Sleep paralysis is a state of involuntary immobility occurring at sleep onset or offset, often accompanied by uncanny "ghost-like" hallucinations and extreme fear reactions. I provide here a neuropharmacological account for these hallucinatory experiences by evoking the role of the serotonin 2A receptor (5-HT2AR). Research has shown that 5-HT2AR activation c...
Psilocin (3-[2-(dimethylamino)ethyl]-1H-indol-4-ol) is a hallucinogenic component of the Mexican mushroom Psilocybe mexicana and a skeletal serotonin (5-HT) analogue. Psilocin is the active metabolite of psilocybin (3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate). In the present study, we examined the effects of systemically administered psilo...
It has been observed that agents with agonist activity at 5-HT2A receptors prevent neurotoxicity induced by the non-competitive NMDA antagonist, dizocilpine (MK-801). Subsequent behavioral studies reported complete antagonism by LSD and DOM of the stimulus effects of the related NMDA antagonist, phencyclidine [PCP]. The present study sought to extend those o...
Activation of 5-HT(2A) receptors is thought to mediate the hallucinogenic effects of LSD. Nevertheless, in a previous report we provided evidence that a delayed temporal phase of the behavioral pharmacology of LSD is mediated by D(2)-like dopamine receptor stimulation. In this study rats were trained to discriminate LSD with either a 30 min preinjection time...
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...
Hallucinogenic psilocybin is known to alter the subjective experience of time. However, there is no study that systematically investigated objective measures of time perception under psilocybin. Therefore, we studied dose-dependent effects of the serotonin (5-HT)2A/1A receptor agonist psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) on temporal processin...
The modulating effects of serotonin on dopamine neurotransmission are not well understood, particularly in acute psychotic states. Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psiloc...
Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone, but were increased by the dopamine antag...
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...
To date, there is no doubt that dopamine plays a key role in the behavioural disorders associated with schizophrenia. However, dopamine is not the only neurotransmitter involved in this syndrome, as it interacts with many neuronal systems in brain. Of special interest is the interaction between dopaminergic and serotoninergic systems with evidence from pharm...
In order to further evaluate the extent to which particular 5-HT receptor subtypes (5-HT1, 5-HT2) might be involved in the behavioral effects of hallucinogenic drugs, rats were trained to discriminate mescaline (10 mg/kg i.p.) from saline and were given substitution (generalization) and combination (antagonism) tests with putatively selective serotonergic an...
Two aspects of the complexities of the mode of action of drugs are described. One is the criteria and pitfalls of defining the interaction with specific receptors. The other is the need to consider each of the pharmacological effects of a drug as a concatenation of receptor events, because it has become clear that each drug may have substantial affinity for ...
The dopaminergic actions of various hallucinogenic drugs were assessed by examining their effects on turning behavior in rats with unilateral 6-hydroxydopamine lesions of the nigro-striatal pathway. LSD (0.1 and 0.2 mg/kg) produced strong contralateral turning, indicating that it is a potent dopamine receptor agonist, while BOL (5 mg/kg), a non-hallucinogeni...
Investigations were carried out on the interactions of the hallucinogenic drug, D-lysergic acid diethylamide (D-LSD), and other serotonin antagonists with catecholamine-sensitive adenylate cyclase systems in cell-free preparations from different regions of rat brain. In equimolar concentration, D-LSD, 2-brono-D-lysergic acid diethylamide (BOL), or methysergi...
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