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Psychology

Question-based Drug Development for psilocybin

Abstract

In The Lancet Psychiatry, Robin Carhart-Harris and colleagues conclude that there is preliminary support for the safety and efficacy of psilocybin for treatment-resistant unipolar depression. This finding is important because more effective pharmacological treatments with acceptable side-effects are urgently needed for patients suffering from depression. We support the limitations the authors have pointed out about the study population and trial design. We also recognise the paucity of well-designed trials in psychiatry that are based on the principles of clinical pharmacology.

Dijkstra, F. M., Jacobs, G. E., & Cohen, A. F. (2016). Question-based Drug Development for psilocybin. The Lancet Psychiatry, 3(9), 806-807. http://dx.doi.org/10.1016/S2215-0366(16)30214-0
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Return of the psychedelics: Psilocybin for treatment resistant depression

Abstract

Psilocybin, the clinically most researched classic psychedelic has recently been tested for its safety and efficacy in a clinical population of treatment resistant depression. The efficacy of psilocybin in clinical depression previously demonstrated in the elecrophysiologic and neuroimaging findings as also in neuropsychological assessments is further validated by the findings of this rigorously conducted randomized trial. Mechanism of action of psilocybin and efficacy in treatment resistant depression are discussed in this paper. Ethical issues of conducting clinical trials with psychedelics are also discussed with particular emphasis on their relative safety and absence of addiction potential. Implications of these issues for conduct of larger trials for establishing risk benefit ratio in treatment resistant depression are further suggested.

Patra, S. (2016). Return of the psychedelics: Psilocybin for treatment resistant depression. Asian Journal of Psychiatry, 24, 51-52. http://dx.doi.org/10.1016/j.ajp.2016.08.010
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Psilocybin for treating substance use disorders?

Abstract

INTRODUCTION: Evidence based treatment for Substance use disorders (SUD) includes psychotherapy and pharmacotherapy. However, these are only partially effective. Hallucinogens, such as psilocybin, may represent potential new treatment options for SUD. This review provides a summary of (human) studies on the putative therapeutic effects of psilocybin, and discusses the receptor systems, brain regions and cognitive and emotional processes mediating psilocybin’s effects. Psilocybin’s chemical structure is similar to that of serotonin. Dysregulations in the serotonin system are associated with alterations in stress hormones, such as cortisol, and mood disorders. After psilocybin administration cortisol levels spike and activate the executive control network, with subsequent increased control over emotional processes, and relief of negative thinking and persistent negative emotions. Preliminary data of ongoing alcohol and smoking addiction studies in humans shows promising effects of psilocybin administration on substance use. Importantly, psilocybin has a low risk of toxicity and dependence and can be used safely under controlled clinical conditions.

AREAS COVERED: This paper is a narrative review based on the search terms: psilocybin, substance use disorder, addiction, depression, serotonin. Literature on potential efficacy and mechanisms of action of psilocybin in SUD is discussed. Expert commentary: Recent positive findings with psilocybin need confirmation in well-designed placebo controlled randomized trials employing a large sample size.

de Veen, B. T., Schellekens, A. F., Verheij, M. M., & Homberg, J. R. (2016). Psilocybin for treating substance use disorders?. Expert Review of Neurotherapeutics, 1-10. 10.1080/14737175.2016.1220834
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The Associations of Naturalistic Classic Psychedelic Use, Mystical Experience, and Creative Problem Solving

Abstract

Developing methods for improving creativity is of broad interest. Classic psychedelics may enhance creativity; however, the underlying mechanisms of action are unknown. This study was designed to assess whether a relationship exists between naturalistic classic psychedelic use and heightened creative problem-solving ability and if so, whether this is mediated by lifetime mystical experience. Participants (N = 68) completed a survey battery assessing lifetime mystical experience and circumstances surrounding the most memorable experience. They were then administered a functional fixedness task in which faster completion times indicate greater creative problem-solving ability. Participants reporting classic psychedelic use concurrent with mystical experience (n = 11) exhibited significantly faster times on the functional fixedness task (Cohen’s d = –.87; large effect) and significantly greater lifetime mystical experience (Cohen’s d = .93; large effect) than participants not reporting classic psychedelic use concurrent with mystical experience. However, lifetime mystical experience was unrelated to completion times on the functional fixedness task (standardized β = –.06), and was therefore not a significant mediator. Classic psychedelic use may increase creativity independent of its effects on mystical experience. Maximizing the likelihood of mystical experience may need not be a goal of psychedelic interventions designed to boost creativity.

Sweat, N. W., Bates, L. W., & Hendricks, P. S. (2016). The Associations of Naturalistic Classic Psychedelic Use, Mystical Experience, and Creative Problem Solving. Journal of Psychoactive Drugs, 1-7. 10.1080/02791072.2016.1234090
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Semantic activation in LSD: evidence from picture naming

Lysergic acid diethylamide (LSD) is a classic psychedelic drug that alters cognition in a characteristic way. It has been suggested that psychedelics expand the breadth of cognition via actions on the central nervous system. Previous work has shown changes in semantic processing under psilocybin (a related psychedelic to LSD) that are consistent with an increased spread of semantic activation. The present study investigates this further using a picture-naming task and the psychedelic, LSD. Ten participants completed the task under placebo and LSD. Results revealed significant effects of LSD on accuracy and error correction that were consistent with an increased spread of semantic activation under LSD. These results are consistent with a generalised “entropic” effect on the mind. We suggest incorporating direct neuroimaging measures in future studies, and to employ more naturalistic measures of semantic processing that may enhance ecological validity.

Family, N., Vinson, D., Vigliocco, G., Kaelen, M., Bolstridge, M., Nutt, D. J., & Carhart-Harris, R. L. (2016). Semantic activation in LSD: evidence from picture naming. Language, Cognition and Neuroscience, 1-8. http://dx.doi.org/10.1080/23273798.2016.1217030
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New use for an old drug: oral ketamine for treatment-resistant depression

Abstract

Treatment-resistant depression (TRD) is a disabling disorder that can interfere with a patient’s capacity to understand and participate in medical care and thus negatively impact individual morbidity and mortality. Hospitalised patients with TRD may require rapid alleviation of severe symptomatology, particularly when suicidal or if unable to participate in care decisions. Ketamine is well known for its anaesthetic effects and its use as a ‘street’ drug; however, its action as an N-methyl-D-aspartate receptor antagonist makes ketamine a potential therapy for TRD. The majority of studies investigating ketamine for TRD have used intravenous drug delivery, demonstrating benefit for rapid alleviation and sustained response of depression symptoms. Oral ketamine for urgent alleviation of TRD symptoms is less reported. We describe rapid alleviation of severe TRD with oral ketamine in a severely ill postoperative hospitalised patient, and review the current literature on ‘off-label’ use of ketamine for treatment of refractory depression.

Swiatek, K. M., Jordan, K., & Coffman, J. (2016). New use for an old drug: oral ketamine for treatment-resistant depression. BMJ Case Reports, 2016, bcr2016216088. 10.1136/bcr-2016-216088

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Investigation of Personality Change Following MDMA-Assisted Psychotherapy for Post Traumatic Stress Disorder

Wagner, M., Mithoefer, M., Mithoefer, A., MacAulay, R., Jerome, L., Bazaar-Klosinski, B., & Doblin, R. (2016). B-56Investigation of Personality Change Following MDMA-Assisted Psychotherapy for Post Traumatic Stress Disorder. Archives of Clinical Neuropsychology, 31(6), 634-634. 10.1093/arclin/acw043.131
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Measuring the subjective: revisiting the psychometric properties of three rating scales that assess the acute effects of hallucinogens

Abstract

Objective: In the present study we explored the psychometric properties of three widely used questionnaires to assess the subjective effects of hallucinogens: the Hallucinogen Rating Scale (HRS), the Mystical Experience Questionnaire (MEQ), and the Addiction Research Center Inventory (ARCI).

Methods: These three questionnaires were administered to a sample of 158 subjects (100 men) after taking ayahuasca, a hallucinogen whose main active component is N,N-dimethyltryptamine (DMT). A confirmatory factorial study was conducted to check the adjustment of previous data obtained via theoretical proposals. When this was not possible, we used an exploratory factor analysis without restrictions, based on tetrachoric and polychoric matrices and correlations.

Results: Our results sparsely match the theoretical proposals of the authors, perhaps because previous studies have not always employed psychometric methods appropriate to the data obtained. However, these data should be considered preliminary, pending larger samples to confirm or reject the proposed structures obtained.

Conclusions: It is crucial that instruments of sufficiently precise measurement are utilized to make sense of the information obtained in the study of the subjective effects of psychedelic drugs.

Bouso, J. C., Pedrero‐Pérez, E. J., Gandy, S., & Alcázar‐Córcoles, M. Á. (2016). Measuring the subjective: revisiting the psychometric properties of three rating scales that assess the acute effects of hallucinogens. Human Psychopharmacology: Clinical and Experimental, 31(5), 356-372. 10.1002/hup.2545
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