Cannabinoidi per il trauma cranico grave

Mechanisms of initial and secondary brain damage have been characterized in recent years. They have been explored in the cerebral tissue and in the brain vasculature. At cellular level, multiple events follow traumatic injury. Activation of receptors due to a massive surge of excitatory aminoacids causes an influx of calcium; free radicals generation exceeds the scavenger capabilities and directly damage the membranes; inflammatory pathways are activated and over-activated. The blood-brain barrier opens, water is accumulated in the extracellular compartment, or intracellularly, when ionic pumps become ineffective. Dexanabinol, a synthetic cannabinoid derivative without psychotropic activity, has shown in the experimental setting to have anti-inflammatory capabilities and to counteract free radical damage and glutamate excitotoxicity. Clinical trials with Dexanabinol: after Dexanabinol was proved safe and well tolerated in phase I atudies, two clinical trials have been performed in traumatic brain injury (TBI). The first was a phase II study for assessing safety. It involved 67 patients randomized to placebo, 48 mg or 150 mg of Dexanabinol injected within 6 hours after injury. In this small sample Dexanabinol seemed protective, especially because intracranial pressure (ICP) was lower compared to placebo. The second trial was a randomized, controlled, double blind study which enrolled 861 patients from 2001-2004 in 86 trauma centers. Eight hundred and forty-six patients were available for analysis, 428 treated with Dexanabinol 150 mg and 418 treated with placebo. The randomization provided well-balanced groups. The study demonstrated an excellent safety profile but no difference between the two groups in terms of primary (Glasgow Outcome Scale extended) or secondary (neuroworsening, mortality, ICP control) end-points. In conclusion neuroprotection has been demonstrated by various agents in multiple animal models; unfortunately protection has not been demonstrated in humans by all compounds investigated so far. Dexanabinol comes last in a series of promising agents, and, despite a strong experimental background and various innovations in the trail's design, has not shown efficacy.