Basic Research Studies > Cannabinoids and
Noradrenergic function
Cannabinoids and Noradrenergic
function
Modulation of norepinephrine by cannabinoids
The existence of an endogenous cannabinoid system, comprising
cannabinoid receptors and endogenous ligands is now well
recognized. However, the distribution of cannabinoid receptors
and the impact of cannabinoid agonists on monoaminergic neurotransmitter
systems is only slowly beginning to emerge. This information
is essential for understanding cellular adaptations following
chronic recreational drug exposure as well as elucidating
potential therapeutic uses for cannabinoid-based compounds.
Acute (short-term) effects of cannabinoid receptor agonist
administration include deficits in learning and memory, distorted
perception, difficulty in problem solving and loss of coordination.
Repeated administration (long-term) leads to increases in
the activation of the stress-response system, anxiety, depression,
cognitive impairment, and psychosis.
The question remains as to where cannabinoids act to induce
cellular adaptations that may result in long term behavioral
dysfunction. Preliminary data from our laboratories suggest
that one potential target is the noradrenergic coeruleo-cortical
pathway, a biogenic amine system involved in modulating higher
cognitive function and mood. This system is implicated in
setting the attentional mode, and is engaged as part of the
stress response to facilitate arousal.
Our guiding hypothesis is that chronic cannabinoid administration
results in a potentiated noradrenergic system that may contribute
to the pathophysiology of affective disorders. Reports of
the efficacy of cannabinoid antagonists in modulating monoaminergic
function suggest that targeting noradrenergic transmission
with this class of compounds may lead to novel therapeutic
possibilities for the treatment of psychiatric disorders
(e.g. depression and anxiety).
|