Cannabinoids

Dexanabinol (HU-211) is a synthetic, non-psychotropic cannabinoid (Mechoulam et al. 1988) thought to act as a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist (Feigenbaum et al. 1989) to decrease glutamate excitotoxicity. This drug is also believed to possess antioxidant properties (Eshhar et al. 1995). Dexanabinol has shown very encouraging neuroprotective effects in animal models of TBI (Shohami et al. 1995). 

KN38-7271 is a cannabinoid receptor agonist, thought to elicit a robust response upon binding to its target receptor. Its efficacy as an acute therapeutic strategy post ABI has been examined through a recent RCT (Firsching et al. 2012).

Table: Effects of Cannabinoids as an Acute Therapeutic Strategy

Discussion

Two RCTs examined the effects of dexanabinol, a synthetic cannabinoid analogue, on both acute and long-term outcomes of patients with TBI. In an earlier trial by Knoller et al. (2002) the authors found positive effects associated with cannabinoid use, showing improved control of ICP and CPP. Improvements were also shown for functional outcomes as per the GOS and Disability Rating Scale (DRS) at 1 and 3 months post injury. However, in a later multinational trial by Maas et al. (2006) dexanabinol was found to be ineffective, citing lack of improvements in ICP and/or CPP control, and in long-term functional outcomes. The discrepancy in findings, in terms of the initial benefits reported by Knoller et al. (2002), may be due to the studies small sample size.

The role of a cannabinoid receptor agonist KN38-7271 in the management of acute TBI was studied in a more recent RCT by Firsching et al. (2012). Unlike dexanabinol, KN38-7271 binds very strongly to the cannabinoid receptor and elicits a robust receptor response. Treatment with KN38-7271 led to moderate improvements in ICP levels, and significant improvements in CPP levels. The treatment, however, was not shown to improve long-term outcomes as per the Galveston Orientation and Amnesia Test (GOAT) at the 6 month follow-up.  

Conclusions

There is Level 1b evidence, based on a large RCT, that dexanabinol does not provide improvements in intracranial pressure during the acute phase or in long-term clinical benefits post ABI; however, this conflicts with Level 1b evidence from a small RCT that has shown its effectiveness.

There is Level 1b evidence that treatment with KN38-7271 provides some aid in managing acute ABI by increasing cerebral perfusion pressure levels.

 

There is conflicting evidence on the effectiveness of dexanabinol; however, based on a high quality RCT with a large sample size, is not effective in controlling intracranial pressure or in improving clinical outcomes post ABI.

KN38-7271 provides improvements in cerebral perfusion pressure control during the acute phase post ABI.