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Transient memory impairment after acute dose of 75mg 3.4-Methylene-dioxymethamphetamine

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

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

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

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

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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Report on psychoactive drug use among adolescents using ayahuasca within a religious context

Ritual use of ayahuasca within the context of the Brazilian ayahuasca churches often starts during late childhood or early adolescence. Premature access to psychoactive drugs may represent a risk factor for drug misuse. Conversely, religious affiliation seems to play a protective role in terms of substance abuse. The objective of this study was to describe patterns of drug use in a sample of adolescents using ayahuasca within a religious setting. Forty-one adolescents from a Brazilian ayahuasca sect were compared with 43 adolescents who never drank ayahuasca. No significant differences were identified in terms of lifetime substance consumption. Throughout the previous year period, ayahuasca adolescents used less alcohol (46.31%) than the comparison group (74.4%). Recent use of alcohol was also more frequent among the latter group (65.1%) than among ayahuasca drinkers (32.5%). Although not statistically significant, slight differences in terms of patterns of drug use were definitely observed among groups. Despite their early exposure to a hallucinogenic substance, adolescents using ayahuasca in a controlled setting were mostly comparable to controls except for a considerably smaller proportion of alcohol users. Religious affiliation may have played a central role as a possible protective factor for alcohol use. Thus, ayahuasca seems to be a relatively safe substance as far as drug misuse is concerned.

Doering-Silveira, E., Grob, C. S., de Rios, M. D., Lopez, E., Alonso, L. K., Tacla, C., & Da Silveira, D. X. (2005). Report on psychoactive drug use among adolescents using ayahuasca within a religious context. Journal of psychoactive drugs, 37(2), 141-144. 10.1080/02791072.2005.10399794
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Ecstasy (MDMA) mimics the post-orgasmic state: impairment of sexual drive and function during acute MDMA-effects may be due to increased prolactin secretion

Summary

Methylenedioxymethamphetamine (MDMA or ‘‘Ecstasy’’) is a major stimulant drug of abuse worldwide. MDMA produces euphoria, enhances interpersonal communication and feelings of closeness with others. In contrast to the induced emotions of affection and sensual enhancement, clinical studies show that it impairs sexual drive and functioning. In drug-free humans, sexual stimulation with orgasm induces a pronounced secretion of prolactin, which may mediate the post-orgasmic state. The phenomenological features of the psychological state induced by MDMA show some similarities with features of the post-orgasmic state. In addition, MDMA also induces a prominent increase of prolactin plasma levels with a similar time kinetic compared to the post-orgasmic prolactin increase. Here, we present the hypothesis that the impairment of sexual parameters after MDMA may be mediated by increased prolactin.

 

Passie, T., Hartmann, U., Schneider, U., Emrich, H. M., & Krüger, T. H. (2005). Ecstasy (MDMA) mimics the post-orgasmic state: impairment of sexual drive and function during acute MDMA-effects may be due to increased prolactin secretion. Medical hypotheses, 64(5), 899-903. https://dx.doi.org/10.1016/j.mehy.2004.11.044

 

Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine

Abstract

The presence of the potent hallucinogenic psychoactive chemical N,N-dimethyltryptamine (DMT) in the human body has puzzled scientists for decades. Endogenous DMT was investigated in the 1960s and 1970s and it was proposed that DMT was involved in psychosis and schizophrenia. This hypothesis developed from comparisons of the blood and urine of schizophrenic and control subjects. However, much of this research proved inconclusive and conventional thinking has since held that trace levels of DMT, and other endogenous psychoactive tryptamines, are insignificant metabolic byproducts. The recent discovery of a G-protein-coupled, human trace amine receptor has triggered a reappraisal of the role of compounds present in limited concentrations in biological systems. Interestingly enough, DMT and other psychoactive tryptamine hallucinogens elicit a robust response at the trace amine receptor. While it is currently accepted that serotonin 5-HT2A receptors play a pivotal role in the activity of hallucinogenic/ psychedelic compounds, we propose that the effects induced by exogenous DMT administration, especially at low doses, are due in part to activity at the trace amine receptor. Furthermore, we suggest that endogenous DMT interacts with the TA receptor to produce a calm and relaxed mental state, which may suppress, rather than promote, symptoms of psychosis. This hypothesis may help explain the inconsistency in the early analysis of endogenous DMT in humans. Finally, we propose that amphetamine action at the TA receptor may contribute to the calming effects of amphetamine and related drugs, especially at low doses.

Jacob, M. S., & Presti, D. E. (2004). Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine. Medical Hypotheses, 64(5), 930-937. http://dx.doi.org/10.1016/j.mehy.2004.11.005

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Psychotherapeutic interventions at the end of life: a focus on meaning and spirituality

Abstract

Medical and psychological discourse on end-of-life care has steadily shifted over the years from focusing primarily on symptom control and pain management to incorporating more person-centred approaches to patient care. Such approaches underscore the significance of spirituality and meaning making as important resources for coping with emotional and existential suffering as one nears death. Though existential themes are omnipresent in end-of-life care, little has been written about their foundations or import for palliative care practitioners and patients in need. In this article, we explore the existential foundations of meaning and spirituality in light of terminal illness and palliative care. We discuss existential themes in terms of patients’ awareness of death and search for meaning and practitioners’ promotion of personal agency and responsibility as patients face life-and-death issues. Viktor Frankl’s existential logotherapy is discussed in light of emerging psychotherapeutic interventions. Meaning-centred group therapy is one such novel modality that has successfully integrated themes of meaning and spirituality into end-of-life care. We further explore spiritual and existential themes through this meaning-oriented approach that encourages dying patients to find meaning and purpose in living until their death.

Breitbart, W., Gibson, C., Poppito, S. R., & Berg, A. (2004). Psychotherapeutic interventions at the end of life: a focus on meaning and spirituality. Canadian Journal of Psychiatry, 49, 366-372. http://dx.doi.org/10.1176/foc.5.4.foc451
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Effects of the South American psychoactive beverage ayahuasca on regional brain electrical activity in humans: a functional neuroimaging study using low-resolution electromagnetic tomography

Abstract

Ayahuasca, a South American psychotropic plant tea obtained from Banisteriopsis caapi and Psychotria viridis, combines monoamine oxidase-inhibiting β-carboline alkaloids with N,N-dimethyltryptamine (DMT), a psychedelic agent showing 5-HT2A agonist activity. In a clinical research setting, ayahuasca has demonstrated a combined stimulatory and psychedelic effect profile, as measured by subjective effect self-assessment instruments and dose-dependent changes in spontaneous brain electrical activity, which parallel the time course of subjective effects. In the present study, the spatial distribution of ayahuasca-induced changes in brain electrical activity was investigated by means of low-resolution electromagnetic tomography (LORETA). Electroencephalography recordings were obtained from 18 volunteers after the administration of a dose of encapsulated freeze-dried ayahuasca containing 0.85 mg DMT/kg body weight and placebo. The intracerebral power density distribution was computed with LORETA from spectrally analyzed data, and subjective effects were measured by means of the Hallucinogen Rating Scale (HRS). Statistically significant differences compared to placebo were observed for LORETA power 60 and 90 min after dosing, together with increases in all six scales of the HRS. Ayahuasca decreased power density in the alpha-2, delta, theta and beta-1 frequency bands. Power decreases in the delta, alpha-2 and beta-1 bands were found predominantly over the temporo-parieto-occipital junction, whereas theta power was reduced in the temporomedial cortex and in frontomedial regions. The present results suggest the involvement of unimodal and heteromodal association cortex and limbic structures in the psychological effects elicited by ayahuasca.

Riba, J., Anderer, P., Jané, F., Saletu, B., & Barbanoj, M. J. (2004). Effects of the South American psychoactive beverage ayahuasca on regional brain electrical activity in humans: a functional neuroimaging study using low-resolution electromagnetic tomography. Neuropsychobiology, 50(1), 89-101. 10.1159/000077946
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Online Event - Psychedelic Care in Recreational Settings - 3 October 2024

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