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Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies

/ Mushrooms / Psilocybin, Papers, Psychology, Psychotic Disorders, Publications / / , , ,

Abstract

Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and longterm subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1–4 oral doses of psilocybin (45–315mg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

Studerus, E., Kometer, M., Hasler, F., & Vollenweider, F. X. (2010). Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. Journal of Psychopharmacology, 25(11), 1434-1452. http://dx.doi.org/10.1177/0269881110382466
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Nature smokkelt psychedelica de blogosfeer binnen

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blogo508

In het kader van het recent gepubliceerde artikel The neurobiology of psychedelic drugs: implications for the treatment of mood disorders heeft wetenschappelijk tijdschrift Nature vier bekende neuroscience bloggers benaderd om elk een ander aspect van de geneeskundige toepassingen van psychedelica onder de loep te nemen, en dit toegankelijk te maken voor een breed publiek.

Neuroskeptic beschrijft de invloed van LSD, Psilocybine en Mescaline op het serotonerge systeem en hoe dit tot een behandeling van depressie zou kunnen leiden.

The Neurocritic vraagt zich af of Ketamine wellicht zou helpen tegen deze zelfde aandoening.

Vaughan Bell beschouwt voor Mind Hacks de therapeutische mogelijkheden van DMT.

En tot slot schrijft Moheb Costandi voor Neurophilosophy over het vroegere gebruik van LSD in de psychiatrie. Bovendien vatte hij de vier posts samen in een artikel voor de Britse krant The Guardian.

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Nature brings psychedelics to the blogosphere

/ Publications /

blogo508

In the context of the recent paper The neurobiology of psychedelic drugs: implications for the treatment of mood disorders scientific journal Nature has approached four well-known neuroscience bloggers to each blog about a different aspect of the medical applications of psychedelic drugs.

Neuroskeptic describes how LSD, Psilocybin and Mescaline affect the serotonergic system and considers a psychedelic treatment for depression.

The Neurocritic wonders whether Ketamine might be able to treat this same disorder.

Vaughan Bell over at Mind Hacks covers the therapeutic potential of DMT.

Moheb Costandi from Neurophilosophy investigates the “secret history of psychedelic psychiatry.” On top of that he wrote an overview discussing all four posts for British newspaper The Guardian.

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The neurobiology of psychedelic drugs: implications for the treatment of mood disorders

/ Depressive Disorders, DMT, Ketamine, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications / / ,

Abstract

After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.

Vollenweider, F. X., & Kometer, M. (2010). The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nature Reviews Neuroscience, 11, 642-651. http://dx.doi.org/10.1038/nrn2884
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Intrahippocampal LSD accelerates learning and desensitizes the 5-HT2A receptor in the rabbit

/ LSD, Papers, Publications / / , , , , , ,

Abstract

Rationale: Parenteral injections of d-lysergic acid diethylamide (LSD), a serotonin 5-HT2A receptor agonist, enhance eyeblink conditioning. Another hallucinogen, (±)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), was shown to elicit a 5-HT2A-mediated behavior (head bobs) after injection into the hippocampus, a structure known to mediate trace eyeblink conditioning.

Objective: This study aims to determine if parenteral injections of the hallucinogens LSD, d,l-2,5-dimethoxy-4-methylamphetamine, and 5-methoxy-dimethyltryptamine elicit the 5-HT2A-mediated behavior of head bobs and whether intrahippocampal injections of LSD would produce head bobs and enhance trace eyeblink conditioning.

Materials and methods: LSD was infused into the dorsal hippocampus just prior to each of eight conditioning sessions. One day after the last infusion of LSD, DOI was infused into the hippocampus to determine whether there had been a desensitization of the 5-HT2A receptor as measured by a decrease in DOI-elicited head bobs.

Results: Acute parenteral or intrahippocampal LSD elicited a 5-HT2A but not a 5-HT2C-mediated behavior, and chronic administration enhanced conditioned responding relative to vehicle controls. Rabbits that had been chronically infused with 3 or 10 nmol per side of LSD during Pavlovian conditioning and then infused with DOI demonstrated a smaller increase in head bobs relative to controls.

Conclusions: LSD produced its enhancement of Pavlovian conditioning through an effect on 5-HT2A receptors located in the dorsal hippocampus. The slight, short-lived enhancement of learning produced by LSD appears to be due to the development of desensitization of the 5-HT2A receptor within the hippocampus as a result of repeated administration of its agonist (LSD).

Romano, A. G., Quinn, J. L., Li, L., Dave, K. D., Schindler, E. A., Aloyo, V. J., & Harvey, J. A. (2010). Intrahippocampal LSD accelerates learning and desensitizes the 5-HT2A receptor in the rabbit. Psychopharmacology, 212(3), 441–448. http://dx.doi.org/10.1007/s00213-010-2004-7
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DEA geeft goedkeuring voor MDMA/PTSD-studie

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Wederom nieuws op het onderzoek-vlak: op 27 augustus 2010 heeft de DEA, een Amerikaanse overheidsorganisatie die gaat over de wetten met betrekking tot ‘controlled substances’ in Amerika, zijn goedkeuring gegeven voor een onderzoek naar de effecten van MDMA bij oorlogsveteranen met een posttraumatische stressstoornis. MAPS kan nu aan de slag met het onderzoek, dat $500.000 kost en ongeveer twee jaar in beslag zal nemen. Het grootste deel van het budget moet nog bij elkaar gevonden worden, maar het is zeker een stap in de goede richting!

Op de conferentie van OPEN (23-24 oktober 2010) kun je meer horen over dit soort onderzoeken. Kijk hier voor meer informatie.

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DEA approves MDMA/PTSD study

/ MDMA, Publications /

More news on the subject of research: on august 27th 2010 the DEA, an American government organisation in charge of the laws regarding ‘controlled substances’ in the US, has approved a study regarding the effects of MDMA on war veterans suffering from post-traumatic stress syndrome. MAPS can go ahead with the research, which will cost $500,000 and will take the good part of two years. Most of the budget still has to be found, but it’s a step in the right direction!

On the OPEN conference (october 23/24) you can hear more about these kinds of studies. Click here for more information.

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Dimethyltryptamine (DMT): Subjective effects and patterns of use among Australian recreational users

/ Ayahuasca, DMT, Papers, Psychology, Publications / / ,

Abstract

Dimethyltryptamine (DMT) is an endogenous hallucinogen with traditional use as a sacrament in the orally active preparation of ayahuasca. Although the religious use of ayahuasca has been examined extensively, very little is known about the recreational use of DMT. In this study, Australian participants (n = 121) reporting at least one lifetime use of DMT completed an online questionnaire recording patterns of use, subjective effects and attitudes towards their DMT use. Smoking DMT was by far the most common route of administration (98.3%) with a comparatively smaller proportion reporting use of ayahuasca (30.6%). The reasons for first trying DMT were out of a general interest in hallucinogenic drugs (46.6%) or curiosity about DMT’s effects (41.7%), while almost one-third (31.1%) cited possible psychotherapeutic benefits of the drug. An increase in psychospiritual insight was the most commonly reported positive effect of both smoked DMT (75.5%) and ayahuasca (46.7%), a finding that is consistent with other studies examining the ritualised use of ayahuasca in a religious context. Although previous studies of DMT use have examined ayahuasca use exclusively, the present study demonstrates the ubiquity of smoking as the most prevalent route of administration among recreational DMT users.

Cakica, V., Potkonyakb, J., & Marshalla, A. (2010). Dimethyltryptamine (DMT): Subjective effects and patterns of use among Australian recreational users. Drug and Alcohol Dependence, 111(1-2), 30-37. http://dx.doi.org/10.1016/j.drugalcdep.2010.03.015
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Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV)

/ Ketamine, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , ,

Abstract

This paper describes a refinement of Dittrich’s Altered States of Consciousness questionnaire. This questionnaire is among the most widely used self-report questionnaires for retrospectively assessing subjective experiences induced by psychedelics and other psychoactive drugs. Using data collected over many years from 591 human volunteers, they factored the original four subscales developed by Dittrich into 11 new subscales. This new improved instrument will play an important role in more precisely defining the qualitative subjective experiences in research with psychedelics.

Background: The OAV questionnaire has been developed to integrate research on altered states of consciousness (ASC). It measures three primary and one secondary dimensions of ASC that are hypothesized to be invariant across ASC induction methods. The OAV rating scale has been in use for more than 20 years and applied internationally in a broad range of research fields, yet its factorial structure has never been tested by structural equation modeling techniques and its psychometric properties have never been examined in large samples of experimentally induced ASC.

Methodology/Principal Findings: The present study conducted a psychometric evaluation of the OAV in a sample of psilocybin (n = 327), ketamine (n = 162), and MDMA (n = 102) induced ASC that was obtained by pooling data from 43 experimental studies. The factorial structure was examined by confirmatory factor analysis, exploratory structural equation modeling, hierarchical item clustering (ICLUST), and multiple indicators multiple causes (MIMIC) modeling. The originally proposed model did not fit the data well even if zero-constraints on non-target factor loadings and residual correlations were relaxed. Furthermore, ICLUST suggested that the ‘‘oceanic boundlessness’’ and ‘‘visionary restructuralization’’ factors could be combined on a high level of the construct hierarchy. However, because these factors were multidimensional, we extracted and examined 11 new lower order factors. MIMIC modeling indicated that these factors were highly measurement invariant across drugs, settings, questionnaire versions, and sexes. The new factors were also demonstrated to have improved homogeneities, satisfactory reliabilities, discriminant and convergent validities, and to differentiate well among the three drug groups.

Conclusions/Significance: The original scales of the OAV were shown to be multidimensional constructs. Eleven new lower order scales were constructed and demonstrated to have desirable psychometric properties. The new lower order scales are most likely better suited to assess drug induced ASC.

Studerus, E., Gamma, A., & Vollenweider, F. X. (2010). Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV). PLoS ONE, 5(8). http://dx.doi.org/10.1371/journal.pone.0012412
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A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications / / , , , , , ,

Abstract

Context: Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects—for instance, within a few hours or days—would have an enormous impact on patient care and public health.

Objective: To determine whether an N-methyl-Daspartate–receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression.

Design: A randomized, placebo-controlled, doubleblind, crossover, add-on study conducted from October 2006 to June 2009.

Setting: Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland.

Patients: Eighteen subjects with DSM-IV bipolar depression (treatment-resistant).

Interventions: Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery- Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion.

Results: Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d=0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d=0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point.

Diazgranados, N.,  Ibrahim, L. Brutsche, N. E., Newberg, A., Kronstein, P.,  Khalife, S., … Zarate Jr., Z. A. (2010). A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression. Archives of General Psychiatry, 67(8). http://dx.doi.org/10.1001/archgenpsychiatry.2010.90
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Psychedelics and Acceptance and Commitment Therapy (ACT): A Process-Based Approach - September 15th

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