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

June 21, 2016 / Papers, Philosophy & Religious Studies, Publications / By /

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

June 21, 2016 / Papers, Philosophy & Religious Studies, Publications / By /

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

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

June 16, 2016 / MDMA, Neuroscience, Papers, Publications, Substance Use Disorder / By / , ,

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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The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging

June 10, 2016 / Ayahuasca, Papers, Psychology, Publications, Substance Use Disorder / By / , , ,

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

June 9, 2016 / Biology & Ethnobotany, Papers, Publications, Salvia / Salvinorin A / By / , , ,

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

June 8, 2016 / Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

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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Return of the lysergamides. Part II: Analytical and behavioural characterization of N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2’S,4’S)-lysergic acid 2,4-dimethylazetidide (LSZ)

June 6, 2016 / LSD, Neuroscience, Papers, Publications / By / , , , , , ,

Abstract

Lysergic acid N,N-diethylamide (LSD) is perhaps one of the most intriguing psychoactive substances known and numerous analogs have been explored to varying extents in previous decades. In 2013, N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2’S,4’S)-lysergic acid 2,4-dimethylazetidide (LSZ) appeared on the ‘research chemicals’/new psychoactive substances (NPS) market in both powdered and blotter form. This study reports the analytical characterization of powdered AL-LAD and LSZ tartrate samples and their semi-quantitative determination on blotter paper. Included in this study was the use of nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), low and high mass accuracy electrospray MS(/MS), high performance liquid chromatography diode array detection and GC solid-state infrared analysis. One feature shared by serotonergic psychedelics, such as LSD, is the ability to mediate behavioural responses via activation of 5-HT2A receptors. Both AL-LAD and LSZ displayed LSD-like responses in male C57BL/6 J mice when employing the head-twitch response (HTR) assay. AL-LAD and LSZ produced nearly identical inverted-U-shaped dose-dependent effects, with the maximal responses occurring at 200 µg/kg. Analysis of the dose responses by nonlinear regression confirmed that LSZ (ED50 = 114.2 nmol/kg) was equipotent to LSD (ED50 = 132.8 nmol/kg) in mice, whereas AL-LAD was slightly less potent (ED50  = 174.9 nmol/kg). The extent to which a comparison in potency can be translated directly to humans requires further investigation. Chemical and pharmacological data obtained from NPS may assist research communities that are interested in various aspects related to substance use and forensic identification.

Brandt, S. D., Kavanagh, P. V., Westphal, F., Elliott, S. P., Wallach, J., Colestock, T., … & Halberstadt, A. L. (2016). Return of the lysergamides. Part II: Analytical and behavioural characterization of N6‐allyl‐6‐norlysergic acid diethylamide (AL‐LAD) and (2’S, 4’S)‐lysergic acid 2, 4‐dimethylazetidide (LSZ). Drug testing and analysis. http://dx.doi.org/10.1002/dta.1985
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Serotonin antagonists fail to alter MDMA self-administration in rats

June 2, 2016 / MDMA, Neuroscience, Papers, Publications / By / , , , , , ,

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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Potential involvement of serotonergic signaling in ketamine’s antidepressant actions: A critical review

June 2, 2016 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , , , , ,

Abstract

A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine’s antidepressant effects.

The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine’s antidepressant activity do not appear to preclude the possibility that non-glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine’s antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine’s antidepressant effect is currently not understood, and therefore, more studies are warranted to confirm this hypothesis and explore the specific pathways that might implicate 5-HT.

du Jardin, K. G., Müller, H. K., Elfving, B., Dale, E., Wegener, G., & Sanchez, C. (2016). Potential involvement of serotonergic signaling in ketamine’s antidepressant actions: A critical review. Progress in Neuro-Psychopharmacology and Biological Psychiatry. http://dx.doi.org/10.1016/j.pnpbp.2016.05.007
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