Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Feb 2009
Randomized Controlled TrialSmoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial.
Despite management with opioids and other pain modifying therapies, neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals. Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception. We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV. ⋯ Mood and daily functioning improved to a similar extent during both treatment periods. Although most side effects were mild and self-limited, two subjects experienced treatment-limiting toxicities. Smoked cannabis was generally well tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV DSPN.
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Neuropsychopharmacology · Feb 2009
Anxiolytic effects in mice of a dual blocker of fatty acid amide hydrolase and transient receptor potential vanilloid type-1 channels.
The endocannabinoid-inactivating enzyme, fatty acid amide hydrolase (FAAH), and the transient receptor potential vanilloid type-1 (TRPV1) channel are new targets for the development of anxiolytic drugs. We studied the effect on anxiety-like behavior in the elevated plus maze of a dual FAAH/TRPV1 blocker, N-arachidonoyl-serotonin (AA-5-HT). In male C57BL/6J mice, acute intraperitoneal administration of AA-5-HT (0.1-2.5 mg/kg) increased both the time spent and the number of entries in the open arm, while being inactive at the highest dose tested (5 mg/kg). ⋯ In both strains, the anxiolytic effects of AA-5-HT were paralleled by elevation of brain endocannabinoid levels and were reversed by per se inactive doses of the cannabinoid receptors of type-1 (CB(1)) receptor antagonist AM251, or the TRPV1 agonist, olvanil. Immunohistochemical localization of CB(1) and TRPV1 receptors was observed in mouse prefrontal cortex, nucleus accumbens, amygdala, and hippocampus. Simultaneous 'indirect' activation of CB(1) receptors following FAAH inhibition, and antagonism at TRPV1 receptors might represent a new therapeutic strategy against anxiety.