive",
says Marshall. Mortality was reduced by 26% and neurological outcome
was improved. "Recovery was accelerated in the treated group" and
"return to normal life among most severely injured patients was
outstanding", says lead investigator Nachshon Knoller (Sheba Medical
Center, Tel Hashomer, Israel), who reported the results at the
National Neurotrauma Society in Los Angeles, CA, USA on Nov 5. Phase
III trials on dexanabinol are due to start in 1999.
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Checked-by: Patrick Henry