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OPEN Foundation

Effects of mescaline and lysergic acid (d-LSD-25)

April 6, 2006 / Anxiety disorders / PTSD, Cacti / Mescaline, LSD, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , ,

Abstract

The effects of mescaline and lysergic acid were studied in schizophrenic patients. It was found that physiological changes were produced in these patients and that their mental symptomatology was markedly aggravated. The observations made with the above-mentioned drugs on normal individuals were compared with those seen in schizophrenic patients. Mescaline and lysergic acid are drugs that disorganize the psychic integration of a person. This disorganization is much more apparent in schizophrenics than in normals. The diagnostic, prognostic, and therapeutic use of these drugs is also discussed.

Hoch, P. H., Cattell, J. P., & Pennes, H. H. (1952). Effects of mescaline and lysergic acid (d-LSD-25). American Journal of Psychiatry, 108(8), 579-584.,10.1176/ajp.108.8.579

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Acute dose of MDMA (75 mg) impairs spatial memory for location but leaves contextual processing of visuospatial information unaffected

March 1, 2006 / MDMA, Other subjects, Papers, Psychiatry, Psychology, Publications / By / ,

Abstract

Rationale: Research concerning spatial memory in 3,4-methylenedioxymethamphetamine (MDMA) users has presented conflicting results showing either the presence or absence of spatial memory deficits. Two factors may have confounded results in abstinent users: memory task characteristics and polydrug use.

Objectives: The present study aims to assess whether a single dose of MDMA affects spatial memory performance during intoxication and withdrawal phase and whether spatial memory performance after MDMA is task dependent.

Materials and methods: Eighteen recreational MDMA users participated in a double-blind, placebo-controlled, three-way crossover design. They were treated with placebo, MDMA 75 mg, and methylphenidate 20 mg. Memory tests were conducted between 1.5 and 2 h (intoxication phase) and between 25.5 and 26 h (withdrawal phase) post-dosing. Two spatial memory tasks of varying complexity were used that required either storage of stimulus location alone (spatial memory task) or memory for location as well as processing of content or contextual information (change blindness task).

Results: After a single dose of MDMA, the subjects made larger localization errors and responded faster compared to placebo in the simple spatial memory task during intoxication phase. Inaccuracy was not due to increased response speed, as determined by regression analysis. Performance in the change blindness task was not affected by MDMA. Methylphenidate did not affect performance on any of the tasks.

Conclusion: It is concluded that a single dose of MDMA impairs spatial memory for location but leaves processing of contextual information intact.

Kuypers, K. P., & Ramaekers, J. G. (2007). Acute dose of MDMA (75 mg) impairs spatial memory for location but leaves contextual processing of visuospatial information unaffected. Psychopharmacology, 189(4), 557-563. 10.1007/s00213-006-0321-7

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Mechanisms of antiaddictive actions of ibogaine

February 7, 2006 / Addiction, Iboga / Ibogaine, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / ,

Abstract

Ibogaine, an alkaloid extracted from Tabemanthe iboga, is being studied as a potential long-acting treatment for oploid and stimulant abuse as well as for alcoholism and smoking. Studies in this laboratory have used animal models to characterize ibogaine’s interactions with drugs of abuse, and to investigate the mechanisms responsible. Ibogaine, as well as its metabolite, noribogaine, can decrease both morphine and cocaine self-administration for several days in some rats; shorter-lasting effects appear to occur on ethanol and nicotine intake. Acutely, both ibogaine and noribogaine decrease extracellular levels of dopamine in the nucleus accumbens of rat brain. Ibogaine pretreatment (19 hours beforehand) blocks morphine-induced dopamine release and morphine-induced locomotor hyperactivity while, in contrast, it enhances similar effects of stimulants (cocaine and amphetamine). Ibogaine pretreatment also blocks nicotine-induced dopamine release. Both ibogaine and noribogaine bind to kappa opioid and N-methyl-D-aspartate (NMDA) receptors and to serotonin uptake sites; ibogaine also binds to sigma-2 and nicotinic receptors. The relative contributions of these actions are being assessed. Our ongoing studies in rats suggest that kappa agonist and NMDA antagonist actions contribute to ibogaine’s effects on opioid and stimulant self-administration, while the serotonergic actions may be more important for ibogaine-induced decreases in alcohol intake. A nicotinic antagonist action may mediate ibogaine-induced reduction of nicotine preferences in rats. A sigma-2 action of ibogaine appears to mediate its neurotoxicity. Some effects of ibogaine (e.g., on morphine and cocaine self-administration, morphine-induced hyperactivity, cocaine-induced increases in nucleus accumbens dopamine) are mimicked by kappa agonist (U50,488) and/or a NMDA antagonist (MK-801). Moreover, a combination of a kappa antagonist and a NMDA agonist will partially reverse several of ibogaine’s effects. Ibogaine’s long-term effects may be mediated by slow release from fat tissue (where ibogaine is sequestered) and conversion to noribogaine. Different receptors, or combinations of receptors, may mediate interactions of ibogaine with different drugs of abuse.

Glick, S. D., & Maisonneuve, I. S. (1998). Mechanisms of antiaddictive actions of ibogaine. Annals of the New York Academy of Sciences, 844, 214-226. http://dx.doi.org/10.1111/j.1749-6632.1998.tb08237.x
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Hallucinogenic botanicals of America: A growing need for focused drug education and research

December 22, 2005 / Ayahuasca, Cacti / Mescaline, Ethnobotany, History, Iboga / Ibogaine, Indigenous use, Other disciplines, Other subjects, Other substances, Publications, Safety, Salvia / Salvinorin A, Spirituality / By / ,

Abstract

Botanical sources for medicines in America have been known since long before the arrival of Columbus. Nevertheless, both scientists and the general public are often unaware that some of these botanical drugs are also potent intoxicants. We provide a quick overview of hallucinogenic and dissociative drugs harvested from nature or that are openly and legally cultivated in the United States. Examples of harmful outcomes reported in the media are contrasted with existing responsible ingestion by others, some of whom have the protected right to do so for traditional or sacramental religious purposes. Despite an ongoing and expensive effort to warn people of the potential harms of recreational drug use, little is known about the extent of use of these psychoactive botanicals, and the recent explosion of information available via the Internet could herald a storm of morbidity to come. Mounting more targeted research and educational efforts today may reduce later use and abuse, inform society about the special circumstances of religious use, and better prepare clinicians and other health care providers about the issues involved when people choose to indigenously source psychoactive drugs for human consumption.

Halpern, J. H., & Sewell, R. A. (2005). Hallucinogenic botanicals of America: A growing need for focused drug education and research. Life sciences, 78(5), 519-526. https://dx.doi.org/10.1016/j.lfs.2005.09.005
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Screening the receptorome for plant-based psychoactive compounds

December 22, 2005 / Ayahuasca, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Salvia / Salvinorin A / By / ,

Abstract

Throughout time, humans have used psychoactive plants and plant-derived products for spiritual, therapeutic and recreational purposes. Furthermore, the investigation of psychoactive plants such as Cannabis sativa (marijuana), Nicotiana tabacum (tobacco) and analogues of psychoactive plant derivatives such as lysergic acid diethylamide (LSD) have provided insight into our understanding of neurochemical processes and diseases of the CNS. Currently, many of these compounds are being used to treat a variety of diseases, such as depression and anxiety in the case of Piper methysticum Kava Kava (Martin et al., 2002; Singh and Singh, 2002). G-protein coupled receptors (GPCRs) are the most common molecular target for both psychoactive drugs and pharmaceuticals. The “receptorome” (that portion of the genome encoding ligand reception) encompasses more than 8% of the human genome (Roth et al., 2004) and as such provides a large number of possible targets for psychoactive drug interactions. A systematic, comprehensive study is necessary to identify novel active psychoactive plant-based compounds and the molecular targets of known compounds. Herein we describe the development of a high throughput system (HTS) to screen psychoactive compounds against the receptorome and present two examples (Salvia divinorum, the “magic mint” hallucinogen and Banisteriopsis caapi, the main component of Ayahuasca, a psychoactive beverage) where HTS enabled the identification of the molecular target of each compound.

O’connor, K. A., & Roth, B. L. (2005). Screening the receptorome for plant-based psychoactive compounds. Life sciences, 78(5), 506-511. 10.1016/j.lfs.2005.09.002
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Transient memory impairment after acute dose of 75mg 3.4-Methylene-dioxymethamphetamine

November 1, 2005 / MDMA, Other subjects, Papers, Psychiatry, Psychology, Publications / By / ,

Abstract

A range of studies has indicated that users of 3.4-Methylene-dioxymethamphetamine (MDMA, ‘Ecstasy’) display cognitive deficits, particularly memory impairment, as compared to non-drug using controls. Yet it is difficult to determine whether these deficits are caused by MDMA or some other confounding factor, such as polydrug use. The present study was designed to establish the direct relation between MDMA and memory impairment under placebo-controlled conditions. Eighteen recreational MDMA users participated in a double blind, placebo controlled, 3-way crossover design. They were treated with placebo, MDMA 75mg and methylphenidate 20mg. Memory tests were conducted between 1.5-2h (intoxication phase) and between 25.5-26h (withdrawal phase) post dosing. Results showed that a single dose of MDMA caused impairment of immediate and delayed recall on a verbal learning task during the intoxication phase. However, there was no residual memory impairment during the withdrawal phase. Subjects reported more fatigue and less vigour, but no symptoms of depression during the withdrawal phase of MDMA treatment.

Methylphenidate did not affect memory or mood at any time of testing. A single dose of MDMA produces transient memory impairment.

Kuypers, K. P., & Ramaekers, J. G. (2005). Transient memory impairment after acute dose of 75mg 3.4-Methylene-dioxymethamphetamine. Journal of Psychopharmacology, 19(6), 633-639. 10.1177/0269881105056670
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Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors

October 1, 2005 / Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , , , , ,

Abstract

Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were tested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 Ag/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggesting a primary involvement of the 5-HT1A receptor in the observed deficit. Based on physiological and pharmacological data, we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.

Carter, O. L., Burr, D. C., Pettigrew, J. D., Wallis, G. M., Hasler, F., & Vollenweider, F. X. (2005). Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors. Journal of Cognitive neuroscience, 17(10), 1497-1508. http://dx.doi.org/10.1162/089892905774597191
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Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers

October 1, 2005 / DMT, Ketamine, Papers, Psychiatry, Psychology, Psychopharmacology, Psychosis, Publications / By / , , , , , ,

Abstract

INTRODUCTION:
Pharmacological challenges with hallucinogens are used as models for psychosis in experimental research. The state induced by glutamate antagonists such as phencyclidine (PCP) is often considered as a more appropriate model of psychosis than the state induced by serotonergic hallucinogens such as lysergic acid diethylamide (LSD), psilocybin and N,N-dimethyltryptamine (DMT). However, so far, the psychological profiles of the two types of hallucinogenic drugs have never been studied directly in an experimental within-subject design.

METHODS:
Fifteen healthy volunteers were included in a double-blind, cross-over study with two doses of the serotonin 5-HT2A agonist DMT and the glutamate N-methyl-D-aspartate (NMDA) antagonist (S)-ketamine.

RESULTS:
Data are reported for nine subjects who completed both experimental days with both doses of the two drugs. The intensity of global psychological effects was similar for DMT and (S)-ketamine. However, phenomena resembling positive symptoms of schizophrenia, particularly positive formal thought disorder and inappropriate affect, were stronger after DMT. Phenomena resembling negative symptoms of schizophrenia, attention deficits, body perception disturbances and catatonia-like motor phenomena were stronger after (S)-ketamine.

DISCUSSION:
The present study suggests that the NMDA antagonist model of psychosis is not overall superior to the serotonin 5-HT2A agonist model. Rather, the two classes of drugs tend to model different aspects or types of schizophrenia. The NMDA antagonist state may be an appropriate model for psychoses with prominent negative and possibly also catatonic features, while the 5-HT2A agonist state may be a better model for psychoses of the paranoid type.

Gouzoulis-Mayfrank, E., Heekeren, K., Neukirch, A., Stoll, M., Stock, C., Obradovic, M., & Kovar, K .A. (2005). Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers. Pharmacopsychiatry, 38(6), 301-311. http://dx.doi.org/10.1055/s-2005-916185
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Effects of peritraumatic ketamine medication on early and sustained posttraumatic stress symptoms in moderately injured accident victims

July 13, 2005 / Anxiety disorders / PTSD, Ketamine, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , ,

Abstract

Rationale: Ketamine, an N-methyl-D-aspartate receptor antagonist, produces transient dissociative and psychotic states in healthy humans that resemble symp- toms shown by subjects with acute and chronic posttrau- matic stress disorder (PTSD). Since ketamine is widely used as an analgesic and sedative in emergency care, it might be one factor triggering, modulating, or exacerbat- ing PTSD in accident victims when given in the acute trauma phase. Objectives: The purpose of the present study was to determine whether the peritraumatic administration of ketamine affects acute and sustained PTSD symptoms in accident victims. Methods: A sample of 56 moderate- ly injured accident victims was screened retrospectively for acute (Peritraumatic Dissociative Experiences Ques- tionnaire; Acute Stress Disorder Scale) and for current PTSD symptoms (Impact of Event Scale) approximately 1 year postaccident. All subjects had received a single or fractionated dose of either racemic ketamine (n=17), (S)- ketamine (n=12), or opioids (n=27) during emergency am- bulance transportation. Results: Retrospectively assessed acute symptomatology was strongly increased in (S)-keta- mine subjects in terms of dissociation, reexperiencing, and avoidance, and slightly heightened in racemic ketamines. Current PTSDsymptoms were substantially elevated in (S)- ketamine subjects, while there was no difference observed between opioids and racemic ketamines. Medication groups did not differ in regard to demographic variables, previous or postaccidental traumatic events, time between accident and investigation, and injury severity. Conclusions: The data provide first evidence for a modulating effect of a single-dose ketamine on the severity and duration of post- traumatic stress symptoms in accident victims.

Schönenberg, M., Reichwald, U., Domes, G., Badke, A., & Hautzinger, M. (2005). Effects of peritraumatic ketamine medication on early and sustained posttraumatic stress symptoms in moderately injured accident victims. Psychopharmacology, 182(3), 420-425. https://dx.doi.org/10.1007/s00213-005-0094-4
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Effects of different subanesthetic doses of (S)-ketamine on neuropsychology, psychopathology, and state of consciousness in man

May 12, 2005 / Ketamine, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , ,

Abstract

This is the first neuropsychological study using the S-enantiomer of the noncompetetive N-methyl-D-aspartate antagonist ketamine. In 2 randomized placebo-controlled trials we studied effects of two different doses of (S)-ketamine (low dose/high dose) on neuropsychological functions and psychopathology in 12 healthy male volunteers. Impairment was measured via standardized neuropsychological tests. Results indicate that both subanaesthetic doses produce only nonsignificant impair ment in most of the tasks. Tasks involving divided and sustained attention as well as scores for objective and subjective psychopathology show significant impairment in a dose-dependent manner. Implications of these findings for the neuropsychology of attention and schizophrenia are discussed.

Passie, T., Karst, M., Wiese, B., Emrich, H. M., & Schneider, U. (2005). Effects of different subanesthetic doses of (S)-ketamine on neuropsychology, psychopathology, and state of consciousness in man. Neuropsychobiology, 51(4), 226-233. http://dx.doi.org/10.1159%2F000085724
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7 May - Psychedelics, Nature & Mental Health with Sam Gandy

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