Subj: Cannabinoid is neuroprotective in head trauma



Date: 7 November 1998



Source: The Lancet, Volume 352, Number 9139





Cannabinoid is neuroprotective in head trauma 

By Rachelle H B Fishman



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.