Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Aug 2010
Clinical TrialCannabidiol attenuates the appetitive effects of Delta 9-tetrahydrocannabinol in humans smoking their chosen cannabis.
Worldwide cannabis dependence is increasing, as is the concentration of Delta(9)-tetrahydrocannabinol (THC) in street cannabis. At the same time, the concentration of the second most abundant cannabinoid in street cannabis, cannabidiol (CBD), is decreasing. These two cannabinoids have opposing effects both pharmacologically and behaviorally when administered in the laboratory. ⋯ Those smoking higher CBD : THC strains also showed lower self-rated liking of cannabis stimuli on both test days. Our findings suggest that CBD has potential as a treatment for cannabis dependence. The acute modulation of the incentive salience of drug cues by CBD may possibly generalize to a treatment for other addictive disorders.
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Neuropsychopharmacology · Aug 2010
Calcium/calmodulin-dependent protein kinase II mediates hippocampal glutamatergic plasticity during benzodiazepine withdrawal.
Benzodiazepine withdrawal anxiety is associated with potentiation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) currents in hippocampal CA1 pyramidal neurons attributable to increased synaptic incorporation of GluA1-containing AMPARs. The contribution of calcium/calmodulin-dependent protein kinase II (CaMKII) to enhanced glutamatergic synaptic strength during withdrawal from 1-week oral flurazepam (FZP) administration was further examined in hippocampal slices. As earlier reported, AMPAR-mediated miniature excitatory postsynaptic current (mEPSC) amplitude increased in CA1 neurons from 1- and 2-day FZP-withdrawn rats, along with increased single-channel conductance in neurons from 2-day rats, estimated by non-stationary noise analysis. ⋯ Both GluA1 expression levels and CaMKII alpha-mediated GluA1 Ser(831) phosphorylation were increased in PSD-subfractions from 2-day FZP-withdrawn rats. As phospho-Thr(286)CaMKII alpha was unchanged, CaMKII alpha may be activated through an alternative signaling pathway. Synaptic insertion and subsequent CaMKII alpha-mediated Ser(831) phosphorylation of GluA1 homomers contribute to benzodiazepine withdrawal-induced AMPAR potentiation and may represent an important hippocampal pathway mediating both drug-induced and activity-dependent plasticity.