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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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Ecstasy (MDMA) mimics the post-orgasmic state: impairment of sexual drive and function during acute MDMA-effects may be due to increased prolactin secretion

November 9, 2004 / MDMA, Neuroscience, Other disciplines, Other subjects, Papers, Phenomenology, Publications / By / , , , ,

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

November 4, 2004 / DMT, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / ,

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

June 14, 2004 / Other subjects, Papers, Psychology, Publications, Spirituality / By / , , ,

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

June 1, 2004 / Ayahuasca, Neuroscience, Other subjects, Papers, Psychopharmacology, Publications / By / , , , ,

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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Hallucinogens

January 28, 2004 / Addiction, History, LSD, Medicine, Neuroscience, Other subjects, Other substances, Papers, Psychiatry, Psychopharmacology, Psychosis, Publications, Safety / By /

Abstract

Hallucinogens (psychedelics) are psychoactive substances that powerfully alter perception, mood, and a host of cognitive processes. They are considered physiologically safe and do not produce dependence or addiction. Their origin predates written history, and they were employed by early cultures in a variety of sociocultural and ritual contexts. In the 1950s, after the virtually contemporaneous discovery of both serotonin (5-HT) and lysergic acid diethylamide (LSD-25), early brain research focused intensely on the possibility that LSD or other hallucinogens had a serotonergic basis of action and reinforced the idea that 5-HT was an important neurotransmitter in brain. These ideas were eventually proven, and today it is believed that hallucinogens stimulate 5-HT2A receptors, especially those expressed on neocortical pyramidal cells. Activation of 5-HT2A receptors also leads to increased cortical glutamate levels presumably by a presynaptic receptor-mediated release from thalamic afferents. These findings have led to comparisons of the effects of classical hallucinogens with certain aspects of acute psychosis and to a focus on thalamocortical interactions as key to understanding both the action of these substances and the neuroanatomical sites involved in altered states of consciousness (ASC). In vivo brain imaging in humans using [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][18F]fluorodeoxyglucose has shown that hallucinogens increase prefrontal cortical metabolism, and correlations have been developed between activity in specific brain areas and psychological elements of the ASC produced by hallucinogens. The 5-HT2A receptor clearly plays an essential role in cognitive processing, including working memory, and ligands for this receptor may be extremely useful tools for future cognitive neuroscience research. In addition, it appears entirely possible that utility may still emerge for the use of hallucinogens in treating alcoholism, substance abuse, and certain psychiatric disorders.

Nichols, D. E. (2004). Hallucinogens. Pharmacology & therapeutics, 101(2), 131-181. https://dx.doi.org/10.1016/j.pharmthera.2003.11.002

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Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebocontrolled dose-effect study

November 13, 2003 / Mushrooms / Psilocybin, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , , , , ,

Abstract

Rationale: Serotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT2A agonist psilocybin (PY) is useful in studying the neurobiological basis of cognition and consciousness.

Objective: Investigation of dose-dependent effects of PY on psycho(patho)logical and physiological parameters.

Methods: Eight subjects received placebo (PL), and 45 (“very low dose, VLD”), 115 (“low dose, LD”), 215 (“medium dose, MD”), and 315 (“high dose, HD”) μg/kg body weight PY. The “Altered States of Consciousness Rating Scale” (5D-ASC), the “Frankfurt Attention Inventory” (FAIR), and the “Adjective Mood Rating Scale” (AMRS) were used to assess the effects of PY on psycho(patho)logical core dimensions, attention, and mood. A 24-h electrocardiogram (EKG) was recorded and blood pressure was measured. Plasma concentrations of thyroid-stimulating hormone (TSH), prolactin (PRL), cortisol (CORT), adrenocorticotropic hormone (ACTH), and standard clinical chemical parameters were determined.

Results: PY dose dependently increased scores of all 5D-ASC core dimensions. Only one subject reacted with transient anxiety to HD PY. Compared with PL, MD and HD PY led to a 50% reduction of performance in the FAIR test. “General inactivation”, “emotional excitability”, and “dreaminess” were the only domains of the AMRS showing increased scores following MD and HD PY. The mean arterial blood pressure (MAP) was moderately elevated only 60 min following administration of HD PY. Neither EKG nor body temperature was affected by any dose of PY. TSH, ACTH, and CORT plasma levels were elevated during peak effects of HD PY, whereas PRL plasma levels were increased following MD and HD PY.

Conclusion: PY affects core dimensions of altered states of consciousness and physiological parameters in a dose-dependent manner. Our study provided no cause for concern that PY is hazardous with respect to somatic health.

Hasler, F., Grimberg, U., Benz, M. A., Huber, T., & Vollenweider, F. X. (2004). Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebocontrolled dose-effect study. Psychopharmacology, 172(2), 145-156. http://dx.doi.org/10.1007/s00213-003-1640-6
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Activities of extract and constituents of Banisteriopsis caapi relevant to parkinsonism

June 14, 2003 / Ayahuasca, Neuroscience, Other subjects, Papers, Psychopharmacology, Publications / By / , , , ,

Abstract

Dopamine deficiency is characteristic of Parkinson’s disease (PD) and treatments aim at elevating levels by administration of its precursor l-dihydroxyphenylalanine (l-DOPA), or inhibiting monoamine oxidases (MAOs), thus preventing its breakdown. Reports of improvements in PD patients treated with Banisteriopsis caapi extracts stimulated investigation of B. caapi stem extract and its two ingredients, harmine and harmaline for these activities.

Tests for MAO inhibition using liver homogenate showed that extract and harmaline showed a concentration-dependent inhibition of MAO A (IC50 1.24 μg/ml and IC50 4.54 nM, respectively) but had little effect on MAO B activity.

The extract at 2.5 mg/ml caused a highly significant increase in release of [3H]dopamine from rat striatal slices, as did 200 μM harmine and 6 μM harmaline. In both these experiments, the amount of harmine present could not account for the total activity of the extract.

The ability of harmine and harmaline to stimulate dopamine release is a novel finding. These results give some basis to the reputed usefulness of B. caapi stem extract in the treatment of PD.

Schwarz, M. J., Houghton, P. J., Rose, S., Jenner, P., & Lees, A. D. (2003). Activities of extract and constituents of Banisteriopsis caapi relevant to parkinsonism. Pharmacology Biochemistry and Behavior, 75(3), 627-633. 10.1016/S0091-3057(03)00129-1
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Effects of the 5-HT2A Agonist Psilocybin on Mismatch Negativity Generation and AX-Continuous Performance Task: Implications for the Neuropharmacology of Cognitive Deficits in Schizophrenia

February 1, 2003 / Ketamine, Mushrooms / Psilocybin, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychosis, Publications / By / , , , , , ,

Abstract

Previously the NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was shown to disrupt generation of the auditory event-related potential (ERP) mismatch negativity (MMN) and the performance of an ‘AX’-type continuous performance test (AX-CPT)–measures of auditory and visual context-dependent information processing–in a similar manner as observed in schizophrenia. This placebo-controlled study investigated effects of the 5-HT(2A) receptor agonist psilocybin on the same measures in 18 healthy volunteers. Psilocybin administration induced significant performance deficits in the AX-CPT, but failed to reduce MMN generation significantly. These results indirectly support evidence that deficient MMN generation in schizophrenia may be a relatively distinct manifestation of deficient NMDAR functioning. In contrast, secondary pharmacological effects shared by NMDAR antagonists and the 5-HT(2A) agonist (ie disruption of glutamatergic neurotransmission) may be the mechanism underlying impairments in AX-CPT performance observed during both psilocybin and ketamine administration. Comparable deficits in schizophrenia may result from independent dysfunctions of 5-HT(2A) and NMDAR-related neurotransmission.

Umbricht, D., Vollenweider, F. X., Schmid, L., Gruebel, C., Skrabo, A., Huber, T., & Koller, R. (2003). Effects of the 5-HT2A agonist psilocybin on mismatch negativity generation and AX-continuous performance task: implications for the neuropharmacology of cognitive deficits in schizophrenia. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 28(1), 170-181. http://dx.doi.org/10.1038/sj.npp.1300005
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Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers

June 24, 2002 / Ayahuasca, Neuroscience, Other subjects, Papers, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

Aims: Ayahuasca is a traditional South American psychoactive beverage used in Amazonian shamanism, and in the religious ceremonies of Brazilian-based syncretic religious groups with followers in the US and several European countries. This tea contains measurable amounts of the psychotropic indole N,N-dimethyltryptamine (DMT), and β-carboline alkaloids with MAO-inhibiting properties. In a previous report we described a profile of stimulant and psychedelic effects for ayahuasca as measured by subjective report self-assessment instruments. In the present study the cerebral bioavailability and time-course of effects of ayahuasca were assessed in humans by means of topographic quantitative-electroencephalography (q-EEG), a noninvasive method measuring drug-induced variations in brain electrical activity.

Methods: Two doses (one low and one high) of encapsulated freeze-dried ayahuasca, equivalent to 0.6 and 0.85 mg DMT kg−1 body weight, were administered to 18 healthy volunteers with previous experience in psychedelic drug use in a double-blind crossover placebo-controlled clinical trial. Nineteen-lead recordings were undertaken from baseline to 8 h after administration. Subjective effects were measured by means of the Hallucinogen Rating Scale (HRS).

Results: Ayahuasca induced a pattern of psychoactive effects which resulted in significant dose-dependent increases in all subscales of the HRS, and in significant and dose-dependent modifications of brain electrical activity. Absolute power decreased in all frequency bands, most prominently in the theta band. Mean absolute power decreases (95% CI) at a representative lead (P3) 90 min after the high dose were −20.20±15.23 µV2 and −2.70±2.21 µV2 for total power and theta power, respectively. Relative power decreased in the delta (−1.20±1.31% after 120 min at P3) and theta (−3.30±2.59% after 120 min at P3) bands, and increased in the beta band, most prominently in the faster beta-3 (1.00±0.88% after 90 min at P3) and beta-4 (0.30±0.24% after 90 min at P3) subbands. Finally, an increase was also seen for the centroid of the total activity and its deviation. EEG modifications began as early as 15–30 min, reached a peak between 45 and 120 min and decreased thereafter to return to baseline levels at 4–6 h after administration.

Conclusions: The central effects of ayahuasca could be objectively measured by means of q-EEG, showing a time pattern which closely paralleled that of previously reported subjective effects. The modifications seen for the individual q-EEG variables were in line with those previously described for other serotonergic psychedelics and share some features with the profile of effects shown by pro-serotonergic and pro-dopaminergic drugs. The q-EEG profile supports the role of 5-HT2 and dopamine D2-receptor agonism in mediating the effects of ayahuasca on the central nervous system.

Riba, J., Anderer, P., Morte, A., Urbano, G., Jané, F., Saletu, B., & Barbanoj, M. J. (2002). Topographic pharmaco‐EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers. British journal of clinical pharmacology, 53(6), 613-628. 10.1046/j.1365-2125.2002.01609.x
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30 April - Q&A with Rick Strassman

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