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Psychology

The Meaning-Enhancing Properties of Psychedelics and Their Mediator Role in Psychedelic Therapy, Spirituality, and Creativity

March 6, 2018 / Creativity, Mushrooms / Psilocybin, Papers, Psychology, Publications, Spirituality / By /

Abstract

Past research has demonstrated to the ability of psychedelics to enhance suggestibility, and pointed to their ability to amplify perception of meaning. This paper examines the existing evidence for the meaning-enhancing properties of psychedelics, and argues that the tendency of these agents to enhance the perception of significance offers valuable clues to explaining their reported ability to stimulate a variety of therapeutic processes, enhance creativity, and instigate mystical-type experiences. Building upon previous research, which suggested the potential role of psychedelic meaning-enhancement in enhancing placebo response, the paper explores the mechanisms by which the meaning-amplifying properties of psychedelics might also play a role in enhancing creativity, as well as in effecting mystical-type experiences. The wider social and public-health implications of this hypothesis are discussed, and suggestions are made as to the various ways in which scientific understanding of the meaning-enhancing properties of psychedelics might be advanced and utilized.
Hartogsohn, I. (2018). The meaning-enhancing properties of psychedelics and their mediator role in psychedelic therapy, spirituality and creativity. Frontiers in neuroscience, 12, 129. 10.3389/fnins.2018.00129
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Unifying Theories of Psychedelic Drug Effects

March 2, 2018 / Consciousness, Papers, Personality, Phenomenology, Psychiatry, Psychology, Psychopharmacology, Publications / By /

Abstract

How do psychedelic drugs produce their characteristic range of acute effects in perception, emotion, cognition, and sense of self? How do these effects relate to the clinical efficacy of psychedelic-assisted therapies? Efforts to understand psychedelic phenomena date back more than a century in Western science. In this article I review theories of psychedelic drug effects and highlight key concepts which have endured over the last 125 years of psychedelic science. First, I describe the subjective phenomenology of acute psychedelic effects using the best available data. Next, I review late 19th-century and early 20th-century theories—model psychoses theory, filtration theory, and psychoanalytic theory—and highlight their shared features. I then briefly review recent findings on the neuropharmacology and neurophysiology of psychedelic drugs in humans. Finally, I describe recent theories of psychedelic drug effects which leverage 21st-century cognitive neuroscience frameworks—entropic brain theory, integrated information theory, and predictive processing—and point out key shared features that link back to earlier theories. I identify an abstract principle which cuts across many theories past and present: psychedelic drugs perturb universal brain processes that normally serve to constrain neural systems central to perception, emotion, cognition, and sense of self. I conclude that making an explicit effort to investigate the principles and mechanisms of psychedelic drug effects is a uniquely powerful way to iteratively develop and test unifying theories of brain function.
Swanson, L. R. (2018). Unifying Theories of Psychedelic Drug Effects?. Frontiers in Pharmacology, 9, 172. 10.3389/fphar.2018.00172
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Sex differences in sub-anesthetic ketamine’s antidepressant effects and abuse liability.

March 2, 2018 / Depression, Ketamine, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Substance Use Disorder / By / ,

Abstract

Sub-anesthetic ketamine produces rapid antidepressant effects in patients with bipolar and unipolar major depression where conventional monoaminergic-based antidepressant drugs have been ineffective or ridden with side effects. A single ketamine infusion can produce antidepressant effects lasting up to two weeks, and multiple ketamine infusions prolong this effect. Pre-clinical studies are underway to uncover ketamine’s mechanisms of action, but there are still many questions unanswered regarding the safety of its long-term use. Abuse liability is one area of concern, as recreational ketamine use is an ongoing issue in many parts of the world. Another understudied area is sex differences in responsivity to ketamine. Women are twice as likely as men to be diagnosed with depression, and they progress through stages of drug addiction more rapidly than their male counterparts. Despite this, preclinical studies in ketamine’s antidepressant and addictive-like behaviors in females are limited. These intersecting factors in recent clinical and pre-clinical studies are reviewed to characterize ketamine’s therapeutic potential, its limitations, and its potential mechanisms of action.
Wright, K. N., & Kabbaj, M. (2018). Sex differences in sub-anesthetic ketamine’s antidepressant effects and abuse liability. Current opinion in behavioral sciences, 23, 36-41., 10.1016/j.cobeha.2018.02.001
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Sex differences in sub-anesthetic ketamine's antidepressant effects and abuse liability.

March 2, 2018 / Depression, Ketamine, Papers, Psychiatry, Psychology, Psychopharmacology, Publications, Substance Use Disorder / By / ,

Abstract

Sub-anesthetic ketamine produces rapid antidepressant effects in patients with bipolar and unipolar major depression where conventional monoaminergic-based antidepressant drugs have been ineffective or ridden with side effects. A single ketamine infusion can produce antidepressant effects lasting up to two weeks, and multiple ketamine infusions prolong this effect. Pre-clinical studies are underway to uncover ketamine’s mechanisms of action, but there are still many questions unanswered regarding the safety of its long-term use. Abuse liability is one area of concern, as recreational ketamine use is an ongoing issue in many parts of the world. Another understudied area is sex differences in responsivity to ketamine. Women are twice as likely as men to be diagnosed with depression, and they progress through stages of drug addiction more rapidly than their male counterparts. Despite this, preclinical studies in ketamine’s antidepressant and addictive-like behaviors in females are limited. These intersecting factors in recent clinical and pre-clinical studies are reviewed to characterize ketamine’s therapeutic potential, its limitations, and its potential mechanisms of action.
Wright, K. N., & Kabbaj, M. (2018). Sex differences in sub-anesthetic ketamine’s antidepressant effects and abuse liability. Current opinion in behavioral sciences, 23, 36-41., 10.1016/j.cobeha.2018.02.001
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Convergent Mechanisms Underlying Rapid Antidepressant Action

March 1, 2018 / Depression, Ketamine, Neuroscience, Papers, Psychology, Psychopharmacology, Publications / By / , , , ,

Abstract

Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal, and anti-anhedonic actions following a single administration to patients with depression. Proposed mechanisms of the antidepressant action of ketamine include N-methyl-D-aspartate receptor (NMDAR) modulation, gamma aminobutyric acid (GABA)-ergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites. Downstream actions include activation of the mechanistic target of rapamycin (mTOR), deactivation of glycogen synthase kinase-3 and eukaryotic elongation factor 2 (eEF2), enhanced brain-derived neurotrophic factor (BDNF) signaling, and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs). These putative mechanisms of ketamine action are not mutually exclusive and may complement each other to induce potentiation of excitatory synapses in affective-regulating brain circuits, which results in amelioration of depression symptoms. We review these proposed mechanisms of ketamine action in the context of how such mechanisms are informing the development of novel putative rapid-acting antidepressant drugs. Such drugs that have undergone pre-clinical, and in some cases clinical, testing include the muscarinic acetylcholine receptor antagonist scopolamine, GluN2B-NMDAR antagonists (i.e., CP-101,606, MK-0657), (2R,6R)-HNK, NMDAR glycine site modulators (i.e., 4-chlorokynurenine, pro-drug of the glycineB NMDAR antagonist 7-chlorokynurenic acid), NMDAR agonists [i.e., GLYX-13 (rapastinel)], metabotropic glutamate receptor 2/3 (mGluR2/3) antagonists, GABAA receptor modulators, and drugs acting on various serotonin receptor subtypes. These ongoing studies suggest that the future acute treatment of depression will typically occur within hours, rather than months, of treatment initiation.
Zanos, P., Thompson, S. M., Duman, R. S., Zarate, C. A., & Gould, T. D. (2018). Convergent mechanisms underlying rapid antidepressant action. CNS drugs, 1-31. 10.1007/s40263-018-0492-x
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Neuroendocrine Associations Underlying the Persistent Therapeutic Effects of Classic Serotonergic Psychedelics

March 1, 2018 / Depression, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , ,

Abstract

Recent reports on the effects of psychedelic-assisted therapies for mood disorders and addiction, as well as the effects of psychedelics in the treatment of cluster headache, have demonstrated promising therapeutic results. In addition, the beneficial effects appear to persist well after limited exposure to the drugs, making them particularly appealing as treatments for chronic neuropsychiatric and headache disorders. Understanding the basis of the long-lasting effects, however, will be critical for the continued use and development of this drug class. Several mechanisms, including biological and psychological ones, have been suggested to explain the long-lasting effects of psychedelics. Actions on the neuroendocrine system are some such mechanisms that warrant further investigation in the study of persisting psychedelic effects. In this report, we review certain structural and functional neuroendocrinological pathologies associated with neuropsychiatric disorders and cluster headache. We then review the effects that psychedelic drugs have on those systems and provide preliminary support for potential long-term effects. The circadian biology of cluster headache is of particular relevance in this area. We also discuss methodologic considerations for future investigations of neuroendocrine system involvement in the therapeutic benefits of psychedelic drugs.
Schindler, E. A. D., Wallace, R. M., Sloshower, J. A., & D’Souza, D. C. (2018). Neuroendocrine associations underlying the persistent therapeutic effects of classic serotonergic psychedelics. Frontiers in pharmacology, 9, 177. 10.3389/fphar.2018.00177
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Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)

March 1, 2018 / History, LSD, Papers, Psychology, Psychotherapy, Publications / By /

Abstract

Lysergic acid diethylamide (LSD) is one of the most potent psychoactive agents known, producing dramatic alterations of consciousness after submilligram (≥20 μg) oral doses. Following the accidental discovery of its potent psychoactive effects in 1943, it was supplied by Sandoz Laboratories as an experimental drug that might be useful as an adjunct for psychotherapy, or to give psychiatrists insight into the mental processes in their patients. The finding of serotonin in the mammalian brain in 1953, and its structural resemblance to LSD, quickly led to ideas that serotonin in the brain might be involved in mental disorders, initiating rapid research interest in the neurochemistry of serotonin. LSD proved to be physiologically very safe and nonaddictive, with a very low incidence of adverse events when used in controlled experiments. Widely hailed by psychiatry as a breakthrough in the 1950s and early 1960s, clinical research with LSD ended by about 1970, when it was formally placed into Schedule 1 of the Controlled Substances Act of 1970 following its growing popularity as a recreational drug. Within the past 5 years, clinical research with LSD has begun in Europe, but there has been none in the United States. LSD is proving to be a powerful tool to help understand brain dynamics when combined with modern brain imaging methods. It remains to be seen whether therapeutic value for LSD can be confirmed in controlled clinical trials, but promising results have been obtained in small pilot trials of depression, anxiety, and addictions using psilocybin, a related psychedelic molecule.
Nichols, D. E. (2018). Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD). ACS chemical neuroscience. 10.1021/acschemneuro.8b00043
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The Psychedelic Debriefing in Alcohol Dependence Treatment: Illustrating Key Change Phenomena through Qualitative Content Analysis of Clinical Sessions

February 21, 2018 / Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychotherapy, Publications, Substance Use Disorder / By / , , ,

Abstract

Research on the clinical applications of psychedelic-assisted psychotherapy has demonstrated promising early results for treatment of alcohol dependence. Detailed description of the content and methods of psychedelic-assisted psychotherapy, as it is conducted in clinical settings, is scarce.

Methods: An open-label pilot (proof-of-concept) study of psilocybin-assisted treatment of alcohol dependence (NCT01534494) was conducted to generate data for a phase 2 RCT (NCT02061293) of a similar treatment in a larger population. The present paper presents a qualitative content analysis of the 17 debriefing sessions conducted in the pilot study, which occurred the day after corresponding psilocybin medication sessions.

Results: Participants articulated a series of key phenomena related to change in drinking outcomes and acute subjective effects of psilocybin.

Discussion: The data illuminate change processes in patients’ own words during clinical sessions, shedding light on potential therapeutic mechanisms of change and how participants express effects of psilocybin. This study is unique in analyzing actual clinical sessions, as opposed to interviews of patients conducted separately from treatment.

Nielson, E. M., May, D. G., Forcehimes, A. A., & Bogenschutz, M. P. (2018). The Psychedelic Debriefing in Alcohol Dependence Treatment: Illustrating Key Change Phenomena through Qualitative Content Analysis of Clinical Sessions. Frontiers in Pharmacology, 9, 132. 10.3389/fphar.2018.00132
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Psychedelics: Where we are now, why we got here, what we must do

February 21, 2018 / History, LSD, Other subjects, Papers, Psychology, Psychotherapy, Publications, Sociology / By / ,

Abstract

The purpose of this commentary is to provide an introduction to this special issue of Neuropharmacology with a historical perspective of psychedelic drug research, their use in psychiatric disorders, research-restricting regulatory controls, and their recent emergence as potential breakthrough therapies for several brain-related disorders. It begins with the discovery of lysergic acid diethylamide (LSD) and its promising development as a treatment for several types of mental illnesses during the 1940s. This was followed by its abuse and stigmatization in the 1960s that ultimately led to the placement of LSD and other psychedelic drugs into the most restrictively regulated drug schedule of the United States Controlled Substances Act (Schedule I) in 1970 and its international counterparts. These regulatory controls severely constrained development of psychedelic substances and their potential for clinical research in psychiatric disorders. Despite the limitations, there was continued research into brain mechanisms of action for psychedelic drugs with potential clinical applications which began during the 1990s and early 2000s. Finding pathways to accelerate clinical research in psychedelic drug development is supported by the growing body of research findings that are documented throughout this special issue of Neuropharmacology. Accumulated research to date suggests psychedelic drug assisted psychotherapy may emerge as a potential breakthrough treatment for several types of mental illnesses including depression, anxiety, post-traumatic stress disorder, and addiction that are refractory to current evidenced based therapies. This research equally shows promise in advancing the understanding of the brain, brain related functioning, and the consequential effects of untreated brain related diseases that have been implicated in causing and/or exacerbating numerous physical disease state conditions. The authors conclude that more must be done to effectively address mental illnesses and brain related diseases which have become so pervasive, destructive, and whose treatments are becoming increasingly resistant to current evidenced based therapies.
Belouin, S. J., & Henningfield, J. E. (2018). Psychedelics: Where we are now, why we got here, what we must do. Neuropharmacology. 10.1016/j.neuropharm.2018.02.018
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The re-emergence of hallucinogenic research

February 20, 2018 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / ,

Abstract

Due to the intractability, at times, in the treatment of PTSD, clinicians and researchers continue to explore different options for treatment. This article discusses the renewed interest in hallucinogens for such treatment.
Begola, M. J., & Dowben, J. S. (2018). The re‐emergence of hallucinogenic research. Perspectives in psychiatric care. 10.1111/ppc.12263
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