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Robin Carhart-Harris – Brain imaging and depression research with psychedelics

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Brain imaging and depression research with psychedelics
The talk will review brain imaging work on the action of psychedelics on the brain and describe the results of a clinical trial assessing psilocybin as a treatment for depression. It will also review the broader societal impact of psychedelic drug-use and discuss its implications.
Biography
Robin Carhart-Harris studies the brain effects of LSD, psilocybin (magic mushrooms), and MDMA. Most recently he has completed the first phase of a clinical trial looking at the potential of psilocybin to treat depression.

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Unlocking the Traumatic through the Psychedelic in One Flew over the Cuckoo’s Nest

/ Papers, Philosophy & Religious Studies, Publications / /

Abstract

This is an attempt to investigate the causal relationship existing between the psychedelic literary genre in fiction and the application of trauma theory in the study of One Flew over the Cuckoo’s Nest. Trauma theory, which is a psychological theory in essence; has been widely linked to the study of literature since traumatic responses take narrative forms. Scientifically, many studies have proven that the psychedelic trip leads to a deepened exploration of the unconscious tracing latent emotional traumas. Henceforth, I am going to explore this novel as a psychedelic example of science fiction through a generic analysis due to the numerous parallels I have noticed with the effects of drug administration on real life patients. I will base my claim on a medical theory known as Psychedelic Information Theory which investigates psychedelic hallucinations, expanded consciousness and their impact on the metaphysical aspects of self-exploration. Consequently, I shall presuppose that psychedelics act metaphorically on the text of One Flew over the Cuckoo’s Nest inducing character-based hallucinatory narratives. Hallucinations are caused by an eruption of a psychedelic consciousness that is the antithesis of the normal state of a mind. Hallucinations range from happy enjoyable experiences laden with kaleidoscopic colourful streams of visions to painful manifestations of latent trauma. I endeavour to analyze this novel as a traumatic example of psychedelic fiction through establishing a cause-result relationship between information theory and trauma theory as a fluid encounter between literature and science within science fiction framework. Finally, I attempt to link the cultural integration of psychedelics to the shift of the traumatic experience from cultural to structural. This paper explores primarily the manifestations of Chief Bromden’s historic trauma. It traces secondarily the psychedelic characteristics of the novel. Lastly, it studies the effects of Bromden’s psychedelic journey on his traumatic recovery.

Besbes, M. (2016). Unlocking the Traumatic through the Psychedelic in One Flew over the Cuckoo’s Nest.
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Unlocking the Traumatic through the Psychedelic in One Flew over the Cuckoo's Nest

/ Papers, Philosophy & Religious Studies, Publications / /

Abstract

This is an attempt to investigate the causal relationship existing between the psychedelic literary genre in fiction and the application of trauma theory in the study of One Flew over the Cuckoo’s Nest. Trauma theory, which is a psychological theory in essence; has been widely linked to the study of literature since traumatic responses take narrative forms. Scientifically, many studies have proven that the psychedelic trip leads to a deepened exploration of the unconscious tracing latent emotional traumas. Henceforth, I am going to explore this novel as a psychedelic example of science fiction through a generic analysis due to the numerous parallels I have noticed with the effects of drug administration on real life patients. I will base my claim on a medical theory known as Psychedelic Information Theory which investigates psychedelic hallucinations, expanded consciousness and their impact on the metaphysical aspects of self-exploration. Consequently, I shall presuppose that psychedelics act metaphorically on the text of One Flew over the Cuckoo’s Nest inducing character-based hallucinatory narratives. Hallucinations are caused by an eruption of a psychedelic consciousness that is the antithesis of the normal state of a mind. Hallucinations range from happy enjoyable experiences laden with kaleidoscopic colourful streams of visions to painful manifestations of latent trauma. I endeavour to analyze this novel as a traumatic example of psychedelic fiction through establishing a cause-result relationship between information theory and trauma theory as a fluid encounter between literature and science within science fiction framework. Finally, I attempt to link the cultural integration of psychedelics to the shift of the traumatic experience from cultural to structural. This paper explores primarily the manifestations of Chief Bromden’s historic trauma. It traces secondarily the psychedelic characteristics of the novel. Lastly, it studies the effects of Bromden’s psychedelic journey on his traumatic recovery.

Besbes, M. (2016). Unlocking the Traumatic through the Psychedelic in One Flew over the Cuckoo’s Nest.
Link to full text

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Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: role of serotonin 5HT2-type receptors

/ MDMA, Neuroscience, Papers, Publications, Substance Use Disorder / / , ,

Abstract

Rationale: The synthetic phenethylamines are recreational drugs known to produce psychostimulant effects. However, their abuse potential has not been widely studied.
Objectives: Here, we investigated the rewarding and the hallucinatory effects of 2,5-dimetoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA) in comparison with the classical 3,4-methylenedioxymethamphetamine (MDMA). In addition, the role of serotonin 5-HT2-like receptor on the abovementioned effects was evaluated.
Methods: Zebrafish were intramuscularly (i.m.) treated with a wide range of doses of DOB (0.1–20 mg/kg), PMA (0.0005–2 mg/kg), or MDMA (0.5–160 mg/kg). Animals were submitted to a conditioned place preference (CPP) task, to investigation of the rewarding properties, and to the evaluation of hallucinatory behavior in terms of appearance of a trance-like behavior. The serotonin 5-HT2 subtype receptor antagonist ritanserin (0.025–2.5 mg/kg) in association with the maximal effective dose of MDMA, DOB, and PMA was given i.m., and the effect on CPP or hallucinatory behavior was evaluated.
Results: MDMA and its derivatives exhibited CPP in a biphasic fashion, being PMA the most potent. This effect was accompanied, for DOB (2 mg/kg) and PMA (0.1 mg/kg), by a trance-like hallucinatory behavior. MDMA at a high dose as 160 mg/kg did not induce any hallucinatory behavior. Ritanserin significantly blocked the rewarding and hallucinatory effects suggesting the involvement of serotonin 5HT2 subtype receptor.
Conclusion: Collectively, these findings demonstrate for the first time that the rewarding properties of DOB and PMA are accompanied by hallucinatory behavior through a serotonergic system and reinforce zebrafish as an emerging experimental model for screening new hallucinogens.
Ponzoni, L., Daniela, B., & Sala, M. (2016). Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: role of serotonin 5HT2-type receptors. Psychopharmacology, 1-9. http://dx.doi.org/10.1007/s00213-016-4352-4
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Letter to the Editor: R-ketamine: a rapid-onset and sustained antidepressant without risk of brain toxicity

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

Hashimoto, K. (2016). Letter to the Editor: R-ketamine: a rapid-onset and sustained antidepressant without risk of brain toxicity. Psychological medicine, 1. http://dx.doi.org/10.1017/S0033291716000969
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The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging

/ Ayahuasca, Papers, Psychology, Publications, Substance Use Disorder / / , , ,

Abstract

RATIONALE: In recent decades, the use of ayahuasca (AYA) – a β-carboline- and dimethyltryptamine-rich hallucinogenic botanical preparation traditionally used by Northwestern Amazonian tribes for ritual and therapeutic purposes – has spread from South America to Europe and the USA, raising concerns about its possible toxicity and hopes of its therapeutic potential. Thus, it is important to analyze the acute, subacute, and long-term effects of AYA to assess its safety and toxicity.

OBJECTIVES: The purpose of this study was to conduct a systematic review of human studies assessing AYA effects on psychiatric symptoms, neuropsychological functioning, and neuroimaging.

METHODS: Papers published until 16 December 2015 were included from PubMed, LILACS and SciELO databases following a comprehensive search strategy and pre-determined set of criteria for article selection.

RESULTS: The review included 28 full-text articles. Acute AYA administration was well tolerated, increased introspection and positive mood, altered visual perceptions, activated frontal and paralimbic regions and decreased default mode network activity. It also improved planning and inhibitory control and impaired working memory, and showed antidepressive and antiaddictive potentials. Long-term AYA use was associated with increased cortical thickness of the anterior cingulate cortex and cortical thinning of the posterior cingulate cortex, which was inversely correlated to age of onset, intensity of prior AYA use, and spirituality. Subacute and long-term AYA use was not associated with increased psychopathology or cognitive deficits, being associated with enhanced mood and cognition, increased spirituality, and reduced impulsivity.

CONCLUSIONS: Acute, subacute, and long-term AYA use seems to have low toxicity. Preliminary studies about potential therapeutic effects of AYA need replication due to their methodological limitations.

dos Santos, R. G., Balthazar, F. M., Bouso, J. C., & Hallak, J. E. (2016). The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging. Journal of Psychopharmacology, 0269881116652578.

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Salvia divinorum: toxicological aspects and analysis in human biological specimens

/ Biology & Ethnobotany, Papers, Publications, Salvia / Salvinorin A / / , , ,

Abstract

The identification and quantitation of the main psychoactive component of Salvia divinorum (salvinorin A) in biological specimens are crucial in forensic and clinical toxicology. Despite all the efforts made, its uncontrolled abuse has increased quickly, exposing its users’ health to serious risks both in the short and long term. The use of alternative biological matrices in toxicological analyzes can be advantageous as complementary postmortem samples, or in situations when neither blood nor urine can be collected; they may be useful tools in those determinations, providing important information about prior exposure. The aim of this article is to present a brief summary of legal aspects of Salvia divinorum and salvinorin A, including the methods used for the determination of the latter in biological matrices.

Margalho, C., Corte-Real, F., López-Rivadulla, M., & Gallardo, E. (2016). Salvia divinorum: toxicological aspects and analysis in human biological specimens. Bioanalysis, (0). http://dx.doi.org/10.4155/bio-2016-0067

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Magic mushroom compound is a potential treatment for patients with major depression

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

Abstract

A hallucinogenic compound derived from magic mushrooms could provide a new route for antidepressant research.

Carhart-Harris, R. L. Magic mushroom compound is a potential treatment for patients with major depression. http://dx.doi.org/10.7748/ns.30.41.15.s18
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Underreporting of ecstasy use among high school seniors in the US

/ MDMA, Papers, Publications / / , ,

Abstract

Background: National surveys suggest ecstasy (3,4-methylenedioxymethamphetamine [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”][MDMA]) use has decreased substantially among adolescents in the US since 2001; however, the recent phenomenon of “Molly” (ecstasy marketed as “pure MDMA”) may be leading to underreporting of use as not all users are aware that “Molly” is a form of ecstasy.

Methods: We examined 2014 data from Monitoring the Future, a nationally representative survey of high school seniors in the US (N = 6250, modal age: 18). Three randomly distributed survey forms asked about ecstasy use, and one included “Molly” in the definition. Self-reported lifetime, 12-month, and 30-day ecstasy use were compared to determine whether including “Molly” in the definition was associated with higher prevalence or frequency of use.

Results: The form including “Molly” in the definition had significantly higher prevalence than the two (combined) forms that did not. Lifetime use (8.0% vs. 5.5%) and 12-month use (5.1% vs. 3.6%) were significantly higher with “Molly” in the definition. Lifetime prevalence remained higher with “Molly” in the definition when controlling for correlates of ecstasy use; however, 12-month use did not. Differences in prevalence were associated with lifetime occasions of use, with lower concordance between forms at lower levels of lifetime occasions (e.g., 1–2 times). Survey form was not related to number of times used among more frequent users.

Conclusions: Prevalence of ecstasy use appears to be underestimated when “Molly” is not included in the definition of ecstasy/MDMA. Surveys should include “Molly” in the definition of ecstasy to more adequately assess prevalence of use.

Palamar, J. J., Keyes, K., & Cleland, C. M. (2016). Underreporting of ecstasy use among high school seniors in the US. Drug and Alcohol Dependence. http://dx.doi.org/10.1016/j.drugalcdep.2016.06.001
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Serotonin antagonists fail to alter MDMA self-administration in rats

/ MDMA, Neuroscience, Papers, Publications / / , , , , , ,

Abstract

Acute exposure to ±3,4-methylenedioxymethamphetamine (MDMA) preferentially increases release of serotonin (5-HT), and a role of 5-HT in many of the behavioral effects of acute exposure to MDMA has been demonstrated. A role of 5-HT in MDMA self-administration in rats has not, however, been adequately determined. Therefore, the present study measured the effect of pharmacological manipulation of some 5-HT receptor subtypes on self-administration of MDMA. Rats received extensive experience with self-administered MDMA prior to tests with 5-HT ligands. Doses of the 5-HT1A antagonist, WAY 100635 (0.1-1.0mg/kg), 5-HT1B antagonist, GR 127935 (1.0-3.0mg/kg), and the 5-HT2A antagonist, ketanserin (1.0-3.0mg/kg) that have previously been shown to decrease self-administration of other psychostimulants and that decreased MDMA-produced hyperactivity in the present study did not alter MDMA self-administration. Experimenter-administered injections of MDMA (10.0mg/kg, ip) reinstated extinguished drug-taking behavior, but this also was not decreased by any of the antagonists. In contrast, both WAY 100635 and ketanserin, but not GR 127935, decreased cocaine-produced drug seeking in rats that had been trained to self-administered cocaine. The 5-HT1A agonist, 8-OH-DPAT (0.1-1.0mg/kg), but not the 5-HT1B/1A agonist, RU 24969 (0.3-3.0mg/kg), decreased drug-seeking produced by the reintroduction of a light stimulus that had been paired with self-administered MDMA infusions. These findings suggest a limited role of activation of 5-HT1A, 5-HT1B or 5-HT2 receptor mechanisms in MDMA self-administration or in MDMA-produced drug-seeking following extinction. The data suggest, however, that 5-HT1A agonists inhibit cue-induced drug-seeking following extinction of MDMA self-administration and might, therefore, be useful adjuncts to therapies to limit relapse to MDMA use.

Schenk, S., Foote, J., Aronsen, D., Bukholt, N., Highgate, Q., Van de Wetering, R., & Webster, J. (2016). Serotonin antagonists fail to alter MDMA self-administration in rats. Pharmacology Biochemistry and Behavior. http://dx.doi.org/10.1016/j.pbb.2016.06.002

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Journal Club #22: Applying the EU Regulatory Framework to Determine the Benefit–Risk Profile of Psychedelics - March 3

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