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Spatiotemporal Brain Dynamics of Emotional Face Processing Modulations Induced by the Serotonin 1A/2A Receptor Agonist Psilocybin

Abstract

Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168–189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211–242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168–189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211–242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control.

Bernasconi, F., Schmidt, A., Pokorny, T., Kometer, M., Seifritz, E., & Vollenweider, F. X. (2013). Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin. Cerebral Cortex, bht178. 10.1093/cercor/bht178
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Relationship of ketamine's antidepressant and psychotomimetic effects in unipolar depression

Abstract

OBJECTIVES:
Ketamine and other NMDA (N-methyl-D-aspartate) antagonists produce fast-acting antidepressant-like effects, although the underlying mechanism is unclear. Furthermore, high affinity NMDA antagonists such as ketamine are associated with psychotomimetic effects. To date the link between the antidepressant and psychotomimetic effects of ketamine has not been explored. We examined the relationship between the antidepressant and psychotomimetic effects of a single ketamine infusion in subjects diagnosed with major depressive disorder.
METHODS:
In a double-blind, cross-over, placebo-controlled, two weeks clinical trial we studied the effects of ketamine (0.54 mg/kg within 30 min) in a group of 27 hospitalized depressive patients.
RESULTS:
Higher intensity of psychotomimetic symptoms, measured using BPRS, during ketamine administration correlated with alleviation in mood ratings during the following week with maximum on day seven. Ketamine was superior to placebo in all visits (day 1, 4, and 7) assessed by MADRS with effect size (Cohen´s d) of 0.62, 0.57, and 0.44 respectively. There was no significant correlation between ketamine and nor-ketamine plasma levels and MADRS score change at any study time point.
CONCLUSION:
The substantial relationship between ketamine’s antidepressant and psychotomimetic effects was found. This relationship could be mediated by the initial steps of ketamine’s action, trough NMDA receptors, shared by both ketamine’s clinical effects.
Sos, P., Klirova, M., Novak, T., Kohutova, B., Horacek, J., & Palenicek, T. (2013). Relationship of ketamine’s antidepressant and psychotomimetic effects in unipolar depression. Neuroendocrinology Letters34(4), 287-293.
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Acute effects of ayahuasca on neuropsychological performance: differences in executive function between experienced and occasional users.

Abstract

BACKGROUND:
Ayahuasca, a South American psychotropic plant tea containing the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine, has been shown to increase regional cerebral blood flow in prefrontal brain regions after acute administration to humans. Despite interactions at this level, neuropsychological studies have not found cognitive deficits in abstinent long-term users.

OBJECTIVES:
Here, we wished to investigate the effects of acute ayahuasca intake on neuropsychological performance, specifically on working memory and executive function.

METHODS:
Twenty-four ayahuasca users (11 long-term experienced users and 13 occasional users) were assessed in their habitual setting using the Stroop, Sternberg, and Tower of London tasks prior to and following ayahuasca intake.

RESULTS:
Errors in the Sternberg task increased, whereas reaction times in the Stroop task decreased and accuracy was maintained for the whole sample following ayahuasca intake. Interestingly, results in the Tower of London showed significantly increased execution and resolution times and number of movements for the occasional but not the experienced users. Additionally, a correlation analysis including all subjects showed that impaired performance in the Tower of London was inversely correlated with lifetime ayahuasca use.

CONCLUSIONS:
Acute ayahuasca administration impaired working memory but decreased stimulus-response interference. Interestingly, detrimental effects on higher cognition were only observed in the less experienced group. Rather than leading to increased impairment, greater prior exposure to ayahuasca was associated with reduced incapacitation. Compensatory or neuromodulatory effects associated with long-term ayahuasca intake could underlie preserved executive function in experienced users.

Bouso, J. C., Fábregas, J. M., Antonijoan, R. M., Rodríguez-Fornells, A., & Riba, J. (2013). Acute effects of ayahuasca on neuropsychological performance: differences in executive function between experienced and occasional users. Psychopharmacology, 230(3), 415-424. http://dx.doi.org/10.1007/s00213-013-3167-9
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Effects of Schedule I drug laws on neuroscience research and treatment innovation

Abstract

Many psychoactive drugs are used recreationally, particularly by young people. This use and its perceived dangers have led to many different classes of drugs being banned under national laws and international conventions. Indeed, the possession of cannabis, 3,4‑methylenedioxy‑N‑methylamphetamine (MDMA; also known as ecstasy) and psychedelics is stringently regulated. An important and unfortunate outcome of the controls placed on these and other psychoactive drugs is that they make research into their mechanisms of action and potential therapeutic uses — for example, in depression and post‑traumatic stress disorder — difficult and in many cases almost impossible.

Nutt, D. J., King, L. A., & Nichols, D. E. (2013). Effects of Schedule I drug laws on neuroscience research and treatment innovation. Nature Reviews Neuroscience, 14, 577-585. http://dx.doi.org/10.1038/nrn3530
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2C or not 2C: phenethylamine designer drug review

Abstract

New groups of synthetic “designer drugs” have increased in popularity over the past several years. These products mimic the euphoric effects of other well-known illicit drugs but are advertised as “legal” highs and are sold over the internet, at raves and night clubs, and in head shops. The 2C series drugs are ring-substituted phenethylamines that belong to a group of designer agents similar in structure to 3,4-methylenedioxy-N-methylamphetamine (MDMA, Ecstasy). Understanding the pharmacology and toxicology of these agents is essential in order to provide the best medical care for these patients. This review focuses on the pharmacology, pharmacokinetics, clinical effects, and treatment of 2C drug intoxication based on available published literature. Multiple names under which 2C drugs are sold were identified and tabulated. Common features identified in patients intoxicated with 2Cs included hallucinations, agitation, aggression, violence, dysphoria, hypertension, tachycardia, seizures, and hyperthermia. Patients may exhibit sympathomimetic symptoms or symptoms consistent with serotonin toxicity, but an excited delirium presentation seems to be consistent amongst deaths attributed to 2C drugs; at least five deaths have been reported in the literature in patients intoxicated with 2C drugs. 2C drugs are a group of designer intoxicants, many of which are marketed as legal, but may carry risks that consumers are unaware of. These drugs may be characterized by either serotonergic toxicity or a sympathomimetic toxidrome, but a presentation consistent with excited delirium is consistent amongst the reported 2C-related deaths. Treatment of 2C intoxication is primarily supportive, but immediate action is required in the context of excited delirium, hyperthermia, and seizure activity.

Dean, B. V., Stellpflug, S. J., Burnett, A. M., & Engebretsen, K. M. (2013). 2C or not 2C: phenethylamine designer drug review. Journal of Medical Toxicology, 9(2), 172-178. 10.1007/s13181-013-0295-x
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Entheogens, Society & Law – Towards a Politics of Consciousness, Autonomy & Responsibility

41U01VD7AyL._SX340_BO1,204,203,200_Entheogens, Society & Law takes a major step towards a comprehensive understanding of the human condition, elucidating how empathy, meaning and purpose emerge from three intersecting areas of human life: biology, consciousness and culture.

The term “entheogen” designates a class of psychoactive plant and substance uses that have played, and continue to play, an important role as catalysts of experiences of the “divine,” “sacred” or “numinous,” as well as in divination, healing and, more recently, psychotherapy. The authors expand on these ideas, borrowing from a wide range of disciplines — pharmacology, neurology, consciousness research, psychology, semiotics, theology and mythology — and immersing the reader in a radical and empowering exegesis of influential cultural myths such as that of Original Sin. The resulting insights have practical and ethical implications in many areas of contemporary society, including education, mental health, human rights and law.

Much of the literature on psychedelics and altered states of consciousness remains firmly entrenched in the dualistic logic of prohibition discourse. Unfortunately, this detracts from its ability to engage with the broader existential, ethical and humanitarian questions that, the author’s argue, any bona fide religious or therapeutic tradition needs to address. With its focus on ethics, Entheogens, Society & Law pursues a pragmatic inquiry guided by one paramount question: how can individuals take responsibility for their own lives and wrest power and authority from institutions that deprive them of the very liberties, e.g. to explore consciousness and alter mental functioning, upon which the exercise of responsibility is premised? This question leads to a critical examination of contemporary discourses on emergent ‘technologies of the self,’ human rights, the ‘common good’ — and the extents of state interference with the self-defining choices of sovereign individuals.

The theoretical questions raised by the meta-analysis presented here propose the possibility, if not necessity, of addressing the crises of modernity, including problems surrounding drug use, as a series of contingencies generated by the competing interests of individual’s search for a meaningful existence and powerful institutions exercising hegemonic control over what we can and cannot do towards that ends. This ethical inquiry exposes the faulty premises of exercises of authority and power by demonstrating the central role of human consciousness in the generation of values that ultimately define us and determine what we become. This places discussion on the nature of ‘mind-altering substances’ at the heart of contemporary discourses on human rights, offering empowering and inspiring insights into the future of humanity.

Entheogens, Society & Law — Towards a Politics of Consciousness, Autonomy & Responsibility, by Daniel Waterman, Melrose Books, 496 pages.

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Entheogens, Society & Law – Towards a Politics of Consciousness, Autonomy & Responsibility

Entheogens, Society & Law takes a major step towards a comprehensive understanding of the human condition, elucidating how empathy, meaning and purpose emerge from three intersecting areas of human life: biology, consciousness and culture.

The term “entheogen” designates a class of psychoactive plant and substance uses that have played, and continue to play, an important role as catalysts of experiences of the “divine,” “sacred” or “numinous,” as well as in divination, healing and, more recently, psychotherapy. The authors expand on these ideas, borrowing from a wide range of disciplines — pharmacology, neurology, consciousness research, psychology, semiotics, theology and mythology — and immersing the reader in a radical and empowering exegesis of influential cultural myths such as that of Original Sin. The resulting insights have practical and ethical implications in many areas of contemporary society, including education, mental health, human rights and law.

Much of the literature on psychedelics and altered states of consciousness remains firmly entrenched in the dualistic logic of prohibition discourse. Unfortunately, this detracts from its ability to engage with the broader existential, ethical and humanitarian questions that, the author’s argue, any bona fide religious or therapeutic tradition needs to address. With its focus on ethics, Entheogens, Society & Law pursues a pragmatic inquiry guided by one paramount question: how can individuals take responsibility for their own lives and wrest power and authority from institutions that deprive them of the very liberties, e.g. to explore consciousness and alter mental functioning, upon which the exercise of responsibility is premised? This question leads to a critical examination of contemporary discourses on emergent ‘technologies of the self,’ human rights, the ‘common good’ — and the extents of state interference with the self-defining choices of sovereign individuals.

The theoretical questions raised by the meta-analysis presented here propose the possibility, if not necessity, of addressing the crises of modernity, including problems surrounding drug use, as a series of contingencies generated by the competing interests of individual’s search for a meaningful existence and powerful institutions exercising hegemonic control over what we can and cannot do towards that ends. This ethical inquiry exposes the faulty premises of exercises of authority and power by demonstrating the central role of human consciousness in the generation of values that ultimately define us and determine what we become. This places discussion on the nature of ‘mind-altering substances’ at the heart of contemporary discourses on human rights, offering empowering and inspiring insights into the future of humanity.

Entheogens, Society & Law — Towards a Politics of Consciousness, Autonomy & Responsibility, door Daniel Waterman, Melrose Books, 496 pagina’s.

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Peak Experiences of Psilocybin Users and Non-Users

Maslow (1970) defined peak experiences as the most wonderful experiences of a person’s life, which may include a sense of awe, well-being, or transcendence. Furthermore, recent research has suggested that psilocybin can produce experiences subjectively rated as uniquely meaningful and significant (Griffiths et al. 2006). It is therefore possible that psilocybin may facilitate or change the nature of peak experiences in users compared to non-users. This study was designed to compare the peak experiences of psilocybin users and non-users, to evaluate the frequency of peak experiences while under the influence of psilocybin, and to assess the perceived degree of alteration of consciousness during these experiences. Participants were recruited through convenience and snowball sampling from undergraduate classes and at a musical event. Participants were divided into three groups, those who reported a peak experience while under the influence of psilocybin (psilocybin peak experience: PPE), participants who had used psilocybin but reported their peak experiences did not occur while they were under the influence of psilocybin (non-psilocybin peak experience: NPPE), and participants who had never used psilocybin (non-user: NU). A total of 101 participants were asked to think about their peak experiences and complete a measure evaluating the degree of alteration of consciousness during that experience. Results indicated that 47% of psilocybin users reported their peak experience occurred while using psilocybin. In addition, there were significant differences among the three groups on all dimensions of alteration of consciousness. Future research is necessary to identify factors that influence the peak experiences of psilocybin users in naturalistic settings and contribute to the different characteristics of peak experiences of psilocybin users and non-users.

Cummins, C., & Lyke, J. (2013). Peak Experiences of Psilocybin Users and Non-Users. Journal of psychoactive drugs, 45(2), 189-194. 10.1080/02791072.2013.785855
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Mystic Chemist: The Life of Albert Hofmann and His Discovery of LSD

mysticchemistMystic Chemist begins at the start of the twentieth century, in the Swiss town of Basel which is evolving from a popular health spa into a major industrial city. The story concludes more than a century later, after celebrating Albert Hofmann’s 100th birthday. It tells the unique story of a soon to be famous scientist, highlighting his academic journey, his research at Sandoz and then, as the discoverer of LSD, his meetings and interactions with illustrious writers, artists and thinkers, from all over the world, whose common interest is a fascination with the new wonder-drug. Luminaries like Aldous Huxley, Timothy Leary and Richard Alpert appear on the scene and Hofmann begins a prolific correspondence with them and other interested parties. Sometimes he sends a sample, other times he hears of their “trips” on LSD or other psychedelic substances, like mescaline or psilocybin. From the beginning he takes a positive view towards efforts by physicians and psychotherapists to include LSD in new approaches to the treatment of illnesses. He sees the “psychedelic” potential of this “wonder drug” as beneficial to all. And he expresses his conviction that mystical experiences and trips to other worlds of consciousness are the best preparation for the very last journey he and every one of us well must eventually make. At the age of 102, Albert Hofmann dies at home. His vitality and open mindedness stay with him until his last breath. The life of Albert Hofmann, the Mystic Chemist, is a testimony to how one can reach a great age all the while remaining physically and mentally fit and spiritually aware. Mystic Chemist: The Life of Albert Hofmann and His Discovery of LSD tells the story of Albert Hofmann’s life and the parallel story of the wonder-drug, LSD. The book runs to 408 pages and contains over 500 color and black and white photographs, illustrations and drawings; some of them never published before. With a foreword by world renowned Czech psychiatrist Stanislav Grof, Mystic Chemist will be published in May 2013, and is available in hardcover and softcover editions.

Mystic Chemist: The Life of Albert Hofmann and His Discovery of LSD, door Dieter Hagenbach & Lucius Werthmüller, Synergetic Press, 408 pagina’s.

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Lecture: Psilocybin in the treatment of end-of-life anxiety

flashback-psychedelic-research-returns

Dr. Grob will come all the way from Los Angeles to give a lecture on his research into psilocybin, the active ingredient in ‘magic mushrooms’. The main focus of this lecture will be the investigation into the safety and efficacy of psilocybin as a therapeutic aid in the treatment of severe anxiety in adult patients with advanced-stage cancer. Research into substances such as MDMA and ayahuasca, also investigated at the Harbor-UCLA Medical Center, will be addressed as well. There will be ample time for questions and discussion. Students, health care professionals and therapists are encouraged to attend.

Dr. Charles Grob is professor in Psychiatry & Biobehavioral Sciences at UCLA, Los Angeles (USA). He has published extensively on topics such as substance misuse and the history of hallucinogens in psychiatry. He performed the first FDA approved study of the physiological and psychological effects of MDMA; a multi-national study of ayahuasca in Brazil and has performed a pilot investigation of the safety and efficacy of psilocybin in the treatment of anxiety in adult patients with advanced-stage cancer.
The lecture will take place on Friday 14 June, from 16:00 – 18:00.
LOCATION: CREA (Muziekzaal), Nieuwe Achtergracht 170 Amsterdam.
FEE: €5,- regular / students & alumni get in for free

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Peer Perspectives: How Psychedelics Induce Neuroplasticity - February 26