European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
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Eur Neuropsychopharmacol · Aug 2015
Inhibition of FAAH reduces nitroglycerin-induced migraine-like pain and trigeminal neuronal hyperactivity in mice.
There is evidence to suggest that a dysregulation of endocannabinoid signaling may contribute to the etiology and pathophysiology of migraine. Thus, patients suffering from chronic migraine or medication overuse headache showed alterations in the activity of the arachidonoylethanolamide (AEA) degrading enzyme fatty acid amide hydrolase (FAAH) and a specific AEA membrane transporter, alongside with changes in AEA levels. The precise role of different endocannabinoid system components is, however, not clear. ⋯ Both inhibitors also dose-dependently blocked nitroglycerin-induced hyperalgesia and the activation of trigeminal neurons. The effects of the genetic deletion of pharmacological blockade of FAAH are mediated by CB1 receptors, because they were completely disrupted with the CB1 antagonist rimonabant. These results identify FAAH as a target for migraine pharmacotherapy.
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Eur Neuropsychopharmacol · Apr 2015
Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans.
Psychedelic agents have a long history of use by humans for their capacity to induce profound modifications in perception, emotion and cognitive processes. Despite increasing knowledge of the neural mechanisms involved in the acute effects of these drugs, the impact of sustained psychedelic use on the human brain remains largely unknown. Molecular pharmacology studies have shown that psychedelic 5-hydroxytryptamine (5HT)2A agonists stimulate neurotrophic and transcription factors associated with synaptic plasticity. ⋯ CT values in the PCC were inversely correlated with the intensity and duration of prior use of ayahuasca and with scores on self-transcendence, a personality trait measuring religiousness, transpersonal feelings and spirituality. Although direct causation cannot be established, these data suggest that regular use of psychedelic drugs could potentially lead to structural changes in brain areas supporting attentional processes, self-referential thought, and internal mentation. These changes could underlie the previously reported personality changes in long-term users and highlight the involvement of the PCC in the effects of psychedelics.
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Eur Neuropsychopharmacol · Apr 2015
The dual effect of CA1 NMDA receptor modulation on ACPA-induced amnesia in step-down passive avoidance learning task.
It is well documented that cannabinoids play an important role in certain hippocampal memory processes in rodents. On the other hand, N-Methyl-d-aspartate receptors (NMDARs) mediate the synaptic plasticity related to learning and memory processes which take place in the hippocampus. Such insights prompted us to investigate the influence of dorsal hippocampal (CA1) NMDA receptor agents on amnesia induced by cannabinoid CB1 receptor agonist, arachidonylcyclopropylamide (ACPA) in male mice. ⋯ Further investigation revealed that a subthreshold dose of d-AP7 could potentiate the memory acquisition impairment induced by ACPA. Moreover, the subthreshold dose of AM251 did not alter the ACPA response, while the effective dose of the drug restored the memory acquisition impairment induced by ACPA. According to these results, we concluded that activation of the NMDA receptors in the CA1 mediates a dual effect on ACPA-induced amnesia in step-down passive avoidance learning task.
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Eur Neuropsychopharmacol · Mar 2015
Randomized Controlled TrialAcute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users.
Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8mg), CBD (16mg), THC+CBD (8mg+16mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. ⋯ In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces.
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Eur Neuropsychopharmacol · Jan 2015
1H-MRS of the anterior cingulate cortex in childhood and adolescent obsessive-compulsive disorder: a case-control study.
Abnormal glutamate concentrations in the anterior cingulate cortex (ACC) have been identified in children and adults with obsessive-compulsive disorder (OCD). The purpose of the present study was to measure in vivo (1)H-MRS neurometabolite concentrations in the ACC of children and adolescents with OCD, in order to identify metabolite abnormalities compared to healthy controls and to assess their relationship with clinical variables. 3T proton-magnetic resonance spectroscopy was used to probe ACC biochemistry in 47 paediatric and adolescent OCD patients (11-18 years old) compared to 31 healthy subjects of similar age, sex and estimated intellectual quotient. ⋯ In addition, we found significantly lower levels of myo-inositol adjusted for CSF in the ACC [F1,74=5.686; P=0.02] in patients compared with controls. The present findings do not confirm the hypothesis of differences in Glx concentrations in the ACC between children and adolescents with OCD and healthy controls; however, the observation of differences in the Glx concentration in children and adolescent OCD patients depending on the duration of illness is of interest.