OPEN Foundation

Psychology

Rehabilitating LSD history in postwar America: Dilworth Wayne Woolley and the serotonin hypothesis of mental illness

Abstract

Revisiting the history of postwar LSD (lysergic acid diethylamide) research illuminates how the work of a chemist at the Rockefeller Institute contributed to the development of a biochemical paradigm for mental functioning. Dilworth Wayne Woolley proposed one of the first theories of the biochemistry of mental illness based on empirical evidence. His research with LSD and serotonin had wide-ranging repercussions for pharmacology and fit neatly into the emerging medicalization of mental illness. Reevaluating Woolley’s ideas and the fruits of psychopharmacology leads to possible new approaches toward mental health and illness when considered alongside lessons learned from past research with psychedelic substances, and exemplifies a broader paradigm shift in cultural studies toward a biopsychosocial model that acknowledges the intersections between biology and culture.

Hewitt, K. (2016). Rehabilitating LSD history in postwar America: Dilworth Wayne Woolley and the serotonin hypothesis of mental illness. History of Science, 0073275316674724.
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Ketamine: NMDA Receptors and Beyond

Abstract

Human studies examining the effects of the dissociative anesthetic ketamine as a model for psychosis and as a rapidly acting antidepressant have spurred great interest in understanding ketamine’s actions at molecular, cellular, and network levels. Although ketamine has unequivocal uncompetitive inhibitory effects on N-methyl-d-aspartate receptors (NMDARs) and may preferentially alter the function of NMDARs on interneurons, recent work has questioned whether block of NMDARs is critical for its mood enhancing actions. In this viewpoint, we examine the evolving literature on ketamine supporting NMDARs as important triggers for certain psychiatric effects and the possibility that the antidepressant trigger is unrelated to NMDARs. The rapidly evolving story of ketamine offers great hope for untangling and treating the biology of both depressive and psychotic illnesses.
Zorumski, C. F., Izumi, Y., & Mennerick, S. (2016). Ketamine: NMDA receptors and beyond. Journal of Neuroscience36(44), 11158-11164. 10.1523/JNEUROSCI.1547-16.2016
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Classic Psychedelics and Rational Suicide in the Elderly: Exploring the Potential Utility of a Reemerging Treatment Paradigm

Abstract

The objective of the current chapter is to evaluate the potential utility of classic psychedelics including dimethyltryptamine (found in the Amazonian plant decoction ayahuasca), lysergic acid diethylamide (LSD), mescaline (found in peyote and other psychoactive cacti), and psilocybin (found in certain mushrooms) in addressing rational suicide among the elderly. An overview of the sociopolitical history of classic psychedelics is presented, followed by an examination of empirical findings pertaining to rational suicide. This chapter concludes that classic psychedelics may counteract rational suicide among the elderly by promoting the perception that life is worth living even in the face of great adversity and encourages future study on this important topic.

Hendricks, P. S., & Grob, C. S. (2017). Classic Psychedelics and Rational Suicide in the Elderly: Exploring the Potential Utility of a Reemerging Treatment Paradigm. In Rational Suicide in the Elderly (pp. 203-210). Springer International Publishing. 10.1007/978-3-319-32672-6_14

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Role of psilocybin in the treatment of depression

Abstract

Psilocybin is a naturally occurring alkaloid, pharmacologically similar to the classic hallucinogen lysergic acid diethylamide (LSD). Although primarily used as a recreational drug or an entheogen in particular cultural settings, recent population based studies have shown that it does not lead to serious physical or mental health problems or dependent use. In view of recent work demonstrating psilocybin’s potential to increase subjective sense of wellbeing and because of its novel mechanism of 5-HT2A serotonin receptor agonism, it is being explored for possible therapeutic utility in mood and anxiety disorders.

Mahapatra, A., & Gupta, R. (2016). Role of psilocybin in the treatment of depression. Therapeutic Advances in Psychopharmacology, 2045125316676092.
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Of Roots and Fruits A Comparison of Psychedelic and Nonpsychedelic Mystical Experiences

Abstract

Experiences of profound existential or spiritual significance can be triggered reliably through psychopharmacological means using psychedelic substances. However, little is known about the benefits of religious, spiritual, or mystical experiences (RSMEs) prompted by psychedelic substances, as compared with those that occur through other means. In this study, 739 self-selected participants reported the psychological impact of their RSMEs and indicated whether they were induced by a psychedelic substance. Experiences induced by psychedelic substances were rated as more intensely mystical (d = .75, p < .001), resulted in a reduced fear of death (d = .21, p < .01), increased sense of purpose (d = .18, p < .05), and increased spirituality (d = .28, p < .001) as compared with nonpsychedelically triggered RSMEs. These results remained significant in an expanded model controlling for gender, education, socioeconomic status, and religious affiliation. These findings lend support to the growing consensus that RSMEs induced with psychedelic substances are genuinely mystical and generally positive in outcome.

Yaden, D. B., Le Nguyen, K. D., Kern, M. L., Belser, A. B., Eichstaedt, J. C., Iwry, J., … & Newberg, A. B. (2016). Of Roots and Fruits A Comparison of Psychedelic and Nonpsychedelic Mystical Experiences. Journal of Humanistic Psychology, 0022167816674625.
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Creativity and Psychoactive Substance Use: A Systematic Review

Abstract

The role of psychoactive substance use in the research of artistic creation and creativity is a long-standing topic. Ever since the discovery of LSD, researchers have examined the relationship between the effects of chemical substances and the artistic creative process. The goal of the present study was to systematically review all published empirical publications and case reports in refereed journals that focus on the relationship between psychoactive substances and creativity/creative artistic process. A total of 19 studies were identified that met the inclusion and exclusion criteria. Results were difficult to summarize because of the different study questions asked, the diverse methods used, the different samples applied, and the various substances examined. The general results suggest that there is an association between creativity and substance use. However, the studies were unable to show that substance use directly contributed to the growth of creativity or facilitated creative artistic process. It is concluded that specific skills may be subject to change as a consequence of substance use, and consequently may have an effect on the style of creation.

Iszáj, F., Griffiths, M. D., & Demetrovics, Z. (2016). Creativity and Psychoactive Substance Use: A Systematic Review. International Journal of Mental Health and Addiction, 1-15. 10.1007/s11469-016-9709-8

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Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression

Abstract

Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action. However, there have been no CMS studies of chronic daily ketamine treatment or continued stress following ketamine treatment, which would have greater translational potential in relation to the long-term maintenance of antidepressant effects. Wistar rats were drug treated following an initial 2 weeks of CMS exposure, which continued alongside daily drug treatment. A first experiment tested a range of chronic (5 weeks) ketamine doses (5-30 mg/kg); a second compared the effects of subacute (3-5 days) and chronic (5 weeks) treatment. CMS-induced anhedonic, anxiogenic and dyscognitive effects, as measured, respectively, by decreased sucrose intake, avoidance of open arms in the elevated plus maze and loss of discrimination in the novel object recognition test. A sustained antidepressant-like effect of ketamine in the sucrose intake test was observed in both experiments, with an onset at around 1 week, faster than imipramine, and an optimum dose of 10 mg/kg. Anxiogenic and dyscognitive effects of CMS, in the elevated plus maze and novel object recognition test, respectively, were fully reversed by both subacute and chronic ketamine treatment. Daily treatment with ketamine in the CMS model causes sustained long-term antidepressant, anxiolytic and procognitive effects. The demonstration of a procognitive effect of ketamine may have particular translational value.

Papp, M., Gruca, P., Lason-Tyburkiewicz, M., & Willner, P. (2016). Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression. Behavioural Pharmacology. 10.1097/FBP.0000000000000259

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Development of a Psychotherapeutic Model for Psilocybin-Assisted Treatment of Alcoholism

Abstract

Research activity on the potential clinical value of classic hallucinogens and other psychedelics has increased markedly in the past two decades, and promises to continue to expand. Experimental study of hallucinogen-assisted treatment, and any future clinical use, requires the development of psychotherapeutic models that are appropriate to the disorder being treated and effectively integrated with the pharmacologic component of the treatment. To provide a framework for thinking about possible treatment models, we provide an overview of the history of psychedelic-assisted treatment, review what is known about the therapeutic mechanisms of these treatments, and consider the various purposes of psychotherapy in the context of both research and clinical use of psychedelic-assisted treatment. We then provide a description of a therapy model we have developed and are currently using in a trial of psilocybin-assisted treatment for alcoholism. Finally, we discuss advantages and disadvantages of a range of alternative models, emphasizing the need for research to determine the most effective treatment models for any indications for which efficacy becomes established.

Bogenschutz, M. P., & Forcehimes, A. A. (2016). Development of a Psychotherapeutic Model for Psilocybin-Assisted Treatment of Alcoholism. Journal of Humanistic Psychology, 0022167816673493.
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Alterations of consciousness and mystical-type experiences after acute LSD in humans

Abstract

Rationale: Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration-response functions with regard to alterations of consciousness are lacking.

Methods: We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 μg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 μg.

Results: On the MEQ, 200 μg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 μg compared with 100 μg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 μg.

Conclusions: Mystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 μg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 μg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations.

Liechti, M. E., Dolder, P. C., & Schmid, Y. (2016). Alterations of consciousness and mystical-type experiences after acute LSD in humans. Psychopharmacology, 1-12. 10.1007/s00213-016-4453-0

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Psychological effects of MDMA

Abstract

Zinberg’s Interaction Model implies that the content of a drug-induced experience is a function of the pharmacological properties of the drug, the set (the user’s characteristics e.g. motivation and personality), and the setting (the physical and social context). The current research investigated the function of the set and setting and their role in shaping the psychological effects of 3,4-methylenedioxmethamphetamine (MDMA), as well as their role in reducing the risk of drug abuse.
An online survey was distributed among adult MDMA polydrug users (n = 158) and MDMA-naïve controls (alcohol, nicotine and cannabis users, n = 138). Participants answered questions regarding their pattern of drug use, their motivation for MDMA use and the setting (e.g. clubbing, home with friends), as well as the subjective effects of MDMA. Participants also completed a range of self-report measures of self-reflection and insight, emotional intelligence, and personality, as well as a drug dependency measure.
MDMA users displayed higher levels of self-reflection and insight, openness to new experience and lower levels of neuroticism and conscientiousness, in comparison to the control group. The significant predictors of self-reflection and insight were openness, emotional intelligence, MDMA use, extraversion and neuroticism. When the analysis was rerun only for the MDMA group, the significant predictors of self-reflection and insight were openness, emotional intelligence and self-insight effects of MDMA. High levels of self-reported negative effects of MDMA were predictors of a problematic drug use.
These findings suggest that there might be a relationship between MDMA use and higher levels of self-reflection and insight; however, longitudinal studies are required to further investigate the causality of this relationship. The results add to existing evidence that MDMA has potential for altering emotional experiences. Further research utilising a prospective design is warranted.

Wieliczko, M. J. (2016). Psychological effects of MDMA (Doctoral dissertation, Canterbury Christ Church University).

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