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Psychology

Lysergic Acid Diethylamide and Psilocybin Revisited

August 6, 2015 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

The past decade brought the beginnings of a renaissance in research on psychedelic drugs. Two articles in this issue of Biological Psychiatry signify that the resurrection of this long-ignored topic has begun to mature and bear at least the promise of fruit. In the early 1970s, the onset of the “War on Drugs” brought with it a near-total hiatus in serious research on psychedelic drugs, especially in the United States. The resumption of credible work in this area has come from Switzerland, where many of the original pioneering studies were initiated in the 1950s and 1960s.

Geyer, M. A. (2015). Lysergic Acid Diethylamide and Psilocybin Revisited. Biological psychiatry, 78(8), 516-518. http://dx.doi.org/10.1016/j.biopsych.2015.08.003
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LSD: a new treatment emerging from the past

August 4, 2015 / Humanities & Art, LSD, Papers, Psychology, Publications / By /

Introduction

Psychedelics fell from medical grace nearly half a century ago, but recent activity suggests that some researchers have “high hopes” for their return. 1,2 Over 60 years ago, Albert Hofmann at Sandoz Pharmaceutical Laboratories in Switzerland first synthesized lysergic acid diethylamide (LSD) and personally experienced its effects (later described as a voyage into madness or a chemically induced psychosis) in 1943. Hofmann’s drug opened up a new era of hallucinogenic research. Over the next 15 years, more than a thousand articles on the use of LSD appeared in medical and scientific publications. In 1957, that work gave rise to the term “psychedelic” to describe a mind-manifesting response, described by some as an experience that brought to light matters that had previously been part of the unconscious [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”][…]

Dyck, E. (2015). LSD: a new treatment emerging from the past. CMAJ: Canadian Medical Association journal= journal de l’Association medicale canadienne. https://dx.doi.org/10.1503/cmaj.141358

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Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations

August 1, 2015 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , ,

Abstract

Rationale

During the last years, considerable progress has been made toward understanding the neuronal basis of consciousness by using sophisticated behavioral tasks, brain-imaging techniques, and various psychoactive drugs. Nevertheless, the neuronal mechanisms underlying some of the most intriguing states of consciousness, including spiritual experiences, remain unknown.

Objectives

To elucidate state of consciousness-related neuronal mechanisms, human subjects were given psilocybin, a naturally occurring serotonergic agonist and hallucinogen that has been used for centuries to induce spiritual experiences in religious and medical rituals.

Methods

In this double-blind, placebo-controlled study, 50 healthy human volunteers received a moderate dose of psilocybin, while high-density electroencephalogram (EEG) recordings were taken during eyes-open and eyes-closed resting states. The current source density and the lagged phase synchronization of neuronal oscillations across distributed brain regions were computed and correlated with psilocybin-induced altered states of consciousness.

Results

Psilocybin decreased the current source density of neuronal oscillations at 1.5–20 Hz within a neural network comprising the anterior and posterior cingulate cortices and the parahippocampal regions. Most intriguingly, the intensity levels of psilocybin-induced spiritual experience and insightfulness correlated with the lagged phase synchronization of delta oscillations (1.5–4 Hz) between the retrosplenial cortex, the parahippocampus, and the lateral orbitofrontal area.

Conclusions

These results provide systematic evidence for the direct association of a specific spatiotemporal neuronal mechanism with spiritual experiences and enhanced insight into life and existence. The identified mechanism may constitute a pathway for modulating mental health, as spiritual experiences can promote sustained well-being and psychological resilience.

Kometer, M., Pokorny, T., Seifritz, E., & Vollenweider, F. X. (2015). Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations. Psychopharmacology, 1-14. https://dx.doi.org/10.1007/s00213-015-4026-7

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LSD-associated “Alice in Wonderland Syndrome”(AIWS): A Hallucinogen Persisting Perception Disorder (HPPD) Case Report.

August 1, 2015 / LSD, Papers, Psychology, Publications / By /

Abstract

A side effect associated with the use of LSD is the return of perceptual disturbances which anteriorly emerged during intoxication, despite absence of present use. Here we present the case of a patient with a previous history of sporadic and recreational cannabis, alcohol and LSD consumption who reported LSD associated “Alice in Wonderland Syndrome” (AIWS) or Todd’s syndrome. AIWS is basically characterized by four frequent visual illusions: macropsia, micropsia, pelopsia and teleopsia. AIWS only appeared during LSD consumption and continued after LSD suspension, namely, Hallucinogen Persisting Perception Disorder (HPPD). This phenomenon did not cause a major functional impairment but provoked sufficient worry and concern due to its persistent continuation. The patient refused medical treatment and continued psychiatric follow-up. At the one year follow-up he reported complete remission. To the best of our knowledge this is the first reported case of AIWS which persist after LSD interruption (HPPD) in the professional literature. Reasons for this intriguing, benign, reversible and apparently harmless side effect are proposed.

Lev-Ran, S. (2014). LSD-associated” Alice in Wonderland Syndrome”(AIWS): A Hallucinogen Persisting Perception Disorder (HPPD) Case Report. The Israel journal of psychiatry and related sciences, 52(1), 67-68.
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LSD-associated "Alice in Wonderland Syndrome"(AIWS): A Hallucinogen Persisting Perception Disorder (HPPD) Case Report.

August 1, 2015 / LSD, Papers, Psychology, Publications / By /

Abstract

A side effect associated with the use of LSD is the return of perceptual disturbances which anteriorly emerged during intoxication, despite absence of present use. Here we present the case of a patient with a previous history of sporadic and recreational cannabis, alcohol and LSD consumption who reported LSD associated “Alice in Wonderland Syndrome” (AIWS) or Todd’s syndrome. AIWS is basically characterized by four frequent visual illusions: macropsia, micropsia, pelopsia and teleopsia. AIWS only appeared during LSD consumption and continued after LSD suspension, namely, Hallucinogen Persisting Perception Disorder (HPPD). This phenomenon did not cause a major functional impairment but provoked sufficient worry and concern due to its persistent continuation. The patient refused medical treatment and continued psychiatric follow-up. At the one year follow-up he reported complete remission. To the best of our knowledge this is the first reported case of AIWS which persist after LSD interruption (HPPD) in the professional literature. Reasons for this intriguing, benign, reversible and apparently harmless side effect are proposed.

Lev-Ran, S. (2014). LSD-associated” Alice in Wonderland Syndrome”(AIWS): A Hallucinogen Persisting Perception Disorder (HPPD) Case Report. The Israel journal of psychiatry and related sciences, 52(1), 67-68.
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Psychopharmacological Agents and Suicide Risk Reduction: Ketamine and Other Approaches

August 1, 2015 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

Suicide is a major global public health problem and the leading cause of injury mortality in the USA. Suicide is a complex phenomenon involving several systems and neurobiological pathways, with interacting genetic and environmental mechanisms. The literature on the neurobiology and pharmacotherapy of suicide has been limited. To date, no medications have proven efficacious for treating acute suicidal crises. There is an emerging literature supporting a rapid anti-suicidal effect of ketamine, a non-competitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist, among depressed patients with suicidal ideation. Potential ketamine’s anti-suicidal effect mechanisms are linked to interruption of the kynurenine pathway and modulating pro-inflammatory cytokines exacerbation. However, available data are not sufficient for its routine integration in clinical practice, and larger and replicated randomized control studies are needed.

Al Jurdi, R. K., Swann, A., & Mathew, S. J. (2015). Psychopharmacological Agents and Suicide Risk Reduction: Ketamine and Other Approaches. Current psychiatry reports, 17(10), 1-10. https://dx.doi.org/10.1007/s11920-015-0614-9

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The potential utility of some legal highs in CNS disorders

July 29, 2015 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Over the last decade there has been an explosion of new drugs of abuse, so called legal highs or novel psychoactive substances (NPS). Many of these abused drugs have unknown pharmacology, but their biological effects can be anticipated from their molecular structure and possibly also from online user reports. When considered with the findings that some prescription medications are increasingly abused and that some abused drugs have been tested clinically one could argue that there has been a blurring of the line between drugs of abuse and clinically used drugs. In this review we examine these legal highs/NPS and consider whether, based on their known or predicted pharmacology, some might have the potential to be clinically useful in CNS disorders.

Davidson, C., & Schifano, F. (2015). The potential utility of some legal highs in CNS disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. https://dx.doi.org/10.1016/j.pnpbp.2015.07.010
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Antidepressant mechanism of ketamine: perspective from preclinical studies

July 21, 2015 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , ,

Abstract

A debilitating mental disorder, major depressive disorder is a leading cause of global disease burden. Existing antidepressant drugs are not adequate for the majority of depressed patients, and large clinical studies have demonstrated their limited efficacy and slow response onset. Growing evidence of low-dose ketamine’s rapid and potent antidepressant effects offers strong potential for future antidepressant agents. However, ketamine has considerable drawbacks such as its abuse potential, psychomimetic effects, and increased oxidative stress in the brain, thus limiting its widespread clinical use. To develop superior antidepressant drugs, it is crucial to better understand ketamine’s antidepressant mechanism of action. Recent preclinical studies indicate that ketamine’s antidepressant mechanism involves mammalian target of rapamycin pathway activation and subsequent synaptogenesis in the prefrontal cortex, as well as glycogen synthase kinase-3 beta (GSK-3β) inactivation. Adjunct GSK-3β inhibitors, such as lithium, can enhance ketamine’s efficacy by augmenting and prolonging its antidepressant effects. Given the potential for depressive relapses, lithium in addition to ketamine is a promising solution for this clinical issue.

Scheuing, L., Chiu, C. T., Liao, H. M., & Chuang, D. M. (2015). Antidepressant mechanism of ketamine: perspective from preclinical studies. Frontiers in Neuroscience, 9. http://dx.doi.org/10.3389/fnins.2015.00249
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Acute ketamine challenge increases resting state prefrontal-hippocampal connectivity in both humans and rats.

July 18, 2015 / Ketamine, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , , , , ,

Abstract

RATIONALE:

Aberrant prefrontal-hippocampal (PFC-HC) connectivity is disrupted in several psychiatric and at-risk conditions. Advances in rodent functional imaging have opened the possibility that this phenotype could serve as a translational imaging marker for psychiatric research. Recent evidence from functional magnetic resonance imaging (fMRI) studies has indicated an increase in PFC-HC coupling during working-memory tasks in both schizophrenic patients and at-risk populations, in contrast to a decrease in resting-state PFC-HC connectivity. Acute ketamine challenge is widely used in both humans and rats as a pharmacological model to study the mechanisms of N-methyl-D-aspartate (NMDA) receptor hypofunction in the context of psychiatric disorders.

OBJECTIVES:

We aimed to establish whether acute ketamine challenge has consistent effects in rats and humans by investigating resting-state fMRI PFC-HC connectivity and thus to corroborate its potential utility as a translational probe.

METHODS:

Twenty-four healthy human subjects (12 females, mean age 25 years) received intravenous doses of either saline (placebo) or ketamine (0.5 mg/kg body weight). Eighteen Sprague-Dawley male rats received either saline or ketamine (25 mg/kg). Resting-state fMRI measurements took place after injections, and the data were analyzed for PFC-HC functional connectivity.

RESULTS:

In both species, ketamine induced a robust increase in PFC-HC coupling, in contrast to findings in chronic schizophrenia.

CONCLUSIONS:

This translational comparison demonstrates a cross-species consistency in pharmacological effect and elucidates ketamine-induced alterations in PFC-HC coupling, a phenotype often disrupted in pathological conditions, which may give clue to understanding of psychiatric disorders and their onset, and help in the development of new treatments.

Grimm, O., Gass, N., Weber-Fahr, W., Sartorius, A., Schenker, E., Spedding, M., … & Meyer-Lindenberg, A. (2015). Acute ketamine challenge increases resting state prefrontal-hippocampal connectivity in both humans and rats. Psychopharmacology, 1-11.
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Ketamine induces anxiolytic effects in adult zebrafish: A multivariate statistics approach.

July 14, 2015 / Anxiety Disorders / PTSD, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

Ketamine inappropriate use has been associated with serious consequences for human health. Anesthetic properties of ketamine are well-known but its side effects are poorly described, including the effects on anxiety. In this context, animal models are a safe way to conduct this neurobehavioral research and zebrafish (Danio rerio) is an interesting model which has several advantages. The validation and interpretation of results of behavioral assays requires a suitable statistical approach and the use of multivariate statistical methods has been little explored, especially in zebrafish behavioral models. Here, we investigated the anxiolytic-induced effects of ketamine in adult zebrafish, using Light-Dark Test and Multivariate Statistics methods (PCA, HCA and SIMCA). In addition, we compared the processing of data to the one carried out by analysis of variance (ANOVA) Ketamine produced significant concentration of exposure-dependent anxiolytic effects, increasing time in white area and number of crossings and decreasing latency to first access to white area. Average entry duration behavior resulted in a slight decrease from control to treatment groups, with an observed concentration-dependent increase among the exposed groups. PCA results indicated that two principal components represent 88.74% of all the system information. HCA and PCA results showed a higher similarity among control and treatment groups exposed to lower concentrations of ketamine and among treatment groups exposed to concentrations of 40 and 60 mg.L-1. In SIMCA results, interclasses distances were concentration of exposure-dependent increased and misclassifications and interclasses residues results also support these findings. These findings confirm the anxiolytic potential of ketamine and zebrafish sensibility to this drug. In summary, our study confirms that zebrafish and multivariate statistics data validation is an appropriate and viable behavioral model for the study of psychoactive substances, providing a detailed and reliable analysis.

De Campos, E. G., Bruni, A. T., & De Martinis, B. S. (2015). Ketamine induces anxiolytic effects in adult zebrafish: A multivariate statistics approach. Behavioural Brain Research.  https://dx.doi.org/10.1016/j.bbr.2015.07.017
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