The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine>methamphetamine>hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic vasodilation and, possibly, normal blood flow in the brainstem.
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http://dx.doi.org/10.1016/j.taap.2016.05.020 | DOI Listing |
Drug Test Anal
December 2024
Analytical Toxicology Laboratory, Analytical Toxicology Division, Health Sciences Authority, Singapore.
This study presents the development and validation of a drug testing method in hair, employing a semi-automated sample preparation procedure and gas chromatography-tandem mass spectrometry (GC-MS/MS) for simultaneous multidrug analysis in hair. The method aims to detect and quantify multiple drugs in hair, including amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, ketamine, norketamine, cocaine, benzoylecgonine, morphine, codeine and 6-monoacetylmorphine, using a comprehensive procedure involving decontamination, pulverization, clean-up using supported-liquid extraction (SLE) and a two-step derivatization process. The method validation included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, carryover, robustness and stability.
View Article and Find Full Text PDFLancet Psychiatry
January 2025
Champalimaud Research and Clinical Centre, Champalimaud Foundation, Lisbon, Portugal; Faculdade de Ciências Médicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal. Electronic address:
Although studies of psychedelic-assisted psychotherapy are accumulating, there is no consensus regarding best practice of the psychotherapeutic component. In this systematic review, we summarised the quality of reporting on psychological interventions in research about psychedelic treatments. The design followed PRISMA guidelines and was preregistered in PROSPERO (CRD42022319221).
View Article and Find Full Text PDFInt J Drug Policy
November 2024
Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan; Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Taiwan; Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, USA. Electronic address:
Metabolites
November 2024
Center for Research on Multidimensional Separation Science, School of Chemical Sciences, Universiti Sains Malaysia, USM 11800, Penang, Malaysia.
Eur Addict Res
November 2024
Experimental Pharmacopsychology and Psychological Addiction Research, Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
Introduction: Population-level substance use research primarily relies on self-reports, which often underestimate actual use. Hair analyses offer a more objective estimate; however, longitudinal studies examining concordance are lacking. Previous studies showed that specific psychological and behavioral characteristics are associated with a higher likelihood of underreporting substance use, but the longitudinal stability of these associations remains unclear.
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