Recent Advances in the Neuropsychopharmacology of Serotonergic Hallucinogens Adam L. Halberstadt Behavioral Brain Research, 2015, 15, 277, 99–120. doi : 10.1016/j.bbr.2014.07.016 Abstract Serotonergic hallucinogens, such as (+)-lysergic acid diethylamide, psilocybin, and mescaline, are somewhat enigmatic substances. Although these drugs are derived from multiple chemical families, they all produce remarkably similar effects in animals and humans, and they show cross-tolerance. This article reviews the evidence demonstrating the serotonin 5-HT2A receptor is the primary site of hallucinogen action. The 5-HT2A receptor is responsible for mediating the effects of hallucinogens in human subjects, as well as in animal behavioral paradigms such as drug discrimination, head twitch response, prepulse [...]
Lire la suiteThe paradoxical psychological effects of lysergic acid diethylamide (LSD) R. L. Carhart-Harris, M. Kaelen, M. Bolstridge, T. M. Williams, L. T. Williams, R. Underwood, A. Feilding and D. J. Nutt Psychological Medicine, 2016, 46, 1379–1390. doi:10.1017/S0033291715002901 Background : Lysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study. Method : A total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 μg, intravenously) on one occasion and placebo (saline, intravenously) on another, in a [...]
Lire la suiteRole of the Serotonin 5-HT2A Receptor in Learning John A. Harvey Learning & Memory, 2003, 355-362 www.learnmem.org http://www.learnmem.org/cgi/doi/10.1101/lm.60803. This study reviews the role of the serotonin 5-HT2A receptor in learning as measured by the acquisition of the rabbit’s classically conditioning nictitating membrane response, a component of the eyeblink response. Agonists at the 5-HT2A receptor including LSD (d-lysergic acid diethylamide) enhanced associative learning at doses that produce cognitive effects in humans. Some antagonists such as BOL (d-bromolysergic acid diethylamide), LY53,857, and ketanserin acted as neutral antagonists in that they had no effect on learning, whereas others (MDL11,939, ritanserin, and mianserin) acted as inverse agonists in that [...]
Lire la suiteThe Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future Robin L Carhart-Harris and Guy M Goodwin Neuropsychopharmacology, 2017, 42, 2105–2113 doi:10.1038/npp.2017.84; published online 17 May 2017 Plant-based psychedelics, such as psilocybin, have an ancient history of medicinal use. After the first English language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aids to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial therapeutic promise before prohibitive legislature in the mid-1960s effectively ended all major psychedelic research programs. Since the early 1990s, there has been a steady [...]
Lire la suiteSpectral signatures of serotonergic psychedelics and glutamatergic dissociatives Carla Pallavicini, Martina G. Vilas, Mirta Villarreal, Federico Zamberlan, Suresh Muthukumaraswamy, David Nutt, Robin Carhart-Harris, Enzo Tagliazucchi NeuroImage, 2019 https://doi.org/10.1016/j.neuroimage.2019.06.053 Abstract Classic serotonergic psychedelics are remarkable for their capacity to induce reversible alterations in consciousness of the self and the surroundings, mediated by agonism at serotonin 5-HT2A receptors. The subjective effects elicited by dissociative drugs acting as N-methyl-D-aspartate (NMDA) antagonists (e.g. ketamine and phencyclidine) overlap in certain domains with those of serotonergic psychedelics, suggesting some potential similarities in the brain activity patterns induced by both classes of drugs, despite different pharmacological mechanisms of action. We investigated source-localized [...]
Lire la suiteComparison of the behavioral effects of mescaline analogs using the head twitch response in mice Adam L. Halberstadt, Muhammad Chatha, Stephen J. Chapman and Simon D. Brandt Journal of Psychopharmacology, 2019, 1 –9 DOI: 10.1177/0269881119826610 journals.sagepub.com/home/jop Abstract Background : In recent years, there has been increasing scientific interest in the effects and pharmacology of serotonergic hallucinogens. While a large amount of experimental work has been conducted to characterize the behavioral response to hallucinogens in rodents, there has been little systematic investigation of mescaline and its analogs. The hallucinogenic potency of mescaline is increased by α-methylation and by homologation of the 4-methoxy group but it not clear [...]
Lire la suiteDiscriminative Stimulus Effects of Psychostimulants and Hallucinogens in S()-3,4-Methylene-dioxy-meth amphetamine (MDMA) and R()-MDMA Trained Mice K. S. Murnane, N. Murai, L. L. Howell, and W. E. Fantegrossi THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2009, Vol. 331, No. 2 Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics 156174/3525473 JPET 331:717–723, 2009 Preliminary findings from these experiments were previously presented as follows : Murnane K.S., 2008 Expérimentalement Biology Meeting; San Diego, CA. doi:10.1124/jpet.109.156174. ABSTRACT 3,4-Methylenedioxymethamphetamine (MDMA) is a substituted phenethylamine more commonly known as the drug of abuse “ecstasy.” The acute and persistent neurochemical effects of MDMA in the mice are distinct from those in [...]
Lire la suiteChanges in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5- HT2A receptor Katrin H. Preller, Joshua B. Burt, Jie Lisa Ji, Charles Schleifer, Brendan D. Adkinson, Philipp Stampfli, Erich Seifritz, Grega Repovs, John H. Krystal, John D. Murray, Franz X. Vollenweider, Alan Anticevic eLife, 2018, 7, e35082. DOI: https://doi.org/10.7554/eLife.35082.001 Abstract Background : Lysergic acid diethylamide (LSD) has agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, specific receptor contributions to its neurobiological effects remain unknown. Methods : We therefore conducted a double-blind, randomized, counterbalanced, cross-over study (ClinicalTrials.gov, NCT02451072) during which [...]
Lire la suiteDynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin Louis-David Lord, Paul Expert, Selen Atasoy, Leor Roseman, Kristina Rapuano, Renaud Lambiotte, David J. Nutt, Gustavo Deco, Robin L. Carhart-Harris, Morten L. Kringelbach, Joana Cabral, NeuroImage, 2019, 199, 127–142 https://doi.org/10.1016/j.neuroimage.2019.05.060 A B S T R A C T Growing evidence from the dynamical analysis of functional neuroimaging data suggests that brain function can be understood as the exploration of a repertoire of metastable connectivity patterns (‘functional brain networks’), which potentially underlie different mental processes. The present study characterizes how the brain's dynamical exploration of resting-state networks is rapidly modulated by intravenous [...]
Lire la suitePilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Matthew W Johnson, Albert Garcia-Romeu, Mary P Cosimano and Roland R Griffiths Journal of Psychopharmacology, 2014, Vol. 28(11) 983–992 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269881114548296 Abstract Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an openlabel pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment [...]
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