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Psychiatry

5-HT2A and mGlu2/3 receptor interactions: on their relevance to cognitive function and psychosis

August 19, 2015 / Neuroscience, Other disciplines, Other subjects, Other substances, Papers, Psychiatry, Psychology, Psychosis, Publications / By / ,

Abstract

Serotonin [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”][5-hydroxytryptamine (5-HT)] and glutamate have both been implicated in the pathophysiology of neuropsychiatric disorders but also in the mechanism of antipsychotic and hallucinogenic drug actions. Furthermore, close antagonistic interactions between 5-HT2A and metabotropic glutamate (mGlu)2/3 receptors have been established over the last decades on the basis of numerous electrophysiological, biochemical, and behavioral studies. Besides synaptic mechanisms, more recent findings suggested that heterodimeric 5-HT2A-mGlu2 receptor complexes in the prefrontal cortex may account for the functional crosstalk between these two receptor subtypes. In this review, we focus on in-vitro and in-vivo studies documenting the important relationship between 5-HT2A and mGlu2/3 receptors, with relevance to both normal behavioral function and psychosis.

Wischhof, L., & Koch, M. (2015). 5-HT2A and mGlu2/3 receptor interactions: on their relevance to cognitive function and psychosis. Behavioural pharmacology. https://dx.doi.org/10.1097/FBP.0000000000000183
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Lysergic Acid Diethylamide and Psilocybin Revisited

August 6, 2015 / LSD, Mushrooms / Psilocybin, Papers, Psychiatry, 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-associated “Alice in Wonderland Syndrome”(AIWS): A Hallucinogen Persisting Perception Disorder (HPPD) Case Report.

August 1, 2015 / HPPD, LSD, Papers, Psychiatry, 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 / HPPD, LSD, Papers, Psychiatry, 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 / Depression, Ketamine, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, 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, Depression, Ketamine, LSD, MDMA, Medicine, Mushrooms / Psilocybin, Other subjects, Other substances, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, 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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Developmental outcomes of 3,4-methylenedioxymethamphetamine (ecstasy)-exposed infants in the UK

July 28, 2015 / MDMA, Neuroscience, Other subjects, Papers, Psychiatry, Publications, Safety / By / , , , , , ,

Abstract

OBJECTIVE: This paper aims to review findings from a longitudinal study of prenatal methylenedioxymethamphetamine (MDMA, “ecstasy”) on infant development.

METHODS: In a prospective, longitudinal cohort design, we followed 28 MDMA-exposed and 68 non-MDMA-exposed infants from birth to 2 years of age. Women recruited voluntarily into a study of recreational drug use during pregnancy were interviewed to obtain type, frequency, and amount of recreational drug use. Their children were followed for a 2-year period after birth. A large number of drug and environmental covariates were controlled. Infants were seen at 1, 4, 12, 18, and 24 months using standardized normative tests of mental and motor development.

RESULTS: There were no differences between MDMA-exposed and non-MDMA-exposed infants at birth except that MDMA-exposed infants were more likely to be male. Motor delays were evident in MDMA infants at each age and amount of MDMA exposure predicted motor deficits at 12 months in a dose-dependent fashion.

CONCLUSIONS: Prenatal MDMA exposure is related to fine and gross motor delays in the first 2 years of life. Follow-up studies are needed to determine long-term effects.

Singer, L. T., Moore, D. G., Min, M. O., Goodwin, J., Turner, J. J., Fulton, S., & Parrott, A. C. (2015). Developmental outcomes of 3, 4‐methylenedioxymethamphetamine (ecstasy)‐exposed infants in the UK. Human Psychopharmacology: Clinical and Experimental, 30(4), 290-294. http://dx.doi.org/0.1002/hup.2459

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Antidepressant mechanism of ketamine: perspective from preclinical studies

July 21, 2015 / Depression, Ketamine, Medicine, Neuroscience, Other disciplines, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, 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, Psychiatry, Psychology, Psychopharmacology, Psychosis, 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, Psychiatry, 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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