Background Ketamine has been associated with a unique spectrum of subjective "psychedelic" effects in patients emerging from anesthesia. This study quantified these effects of ketamine and related them to steady-state plasma concentrations. Methods Ketamine or saline was administered in a single-blinded crossover protocol to 10 psychiatrically healthy volunteers using computer-assisted...
Following Albert Hofmann's discovery of LSD's psychoactive properties in 1943, and previous to their scheduling as controlled substances, the psychedelic drugs were widely studied--six international conferences and hundreds of papers discussed their potential therapeutic usefulness. The observation that the frightening experience of delirium tremens sometimes led alcoholics to moderate their...
The phenylisopropylamine derivatives 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) have been compared to both psychostimulants and hallucinogens in drug discrimination investigations. The stereoisomers of these compounds, in particular those of MDA, appear to produce differential effects. Previous studies have demonstrated that animals trained to discriminate...
Ten male N/Nih rats were trained to discriminate between the interoceptive cues produced by the purportedly dopaminergically-mediated drug d-amphetamine at 0.4 mg/kg intraperitoneally administered 20 min prior to training and those produced by the purportedly serotonergically-active agent norfenfluramine at 0.7 mg/kg. Once this discrimination was successfully acquired, the rats were tested with...
Stable transfection of the human neuroblastoma cell line SH-SY5Y with the human 5-hydroxytryptamine2A (5-HT2A) or 5-HT2C receptor cDNA produced cell lines demonstrating ligand affinities that correlated closely with those for the corresponding endogenous receptors in human frontal cortex and choroid plexus, respectively. Stimulation of the recombinant receptors by 5-HT induced phosphoinositide...
Hallucinogenic drugs have been inhaled, ingested, worshipped, and reviled since prehistory. With the purification and synthesis of bontanical preparations and the ensuing discovery of chemically unique agents, hope was raised regarding their therapeutic potential, but this hope has been clouded by an epidemic of abuse and an inventory of adverse effects. This review examines aspects of that...
Tetrahydrobenzodifuran functionalities were employed as conformationally restricted bioisosteres of the aromatic methoxy groups in prototypical hallucinogenic phenylalkylamines 1 and 2. Thus, a series of 8-substituted 1-(2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b']difuran-4-yl)-2-aminoal kanes (7a-e) were prepared and evaluated for activity in the two-lever drug discrimination paradigm in rats trained...
AbstractResearch into treating drug dependence with hallucinogens, although promising, ended with questions still unanswered because of varying, in some cases skeptical, methodology and insufficient adherence to a double-blind, placebo-controlled design. Interest is again emerging, especially with the recent patenting in the United States of ibogaine for its apparent anti-craving properties. A...
The present study was designed to investigate the hypothesis that agonist interactions at 5-HT2C receptors mediate the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP). Three structural classes of compounds have been described to stimulate increases in phosphoinositide (PI) hydrolysis at the 5-HT2C receptor site: phenylpiperazines, phenylalkylamines, and indolamines. Four...
Frontal-subcortical circuits provide a comprehensive framework for understanding the anatomy, biochemistry, and pharmacology of behavior. The three principal behaviorally relevant circuits originate in the dorsolateral prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex, respectively. Circuit-specific marker behaviors associated with each circuit are executive dysfunction...