Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Sep 2012
Amygdala subregions tied to SSRI and placebo response in patients with social anxiety disorder.
The amygdala is a key structure in the pathophysiology of anxiety disorders, and a putative target for anxiolytic treatments. Selective serotonin reuptake inhibitors (SSRIs) and placebo seem to induce anxiolytic effects by attenuating amygdala responsiveness. However, conflicting amygdala findings have also been reported. ⋯ All subgroups, including nonresponders, showed deactivation of the left lateral part of the amygdala. No rCBF differences were found between SSRI responders and placebo responders. This study provides new insights into the brain dynamics underlying anxiety relief by demonstrating common amygdala targets for pharmacologically and psychologically induced anxiety reduction, and by showing that the amygdala is functionally heterogeneous in anxiolysis.
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Neuropsychopharmacology · Sep 2012
The effect of chronic cannabinoids on broadband EEG neural oscillations in humans.
Animal and cellular work has shown that central cannabinoid-1 receptors modulate neural oscillations in the gamma range (40 Hz), which may be important for normal perceptual and cognitive processes. In order to assess the effect of cannabinoids on broadband-frequency neural oscillations in humans, the current study examined the effect of chronic cannabis use on auditory steady-state responses (ASSRs) utilizing electroencephalography (EEG). Passive ASSRs were assessed using varying rates of binaural stimulation (auditory click-trains; 10-50 Hz in increments of 5 Hz; 80 dB SPL) in carefully screened cannabis users and controls. ⋯ Further, within the cannabis group, lower 40 Hz power correlated with an earlier age of onset of cannabis use (p<0.04). These data suggest that chronic exposure to exogenous cannabinoids can alter the ability to generate neural oscillations, particularly in the gamma range. This is consistent with preclinical animal and cellular data, which may have implications for understanding the short- and long-term psychopharmacological effects of cannabis.
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Neuropsychopharmacology · Jun 2012
Randomized Controlled TrialA proof-of-concept randomized controlled study of gabapentin: effects on cannabis use, withdrawal and executive function deficits in cannabis-dependent adults.
There are no FDA-approved pharmacotherapies for cannabis dependence. Cannabis is the most widely used illicit drug in the world, and patients seeking treatment for primary cannabis dependence represent 25% of all substance use admissions. We conducted a phase IIa proof-of-concept pilot study to examine the safety and efficacy of a calcium channel/GABA modulating drug, gabapentin, for the treatment of cannabis dependence. ⋯ Relative to placebo, gabapentin significantly reduced cannabis use as measured both by urine toxicology (p=0.001) and by the Timeline Followback Interview (p=0.004), and significantly decreased withdrawal symptoms as measured by the Marijuana Withdrawal Checklist (p<0.001). Gabapentin was also associated with significantly greater improvement in overall performance on tests of executive function (p=0.029). This POC pilot study provides preliminary support for the safety and efficacy of gabapentin for treatment of cannabis dependence that merits further study, and provides an alternative conceptual framework for treatment of addiction aimed at restoring homeostasis in brain stress systems that are dysregulated in drug dependence and withdrawal.
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Neuropsychopharmacology · Jun 2012
Randomized Controlled TrialDose-related modulation of event-related potentials to novel and target stimuli by intravenous Δ⁹-THC in humans.
Cannabinoids induce a host of perceptual alterations and cognitive deficits in humans. However, the neural correlates of these deficits have remained elusive. The current study examined the acute, dose-related effects of delta-9-tetrahydrocannabinol (Δ⁹-THC) on psychophysiological indices of information processing in humans. ⋯ Overall, these data suggest that at doses that produce behavioral and subjective effects consistent with the known properties of cannabis, Δ⁹-THC reduced P300a and P300b amplitudes without altering the latency of these ERPs. Cannabinoid agonists may therefore disrupt cortical processes responsible for context updating and the automatic orientation of attention, while leaving processing speed and earlier sensory ERP components intact. Collectively, the findings suggest that CB1R systems modulate top-down and bottom-up processing.
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Neuropsychopharmacology · May 2012
Randomized Controlled TrialCourse of improvement in depressive symptoms to a single intravenous infusion of ketamine vs add-on riluzole: results from a 4-week, double-blind, placebo-controlled study.
The N-methyl-D-aspartate antagonist ketamine has rapid antidepressant effects in patients with treatment-resistant major depression (TRD); these effects have been reported to last for 1 week in some patients. However, the extent and duration of this antidepressant effect over longer periods has not been well characterized under controlled conditions. Riluzole, a glutamatergic modulator with antidepressant and synaptic plasticity-enhancing effects, could conceivably be used to promote the antidepressant effects of ketamine. ⋯ Overall, 27% of ketamine responders had not relapsed by 4 weeks following a single ketamine infusion. The average time to relapse was 13.2 days (SE=2.2). However, the difference between the riluzole and placebo treatment groups was not significant, suggesting that the combination of riluzole with ketamine treatment did not significantly alter the course of antidepressant response to ketamine alone.