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Neuroscience

P300-mediated modulations in self-other processing under psychedelic psilocybin are related to connectedness and changed meaning: A window into the self-other overlap

August 21, 2020 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By

Abstract

The concept of self and self-referential processing has a growing explanatory value in psychiatry and neuroscience, referring to the cognitive organization and perceptual differentiation of self-stimuli in health and disease. Conditions in which selfhood loses its natural coherence offer a unique opportunity for elucidating the mechanisms underlying self-disturbances. We assessed the psychoactive effects of psilocybin (230 μg/kg p.o.), a preferential 5-HT1A/2A agonist known to induce shifts in self-perception. Our placebo-controlled, double-blind, within-subject crossover experiment (n = 17) implemented a verbal self-monitoring task involving vocalizations and participant identification of real-time auditory source- (self/other) and pitch-modulating feedback. Subjective experience and task performance were analyzed, with time-point-by-time-point assumption-free multivariate randomization statistics applied to the spatiotemporal dynamics of event-related potentials. Psilocybin-modulated self-experience, interacted with source to affect task accuracy, and altered the late phase of self-stimuli encoding by abolishing the distinctiveness of self- and other-related electric field configurations during the P300 timeframe. This last effect was driven by current source density changes within the supragenual anterior cingulate and right insular cortex. The extent of the P300 effect was associated with the intensity of psilocybin-induced feelings of unity and changed meaning of percepts. Modulations of late encoding and their underlying neural generators in self-referential processing networks via 5-HT signaling may be key for understanding self-disorders. This mechanism may reflect a neural instantiation of altered self-other and relational meaning processing in a stimulus-locked time domain. The study elucidates the neuropharmacological foundation of subjectivity, with implications for therapy, underscoring the concept of connectedness.

Smigielski, L., Kometer, M., Scheidegger, M., Stress, C., Preller, K. H., Koenig, T., & Vollenweider, F. X. (2020). P300‐mediated modulations in self–other processing under psychedelic psilocybin are related to connectedness and changed meaning: A window into the self–other overlap. Human brain mapping, 41(17), 4982-4996; 10.1002/hbm.25174

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Psychedelic science in post-COVID-19 psychiatry

August 19, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications, Substance Use Disorder / By / , , , , , ,

Abstract

The medium- to long-term consequences of COVID-19 are not yet known, though an increase in mental health problems are predicted. Multidisciplinary strategies across socio-economic and psychological levels may be needed to mitigate the mental health burden of COVID-19. Preliminary evidence from the rapidly progressing field of psychedelic science shows that psilocybin therapy offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and maladaptive habitual patterns of cognition and behaviour, notably depression, addiction and obsessive compulsive disorder. The COMPASS Pathways (COMPASS) phase 2b double-blind trial of psilocybin therapy in antidepressant-free, treatment-resistant depression (TRD) is underway to determine the safety, efficacy and optimal dose of psilocybin. Results from the Imperial College London Psilodep-RCT comparing the efficacy and mechanisms of action of psilocybin therapy to the selective serotonin reuptake inhibitor (SSRI) escitalopram will soon be published. However, the efficacy and safety of psilocybin therapy in conjunction with SSRIs in TRD is not yet known. An additional COMPASS study, with a centre in Dublin, will begin to address this question, with potential implications for the future delivery of psilocybin therapy. While at a relatively early stage of clinical development, and notwithstanding the immense challenges of COVID-19, psilocybin therapy has the potential to play an important therapeutic role for various psychiatric disorders in post-COVID-19 clinical psychiatry.

Kelly, J. R., Crockett, M. T., Alexander, L., Haran, M., Baker, A., Burke, L., … & O’Keane, V. (2020). Psychedelic science in post-COVID-19 psychiatry. Irish journal of psychological medicine, 1-6; 10.1017/ipm.2020.94

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Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

August 17, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Introduction: Interest in the use of psychedelic substances for the treatment of mental disorders is increasing. Processes that may affect therapeutic change are not yet fully understood. Qualitative research methods are increasingly used to examine patient accounts; however, currently, no systematic review exists that synthesizes these findings in relation to the use of psychedelics for the treatment of mental disorders.

Objective: To provide an overview of salient themes in patient experiences of psychedelic treatments for mental disorders, presenting both common and diverging elements in patients’ accounts, and elucidating how these affect the treatment process.

Methods: We systematically searched the PubMed, MEDLINE, PsycINFO, and Embase databases for English-language qualitative literature without time limitations. Inclusion criteria were qualitative research design; peer-reviewed studies; based on verbalized patient utterances; and a level of abstraction or analysis of the results. Thematic synthesis was used to analyze and synthesize results across studies. A critical appraisal of study quality and methodological rigor was conducted using the Critical Appraisal Skills Programme (CASP).

Results: Fifteen research articles, comprising 178 patient experiences, were included. Studies exhibited a broad heterogeneity in terms of substance, mental disorder, treatment context, and qualitative methodology. Substances included psilocybin, lysergic acid diethylamide (LSD), ibogaine, ayahuasca, ketamine and 3,4-methylenedioxymethamphetamine (MDMA). Disorders included anxiety, depression, eating disorders, post-traumatic stress disorder, and substance use disorders. While the included compounds were heterogeneous in pharmacology and treatment contexts, patients reported largely comparable experiences across disorders, which included phenomenological analogous effects, perspectives on the intervention, therapeutic processes and treatment outcomes. Comparable therapeutic processes included insights, altered self-perception, increased connectedness, transcendental experiences, and an expanded emotional spectrum, which patients reported contributed to clinically and personally relevant responses.

Conclusions: This review demonstrates how qualitative research of psychedelic treatments can contribute to distinguishing specific features of specific substances, and carry otherwise undiscovered implications for the treatment of specific psychiatric disorders.

Breeksema, J. J., Niemeijer, A. R., Krediet, E., Vermetten, E., & Schoevers, R. A. (2020). Psychedelic treatments for psychiatric disorders: a systematic review and thematic synthesis of patient experiences in qualitative studies. CNS drugs, 1-22; 10.1007/s40263-020-00748-y

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The impact of 3,4-methylendioxymetamphetamine (MDMA) abstinence on seeking behavior and the expression of the D 2-like and mGlu 5 receptors in the rat brain using saturation binding analyses

January 27, 2022 / MDMA, Neuroscience, Papers, Substance Use Disorder / Leave a Comment / By / , , , , , ,

Abstract

The abundance of research indicates that enriched environment acts as a beneficial factor reducing the risks of relapse in substance use disorder. There is also strong evidence showing the engagement of brain dopaminergic and glutamatergic signaling through the dopamine D2-like and metabotropic glutamate type 5 (mGlu5) receptors, respectively, that has a direct impact on drug reward and drug abstinence. The present study involved 3,4-methylendioxymethamphetamine (MDMA) self-administration with the yoked-triad procedure in rats kept under different housing conditions during abstinence – enriched environment (EE) or isolation cage (IC) conditions – aimed at evaluating changes in brain receptors affecting drug-seeking behavior as well as density and affinity of the D2-like and mGlu5 receptors in several regions of the animal brain. Our results show that exposure to EE conditions strongly reduced active lever presses during cue-induced drug-seeking. At the neurochemical level, we demonstrated marked decreases of D2-like receptor affinity in the dorsal striatum in rats previously self-administering MDMA under EE and increases in density under IC conditions. Moreover, we found the increases in the density and decreases in the affinity of the D2-like receptor in the prefrontal cortex and nucleus accumbens provoked by IC conditions. The mGlu5 receptor density decreased only in the prefrontal cortex after IC and EE abstinence. Moreover, our study has revealed a clear decrease in mGlu5 receptor density in the nucleus accumbens in the group actively administering MDMA only under EE conditions. This study demonstrates that housing conditions have impact on drug-seeking behavior in rats during abstinence from MDMA self-administration. The observed changes in the dopamine D2-like and mGlu5 receptor Bmax and/or Kd values were brain-region specific and related to either pharmacological and/or motivational features of MDMA.

Frankowska, M., Miszkiel, J., Pomierny-Chamiolo, L., Pomierny, B., Celeste Borelli, A., Suder, A., & Filip, M. (2020). The impact of 3,4-methylendioxymetamphetamine (MDMA) abstinence on seeking behavior and the expression of the D2-like and mGlu5 receptors in the rat brain using saturation binding analyses. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 71(4), 10.26402/jpp.2020.4.09. https://doi.org/10.26402/jpp.2020.4.09

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Ayahuasca blocks the reinstatement of methylphenidate-induced conditioned place preference in mice: behavioral and brain Fos expression evaluations

February 6, 2022 / Ayahuasca, Neuroscience, Papers, Substance Use Disorder / Leave a Comment / By / , , , , , , , , , , , , , ,

Abstract

Rationale: Accumulating evidence suggests that ayahuasca, a hallucinogenic beverage used in traditional Amazonian communities for ritualistic and curative purposes, has been associated with reduced rates of substance use disorders. However, the brain mechanisms underlying the therapeutic effects of ayahuasca have not yet been fully elucidated.

Objectives: The aim of the present study was to investigate the effects of treatment with ayahuasca on the rewarding properties of the psychostimulant methylphenidate.

Methods: The rewarding properties of ayahuasca (100 mg/kg, orally) and methylphenidate (10 mg/kg, i.p.) were investigated using the conditioned place preference (CPP) model. Furthermore, we evaluated the effects of repeated treatment with ayahuasca on the reinstatement of methylphenidate-induced CPP. Fos expression was evaluated in different limbic structures (cingulate cortex-area 1, prelimbic cortex, infralimbic cortex, orbitofrontal cortex-lateral orbital area, nucleus accumbens core and shell, ventral tegmental area, dorsal striatum, and basolateral amygdala) upon each experimental phase.

Results: Both ayahuasca and methylphenidate induced CPP in mice. However, ayahuasca had limited effects on Fos expression, while methylphenidate altered Fos expression in several brain regions associated with the behavioral effects of drugs of abuse. Treatment with ayahuasca after conditioning with methylphenidate blocked the reinstatement of methylphenidate-induced CPP. Those behavioral effects were accompanied by changes in Fos expression patterns, with ayahuasca generally blocking the changes in Fos expression induced by conditioning with methylphenidate and/or reexposure to methylphenidate.

Conclusions: Our findings suggest that ayahuasca restored normal brain function in areas associated with the long-term expression of drug wanting/seeking in animals conditioned to methylphenidate.

Reis, H. S., Rodrigues, I., Anjos-Santos, A., Libarino-Santos, M., Serra, Y. A., Cata-Preta, E. G., Oliveira-Campos, D., Kisaki, N. D., Barros-Santos, T., Yokoyama, T. S., Cruz, F. C., Oliveira-Lima, A. J., Barbosa, P., Berro, L. F., & Marinho, E. (2020). Ayahuasca blocks the reinstatement of methylphenidate-induced conditioned place preference in mice: behavioral and brain Fos expression evaluations. Psychopharmacology, 237(11), 3269–3281. https://doi.org/10.1007/s00213-020-05609-6

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LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors

January 27, 2022 / LSD, Neuroscience, Papers, Psychology / Leave a Comment / By / , , , ,

Abstract

Adapting one’s attitudes and behaviors to group norms is essential for successful social interaction and, thus, participation in society. Yet, despite its importance for societal and individual functioning, the underlying neuropharmacology is poorly understood. We therefore investigated its neurochemical and neural correlates in a pharmacological functional magnetic resonance imaging study. Lysergic acid diethylamide (LSD) has been shown to alter social processing and therefore provides the unique opportunity to investigate the role of the 5-HT2A receptor in social influence processing. Twenty-four healthy human volunteers received either (1) placebo + placebo, (2) placebo + LSD (100 µg), or (3) the 5-HT2A receptor antagonist ketanserin (40 mg) + LSD (100 µg) at three different occasions in a double-blind, randomized, counterbalanced, cross-over design. LSD increases social adaptation but only if the opinions of others are similar to the individual’s own. These increases were associated with increased activity in the medial prefrontal cortex while participants received social feedback. Furthermore, pretreatment with the 5-HT2A antagonist ketanserin fully blocked LSD-induced changes during feedback processing, indicating a key role of the 5-HT2A system in social feedback processing. Our results highlight the crucial role of the 5-HT-system in social influence and, thus, provide important insight into the neuropharmacological basis of social cognition and behavior.

Duerler, P., Schilbach, L., Stämpfli, P., Vollenweider, F. X., & Preller, K. H. (2020). LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors. Scientific reports, 10(1), 12181. https://doi.org/10.1038/s41598-020-68899-y

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Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca

July 10, 2020 / Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background: Ayahuasca is a traditional Amazon brew and its potential antidepressant properties have recently been explored in scientific settings. We conducted a double-blind placebo-controlled trial of ayahuasca with treatment-resistant depression patients (n = 28) and healthy controls (n = 45).

Aims: We are evaluating the blood inflammatory biomarkers: C-reactive protein and interleukin 6, as a potential consequence of ayahuasca intake and their correlation with serum cortisol and brain-derived neurotrophic factor levels. Blood samples were collected at pre-treatment and 48 hours after substance ingestion to assess the concentration of inflammatory biomarkers, together with administration of the Montgomery-Åsberg Depression Rating Scale.

Results: At pre-treatment, patients showed higher C-reactive protein levels than healthy controls and a significant negative correlation between C-reactive protein and serum cortisol levels was revealed (rho = -0.40, n = 14). C-reactive protein in those patients was not correlated with Montgomery-Åsberg Depression Rating Scale scores. We observed a significant reduction of C-reactive protein levels across time in both patients and controls treated with ayahuasca, but not with placebo. Patients treated with ayahuasca showed a significant correlation (rho = + 0.57) between larger reductions of C-reactive protein and lower depressive symptoms at 48 hours after substance ingestion (Montgomery-Åsberg Depression Rating Scale). No significant result with respect to interleukin 6 and brain-derived neurotrophic factor was found. Furthermore, these biomarkers did not predict the antidepressant response or remission rates observed.

Conclusions: These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca and encourage further clinical trials in adults with depression.

Galvão-Coelho, N. L., de Menezes Galvão, A. C., de Almeida, R. N., Palhano-Fontes, F., Campos Braga, I., Lobão Soares, B., … & de Araujo, D. B. (2020). Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca. Journal of Psychopharmacology, 34(10), 1125-1133; 10.1177/0269881120936486
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Psychedelic Treatment for Trauma-Related Psychological and Cognitive Impairment Among US Special Operations Forces Veterans

July 8, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, DMT, Iboga / Ibogaine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Psychotic Disorders, Publications / By / , , , ,

Abstract

Background

U.S. Special Operations Forces Veterans are at increased risk for a variety of mental health problems and cognitive impairment associated with military service. Current treatments are lacking in effectiveness and adherence. Therefore, this study examined psychedelic treatment with ibogaine and 5-methoxy-N,N-dimethyltryptamine for trauma-related psychological and cognitive impairment among U.S. Special Operations Forces Veterans.

Method

We conducted a survey of Veterans who completed a specific psychedelic clinical program in Mexico between 2017 and 2019. Questions probed retrospective reports of mental health and cognitive functioning during the 30 days before and 30 days after treatment. A total of 65 people completed treatment during this time frame and were eligible for contact. Of these, 51 (78%) completed the survey and were included in data analyses (mean age = 40; male = 96%; married = 55%; Caucasian/White = 92%; Operation Enduring Freedom/Operation Iraqi Freedom Service = 96%).

Results

Results indicated significant and very large reductions in retrospective report of suicidal ideation (p < .001; d = −1.9), cognitive impairment (p < .001; d = −2.8), and symptoms of posttraumatic stress disorder (p < .001; d = −3.6), depression (p < .001; d = −3.7), and anxiety (p < .001; d = −3.1). Results also showed a significant and large increase in retrospective report of psychological flexibility (p < .001; d = 2.9) from before-to-after the psychedelic treatment. Increases in the retrospective report of psychological flexibility were strongly associated with retrospective report of reductions in cognitive impairment, and symptoms of posttraumatic stress disorder, depression, and anxiety (rs range −0.61 to −0.75; p < .001). Additionally, most participants rated the psychedelic experiences as one of the top five personally meaningful (84%), spiritually significant (88%), and psychologically insightful (86%) experiences of their lives.
Limitations: Several limitations should be considered including the retrospective, self-report, survey design of the study, and the lack of randomization and blinding, thus making these finding preliminary.

Conclusion

U.S. Special Operations Forces Veterans may have unique treatment needs because of the sequela of problems associated with repeated trauma exposure and the nature of the exposure. Psychedelic-assisted therapy with these under-researched psychedelics may hold unique promise for this population. However, controlled studies are needed to determine whether this treatment is efficacious in relieving mental health and cognitive impairment among U.S. Special Operations Forces Veterans.

Davis, A. K., Averill, L. A., Sepeda, N. D., Barsuglia, J. P., & Amoroso, T. (2020). Psychedelic Treatment for Trauma-Related Psychological and Cognitive Impairment Among US Special Operations Forces Veterans. Chronic Stress, 4, 2470547020939564; 10.1177/2470547020939564
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The pharmacological interaction of compounds in ayahuasca: a systematic review

July 3, 2020 / Ayahuasca, Neuroscience, Papers, Pharmacology & Chemistry, Publications / By / , , , ,

Abstract

Ayahuasca is a South American psychoactive plant brew used as traditional medicine in spiritual and in cultural rituals. This is a review of the current understanding about the pharmacological mechanisms that may be interacting in ayahuasca. Searches were performed using PubMed, PsycINFO, and Web of Science databases and 16 papers were selected. As hypothesized, the primary narrative in existing research revolved around prevention of deamination of N,N-dimethyltryptamine (N,N-DMT, also referred to as DMT) by monoamine oxidase inhibitors (MAOIs) in ayahuasca. Two of the constituents, DMT and harmine, have been studied more than the secondary harmala alkaloids. At present, it is unclear whether the pharmacological interactions in ayahuasca act synergistically or additively to produce psychoactive drug effects. The included studies suggest that our current understanding of the preparation’s synergistic mechanisms is limited and that more complex processes may be involved; there is not yet enough data to determine any potential synergistic interaction between the known compounds in ayahuasca. Our pharmacological understanding of its compounds must be increased to avoid the potential risks of ayahuasca use.

Ruffell, S., Netzband, N., Bird, C., Young, A. H., & Juruena, M. F. (2020). The pharmacological interaction of compounds in ayahuasca: a systematic review. Brazilian Journal of Psychiatry, 42(6), 646-656.; 10.1590/1516-4446-2020-0884
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The Effects of 3,4-methylenedioxymethamphetamine on Neurogenesis in the Hippocampus of Male Rats

February 6, 2022 / MDMA, Neuroscience, Papers / Leave a Comment / By / , , , , , ,

Abstract

Introduction: The administration of 3,4-methylenedioxymethamphetamine (MDMA) or ecstasy causes memory impairment, whereas neurogenesis improves memory and learning. Hence, this study evaluated the effects of MDMA on neurogenesis in the hippocampus of male rats.

Methods: Adult male Wistar rats received Intraperitoneal (IP) injections of MDMA (10 mg/ kg). We assessed nestin, sex-determining region Y-box 2 (Sox2), and NeuroD expressions according to the immunohistochemistry analyses.

Results: MDMA reduced the expressions of nestin, Sox2, and NeuroD compared with the control groups. The reduction in NeuroD expression was age-related.

Conclusion: MDMA possibly has negative effects on neurogenesis, which specifically results from impaired survival of newborn cells.

Soleimani Asl, S., Ghasemi Moravej, F., Kowsari, G., Farhadi, M. H., Pourhaydar, B., Ghasemi Hamidabadi, H., & Mehdizadeh, M. (2020). The Effects of 3,4-methylenedioxymethamphetamine on Neurogenesis in the Hippocampus of Male Rats. Basic and clinical neuroscience, 11(4), 457–464. https://doi.org/10.32598/bcn.9.10.420

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