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Neurovascular and neuroimaging effects of the hallucinogenic serotonin receptor agonist psilocin in the rat brain.

July 17, 2015 / Mushrooms / Psilocybin, Neuroscience, Papers, Publications / By / , , , , ,

Abstract

The development of pharmacological magnetic resonance imaging (phMRI) has presented the opportunity for investigation of the neurophysiological effects of drugs in vivo. Psilocin, a hallucinogen metabolised from psilocybin, was recently reported to evoke brain region-specific, phMRI signal changes in humans. The present study investigated the effects of psilocin in a rat model using phMRI and then probed the relationship between neuronal and haemodynamic responses using a multimodal measurement preparation. Psilocin (2 mg/kg or 0.03 mg/kg i.v.) or vehicle was administered to rats (N = 6/group) during either phMRI scanning or concurrent imaging of cortical blood flow and recording of local field potentials. Compared to vehicle controls psilocin (2 mg/kg) evoked phMRI signal increases in a number of regions including olfactory and limbic areas and elements of the visual system. PhMRI signal decreases were seen in other regions including somatosensory and motor cortices. Investigation of neurovascular coupling revealed that whilst neuronal responses (local field potentials) to sensory stimuli were decreased in amplitude by psilocin administration, concurrently measured haemodynamic responses (cerebral blood flow) were enhanced. The present findings show that psilocin evoked region-specific changes in phMRI signals in the rat, confirming recent human data. However, the results also suggest that the haemodynamic signal changes underlying phMRI responses reflect changes in both neuronal activity and neurovascular coupling. This highlights the importance of understanding the neurovascular effects of pharmacological manipulations for interpreting haemodynamic neuroimaging data.

Spain, A., Howarth, C., Khrapitchev, A., Sharp, T., Sibson, N. R., & Martin, C. (2015). Neurovascular and neuroimaging effects of the hallucinogenic serotonin receptor agonist psilocin in the rat brain. Neuropharmacology. https://dx.doi.org/10.1016/j.neuropharm.2015.07.018
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Ketamine induces anxiolytic effects in adult zebrafish: A multivariate statistics approach.

July 14, 2015 / Anxiety Disorders / PTSD, Ketamine, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

Ketamine inappropriate use has been associated with serious consequences for human health. Anesthetic properties of ketamine are well-known but its side effects are poorly described, including the effects on anxiety. In this context, animal models are a safe way to conduct this neurobehavioral research and zebrafish (Danio rerio) is an interesting model which has several advantages. The validation and interpretation of results of behavioral assays requires a suitable statistical approach and the use of multivariate statistical methods has been little explored, especially in zebrafish behavioral models. Here, we investigated the anxiolytic-induced effects of ketamine in adult zebrafish, using Light-Dark Test and Multivariate Statistics methods (PCA, HCA and SIMCA). In addition, we compared the processing of data to the one carried out by analysis of variance (ANOVA) Ketamine produced significant concentration of exposure-dependent anxiolytic effects, increasing time in white area and number of crossings and decreasing latency to first access to white area. Average entry duration behavior resulted in a slight decrease from control to treatment groups, with an observed concentration-dependent increase among the exposed groups. PCA results indicated that two principal components represent 88.74% of all the system information. HCA and PCA results showed a higher similarity among control and treatment groups exposed to lower concentrations of ketamine and among treatment groups exposed to concentrations of 40 and 60 mg.L-1. In SIMCA results, interclasses distances were concentration of exposure-dependent increased and misclassifications and interclasses residues results also support these findings. These findings confirm the anxiolytic potential of ketamine and zebrafish sensibility to this drug. In summary, our study confirms that zebrafish and multivariate statistics data validation is an appropriate and viable behavioral model for the study of psychoactive substances, providing a detailed and reliable analysis.

De Campos, E. G., Bruni, A. T., & De Martinis, B. S. (2015). Ketamine induces anxiolytic effects in adult zebrafish: A multivariate statistics approach. Behavioural Brain Research.  https://dx.doi.org/10.1016/j.bbr.2015.07.017
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‘Whatever you want to believe’ kaleidoscopic individualism and ayahuasca healing in Australia

July 14, 2015 / Anthropology & Sociology, Ayahuasca, Biology & Ethnobotany, Papers, Psychology, Publications / By /

Abstract

Over the last fifteen years the use of the indigenous Amazonian psychoactive beverage ayahuasca has been reimagined in alternative healing circles of Western countries. This paper explores the practice of ayahuasca neoshamanism in Australia and examines ways in which acts of vomiting and ecstatic trance-visions involve heightened affective states and moral projects of healing. Aspects of everyday life are purged, rearticulated, and reconstituted in rituals where codes of conduct and discursive exchange encourage practices of personal evaluation and reflexivity that appear to index ideologies of individualism. Through exploring social and discursive prohibitions and forms of sensory organisation, the practice of drinking ayahuasca in Australia is shown to be constituted by ritual conventions that define the individual as autonomous and responsible in relation to ecstatic trance and articulations of wellbeing.

Gearin, A. K. (2015). ‘Whatever you want to believe’kaleidoscopic individualism and ayahuasca healing in Australia. The Australian Journal of Anthropology. https://dx.doi.org/10.1111/taja.12143
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Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities

July 14, 2015 / DMT, LSD, MDMA, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By /

Abstract

Classical psychedelics are psychoactive substances, which, besides their psychopharmacological activity, have also been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation, and cell survival via activating NF-κB and mitogen-activated protein kinases. Recently, several neurotransmitter receptors involved in the pharmacology of psychedelics, such as serotonin and sigma-1 receptors, have also been shown to play crucial roles in numerous immunological processes. This emerging field also offers promising treatment modalities in the therapy of various diseases including autoimmune and chronic inflammatory conditions, infections, and cancer. However, the scarcity of available review literature renders the topic unclear and obscure, mostly posing psychedelics as illicit drugs of abuse and not as physiologically relevant molecules or as possible agents of future pharmacotherapies. In this paper, the immunomodulatory potential of classical serotonergic psychedelics, including N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-iodoamphetamine, and 3,4-methylenedioxy-methamphetamine will be discussed from a perspective of molecular immunology and pharmacology. Special attention will be given to the functional interaction of serotonin and sigma-1 receptors and their cross-talk with toll-like and RIG-I-like pattern-recognition receptor-mediated signaling. Furthermore, novel approaches will be suggested feasible for the treatment of diseases with chronic inflammatory etiology and pathology, such as atherosclerosis, rheumatoid arthritis, multiple sclerosis, schizophrenia, depression, and Alzheimer’s disease.

Szabo, A. Psychedelics and immunomodulation: Novel approaches and therapeutic opportunities. Frontiers in Immunology, 0. https://dx.doi.org/10.3389/fimmu.2015.00358
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A Model of Enlightened/Mystical/Awakened Experience.

July 13, 2015 / Papers, Psychology, Publications / By /

Abstract

Awakening experiences are powerful and transcendent experiences that profoundly affect the individual. There appears to be an essential core experience of oneness. It is experienced as a completely subjective phenomenon where awareness contains reality and the notions of an external reality and a separate self are perceived as delusions. A model is presented of awakening experiences that postulates 3 layers of processing, sensory, perceptual, and cognitive, that separate external energy from awareness. The model hypothesizes that awakening experiences results from the progressive removal of the cognitive, perceptual, and sensory layers of information processing. This to some extent returns awareness to a primal state that was present before the development of neural information processing. The model simplifies, summarizes, and explains awakening experiences and is consistent with neural system activity observed during contemplative practice, transcendent states, and hallucinatory drug use and with the effects of changes in the neural systems on experiences.

de Castro, J. M. (2015). A Model of Enlightened/Mystical/Awakened Experience. http://dx.doi.org/10.1037/rel0000037
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Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder

July 7, 2015 / Depressive Disorders, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

Depression is a devastating disorder that places a significant burden on both the individual and society. As such, the discovery of novel therapeutics and innovative treatments—especially for treatment-resistant depression (TRD)—are essential. Research into antidepressant therapies for TRD has evolved from explorations of antidepressants with primary mechanisms of action on the monoaminergic neurotransmitter system to augmentation agents with primary mechanisms both within and outside of the serotonin/norepinephrine system. Now the field of antidepressant research has changed trajectories yet again; this time, compounds with primary mechanisms of action on the glutamatergic, cholinergic and opioid systems are in the forefront of antidepressant exploration. In this review, we will discuss the most recent research surrounding these novel compounds. In addition, we will discuss novel device-based therapeutics, with a particular focus on transcranial magnetic stimulation. In many cases of antidepressant drug discovery, the role of serendipity coupled with meticulous clinical observation in drug development in medicine was crucial. Moving forward, we must look toward the combination of innovation plus improvements on the remarkable discoveries thus far to advance the field of antidepressant research.

Papakostas, G. I., & Ionescu, D. F. (2015). Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder. Molecular psychiatry. https://dx.doi.org/10.1038/mp.2015.92
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Perceptual distortions and delusional thinking following ketamine administration are related to increased pharmacological MRI signal changes in the parietal lobe

July 6, 2015 / Ketamine, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , , , ,

Abstract

Ketamine produces effects in healthy humans that resemble the positive, negative and cognitive symptoms of schizophrenia. We investigated the effect of ketamine administration on brain activity as indexed by blood-oxygen-level-dependent (BOLD) signal change response, and its relationship to ketamine-induced subjective changes, including perceptual distortion. Thirteen healthy participants volunteered for the study. All underwent a 15-min functional MRI acquisition with a ketamine infusion commencing after 5 min (approx 0.26 mg/kg over 20s followed by an infusion of approx. 0.42 mg/kg/h). Following the scan, participants self-rated ketamine-induced effects using the Psychotomimetic States Inventory. Ketamine led to widespread cortical and subcortical increases in BOLD response (FWE-corrected p < 0.01). Self-rated perceptual distortions and delusional thoughts correlated with increased BOLD response in the paracentral lobule (FWE-corrected p < 0.01). The findings suggest that BOLD increases in parietal cortices reflect ketamine effects on circuits that contribute to its capacity to produce perceptual alterations and delusional interpretations.

Stone, J., Kotoula, V., Dietrich, C., De Simoni, S., Krystal, J. H., & Mehta, M. A. (2015). Perceptual distortions and delusional thinking following ketamine administration are related to increased pharmacological MRI signal changes in the parietal lobe. Journal of Psychopharmacology, 0269881115592337. https://dx.doi.org/10.1177/0269881115592337
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Ayahuasca Alters Structural Parameters of the Rat Aorta

July 1, 2015 / Ayahuasca, Papers, Psychiatry & Medicine, Publications / By / , , , , , ,

Abstract

Ayahuasca is a hallucinogenic brew traditionally used by Northwestern Amazonian indigenous groups for therapeutic purposes. It is prepared by the decoction of Banisteriopsis caapi with the leaves of Psychotria viridis. Banisteriopsis caapi contains β-carbolines that are inhibitors of monoamine oxidase and P. viris is rich in dimethyltryptamine, a 5-HT1A/2A/2C agonist. Acute ayahuasca administration produces moderate cardiovascular effects in healthy volunteers, but information regarding long-term use is lacking. This study investigated the effects of ayahuasca (2–4 mL/kg) in the rat aorta after acute and chronic (14 days) administration. Ayahuasca caused flattening and stretching of vascular smooth muscle cells and changes in the arrangement and distribution of collagen and elastic fibers. Chronic treatment with the higher dose significantly increased media thickness and the ratio of media thickness to lumen diameter. More research is needed on the cardiovascular function of long-term ayahuasca consumers.

Pitol, D. L., Siéssere, S., Dos Santos, R. G., Nunes, M. R. M., Cecilio, H. J., Scalize, P. H., … & Hallak, R. S. (2015). Ayahuasca alters structural parameters of the rat aorta. Journal of cardiovascular pharmacology. http://dx.doi.org/10.1097/FJC.0000000000000243
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Psychedelics and creativity: a review of the quantitative literature

June 30, 2015 / LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

After a 40-year hiatus, the question of whether psychedelics can increase creativity is being asked with renewed vigor. This article critically reviews the conceptual issues of studying psychedelic-induced creativity by summarizing the limited evidence on the question and suggesting two broader frameworks. There are two important challenges to researchers on this topic. One is to separate creativity from other effects of the drug that may be mistaken for creativity. The second is to develop operational measures to quantify it. This article reviews the major studies assessing creativity (or related constructs) induced by psychedelics, including a reanalysis of raw data from one study. Results are modest and inconclusive but are consistent with reports that psychedelics give rise to unusual or novel thoughts. Given the lack of robust changes in creativity measures, I suggest creativity may be too specific of a construct to accurately and fully characterize the putatively beneficial cognitive changes that psychedelic users report. Feelings of creativity may be an inconsistent result of a more general effect of these drugs, such as alterations in availability of mental representations or changes in Bayesian inference. Ultimately, creativity may not be a sufficiently creative construct to capture the beneficial effects of psychedelics.

Baggott, M. J. (2015). Psychedelics and creativity: a review of the quantitative literature. PeerJ PrePrints, 3, e1468. https://dx.doi.org/10.7287/peerj.preprints.1202v1
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Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression

June 29, 2015 / Depressive Disorders, Ketamine, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

Objective The authors conducted a systematic review and meta-analysis of ketamine and other N-methyl-d-aspartate (NMDA) receptor antagonists in the treatment of major depression.

Method Searches of MEDLINE, PsycINFO, and other databases were conducted for placebo-controlled, double-blind, randomized clinical trials of NMDA antagonists in the treatment of depression. Primary outcomes were rates of treatment response and transient remission of symptoms. Secondary outcomes included change in depression symptom severity and the frequency and severity of dissociative and psychotomimetic effects. Results for each NMDA antagonist were combined in meta-analyses, reporting odds ratios for dichotomous outcomes and standardized mean differences for continuous outcomes.

Results Ketamine (seven trials encompassing 147 ketamine-treated participants) produced a rapid, yet transient, antidepressant effect, with odds ratios for response and transient remission of symptoms at 24 hours equaling 9.87 (4.37–22.29) and 14.47 (2.67–78.49), respectively, accompanied by brief psychotomimetic and dissociative effects. Ketamine augmentation of ECT (five trials encompassing 89 ketamine-treated participants) significantly reduced depressive symptoms following an initial treatment (Hedges’ g=0.933) but not at the conclusion of the ECT course. Other NMDA antagonists failed to consistently demonstrate efficacy; however, two partial agonists at the NMDA coagonist site, d-cycloserine and rapastinel, significantly reduced depressive symptoms without psychotomimetic or dissociative effects.

Conclusions The antidepressant efficacy of ketamine, and perhaps D-cycloserine and rapastinel, holds promise for future glutamate-modulating strategies; however, the ineffectiveness of other NMDA antagonists suggests that any forthcoming advances will depend on improving our understanding of ketamine’s mechanism of action. The fleeting nature of ketamine’s therapeutic benefit, coupled with its potential for abuse and neurotoxicity, suggest that its use in the clinical setting warrants caution.

Newport, D. J., Carpenter, L. L., McDonald, W. M., Potash, J. B., Tohen, M., & Nemeroff, C. B. (2015). Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. American Journal of Psychiatry, 172(10), 950-966. http://dx.doi.org/10.1176/appi.ajp.2015.15040465

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