The involvement of the serotonin system in the pathophysiology of schizophrenia has been elucidated by experiments with hallucinogens. Application of a hallucinogen to humans leads to changes in perception, cognition, emotions, and induction of psychotic-like symptoms that resemble symptoms of schizophrenia. In rodent studies, their acute administration affe...
Psilocybin, a psychoactive alkaloid contained in hallucinogenic mushrooms, is nowadays given a lot of attention in the scientific community as a research tool for modeling psychosis as well as due to its potential therapeutic effects. However, it is also a very popular and frequently abused natural hallucinogen. This review summarizes all the past and recent...
One of the oldest models of schizophrenia is based on the effects of serotonergic hallucinogens such as mescaline, psilocybin, and (+)-lysergic acid diethylamide (LSD), which act through the serotonin 5-HT(2A) receptor. These compounds produce a 'model psychosis' in normal individuals that resembles at least some of the positive symptoms of schizophrenia. Ba...
Recent clinical trials suggest that 3 single biological treatments have effects that persist. Based on research showing that the muscles involved in facial expressions can feed back to influence mood, a single trial diminishing glabella frown lines with botulinum toxin demonstrated a significant antidepressant effect for 16 weeks. Based primarily on research...
The serotonin 5-HT(2A) receptor is the major target of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Serotonergic psychedelics induce profound effects on cognition, emotion, and sensory processing that often seem uniquely human. This raises questions about the validity of animal models of psychedelic drug action. None...
Mescaline, phencyclidine (PCP) and psilocybin are potent hallucinogenic drugs strongly affecting both human and animal behavior. However, these compounds have not been previously investigated in zebrafish (Danio rerio), rapidly gaining popularity as a model in psychopharmacology research. Here, we examine the effects of mescaline, PCP and psilocybin in multi...
Hallucinogenic drugs, including mescaline, psilocybin and lysergic acid diethylamide (LSD), act at serotonin 5-HT2A receptors (5-HT2ARs). Metabotropic glutamate receptor 2/3 (mGluR2/3) ligands show efficacy in modulating the responses induced by activation of 5-HT2ARs. The formation of a 5-HT2AR-mGluR2 complex suggests a functional interaction that affects t...
Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce rem...
Psilocybe argentipes is a hallucinogenic mushroom. The present study examined the effects of P. argentipes on marble-burying behavior, which is considered an animal model of obsessive-compulsive disorder. P. argentipes significantly inhibited marble-burying behavior without affecting locomotor activity as compared with the same dose of authentic psilocybin. ...
Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the pharmacological receptors essential for stimulus control. In the present investigation rats were trained with psilocybin and tests were then conducted employing a series of other hallucinogens and presumed antagonists. An intermediate degree of antagonism of ...
Hallucinogens, including mescaline, psilocybin, and lysergic acid diethylamide (LSD), profoundly affect perception, cognition, and mood. All known drugs of this class are 5-HT(2A) receptor (2AR) agonists, yet closely related 2AR agonists such as lisuride lack comparable psychoactive properties. Why only certain 2AR agonists are hallucinogens and which neural...
Recent research into the pharmacological mechanism of hallucinogens (LSD, psilocybin) and dissociative anesthetics (PCP, ketamine) suggest that multiple neurotransmitter systems are involved in drug-induced and possibly also in naturally occurring psychoses. Specifically, animal models suggest that a dysbalance between serotonin, glutamate, and dopamine in t...
Tryptamine produces pharmacologic effects in man and the chronic spinal dog which are similar to those produced by LSD, mescaline, psilocin, DMT, DOM and DOB. These effects include tachycardia, tachypnea, mydriasis, hyperreflexia, behavioral changes and in man, hallucinations. Chronic spinal dogs treated chronically with LSD became tolerant to its ability to...
The objective was to determine the behavioral effects and duration of action of bromocriptine (BC) doses from 6 to 60 mg/kg i.p. Cats were housed in large outdoors cages designed for prolonged observation using an ethological approach. Baseline behavior was measured after a 3 month period of habituation. The frequency of 12 behaviors was then scored continuo...
Previous studies from our laboratory have demonstrated that there are a number of important dissociations between the effects of hallucinogenic drugs on the activity of serotonin-containing dorsal raphe neurons and behavior in freely moving cats. In the present study, we extended this analysis to serotonergic units in the nucleus centralis superior (NCS) and...
Fifteen rats were trained to discriminate between the tryptamine hallucinogen psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine; 1.0 mg/kg) and saline in a two-lever choice task. Dose-response and time-response curves were obtained. The psilocybin cue generalized to psilocin (the dephosphorylated congener of psilocybin) and to the prototypical indoleamine h...
The hypothesis that the action of hallucinogenic drugs is mediated by a depression of the activity of brain serotonergic (raphe) neurons was tested by examining the behavioral effects of several hallucinogenic drugs while concurrently monitoring the activity of raphe neurons in freely moving cats. LSD produced a dose-dependent decrease in raphe unit activity...
The disruption of the temporal distribution of investigatory responses by rats in a novel hole-board following lysergic acid diethylamide-25 (LSD), as described in a companion paper (Geyer and Light, 1979), was found to be a characteristic effect of a variety of hallucinogens. Similar effects were produced by indoleamine hallucinogens, such as LSD, N,N-dimet...
In the course of examining the complete dose-response relationship for the behavioral effects of LSD in the cat, we discovered that, in addition to large increases in investigatory and hallucinatory-like responses, two behaviors, not previously reported, are emitted with a high probability under LSD. Beginning from a baseline of essentially zero in saline-tr...
