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Do the dissociative side effects of ketamine mediate its antidepressant effects?

February 18, 2014 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , , , , , ,

Abstract

Background

The N-methyl-d-aspartate receptor antagonist ketamine has rapid antidepressant effects in major depression. Psychotomimetic symptoms, dissociation and hemodynamic changes are known side effects of ketamine, but it is unclear if these side effects relate to its antidepressant efficacy.

Methods

Data from 108 treatment-resistant inpatients meeting criteria for major depressive disorder and bipolar disorder who received a single subanesthetic ketamine infusion were analyzed. Pearson correlations were performed to examine potential associations between rapid changes in dissociation and psychotomimesis with the Clinician-Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale (BPRS), respectively, manic symptoms with Young Mania Rating Scale (YMRS), and vital sign changes, with percent change in the 17-item Hamilton Depression Rating scale (HDRS) at 40 and 230 min and Days 1 and 7.

Results

Pearson correlations showed significant association between increased CADSS score at 40 min and percent improvement with ketamine in HDRS at 230 min (r=−0.35, p=0.007) and Day 7 (r=−0.41, p=0.01). Changes in YMRS or BPRS Positive Symptom score at 40 min were not significantly correlated with percent HDRS improvement at any time point with ketamine. Changes in systolic blood pressure, diastolic blood pressure, and pulse were also not significantly related to HDRS change.

Limitations

Secondary data analysis, combined diagnostic groups, potential unblinding.

Conclusions

Among the examined mediators of ketamine׳s antidepressant response, only dissociative side effects predicted a more robust and sustained antidepressant. Prospective, mechanistic investigations are critically needed to understand why intra-infusion dissociation correlates with a more robust antidepressant efficacy of ketamine.

Luckenbaugh, D. A., Niciu, M. J., Ionescu, D. F., Nolan, N. M., Richards, E. M., Brutsche, N. E., … & Zarate, C. A. (2014). Do the dissociative side effects of ketamine mediate its antidepressant effects?. Journal of affective disorders, 159, 56-61. http://dx.doi.org/10.1016/j.jad.2014.02.017

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MDMA decreases the effects of simulated social rejection

February 8, 2014 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

3-4-Methylenedioxymethamphetamine (MDMA) increases self-reported positive social feelings and decreases the ability to detect social threat in faces, but its effects on experiences of social acceptance and rejection have not been determined. We examined how an acute dose of MDMA affects subjective and autonomic responses to simulated social acceptance and rejection. We predicted that MDMA would decrease subjective responses to rejection. On an exploratory basis, we also examined the effect of MDMA on respiratory sinus arrhythmia (RSA), a measure of parasympathetic cardiac control often thought to index social engagement and emotional regulation. Over three sessions, healthy adult volunteers with previous MDMA experience (N = 36) received capsules containing placebo, 0.75 or 1.5 mg/kg of MDMA under counter-balanced double-blind conditions. During expected peak drug effect, participants played two rounds of a virtual social simulation task called “Cyberball” during which they experienced acceptance in one round and rejection in the other. During the task we also obtained electrocardiograms (ECGs), from which we calculated RSA. After each round, participants answered questionnaires about their mood and self-esteem. As predicted, MDMA decreased the effect of simulated social rejection on self-reported mood and self-esteem and decreased perceived intensity of rejection, measured as the percent of ball tosses participants reported receiving. Consistent with its sympathomimetic properties, MDMA decreased RSA as compared to placebo. Our finding that MDMA decreases perceptions of rejection in simulated social situations extends previous results indicating that MDMA reduces perception of social threat in faces. Together these findings suggest a cognitive mechanism by which MDMA might produce pro-social behavior and feelings and how the drug might function as an adjunct to psychotherapy. These phenomena merit further study in non-simulated social environments.

Frye, C. G., Wardle, M. C., Norman, G. J., & de Wit, H. (2014). MDMA decreases the effects of simulated social rejection. Pharmacology Biochemistry and Behavior, 117, 1-6. https://dx.doi.org/10.1016/j.pbb.2013.11.030

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The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

February 3, 2014 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , , , , ,

Abstract

Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.

Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., Chialvo, D. R., & Nutt, D. (2014). The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Frontiers in Human Neuroscience, 8, 1-22. http://dx.doi.org/10.3389/fnhum.2014.00020
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New study may explain magic mushrooms' effects

February 7, 2022 / Mushrooms / Psilocybin / By

New research by a group of mainly Britisch scientists, based on fMRI brain scans, has shown that the use of psilocybin (the active constituent of magic mushrooms) decreases the activity of certain parts of the brain in test subjects. Brain activity decreased especially in those parts that are involved in the managing and filtering of information.

This may explain why users often report that under the influence of magic mushrooms they experience impressions and feelings that were previously unnoticed. Logically, when the brain’s ability to filter and handle information is decreased, more information may reach our consciousness. This may also explain why users often report new insights after the use of magic mushrooms, sometimes having therapeutic effects.

Another indication for the therapeutic effects of magic mushrooms is that brain activity also decreased in the medial prefrontal cortex, a brain part that is often hyperactive in patients suffering from depression.

Remarkably, these new results confirm the ideas of Aldous Huxley (1894-1963). Huxley saw the brain as a ‘reducing valve’, filtering and making information more manageable for our consciousness. He posed that psychedelic drugs might decrease these reducing properties of the brain.

Click here for the abstract and a link to the full article.

Nieuwe studie verklaart mogelijk effecten 'paddo's'

December 2, 2021 / Uncategorized / By

Uit nieuw onderzoek van een groep van vooral Britse wetenschappers, op basis van fMRI-hersenscans, is gebleken dat het innemen van psilocybine (de werkzame stof in paddo’s) bij proefpersonen de activiteit in bepaalde hersendelen vermindert. Dit geldt vooral voor de hersendelen die betrokken zijn bij het kanaliseren en filteren van informatie.

Dit verklaart wellicht waarom gebruikers vaak melden dat ze onder invloed van paddo’s indrukken en gevoelens ervaren die normaal gesproken voor ze verborgen blijven. Wanneer door de hersenen informatie minder goed gefilterd en gestuurd wordt, kunnen immers meer indrukken ons bewustzijn bereiken. Ook kan dit wellicht verklaren waarom gebruikers na het gebruik van paddo’s vaak nieuwe inzichten melden, soms met therapeutisch effect.

Een andere aanwijzing voor het therapeutische effect van psilocybine, is dat in dit onderzoek bleek dat de activiteit van de mediale prefrontale cortex afnam na het toedienen van psilocybine, een hersengebied dat bij depressieve mensen juist extra actief is.

Deze nieuwe resultaten komen opvallend overeen met de ideeën van Aldous Huxley (1894-1963). Huxley zag het brein vooral als een instrument dat informatie voor het bewustzijn behapbaar maakt, en stelde dat psychedelische middelen deze filterende functie van het brein tijdelijk doen verminderen.

Klik hier voor de abstract van de studie en een linke naar de volledige tekst.

Nieuwe studie verklaart mogelijk effecten ‘paddo’s’

December 2, 2021 / Uncategorized / By

Uit nieuw onderzoek van een groep van vooral Britse wetenschappers, op basis van fMRI-hersenscans, is gebleken dat het innemen van psilocybine (de werkzame stof in paddo’s) bij proefpersonen de activiteit in bepaalde hersendelen vermindert. Dit geldt vooral voor de hersendelen die betrokken zijn bij het kanaliseren en filteren van informatie.

Dit verklaart wellicht waarom gebruikers vaak melden dat ze onder invloed van paddo’s indrukken en gevoelens ervaren die normaal gesproken voor ze verborgen blijven. Wanneer door de hersenen informatie minder goed gefilterd en gestuurd wordt, kunnen immers meer indrukken ons bewustzijn bereiken. Ook kan dit wellicht verklaren waarom gebruikers na het gebruik van paddo’s vaak nieuwe inzichten melden, soms met therapeutisch effect.

Een andere aanwijzing voor het therapeutische effect van psilocybine, is dat in dit onderzoek bleek dat de activiteit van de mediale prefrontale cortex afnam na het toedienen van psilocybine, een hersengebied dat bij depressieve mensen juist extra actief is.

Deze nieuwe resultaten komen opvallend overeen met de ideeën van Aldous Huxley (1894-1963). Huxley zag het brein vooral als een instrument dat informatie voor het bewustzijn behapbaar maakt, en stelde dat psychedelische middelen deze filterende functie van het brein tijdelijk doen verminderen.

Klik hier voor de abstract van de studie en een linke naar de volledige tekst.

Lezing Amsterdam: Psychedelica als medicijn?

December 2, 2021 / Uncategorized / By

vspvu

De VSPVU organiseert samen met Stichting OPEN een lezing over het geneeskrachtige potentieel van psychedelica, op maandag 3 februari aan de VU in Amsterdam. Kunnen ibogaïne en andere stoffen helpen om van een zware verslaving of andere problemen af te komen?

Joost Breeksema, voorzitter van Stichting OPEN, opent de lezing met een overzicht van recent en historisch onderzoek naar de psychotherapeutische toepassingen van psychedelica. Daarna gaan Maarten Belgers en Thomas Knuijver, beiden verslavingsarts bij Iriszorg, dieper in op ibogaïne en hun onderzoek hiernaar. Wat is de wetenschappelijke kennis over ibogaïne tot nu toe, waarom willen zij dit middel onderzoeken, en hoe ziet dit onderzoek eruit?

Meld je hier alvast aan op het Facebook event.

Praktische informatie:

Waar: Vrije Universiteit. Van der Boechorststraat 7, Amsterdam.

Wanneer: Maandag 03 februari 2014. Van 16:00 tot 18:00 uur.

Prijs: Leden VSPVU €3,-. Overig: €4,50

Kaartverkoop in de VSPVU-kamer en aan de deur (alleen contact geld). Er zijn 150 plaatsen beschikbaar. We verwachten een grote opkomst dus wacht niet te lang met een kaartje kopen.

Lecture VU Amsterdam: Psychedelica als medicijn?

December 6, 2021 / Uncategorized / By

vspvu

OPEN organizes a lecture about the potential medicinal and therapeutic values of psychedelic substances at the VU University on Monday February 3rd. Can ibogaine or other substances help to get rid of an addiction or psychological disorders?

Joost Breeksema, the president of OPEN, will open this lecture with an overview of recent and historical research into the therapeutic applications of psychedelics. After that, Maarten Belgers and Thomas Knuijver, both physicians specialized in addiction, will talk about ibogaine and their research into this substance. What is the scientific knowledge about ibogaine until now, why do they want to research this substance, and what does this study look like? There are only 150 seats available, so if you want to ensure yourself of a ticket please arrive early. Ticket sales will start at 15:30.

Practical information:

Where: Vrije Universiteit. Van der Boechorststraat 7, Amsterdam.

When: Monday February 3rd 2014. From 16:00 until 18:00.

Price: Members VSPVU: €3 / Others: €4,50

Please note that this lecture will be in Dutch.

The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labelling and Blood Oxygen Level-Dependent Resting-State Functional Connectivity

January 10, 2014 / MDMA, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background
3,4-methylenedioxymethamphetamine (MDMA) is a potent monoamine releaser that produces an acute euphoria in most individuals.

Methods
MDMA was orally administered to 25 physically and mentally healthy individuals in a double-blind, placebo-controlled, balanced-order study. Arterial spin labelling (ASL) and seed-based resting state functional connectivity (RSFC) were used to produce spatial maps displaying changes in cerebral blood flow (CBF) and RSFC after MDMA. Participants underwent two ASL and two BOLD scans in a 90 minute scanning session and the MDMA and placebo study days were separated by one week.

Results
MDMA produced marked increases in positive mood. Only decreased CBF was observed after MDMA and this was localised to the right medial temporal lobe (MTL), thalamus, inferior visual cortex and the somatosensory cortex. Decreased CBF in the right amygdala and hippocampus correlated with ratings of the intensity of MDMA’s global subjective effects. The RSFC results complemented the CBF results, with decreases in RSFC between midline cortical regions, the medial prefrontal cortex and MTL regions, and increases between the amygdala and hippocampus. There were trend-level correlations between these effects and ratings of intense and positive subjective effects.

Conclusions
The MTLs appear to be specifically implicated in the mechanism of action of MDMA but further work is required to elucidate how the drug’s characteristic subjective effects arise from its modulation of spontaneous brain activity.

Carhart-Harris, R. L., Murphy, K., Leech, R., Erritzoe, D., Wall, M. B., Ferguson, B., … Nutt, D. J. (2014). The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labelling and Blood Oxygen Level-Dependent Resting-State Functional Connectivity. Biological Psychiatry. http://dx.doi.org/10.1016/j.biopsych.2013.12.015
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Hallucinogen use predicts reduced recidivism among substance-involved offenders under community corrections supervision

January 2, 2014 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Hallucinogen-based interventions may benefit substance use populations, but contemporary data informing the impact of hallucinogens on addictive behavior are scarce. Given that many individuals in the criminal justice system engage in problematic patterns of substance use, hallucinogen treatments also may benefit criminal justice populations. However, the relationship between hallucinogen use and criminal recidivism is unknown. In this longitudinal study, we examined the relationship between naturalistic hallucinogen use and recidivism among individuals under community corrections supervision with a history of substance involvement (n=25,622). We found that hallucinogen use predicted a reduced likelihood of supervision failure (e.g. noncompliance with legal requirements including alcohol and other drug use) while controlling for an array of potential confounding factors (odds ratio (OR)=0.60 (0.46, 0.79)). Our results suggest that hallucinogens may promote alcohol and other drug abstinence and prosocial behavior in a population with high rates of recidivism.

Hendricks, P. S., Clark, C. B., Johnson, M. W., Fontaine, K. R. & Cropsey, K. L. (2014). Hallucinogen use predicts reduced recidivism among substance-involved offenders under community corrections supervision. Journal of Psychopharmacology, 28(1), 62-66. http://dx.doi.org/10.1177/0269881113513851
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