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Semantic activation in LSD: evidence from picture naming

August 11, 2016 / LSD, Papers, Psychology, Publications / By / , , , , , ,

Abstract

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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Chemogenomics knowledgebase and systems pharmacology for hallucinogen target identification-Salvinorin A as a case study

August 8, 2016 / Neuroscience, Papers, Publications, Salvia / Salvinorin A, Substance Use Disorder / By /

Abstract

Drug abuse is a serious problem worldwide. Recently, hallucinogens have been reported as a potential preventative and auxiliary therapy for substance abuse. However, the use of hallucinogens as a drug abuse treatment has potential risks, as the fundamental mechanisms of hallucinogens are not clear. So far, no scientific database is available for the mechanism research of hallucinogens. We constructed a hallucinogen-specific chemogenomics database by collecting chemicals, protein targets and pathways closely related to hallucinogens. This information, together with our established computational chemogenomics tools, such as TargetHunter and HTDocking, provided a one-step solution for the mechanism study of hallucinogens. We chose salvinorin A, a potent hallucinogen extracted from the plant Salvia divinorum, as an example to demonstrate the usability of our platform. With the help of HTDocking program, we predicted four novel targets for salvinorin A, including muscarinic acetylcholine receptor 2, cannabinoid receptor 1, cannabinoid receptor 2 and dopamine receptor 2. We looked into the interactions between salvinorin A and the predicted targets. The binding modes, pose and docking scores indicate that salvinorin A may interact with some of these predicted targets. Overall, our database enriched the information of systems pharmacological analysis, target identification and drug discovery for hallucinogens.

Xu, X. (2015). Chemogenomics Knowledgebase and Systems Pharmacology for Hallucinogen Target Identification-Salvinorin A as a Case Study (Doctoral dissertation, University of Pittsburgh). 10.1016/j.jmgm.2016.08.001
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New use for an old drug: oral ketamine for treatment-resistant depression

August 3, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , ,

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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Acid Brothers: Henry Beecher, Timothy Leary, and the psychedelic of the century

August 1, 2016 / Humanities & Art, LSD, Papers, Publications / By /

Abstract

Henry Knowles Beecher, an icon of human research ethics, and Timothy Francis Leary, a guru of the counterculture, are bound together in history by the synthetic hallucinogen lysergic acid diethylamide (LSD). Both were associated with Harvard University during a critical period in their careers and of drastic social change. To all appearances the first was a paragon of the establishment and a constructive if complex hero, the second a rebel and a criminal, a rogue and a scoundrel. Although there is no evidence they ever met, Beecher’s indirect struggle with Leary over control of the 20th century’s most celebrated psychedelic was at the very heart of his views about the legitimate, responsible investigator. That struggle also proves to be a revealing bellwether of the increasingly formalized scrutiny of human experiments that was then taking shape.

Moreno, J. D. (2016). Acid Brothers: Henry Beecher, Timothy Leary, and the psychedelic of the century. Perspectives in Biology and Medicine, 59(1), 107-121. 10.1353/pbm.2016.0019

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

August 1, 2016 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , , , ,

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

July 29, 2016 / Ayahuasca, DMT, Papers, Psychology, Publications / By / , , ,

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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Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics

July 25, 2016 / Ayahuasca, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Despite reports of apparent benefits, social and political pressure beginning in the late 1960s effectively banned scientific inquiry into psychedelic substances. Covert examination of psychedelics persisted through the 1990s; the turn of the century and especially the past 10 years, however, has seen a resurgent interest in psychedelic substances (eg, LSD, ayahuasca, psilocybin). This chapter outlines relevant EEG and brain imaging studies evaluating the effects of psychedelics on the brain. This chapter also reviews evidence of the use of psychedelics as adjunct therapy for a number of psychiatric and addictive disorders. In particular, psychedelics appear to have efficacy in treating depression and alcohol-use disorders.

Tófoli, L. F., & de Araujo, D. B. (2016). Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics. International Review of Neurobiology. 10.1016/bs.irn.2016.06.005
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Neurovascular Plasticity of the Hippocampus One Week after a Single Dose of Ketamine in Genetic Rat Model of Depression

July 21, 2016 / Depressive Disorders, Ketamine, Neuroscience, Papers, Publications / By / , , , ,

Abstract

Glutamatergic system and the structural plasticity hypothesis are principal components for rapid and sustained antidepressant effects of novel antidepressant therapeutics. This study represents the first investigation of the structural plasticity of the hippocampus as one of the main contributed mechanisms to the sustained anti-depressive effect of ketamine. Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were given a single intraperitoneal injection of ketamine (15 mg/kg) or saline 7 days before perfusion-fixed. The optical fractionator method was used to estimate the total number of neurons in the granular cell layer. Microvessel length in the molecular layer of DG was evaluated with global spatial sampling method. By use of the physical disector method, the number of synapses was estimated. The volume of the hippocampus was larger in the FRL-vehicle rats compared with FSL-vehicle group and in FSL-ketamine versus FSL-vehicle rats (P < 0.05). The number of non-perforated synapses was significantly higher in the FSL-ketamine versus FSL-vehicle group, (P = 0.01). A significant effect of ketamine on enhancement of the number of neurons in DG in FSL rats was observed (P = 0.01). The total length of the microvessels 1 week after ketamine treatment in the FSL rats significantly increased (P  < 0.05). Our results indicate that neurovascular changes of hippocampus could be one of the possible mechanisms underlying the sustained antidepressant effect of ketamine by reversing alteration of the number of the excitatory synapses, neuronal number and length of the microvessels in the hippocampus.

Ardalan, M., Wegener, G., Polsinelli, B., Madsen, T. M., & Nyengaard, J. R. (2016). Neurovascular Plasticity of the Hippocampus One Week after a Single Dose of Ketamine in Genetic Rat Model of Depression. Hippocampus. http://dx.doi.org/10.1002/hipo.22617
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Long-term follow up of psilocybin-assisted smoking cessation

July 21, 2016 / Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , ,

Abstract

Background: A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. Objectives: To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration.
Methods: The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin.
Results: All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16–57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives.
Conclusion: These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.

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Ayahuasca enhances creative divergent thinking while decreasing conventional convergent thinking

July 19, 2016 / Ayahuasca, Papers, Psychology, Publications / By / , , , , ,

Abstract

Introduction: Ayahuasca is a South American psychotropic plant tea traditionally used in Amazonian shamanism. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus β-carboline alkaloids with monoamine oxidase-inhibiting properties. Increasing evidence from anecdotal reports and open-label studies indicates that ayahuasca may have therapeutic effects in treatment of substance use disorders and depression. A recent study on the psychological effects of ayahuasca found that the tea reduces judgmental processing and inner reactivity, classic goals of mindfulness psychotherapy. Another psychological facet that could potentially be targeted by ayahuasca is creative divergent thinking. This mode of thinking can enhance and strengthen psychological flexibility by allowing individuals to generate new and effective cognitive, emotional, and behavioral strategies. The present study aimed to assess the potential effects of ayahuasca on creative thinking.

Methods: We visited two spiritual ayahuasca workshops and invited participants to conduct creativity tests before and during the acute effects of ayahuasca. In total, 26 participants consented. Creativity tests included the “pattern/line meanings test” (PLMT) and the “picture concept test” (PCT), both assessing divergent thinking and the latter also assessing convergent thinking.

Results: While no significant effects were found for the PLMT, ayahuasca intake significantly modified divergent and convergent thinking as measured by the PCT. While convergent thinking decreased after intake, divergent thinking increased.

Conclusions: The present data indicate that ayahuasca enhances creative divergent thinking. They suggest that ayahuasca increases psychological flexibility, which may facilitate psychotherapeutic interventions and support clinical trial initiatives.

Kuypers, K. P. C., Riba, J., de la Fuente Revenga, M., Barker, S., Theunissen, E. L., & Ramaekers, J. G. (2016). Ayahuasca enhances creative divergent thinking while decreasing conventional convergent thinking. Psychopharmacology, 1-9. 10.1007/s00213-016-4377-8

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