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PubMed1989

Hallucinogenic and stimulatory amphetamine derivatives: fingerprinting DOM, DOI, DOB, MDMA, and MBDB by spectral analysis of brain field potentials in the freely moving rat (Tele-Stereo-EEG).

Telemetric recordings of field potentials from frontal cortex, hippocampus, striatum and reticular formation of freely moving rats were analysed before and after injection of the enantiomeric hallucinogenic amphetamine derivatives R-DOB [(-)-1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane], R-DOM [(-)-1-(2,5-dimethoxy-4-methylphenyl)-2-amino-propane] and R-DOI [(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] as well as the nonhallucinogenic amphetamine derivatives S-MBDB [(+)-N-methyl-1-(1,3-benzodioxol-5-yl)butanamine] and S-MDMA [(+)-3,4-methylenedioxymethamphetamine] and S-(+)-amphetamine. The frequency analysis of the field potentials revealed a clearcut difference between them. The spectral patterns emerging after injection of the non-hallucinogens were characterized by a general decrease of power, the changes in the alpha2 and delta band being the most prominent, whereas only after the application of the hallucinogenic compounds was a contrasting increase of power observed in the alpha 1 frequency band, especially in the striatum. As increases in alpha 1 power have been correlated in the same pharmacological model to serotonergic control mechanisms, the results are in line with the hypothesis that 5-HT2 receptors, predominantly occurring in the striatum, might be involved in the hallucinogenic action of drugs.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1978

Screening hallucinogenic drugs II. Systematic study of two behavioral tests.

The effects of hallucinogenic and nonhallucinogenic drugs were studied on two behavioral tests: (1) discriminated Sidman avoidance, using modified Bovet-Gatti profiles, which have been proposed as specific in detecting hallucinogenic activity and (2) a drug discrimination experiment. By the first method, the "hallucinogenic profile" was obtained with both hallucinogenic and nonhallucinogenic drugs and, at least as used here, was not a suitable screening method. In the drug discrimination experiment, data from the present study along with other available evidence suggest the potential value of this method for drug screening procedures.

Animals↗
PubMed1995

Role of 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. II: Reassessment of LSD false positives.

In the context of animal studies of hallucinogens, an LSD-false positive is defined as a drug known to be devoid of hallucinogenic activity in humans but which nonetheless fully mimics LSD in animals. Quipazine, MK-212, lisuride, and yohimbine have all been reported to be LSD false positives. The present study was designed to determine whether these compounds also substitute for the stimulus effects of the more pharmacologically selective hallucinogen (-)DOM (0.56 mg/kg, 75-min pretreatment time). The LSD and (-)DOM stimuli fully generalized to quipazine (3.0 mg/kg) and lisuride (0.2 mg/kg), but only partially generalized to MK-212 (0.1-1.0 mg/kg) and yohimbine (2-20 mg/kg). In combination tests, pirenpirone (0.08 mg/kg), a compound with both D2 and 5-HT2A affinity, blocked the substitution of quipazine and lisuride for the (-)DOM stimulus. Ketanserin (2.5 mg/kg), an antagonist with greater than 1 order of magnitude higher affinity for 5-HT2A receptors than either 5-HT2C or D2 receptors, also fully blocked the substitution of these compounds for the (-)DOM stimulus, while the selective D2 antagonist thiothixene (0.1-1.0 mg/kg) failed to block the substitution of lisuride for the (-)DOM stimulus. These results suggest that quipazine and lisuride substitute for the stimulus properties of the phenylalkglamine hallucinogen (-)DOM via agonist activity at 5-HT2A receptors. In addition, these results suggest that 5-HT2A agonist activity may be required, but is not in itself sufficient, for indolamine and phenylalkglamine compounds to elicit hallucinations in humans. Finally, it is concluded that MK-212 and yohimbine are neither LSD nor (-)DOM false positives.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMedDate not supplied

Clinical features and management of intoxication due to hallucinogenic drugs.

Hallucinogenic drugs are unique in that they produce the desired hallucinogenic effects at what are considered non-toxic doses. The hallucinogenic drugs can be categorised into 4 basic groups: indole alkaloid derivatives, piperidine derivatives, phenylethylamines and the cannabinols. The drugs reviewed include lysergic acid diethylamide (LSD), phencyclidine (PCP), cocaine, amphetamines, opiates, marijuana, psilocybin, mescaline, and 'designer drugs.' Particularly noteworthy is that each hallucinogen produces characteristic behavioural effects which are related to its serotonergic, dopaminergic or adrenergic activity. Cocaine produces simple hallucinations, PCP can produce complex hallucinations analogous to a paranoid psychosis, while LSD produces a combination of hallucinations, pseudohallucinations and illusions. Dose relationships with changes in the quality of the hallucinatory experience have been described with amphetamines and, to some extent, LSD. Flashbacks have been described with LSD and alcohol. Management of the intoxicated patient is dependent on the specific behavioural manifestation elicited by the drug. The principles involve differentiating the patient's symptoms from organic (medical or toxicological) and psychiatric aetiologies and identifying the symptom complex associated with the particular drug. Panic reactions may require treatment with a benzodiazepine or haloperidol. Patients with LSD psychosis may require an antipsychotic. Patients exhibiting prolonged drug-induced psychosis may require a variety of treatments including ECT, lithium and l-5-hydroxytryptophan.

Hallucinogens↗
PubMed2003

The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like discriminative effects in rhesus monkeys.

RATIONALE: Salvinorin A is the active component of the hallucinogenic plant Salvia divinorum. The potential mode of action of this hallucinogen was unknown until recently. A recent in vitro study detected high affinity and efficacy of salvinorin A at kappa-opioid receptors. It was postulated that salvinorin A would produce discriminative stimulus effects similar to those of a high efficacy kappa-agonist (U69,593) in rhesus monkeys. METHODS: Monkeys were previously trained to discriminate U69,593 (0.0056 or 0.013 mg/kg; s.c.) from vehicle in a food-reinforced FR20 (fixed ratio 20) operant conditioning procedure (n=3). The ability of salvinorin A to cause generalization (> or =90% U69,593-appropriate responding) was examined in time course and cumulative dose-effect curve studies. RESULTS: All subjects dose-dependently emitted full U69,593-appropriate responding after salvinorin A (0.001-0.032 mg/kg, SC). Salvinorin A-induced generalization started 5-15 min after injection, and dissipated by 120 min. The opioid antagonist quadazocine (0.32 mg/kg) fully blocked the effects of salvinorin A. The kappa-selective antagonist GNTI (1 mg/kg; 24 h pretreatment) did not cause significant antagonism of the effects of salvinorin A (GNTI, under these conditions, was only effective as an antagonist in two of three monkeys). The NMDA antagonist ketamine (0.1-3.2 mg/kg) was not generalized by any subject, indicating that not all compounds that produce hallucinogenic or psychotomimetic effects in humans are generalized by subjects trained to discriminate U69,593. CONCLUSIONS: The naturally occurring hallucinogen salvinorin A produces discriminative stimulus effects similar to those of a high efficacy kappa-agonist in non-human primates.

Animals↗
PubMed1986

Effect of hallucinogens on spontaneous and sensory-evoked locus coeruleus unit activity in the rat: reversal by selective 5-HT2 antagonists.

As previously reported, systemic administration of the hallucinogens D-lysergic acid diethylamide (LSD) (5-10 micrograms/kg) and mescaline (2 mg/kg) in the anesthetized rat produced a decrease in spontaneous activity but, paradoxically, facilitated activation of locus coeruleus (LC) neurons by sciatic nerve stimulation. In the present study, the hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) (20-80 micrograms/kg) was found to have similar effects. Systemic administration of the selective 5-HT2 antagonists LY 53857 (0.02-0.8 mg/kg) and ritanserin (0.1-0.3 mg/kg) completely reversed both actions of the hallucinogens on the LC. In contrast, LY 53857 did not reverse the effects of (+)-amphetamine (0.5 mg/kg) on the spontaneous or sensory-evoked activity of the LC. These results suggest that the common actions of indoleamine and phenethylamine hallucinogens displayed in the LC are mediated via 5-HT2 receptors; however, these receptors appear to be located outside the LC itself.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1982

Anorexia and hyperphagia produced by five pharmacologic classes of hallucinogens.

The acute actions of five prototype hallucinogens administered SC on food consumption in 23 hr food deprived dogs were compared with the anorexic effect of d-amphetamine and the hyperphagic effect of sodium pentobarbital. Comparisons were made on the basis of dose-response relationships. Among the hallucinogens decreasing food intake, both LSD and atropine produced substantial anorexia, but the slopes of their dose-response curves were clearly different from d-amphetamine. Phencyclidine and the opioid SKF 10,047 suppressed food intake also; their individual dose-effect curves were parallel to the amphetamine curve, although both were less potent. Of the hallucinogens tested, only delta-9-tetrahydrocannabinol (delta 9-THC) stimulated food consumption, and though it was less potent, it resembled pentobarbital both qualitatively and by having a parallel dose-response curve. The appetitive responses are discussed in relation to other pharmacologic actions of these hallucinogens in the dog, and consideration is given to the possible modes of action for phencyclidine- and SKF 10,047-induced anorexia.

Amphetamine↗
PubMed1986

Comparative effects of LSD and lisuride: clues to specific hallucinogenic drug actions.

This review compares the effects of LSD and its nonhallucinogenic congener lisuride hydrogen maleate (LHM) on various biochemical, behavioral and electrophysiological indices of neuronal function. The underlying rationale is that any differences between the effects of LSD and LHM might be relevant to neuronal actions which are unique and specific to hallucinogenic drugs and thereby provide clues to the neurobiological substrates of hallucinogenesis. In biochemical studies, LHM appears to be very similar to LSD with respect to its actions on monoaminergic (5-HT, DA, NE) systems. The major difference between the two ergots appears quantitative in nature since LHM is more potent than LSD, especially on DA neurochemistry. Needed at the present time are additional comparative studies of LSD and LHM with respect to other biochemical measures, for example on the release of 5-HT and DA and comparisons at more molecular levels such as subcellular compartmentation. Also necessary are more intensive regional analyses on specific subpopulations of 5-HT and DA systems (mesolimbic, mesostriatal and mesocortical). Behavioral studies are relatively uniform in their characterization of the greater DA-ergic activity of LHM as compared to LSD. In particular, the drug discrimination (DD) procedure has indicated a more specific interaction of LSD with 5-HT neuronal systems as compared to LHM and has successfully differentiated the relative roles of 5-HT and DA systems in the behavioral effects of LSD and LHM. Electrophysiological studies have been consistent with both biochemical and behavioral findings with respect to the much greater effect of LHM on DA receptors. In fact, the effects of LSD on DA-containing neurons are both weak and heterogeneous, again indicating a need for more detailed analyses of specific DA projection systems. The greater potency of LHM than LSD on 5-HT containing dorsal raphe neurons has lessened the attractiveness of the once popular theory that hallucinogenic efficacy is related to diminution of impulse flow in 5-HT systems but has also spawned greater interest in the possible role of postsynaptic 5-HT receptors in hallucinogenic drug action. Thus far, the most interesting finding is the ability of LSD and other hallucinogens, but not LHM, to potentiate an excitomodulatory effect of 5-HT in the facial motor nucleus. If such a phenomenon occurs more generally in the CNS, the importance of this finding will be greatly enhanced. Preliminary data is presented which suggests that LSD may also induce such an effect in a limbic forebrain structure, the nucleus accumbens.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗
PubMed1996

Plant hallucinogens: springboards for psychotherapeutic drug discovery.

Medicinal chemists have traditionally looked to the biosynthetic diversity found in nature to provide structural templates for the development of novel therapeutic agents, and the field of hallucinogen chemistry is similar to other fields in this respect. Even LSD, for many psychopharmacologists the prototype hallucinogen, is not itself a natural compound but rather is a semisynthetic analogue of alkaloids found in plants and fungi. A similar statement could be made about the other major structural classes of hallucinogenic agents: the phenylethylamine derivatives, the tryptamine derivatives, and the beta-carboline derivatives. In each case, compounds occurring naturally in some plant, usually associated with a long tradition of ethnomedical or ceremonial use, have been the starting point for the synthesis of numerous analogues. Some of these, such as the methoxylated amphetamine derivatives, display a pharmacological profile that differs in important respects from their natural product templates. In some instances the analogues have proven to be useful tools in the hands of neurobiologists characterizing the structure and function of brain neurotransmitter systems; in other cases, they have led to the development of new psychopharmacological agents with realized or potential clinical utility. This paper gives a brief historical overview of the role of natural products in the history and development of medicinal chemistry and experimental pharmacology, particularly with respect to the development of psychopharmacology and the discovery of CNS-active agents. It discusses the potential for the discovery of new medications with psychotherapeutic and/or research applications though the investigation of plants and natural compounds with serotonergic activities. Finally, consideration is given to some lesser known plant hallucinogens which may provide further useful leads for psychotherapeutic drug discovery.

Animals↗
PubMed1985

Effects of DOM and DMT in a proposed animal model of hallucinogenic activity.

A previously proposed animal model of lysergic acid diethylamide's (LSD) effects in humans was tested for its applicability to other hallucinogens, 2,5-dimethoxy-4-methyl amphetamine (DOM) and N,N-dimethyltryptamine (DMT). Both "free" and "forced" exploration tests in a behavioral pattern monitor were used to determine the effects of these hallucinogens on the normal tendencies of rats to avoid novel and central areas, respectively. The effects of DOM (0.3-1.0 mg/kg) were quite similar to those previously reported for LSD. Specifically, DOM reduced crossovers, holepokes, and rearings when rats were tested in a novel environment. In a familiar environment, only rearing activity was reduced with minimal effect on ambulation. Like LSD, entries into the central area were reduced in both situations. DOM also produced a dose-dependent reduction of entries into the novel chamber in a free exploration test. Pretreatment with the serotonin (5-HT) antagonist cyproheptadine (1.0 mg/kg), which does not block the psychological effects of hallucinogens in humans, selectively blocked DOM's reduction of rearings without altering DOM's reduction of center entries, crossovers, or holepokes. Like LSD and DOM, DMT (0.5, 1.0, and 2.0 mg/kg) produced a selective reduction of entries into the center region when rats were forced to explore a novel holeboard chamber. All three doses also selectively reduced holepoke responses without affecting crossovers or rearings. In conclusion, enhanced avoidance of novel and central areas appears to be a valid indicator of hallucinogenic activity since LSD, DMT, and DOM all share this property. Conversely, the reduction of rearings produced by LSD and DOM is not a suitable model behavior since the effect is not produced by DMT and cyproheptadine is capable of selectively blocking this effect.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1987

Comparison of stimulants and hallucinogens on shuttle avoidance in rats.

Rats were trained to a high level of performance of a conditioned avoidance response in a shuttlebox to test effects of several classical stimulants in comparison to a variety of hallucinogens. A previously-reported biphasic pattern of effects of mescaline on shuttle avoidance was replicated and extended to 12 other hallucinogens of both phenylethylamine and indolealkylamine classes. Response patterns of hallucinogens could be differentiated from 3 stimulants and from a methoxyamphetamine compound that lacks hallucinogenic activity.

Amphetamines↗
PubMed1990

The major hallucinogens and the central cytoskeleton: an association beyond coincidence? Towards sub-cellular mechanisms in schizophrenia.

There appears to be a remarkably consistent structural and functional relationship between the phenylethylamine hallucinogens and the microtubule inhibitor colchicine. Such a relationship is not sustained in simple form through to the indoleamine hallucinogens and the indole based Vinca alkaloids. However, LSD and the more potent hallucinogens retain the full potential to disrupt the structure of the brain's cytoskeleton indirectly via serotonin and the raphe system. Serotonin appears to have a direct role in regulating and maintaining microtubules and microfilaments. It appears that a second receptor mediated action is required for full hallucinogenic activity. It is deduced that cytoskeletal restraints may have a role in governing central information processing. A theory for the cellular mechanisms of thought disorder and drug induced hallucinations is proposed. Schizophrenia may reflect a subtle disorder of central cytoskeletal function.

Animals↗
PubMed2002

5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens.

The role of 5-HT2A-mediated stimulation of phosphoinositide hydrolysis in the discriminative effects of hallucinogens was investigated in PC12 cells stably expressing the rat 5-HT2A receptor (PC12-5-HT2A cells). The hallucinogenic compounds, D-lysergic acid diethylamide (LSD), (-)2,5-dimethoxy-4-methylamphetamine (DOM), psilocybin, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (MDMT) and N,N-diethyltryptamine (DET), all caused a concentration-dependent increase in the generation of [3H]inositol phosphates. The nonhallucinogenic compounds, 6-fluoro-N,N-diethyltryptamine (6-F-DET), lisuride and quipazine, also displayed significant efficacy in stimulating phosphoinositide hydrolysis, while 2-bromo-lysergic acid diethylamide (BOL), which is not a hallucinogen, did not alter inositol phosphate generation. The beta-carbolines, harmaline and harmane, also did not alter phosphoinositide hydrolysis. Comparison of these results with previous drug discrimination studies indicated the apparent lack of correlation between the degree of substitution in LSD- and DOM-trained animals and efficacy in stimulating phosphoinositide hydrolysis. The present study indicates that 5-HT2A-mediated stimulation of phosphoinositide hydrolysis does not appear to be the sole critical signaling mechanism involved in the discriminative effects of hallucinogens.

Animals↗
PubMed2003

Hallucinogen persisting perception disorder: what do we know after 50 years?

'Flashbacks' following use of hallucinogenic drugs have been reported for decades; they are recognized in DSM-IV as 'Hallucinogen Persisting Perception Disorder (Flashbacks)', or HPPD. We located and analyzed 20 quantitative studies between 1955 and 2001 examining this phenomenon. However, many of these studies were performed before operational criteria for HPPD were published in DSM-III-R, so they are difficult to interpret in the light of current diagnostic criteria. Overall, current knowledge of HPPD remains very limited. In particular (1) the term 'flashbacks' is defined in so many ways that it is essentially valueless; (2) most studies provide too little information to judge how many cases could meet DSM-IV criteria for HPPD; and consequently (3) information about risk factors for HPPD, possible etiologic mechanisms, and potential treatment modalities must be interpreted with great caution. At present, HPPD appears to be a genuine but uncommon disorder, sometimes persisting for months or years after hallucinogen use and causing substantial morbidity. It is reported most commonly after illicit LSD use, but less commonly with LSD administered in research or treatment settings, or with use of other types of hallucinogens. There are case reports, but no randomized controlled trials, of successful treatment with neuroleptics, anticonvulsants, benzodiazepines, and clonidine. Although it may be difficult to collect large samples of HPPD cases, further studies are critically needed to augment the meager data presently available regarding the prevalence, etiology, and treatment of HPPD.

Clinical Trials as Topic↗
PubMed2000

Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors.

Recent electrophysiological studies in our laboratory have demonstrated a physiological interaction between 5-HT(2A) and metabotropic glutamate2/3 (mGlu2/3) receptors in the medial prefrontal cortex. Several behavioral studies have found that phenethylamine hallucinogens with partial agonist activity at 5-HT(2A) receptors induce head shakes when directly administered into the medial prefrontal cortex. The purpose of the present experiments was to examine whether an interaction occurs between mGlu2/3 and 5-HT(2A) receptors on a behavioral level using head shakes induced by phenethylamine hallucinogens as a model of 5-HT(2A) receptor activation. Administration of the mGlu2/3 agonist LY354740 (0.3-10 mg/kg, ip) suppressed head shakes induced by the phenethylamine hallucinogen 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Conversely, administration of the mGlu2/3 antagonist LY341495 (1 mg/kg, ip) enhanced the frequency of DOI-induced head shakes. Taken together, these results raise the possibility that the psychomimetic properties of hallucinogenic drugs may be mediated in part, via increased glutamate release following activation of 5-HT(2A) receptors.

Amino Acids↗
PubMed2006

1-Aminomethylbenzocycloalkanes: conformationally restricted hallucinogenic phenethylamine analogues as functionally selective 5-HT2A receptor agonists.

A series of conformationally restricted analogues of the hallucinogenic phenethylamine 1 (2,5-dimethoxy-4-bromophenethylamine, 2C-B) was synthesized to test several hypotheses concerning the bioactive conformation of phenethylamine ligands upon binding to the 5-HT(2A) receptor. These benzocycloalkane analogues were assayed for their receptor binding affinity and ability to activate downstream signaling pathways, and one exceptional compound was selected for testing in an in vivo drug discrimination model of hallucinogenesis. All compounds were examined in silico by virtual docking into a homology model of the 5-HT(2A) receptor. On the basis of these docking experiments, it was predicted that the R enantiomer of benzocyclobutene analogue 2 would be the most potent. Subsequent chemical resolution and X-ray crystallography confirmed this prediction, as (R)-2 proved to be equipotent to LSD in rats trained to discriminate LSD from saline. Thus, we propose that the conformation of 2 mimics the active binding conformation of the more flexible phenethylamine type hallucinogens. In addition, (R)-2 is one of the most potent and selective compounds yet discovered in the in vivo drug discrimination assay. Further, 2 was found to be a functionally selective agonist at the 5-HT(2A) receptor, having 65-fold greater potency in stimulating phosphoinositide turnover than in producing arachidonic acid release. If hallucinogenic effects are correlated with arachidonic acid production, such functionally selective 5-HT(2A) receptor agonists may lack the intoxicating properties of hallucinogens such as LSD.

Animals↗
PubMed2005

Hallucinogen-induced UP states in the brain slice of rat prefrontal cortex: role of glutamate spillover and NR2B-NMDA receptors.

Psychedelic hallucinogens (eg LSD or DOI) induce disturbances of mood, perception, and cognition through stimulation of serotonin 5-HT2A receptors. While these drugs are not proconvulsant, they have been shown by microdialysis to increase extracellular glutamate in the prefrontal cortex. Electrophysiological studies in the rat prefrontal slice have shown that both LSD and DOI enhance a prolonged, late wave of glutamate release onto layer V pyramidal neurons after an electrical stimulus. Here, we hypothesize that the network activity underlying this UP state involves glutamate spillover from excitatory synapses. To test this hypothesis, we raised the viscosity of the extracellular solution by adding the inert macromolecule dextran (approximately 1 mM) that is known to retard glutamate overflow into the extrasynaptic space. Dextran suppressed the UP state or late excitatory postsynaptic current (EPSC), but neither the fast EPSC, the traditional polysynaptic EPSC, nor a synaptic form of 5-HT2A-mediated transmission (serotonin-induced spontaneous EPSCs). Consistent with the previous work showing that extrasynaptic glutamate transmission in adult depends on NR2B-containing NMDA receptors, we found that NR2B-selective antagonists, ifenprodil and Ro25-6981, also suppressed the late EPSCs. The effect of psychedelic hallucinogens on UP states could be partially mimicked by inhibiting glutamate uptake but only after blocking inhibitory group II metabotropic glutamate receptors. This difference suggests that hallucinogens increase glutamate spillover in a phasic manner unlike glutamate uptake inhibitors. Increases in glutamate spillover have been suggested to recruit synapses not directly in the pathway activated by the electrical stimulus. Such recruitment could account for certain cognitive, affective, and sensory perturbations generated by psychedelic hallucinogens.

Animals↗
PubMed1998

Advances and pathophysiological models of hallucinogenic drug actions in humans: a preamble to schizophrenia research.

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 the limbic cortico-striato-thalamic circuitry may be critical to psychotic symptom formation. To test this hypothesis, psychometric measures and metabolic PET investigations were performed (1) with FDG to elucidate the common neuronal substrates of different hallucinogens, (2) with specific receptor ligands before and after pretreatment with specific receptor antagonists to explore the putative interactions of hallucinogens with various neurotransmitter systems. Our data demonstrate that the neuronal substrate of normal and abnormal thought and behavior is associated with a distributed neuronal network and with multiple interactive neurotransmitter systems. The data also support the view that the hallucinogen challenge paradigm constitutes a powerful tool for elucidating the pathophysiology of neuropsychiatric disorders.

Anesthetics, Dissociative↗