Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hallucinogens”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1979

A characteristic effect of hallucinogens on investigatory responding in rats.

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-dimethyltryptamine, and psilocin, and by phenylethylamine hallucinogens, such as mescaline or 2,5-dimethoxy-4-methylamphetamine (DOM). Congeners of DOM that are inactive in humans had no significant effects. Furthermore, of a variety of other psychoactive drugs tested, only apomorphine produced an effect similar to that of the hallucinogens. These results suggest that a simple behavioral measure of exploration in a hole-board may provide a useful animal model with which to examine the common effects of hallucinogens.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1991

Choroid plexus epithelial cells in primary culture: a model of 5HT1C receptor activation by hallucinogenic drugs.

Behavioral, electrophysiological and biochemical evidence suggest that the 5HT2 receptor plays a role in the action of hallucinogenic agents. Considering the structural and functional similarities between the 5HT2 and 5HT1C receptors, we hypothesized that the 5HT1C receptor may also be an important site of action of hallucinogens. The present manuscript evaluates this hypothesis by examining the properties of hallucinogens in the phenalkylamine and indolealkylamine classes at 5HT1C receptors. Epithelial cells isolated from the rat choroid plexus have a high density of 5HT1C receptors linked to phosphoinositide hydrolysis. Comparison of the actions of drugs in cultured cells and whole choroid plexus confirmed that the cell culture system can serve as an in vitro model of 5HT1C receptor activation. 2,5-Dimethoxy-4-bromoamphetamine (DOB), 2,5-dimethoxy-4-methylamphetamine (DOM), 2,5-dimethoxy-4-iodoamphetamine (DOI) and 3,4-methylenedioxyamphetamine (MDA) were evaluated. The rank order of potency to activate 5HT1C receptors [(-)DOB greater than (+/-) DOI greater than (+)DOB greater than (-)DOM much greater than (-)MDA greater than (+) MDA] was consistent with the rank order of effective behavioral doses in rats and humans. The indolealkylamine hallucinogen, 5-methoxy-N,N-dimethyltryptamine was also a 5HT1C receptor agonist, as is the primary amine, 5-methoxytryptamine. These data, combined with previous studies showing that (+)LSD potently activates 5HT1C receptors, suggest that future investigations of the mechanism of action of hallucinogens should consider the role of 5HT1C receptors in addition to the more commonly investigated 5HT2 receptors.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1995

Comparative behavioural and neurochemical studies with a psychomotor stimulant, an hallucinogen and 3,4-methylenedioxy analogues of amphetamine.

Spontaneous behaviours were assessed in freely moving rats after treatment with equimolar doses of drugs that share a basic amphetamine structure. The drugs used included a psychomotor stimulant [(+)-amphetamine (AMPH)], an hallucinogen [para-methoxyamphetamine (PMA)] and the entactogens 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxy-N-ethylamphetamine (MDE). A detailed analysis of the frequency and duration of 30 different behaviours and the temporal organization of the behaviours was conducted in addition to measuring motor activity with an automated device. Levels of the biogenic amines and their acid metabolites in discrete brain regions and brain drug levels were also obtained. The automated motor activity measures discriminated among entactogens, the stimulant and the hallucinogen, but failed to distinguish between the hallucinogen and vehicle. Principal components analysis and cluster analysis of the frequencies and durations of the behaviours did not improve the classification of the drugs over the automated motor activity measures. Only the cluster analysis of the transitions between individual behaviours succeeded in differentiating the drug classes from each other and from vehicle treatment. All the behavioural measures classified one entactogen (MDE) as an hallucinogen. Cortical 5-hydroxytryptamine (5-HT) measures grouped MDE with the other entactogens but did not distinguish AMPH from vehicle. However, striatal dopamine measures differentiated AMPH from vehicle treatment. Variations in the durations of behavioural effects across drugs were associated with large differences in drug levels 3 h after injection. Although the neurochemical data provided a classification system that most closely parallels human subjective effects of these drugs, both the neurochemical and the behavioural measures supported the existence of an entactogen class distinct from a psychomotor stimulant and an hallucinogen.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, -HT(2B) and 5-HT2C receptors.

Since the classical hallucinogens were initially reported to produce their behavioral effects via a 5-HT2 agonist mechanism (i.e., the 5-HT2 hypothesis of hallucinogen action), 5-HT2 receptors have been demonstrated to represent a family of receptors that consists of three distinct subpopulations: 5-HT2A, 5-HT2B, and 5-HT2C receptors. Today, there is greater support for 5-HT2A than for 5-HT2C receptor involvement in the behavioral effects evoked by these agents. However, with the recent discovery of 5-HT2B receptors, a new question arises: do classical hallucinogens bind at 5-HT2B receptors? In the present study we examined and compared the binding of 17 phenylisopropylamines at human 5-HT2A, 5-HT2B, and 5-HT2C receptors. Although there was a notable positive correlation (r>0.9) between the affinities of the agents at all three populations of 5-HT2 receptors, structural modification resulted only in small differences in 5-HT2B receptor affinity such that the range of affinities was only about 50-fold. As with 5-HT2A and 5-HT2C receptor affinity, there is a significant correlation (r>0.9, n=8) between 5-HT2B receptor affinity and human hallucinogenic potency. Nevertheless, given that 5-HT2A and 5-HT2A/2C antagonists - antagonists with low affinity for 5-HT2B receptors - have been previously shown to block the stimulus effects of phenylisopropylamine hallucinogens, it is likely that 5-HT2A receptors play a more prominent role than 5-HT2B and 5-HT2C receptors in mediating such effects despite the affinity of these agents for all three 5-HT2 receptor subpopulations.

Amphetamines↗
PubMed1989

Hallucinogenic drugs are partial agonists of the human platelet shape change response: a physiological model of the 5-HT2 receptor.

We have assayed several phenylalkylamine and indolealkylamine hallucinogens, as well as structurally similar nonhallucinogens, for their effect on human platelet shape change, a physiological model for the central serotonergic 5-HT2 receptor. The hallucinogenic drugs lysergic acid diethylamide (LSD-25), N,N-dimethyltryptamine (N,N-DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), 4-iodo-2,5-dimethoxyphenylisopropylamine (DOI), bufotenine, and mescaline all showed a characteristic 5-HT2 partial agonist effect on platelet shape change. Nonhallucinogens with structural similarity to hallucinogens did not share this profile. Lisuride, methysergide, and lysergic acid showed antagonism of 5-HT-induced shape change, but none were shape change agonists. Other "psychoactive" or mood-altering drugs (cocaine, amphetamine, phencyclidine) showed poor antagonism of 5-HT-induced platelet shape change. This work refines recent ideas that some of the behavioral effects of LSD-type hallucinogens in humans are due to their actions at 5-HT2 receptors and suggests that these hallucinogens are partial 5-HT2 agonists.

Blood Platelets↗
PubMed1981

Lack of specificity of an animal behavior model for hallucinogenic drug action.

It has been proposed recently that the occurrence of drug-induced limb-flicking (LF) and abortive grooming (AG) in cats can serve as a viable animal behavior model for the actions of hallucinogens in humans. If this is the case, such behaviors should occur reliably following the administration of drugs that produce hallucinations in humans and should not occur after administration of other, non-hallucinogenic drugs--a hypothesis that was examined in the present experiment. The frequency of LF and AG were observed in 12 cats which were given a wide range of doses of the potent hallucinogen, d-LSD (0.01-0.16 mg/kg), as well as several other compounds. The results showed that three non-hallucinogenic agents which are related to LSD in various ways, the ergot derivative lisuride, the serotonin agonist, quipazine, and the dopamine agonist, apomorphine, significantly increased LF frequency. Lisuride and quipazine also caused AG. Cocaine did not elicit either behavior. Thus, it was concluded that the proposed model cannot be regarded as specific to hallucinogenic drugs. In addition, the frequency of these behaviors, as well as their reliability and robustness, were shown to be party dependent on the environment in which observation occurs.

Animals↗
PubMed1985

The 5HT2 antagonist pirenperone reverses disruption of FR-40 by hallucinogenic drugs.

Indolealkylamine and phenethylamine hallucinogens disrupted responding maintained under a fixed-ratio 40 (FR-40) schedule of reinforcement. LSD, DMT, mescaline and DOM produced dose-dependent decreases in number of reinforcers and increases in 10-sec periods of non-responding (pause-intervals). The 5HT agonist quipazine, as well as the LSD congener lisuride, altered response patterns in a similar manner. The effects of these drugs were examined after pretreatment with pirenperone, an antagonist with specificity toward the 5HT2 receptor with reference to the 5HT1 receptor. The dose-response curves for the phenethylamine hallucinogens were shifted significantly to the right and to a greater degree than were those for the indolealkylamine hallucinogens. Pirenperone also antagonized the effects of quipazine to a degree similar to that observed with the phenethylamine-type hallucinogens. Pirenperone did not significantly shift the dose-response pattern to lisuride. These data suggest that the behavioral disruption induced by these hallucinogens and quipazine relates at least in part to an effect on 5HT2 receptors, while the effects of lisuride do not involve a significant interaction at the 5HT2 receptor.

Animals↗
PubMed1989

LSD and other related hallucinogens elicit myoclonic jumping behavior in the guinea pig.

1. We evaluated the behavioral response of guinea pigs to hallucinogenic agents in order to characterize the response of this species to a variety of known hallucinogenic drugs. 2. The systemic injection of LSD in the guinea pig elicited a "myoclonic-like" response the frequency of which was dose-dependent. This behavior exhibited rapid tolerance which was more prominent at higher doses. 3. Subacute mescaline pretreatment reduced the myoclonic response to LSD suggesting cross-tolerance. 4. Mescaline, DOM, TMA, DMA and 5 Me-ODMT also elicited myoclonus in a dose-dependent manner and in potency ratios which approximate the human experience for hallucinogenic activity. 5. Brom-LSD failed to induce myoclonus. 6. Since the myoclonic response of the guinea pig shares a number of pharmacologic characteristics with the human hallucinogenic event, this species may be useful in the study of hallucinogenic compounds.

Animals↗
PubMed1996

The psychopharmacology of hallucinogens.

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 controversy, including the history of hallucinogens, epidemiology of current hallucinogen abuse, the association of LSD use with prolonged psychoses and hallucinogen persisting perception disorder, and the efforts to demonstrate the drug's therapeutic efficacy. Human subject ramifications in hallucinogen experimentation are discussed. Future lines of research are suggested in human, animal, and tissue culture paradigms.

Hallucinogens↗
PubMed1998

Investigation of hallucinogenic and related beta-carbolines.

Certain beta-carbolines are known to be hallucinogenic in humans, and several produce stimulus effects in animals similar to those of the classical hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). Classical hallucinogens bind at 5-HT2 serotonin receptors and these receptors are thought to play a role in their mechanism of action. In the present study, we examined the binding of 15 beta-carbolines at rat 5-HT2A and 5-HT2C receptors. Affinities (Ki values) of the beta-carbolines ranged from about 100 nM to greater than 10,000 nM depending upon the degree of saturation of the pyridyl ring, and upon the presence and location of methoxy substituents in the benzenoid ring. In a further study, six rats were trained to discriminate the hallucinogenic beta-carboline harmaline (3.0 mg/kg, i.p.) from vehicle using a VI-15s schedule of reinforcement. This represents the first time a hallucinogenic beta-carboline has been used as a training drug in a drug discrimination study. Administration of DOM to the harmaline-trained animals resulted in 76% harmaline-appropriate responding at 1.25 mg/kg DOM and disruption of behavior at a higher dose. Taken together, the results of the present investigation demonstrate that: (a) certain beta-carbolines bind at 5-HT2 receptors; (b) that harmaline serves as a training drug at 3.0 mg/kg in drug discrimination studies with rats as subjects; and that (c) there is some similarity between the stimulus effects produced by harmaline and DOM.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1999

Serotonin and hallucinogens.

This brief review traces the serotonin (5-HT) hypothesis of the action of hallucinogenic drugs from the early 1950s to the present day. There is now converging evidence from biochemical, electrophysiological, and behavioral studies that the two major classes of psychedelic hallucinogens, the indoleamines (e.g., LSD) and the phenethylamines (e.g., mescaline), have a common site of action as partial agonists at 5-HT2A and other 5-HT2 receptors in the central nervous system. The noradrenergic locus coeruleus and the cerebral cortex are among the regions where hallucinogens have prominent effects through their actions upon a 5-HT2A receptors. Recently, we have observed a novel effect of hallucinogens--a 5-HT2A receptor-mediated enhancement of nonsynchronous, late components of glutamatergic excitatory postsynaptic potentials at apical dendrites of layer V cortical pyramidal cells. We propose that an effect of hallucinogens upon glutamatergic transmission in the cerebral cortex may be responsible for the higher-level cognitive, perceptual, and affective distortions produced by these drugs.

Animals↗
PubMed1970

Steric and electronic relationships among some hallucinogenic compounds.

Stereochemical considerations and total valence electron calculations suggest congruities among the ostensibly dissimilar hallucinogenic compounds, D-lysergic acid diethylamide (LSD), indolcalkylamines, and methoxylated amphetamines. In LSD the aromatic benzene ring A and the N-6 nitrogen are essential for hallucinogenic activity; these sites may react with the receptor. The conformations of amphetamines and indolealkylamines at the receptor are such that the aromatic benzene ring lies like ring A of LSD and the alkylamino nitrogen lies like the N-6 of LSD. Ring A may interact with the receptor by forming a pi-molecular complex, as suggested by the correlation between hallucinogenic activity and energy of the highest occupied molecular orbital (E(H)) of congeneric series. The N-6 nitrogen of LSD and the sterically congruent nitrogen of the other hallucinogenic compounds may react with the receptor by forming a donor acceptor complex of the n-pi(*) or n-sigma(*) type. Other portions of the hallucinogenic molecules confer a favorable E(H): these include the methoxy and hydroxyl groups of the amphetamines (and mescaline), and the indolealkylamines; and the pyrrole ring of LSD and the indolealkylamines.

Amphetamine↗
PubMed1998

Is the use of ecstasy and hallucinogens increasing? Results from a community study.

UNLABELLED: This report presents findings of a community survey of 3,021 adolescents and young adults aged 14-24 years in Munich, Germany, carried out to determine the prevalence of use and abuse of and dependence on ecstasy, amphetamines and hallucinogens. The response rate was 71%. RESULTS: (1) In 1995, 4% of the male and 2.3% of the female respondents aged 14-24 reported the use of ecstasy. Ecstasy-related substances (amphetamines and chemically related substances) were reported by 3.6% of men and 1.6% of women. Hallucinogens were reported slightly less frequently by 3% of men and about 2% of women (LSD combined with others). (2) Compared to findings from a 1990 survey this constitutes a substantial, at least twofold, increase in consumption rate of both types of substances. (3) Among lifetime users of both ecstasy and related substances as well as hallucinogens about two thirds could be regarded as regular users. (4) The prevalence of DSM-IV abuse and dependence on ecstasy and related substances is about 1%, identical to rates of hallucinogen abuse and dependence. Findings also point to a significant dependence potential for both substances. (5) Furthermore, considerable overlap between the two substances was found. CONCLUSION: Our study suggests a substantial increase in both the use of ecstasy and related substances as well as hallucinogens. The data further suggest that the increase is strongest in younger age groups, but the risk of first use of these substances continues to be present up to the age of 24 years. The higher proportion of women contributing to this increase is noteworthy.

Adolescent↗
PubMedDate not supplied

[Neurological syndromes associated with the ingestion of plants and fungi with a toxic component (II). Hallucinogenic fungi and plants, mycotoxins and medicinal herbs].

INTRODUCTION: A wide range of fungi and medicinal herbs, rich in hallucinogenic substances and widely used for mystic and medicinal purposes, can give rise to neurotoxic symptoms. DEVELOPMENT: We review the toxic syndromes that can arise from the ingestion of hallucinogenic fungi, cacti and plants, together with descriptions of cases of acute poisoning resulting from the use of medicinal herbs and from foodstuffs that are contaminated by mycotoxins. A series of different psychedelic fungi belonging to the Psilocybe, Panaeolus and Stropharia genera contain hallucinogenic alkaloids such as psilocybin. Some of the most notable plants displaying hallucinogenic and sedative properties are Papaver somniferum, Erytroxylum sp. and Cannabis sativa. Infusions of ayahuasca are obtained from the lianas and roots of different plants with psychoactive properties, such as Banisteriopsis caapi and Psychotria viridis, which contain alkaloids derived from tryptamine and from the beta carboline harmala. Peyote, a cactus rich in mescaline, and Claviceps purpurea (a fungus rich in LSD) are strong hallucinogens. We also examine ergotism and mycotoxicosis from Arthrinium sp. Poisoning from mycotoxin containing moulds on sugar cane can give rise to encephalopathy and late dystonia. Some of the more noteworthy medicinal plants for which neurological toxicity has been reported are Hypericum perforatum, kava kava (Piper methysticum), Aconitum sp. and Callilepis laureola. CONCLUSIONS: Because of the increasingly more widespread consumption of herbs and fungi and their potentially neurotoxic effects, in clinical practice there is a need to be aware of the neurological syndromes deriving from their use.

Administration, Oral↗
PubMed1992

[Consumption of psilocybin-containing hallucinogenic mushrooms by young people].

The aim of this questionnaire survey was to investigate the extent of hallucinogenic mushroom consumption among students from a high school in the county of Aarhus, Denmark and among students at the University of Aarhus and students from the Danish school of journalism in Aarhus, Denmark. 3% of the high school students had used psilocybine-containing mushrooms as a hallucinogen. Only 1% had experience with LSD. Of the students at the University of Aarhus, and students from the Danish school of journalism in Aarhus, 333 persons (83%) returned the anonymous questionnaire. 9% had experience with hallucinogenic psilocybine containing mushrooms while only 2% had LSD experience. The use of hallucinogenic mushrooms was surprisingly high. This suggest that mushrooms are the most commonly used hallucinogenic substance in Denmark and that the use has exceeded that of LSD. Compared to non-users mushrooms users had significant more friends with mushroom experience. Furthermore, the study shows that the intention to use mushroom is commoner in persons who have friends with HPS experience. We find that the use of mushroom takes place in minor groups known to each other. Compared to non-users, mushroom-users are significant more experienced with marijuana and other substances. Unfortunately, our data do not permit us to show whether mushroom users are more inclined to try other drugs or whether persons with a high drug experience use mushrooms as well. Further investigation on the subject is recommended.

Adolescent↗
PubMed2006

The adverse effects of hallucinogens from intramural perspective.

UNLABELLED: Very recently, after a long-lasting, worldwide moratorium on research of hallucinogenic agents, a good number of advanced countries have been revising their position, and start to approve testing the physiological and therapeutic effects of hallucinogens in human subjects. The purpose of this article is to review safety information available in the literature on hallucinogen use, and sort out those data from the reported complications of their abuse. Because of prohibitory regulations of the last 35 years, there are difficulties in achieving this kind of evaluation. Our approach has to be broad, and at times retrospective, in contrast to the well-controlled, focused, prospective design of the premarketing trials of legal drugs. The article summarizes the analyses in anticipation of supportive regulatory changes for the use of hallucinogens in well controlled studies and strictly supervised clinical trials. KEYWORDS: adverse effects, ayahuasca, N,N-dimethyltryptamine, hallucinogenic agents, ibogaine, lysergic acid diethylamide, N-methyl-3,4-methylenedioxyamphetamine, psilocybin, therapeutic use.

Drug Interactions↗
PubMedDate not supplied

Do classical hallucinogens act as 5-HT2 agonists or antagonists?

There has long been controversy over whether the classical hallucinogens behave as serotonin (5-hydroxytryptamine [5-HT]) agonists or antagonists. Now that there is evidence that many of the effects produced by these agents involve a 5-HT2 mechanism, a new controversy has arisen: do they behave as 5-HT2 agonists or as 5-HT2 antagonists? A review of the existing literature suggests that where a 5-HT2 mechanism has been implicated (such as in phosphoinositide turnover, contraction of certain smooth muscle, rat-paw edema, head-twitch behavior, discriminative stimulus effects, hyperthermia, platelet aggregation, and in various other effects), the classical hallucinogens are most likely acting via an agonist, or at least via a partial agonist, mechanism. A partial agonist mechanism would explain why classical hallucinogens occasionally appear to act as antagonists. Furthermore, in certain instances, and due to their nonselective nature, indolealkylamine hallucinogens may be able to modulate their own 5-HT2-mediated effects by simultaneous costimulation of 5-HT1 receptors. These agents can also modulate the agonist effects of other, more selective 5-HT2 agonists. Nevertheless, it is very unlikely that the classical hallucinogens are acting as pure 5-HT2 antagonists.

Animals↗
PubMed1994

Autoradiographic approaches to studying hallucinogens or other drugs.

Autoradiography provides a powerful tool whereby an investigator can study different aspects of hallucinogens in the laboratory and the clinic. Receptor autoradiography can be performed in vitro to map binding sites of hallucinogens or to assess potential neurotoxic sequelae of hallucinogen treatments. Similarly, such studies can be performed in vivo to the same end. Receptor autoradiography can be performed in a clinical setting using PET to study acute dynamic binding properties of hallucinogens in humans or for long-term followup studies. In vivo autoradiography of metabolic markers appears useful in the laboratory and potentially in the clinic to help researchers understand not only where, but also the manner in which, the brain responds functionally to hallucinogens.

Animals↗