Sequoiacrone
January 2nd, 2009, 02:50 PM
Cannabinoids and
brain injury:
therapeutic
implications
Raphael Mechoulam,David Panikashvili
and Esther Shohami
Mounting in vitro and in vivo data suggest that the endocannabinoids
anandamide and 2-arachidonoyl glycerol, as well as some plant and synthetic
cannabinoids, have neuroprotective effects following brain injury. Cannabinoid
receptor agonists inhibit glutamatergic synaptic transmission and reduce the
production of tumour necrosis factor-α and reactive oxygen intermediates,
which are factors in causing neuronal damage. The formation of the
endocannabinoids anandamide and 2-arachidonoyl glycerol is strongly
enhanced after brain injury, and there is evidence that these compounds reduce
the secondary damage incurred. Some plant and synthetic cannabinoids,
which do not bind to the cannabinoid receptors, have also been shown to be
neuroprotective, possibly through their direct effect on the excitatory
glutamate system and/or as antioxidants
Traumatic brain injury (TBI) is a leading cause of
death in young people, particularly in males. No
specific therapy is available, because of the lack of
understanding of the pathological mechanisms that
are involved in the development of secondary damage.
Numerous treatments – corticosteroids, mannitol,
barbiturates, hyperventilation, cerebrospinal fluid
drainage and hypothermia – are employed today to
reduce the neurological damage caused by TBI.
However, a critical evaluation of the literature on the
first five treatments mentioned [1] and clinical
experimental work on hypothermia [2] have shown
that none of these methods brings significant
improvement. There are preliminary indications that
progesterone could be of value in post-injury
treatment of TBI [3]. Obviously, novel approaches are
urgently needed and, indeed the clinical importance
of TBI has led to a large number of investigations on
the mechanisms of the secondary damage produced
by the injury, as well as on the endogenous
neuroprotective, restorative mechanisms available to
the injured brain.
Excitotoxicity, produced primarily by high
concentrations of glutamate, and activation of
glutamate receptors, is widely accepted as a central
process in secondary damage and cell death. This is
mainly due to the intracellular accumulation of
cytotoxic levels of calcium, which leads to activation of
numerous destructive pathways, with reactive
oxygen intermediates (ROI), calpains and caspases
for the entire article see http://www.ukcia.org/research/CannabinoidsAndBrainInjury.pdf
brain injury:
therapeutic
implications
Raphael Mechoulam,David Panikashvili
and Esther Shohami
Mounting in vitro and in vivo data suggest that the endocannabinoids
anandamide and 2-arachidonoyl glycerol, as well as some plant and synthetic
cannabinoids, have neuroprotective effects following brain injury. Cannabinoid
receptor agonists inhibit glutamatergic synaptic transmission and reduce the
production of tumour necrosis factor-α and reactive oxygen intermediates,
which are factors in causing neuronal damage. The formation of the
endocannabinoids anandamide and 2-arachidonoyl glycerol is strongly
enhanced after brain injury, and there is evidence that these compounds reduce
the secondary damage incurred. Some plant and synthetic cannabinoids,
which do not bind to the cannabinoid receptors, have also been shown to be
neuroprotective, possibly through their direct effect on the excitatory
glutamate system and/or as antioxidants
Traumatic brain injury (TBI) is a leading cause of
death in young people, particularly in males. No
specific therapy is available, because of the lack of
understanding of the pathological mechanisms that
are involved in the development of secondary damage.
Numerous treatments – corticosteroids, mannitol,
barbiturates, hyperventilation, cerebrospinal fluid
drainage and hypothermia – are employed today to
reduce the neurological damage caused by TBI.
However, a critical evaluation of the literature on the
first five treatments mentioned [1] and clinical
experimental work on hypothermia [2] have shown
that none of these methods brings significant
improvement. There are preliminary indications that
progesterone could be of value in post-injury
treatment of TBI [3]. Obviously, novel approaches are
urgently needed and, indeed the clinical importance
of TBI has led to a large number of investigations on
the mechanisms of the secondary damage produced
by the injury, as well as on the endogenous
neuroprotective, restorative mechanisms available to
the injured brain.
Excitotoxicity, produced primarily by high
concentrations of glutamate, and activation of
glutamate receptors, is widely accepted as a central
process in secondary damage and cell death. This is
mainly due to the intracellular accumulation of
cytotoxic levels of calcium, which leads to activation of
numerous destructive pathways, with reactive
oxygen intermediates (ROI), calpains and caspases
for the entire article see http://www.ukcia.org/research/CannabinoidsAndBrainInjury.pdf