Neurons to Nirvana screening – June 23rd in Amsterdam
Watch the trailer of this documentary here.
Book your tickets (€10) now by mailing rsvp@stichtingopen.nl
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Restructuring consciousness -the psychedelic state in light of integrated information theory
Abstract
The psychological state elicited by the classic psychedelics drugs, such as LSD and psilocybin, is one of the most fascinating and yet least understood states of consciousness. However, with the advent of modern functional neuroimaging techniques, the effect of these drugs on neural activity is now being revealed, although many of the varied phenomenological features of the psychedelic state remain challenging to explain. Integrated information theory (IIT) is one of the foremost contemporary theories of consciousness, providing a mathematical formalization of both the quantity and quality of conscious experience. This theory can be applied to all known states of consciousness, including the psychedelic state. Using the results of functional neuroimaging data on the psychedelic state, the effects of psychedelic drugs on both the level and structure of consciousness can be explained in terms of the conceptual framework of IIT. This new IIT-based model of the psychedelic state provides an explanation for many of its phenomenological features, including unconstrained cognition, alterations in the structure and meaning of concepts and a sense of expanded awareness. This model also suggests that whilst cognitive flexibility, creativity, and imagination are enhanced during the psychedelic state, this occurs at the expense of cause-effect information, as well as degrading the brain’s ability to organize, categorize, and differentiate the constituents of conscious experience. Furthermore, the model generates specific predictions that can be tested using a combination of functional imaging techniques, as has been applied to the study of levels of consciousness during anesthesia and following brain injury.
Gallimore, A. R. (2015). Restructuring Consciousness–the Psychedelic State in Light of Integrated Information Theory. Name: Frontiers in Human Neuroscience, 9, 346. https://dx.doi.org/10.3389/fnhum.2015.00346
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A Thread in The Vine: The Deep Ecology of Contemporaray Ayahuasca Discourse
Abstract
This thesis uses the philosophy of deep ecology as a theoretical framework to explore ecospiritual themes as a key feature of increasing discourse around the ayahuasca phenomenon. The broad objective of the research is to use contemporary ayahuasca discourse to reveal the way cross-cultural seekers engage with and discuss shamanic practices that inform a postmodern ecosophical ontology and deep ecological praxis. Three convergent discourses inform this research; the transcultural ayahuasca phenomenon, nature-based spiritualities of the New Age and the philosophy of deep ecology. Threading through these discourses are ecological and spiritual themes that capture a web of meanings for contextualising the transcultural emergence of ayahuasca
spirituality. A key paradigmatic shift suggested by contemporary ayahuasca discourse is a shift in human consciousness toward a non-dualistic ontology regarding humanity’s place in nature. An ecocultural studies approach provides theoretical support for interpreting how the elements of this paradigmatic shift are discussed, understood and practiced. As the internet functions as a superlative site for discursive formations of ayahuasca, a thematic content analysis of selected discussion forums within the Ayahuasca.com website was conducted using a multiparadigmatic, deductive and inductive approach. Naess and Sessions’ (1984) eight platform principles of deep ecology were used as a framework to deductively locate textual articulations of the philosophy. Further inductive analysis revealed not only embedded deep ecological themes but also articulations of an ecocentric praxis arising from experiences of unitary consciousness and plant sentience. The deep ecology articulated in contemporary ayahuasca discourse further raised an explicit challenge to hegemonic anthropocentricism through expressions of an expanded sense of self that accentuates the countercultural bearings of entheogenic informed ecospirituality.
Baker, J., & Coco, D. A. A Thread in the Vine: The Deep Ecology of Contemporary Ayahuasca Discourse. https://dx.doi.org/10.13140/RG.2.1.3040.2729
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Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers
Abstract
While hippocampus is a brain region particularly susceptible to the effects of MDMA, the cellular and molecular changes induced by MDMA are still to be fully elucidated, being the dosage regimen, the species and the developmental stage under study great variables. This study compared the effects of one and four days of MDMA administration following a binge paradigm (3×5 mg/kg, i.p., every 2 h) on inducing hippocampal neurochemical changes in adolescent (PND 37) and young adult (PND 58) rats. The results showed that chronic MDMA caused hippocampal protein deficits in adolescent and young adult rats at different levels: (1) impaired serotonergic (5-HT2A and 5-HT2C post-synaptic receptors) and GABAergic (GAD2 enzyme) signaling, and (2) decreased structural cytoskeletal neurofilament proteins (NF-H, NF-M and NF-L). Interestingly, these effects were not accompanied by an increase in apoptotic markers. In fact, chronic MDMA inhibited proteins of the apoptotic pathway (i.e., pro-apoptotic FADD, Bax and cytochrome c) leading to an inhibition of cell death markers (i.e., p-JNK1/2, cleavage of PARP-1) and suggesting regulatory mechanisms in response to the neurochemical changes caused by the drug. The data, together with the observed lack of GFAP activation, support the view that chronic MDMA effects, regardless of the rat developmental age, extends beyond neurotransmitter systems to impair other hippocampal structural cell markers. Interestingly, inhibitory changes in proteins from the apoptotic pathway might be taking place to overcome the protein deficits caused by MDMA.
García-Cabrerizo, R., & García-Fuster, M. J. (2015). Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers. Neurotoxicology, 49, 104-113. http://dx.doi.org/10.1016/j.neuro.2015.06.001
Antidepressant drug action – From rapid changes on network function to network rewiring
Abstract
There has been significant recent progress in understanding the neurobiological mechanisms of antidepressant treatments. The delayed-onset of action of monoamine-based antidepressant drugs have been linked to their ability to slowly increase synaptic plasticity and neuronal excitability via altering neurotrophic signaling (synthesis of BDNF and activation of its receptor TrkB), dematuration of GABAergic interneurons and inhibition of “breaks of plasticity”. On the other hand, antidepressants rapidly regulate emotional processing that – with the help of heightened plasticity and appropriate rehabilitation – gradually lead to significant changes on functional neuronal connectivity and clinical recovery. Moreover, the discovery of rapid-acting antidepressants, most notably ketamine, has inspired renewed interest for novel antidepressant developments with better efficacy and faster onset of action. Therapeutic effects of rapid-acting antidepressants have been linked with their ability to rapidly regulate neuronal excitability and thereby increase synaptic translation and release of BDNF, activation of the TrkB-mTOR-p70S6k signaling pathway and increased synaptogenesis within the prefrontal cortex. Thus, alterations in TrkB signaling, synaptic plasticity and neuronal excitability are shared neurobiological phenomena implicated in antidepressant responses produced by both gradually and rapid acting antidepressants. However, regardless of antidepressant, their therapeutic effects are not permanent which suggests that their effects on neuronal connectivity and network function remain unstable and vulnerable for psychosocial challenges.
Rantamäki, T., & Yalcin, I. (2015). Antidepressant drug action–from rapid changes on network function to network rewiring. Progress in Neuro-Psychopharmacology and Biological Psychiatry. https://dx.doi.org/10.1016/j.pnpbp.2015.06.001
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In vivo effects of ketamine on glutamate-glutamine and gamma-aminobutyric acid in obsessive-compulsive disorder: Proof of concept
Abstract
We previously reported the rapid and robust clinical effects of ketamine versus saline infusions in a proof-of-concept crossover trial in unmedicated adults with obsessive-compulsive disorder (OCD). This study examined the concurrent neurochemical effects of ketamine versus saline infusions using proton magnetic resonance spectroscopy (H MRS) during the clinical proof-of-concept crossover trial. Levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the excitatory neurochemicals glutamate+glutamine (Glx) were acquired in the medial prefrontal cortex (MPFC), a region implicated in OCD pathology. Seventeen unmedicated OCD adults received two intravenous infusions at least 1 week apart, one of saline and one of ketamine, while lying supine in a 3.0 T GE MR scanner. The order of each infusion pair was randomized. Levels of GABA and Glx were measured in the MPFC before, during, and after each infusion and normalized to water (W). A mixed effects model found that MPFC GABA/W significantly increased over time in the ketamine compared with the saline infusion. In contrast, there were no significant differences in Glx/W between the ketamine and saline infusions. Together with earlier evidence of low cortical GABA in OCD, our findings suggest that models of OCD pathology should consider the role of GABAergic abnormalities in OCD symptomatology.
Rodriguez, C. I., Kegeles, L. S., Levinson, A., Ogden, R. T., Mao, X., Milak, M. S., … & Simpson, H. B. (2015). In vivo effects of ketamine on glutamate-glutamine and gamma-aminobutyric acid in obsessive-compulsive disorder: Proof of concept. Psychiatry Research: Neuroimaging. http://dx.doi.org/10.1016/j.pscychresns.2015.06.001
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Salvinorin-A induces intense dissociative effects, blocking external sensory perception and modulating interoception and sense of body ownership in humans
Abstract
Background: Salvinorin-A is a terpene with agonist properties at the kappa-opioid receptor, the binding site of endogenous dynorphins. Salvinorin-A is found in Salvia divinorum, a psychoactive plant traditionally used by the Mazatec people of Oaxaca, Mexico, for medicinal and spiritual purposes. Previous studies with the plant and salvinorin-A have reported psychedelic-like changes in perception but also unusual changes in body awareness and detachment from external reality. Here we comprehensively studied the profile of subjective effects of increasing doses of salvinorin-A in healthy volunteers with special emphasis on interoception.
Methods: A placebo and three increasing doses of vaporized salvinorin-A (0.25, 0.50, and 1 mg) were administered to eight healthy volunteers with previous experience in the use of psychedelics. Drug effects were assessed using a battery of questionnaires that included among others: the Hallucinogen Rating Scale (HRS), the Altered States of Consciousness (APZ), and a new instrument that evaluates different aspects of body awareness: the Multidimensional Assessment for Interoceptive Awareness (MAIA).
Results: Salvinorin-A led to a disconnection from external reality, induced elaborate visions and auditory phenomena, and modified interoception. The lower doses increased somatic sensations, but the high dose led to a sense of a complete loss of contact with the body.
Conclusions: Salvinorin-A induced intense psychotropic effects characterized by a dose-dependent gating of external audio-visual information and an inverted-U dose-response effect on body awareness. These results suggest a prominent role for the kappa opioid receptor in the regulation of sensory perception, interoception and the sense of body ownership in humans.
Maqueda, A. E., Valle, M., Addy, P. H., Antonijoan, R. M., Puntes, M., Coimbra, J., … & Riba, J. (2015). Salvinorin-A induces intense dissociative effects, blocking external sensory perception and modulating interoception and sense of body ownership in humans. International Journal of Neuropsychopharmacology, pyv065. http://dx.doi.org/10.1093/ijnp/pyv065
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The use of ketamine for the treatment of depression in the context of psychotic symptoms
Abstract
Mounting evidence from a series of small clinical trials and case series suggests ketamine can have rapid and robust antidepressant(1), and possibly anti-suicidal effects(2) in patients who had not responded to standard treatment options. However, due to ketamine’s variable psychotomimetic effects in healthy volunteers and exacerbation of previously experienced positive symptoms in schizophrenic volunteers(3,4), patients previously experiencing psychotic features have been excluded from the reported studies and trials.
da Frota Ribeiro, C. M., Sanacora, G., Hoffman, R., & Ostroff, R. (2015). The use of ketamine for the treatment of depression in the context of psychotic symptoms. Biological Psychiatry. http://dx.doi.org/10.1016/j.biopsych.2015.05.016
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Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat.
Abstract
Ayahuasca, a psychoactive beverage used by indigenous and religious groups, is generally prepared by the coction of Psychotria viridis and Banisteriopsis caapi plants containing N,N-dimethyltryptamine (DMT) and β-carboline alkaloids, respectively. To investigate the acute toxicity of ayahuasca, the infusion was administered by gavage to female Wistar rats at doses of 30X and 50X the dose taken during a religious ritual, and the animals observed for 14 days. Behavioural functions were investigated one hour after dosing at 15X and 30X using the open field, elevated plus maze, and forced swimming tests. Neuronal activation (c-fos marked neurons) and toxicity (Fluoro-Jade B and Nissl/Cresyl staining) were investigated in the dorsal raphe nuclei (DRN), amygdaloid nucleus, and hippocampal formation brain areas of rats treated with a 30X ayahuasca dose. The actual lethal oral dose in female Wistar rats could not be determined in this study, but was shown to be higher than the 50X (which corresponds to 15.1 mg/kg bw DMT). The ayahuasca and fluoxetine treated groups showed a significant decrease in locomotion in the open field and elevated plus-maze tests compared to controls. In the forced swimming test, ayahuasca treated animals swam more than controls, a behaviour that was not significant in the fluoxetine group. Treated animals showed higher neuronal activation in all brain areas involved in serotoninergic neurotransmission. Although this led to some brain injury, no permanent damage was detected. These results suggest that ayahuasca has antidepressant properties in Wistar female at high doses, an effect that should be further investigated.
Pic-Taylor, A., da Motta, L. G., de Morais, J. A., Junior, W. M., Santos, A. D. F. A., Campos, L. A., … & Caldas, E. D. (2015). Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat. Behavioural processes. http://dx.doi.org/10.1016/j.beproc.2015.05.004
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Anti-mycobacterial and anti-inflammatory activity of Peganum harmala.
Abstract
The aim of this study was to evaluate the antimycobacterial and anti-inflammatory activity of the methanolic extracts of Peganum harmala (Esphand) collected from Golestan province, north of Iran. Methods: Hydroalcoholic extract of seeds of Peganum harmala were obtained and screened for anti-mycobacterial activity by disc diffusion (DD) method. The anti-inflammatory activity of the extract was evaluated by cytokines measurement using ELISA in a model of phagocytized intracellular Mycobacterium tuberculosis, H37Rv strain, in dU937cells. Free radical-scavenging activity, total phenolic, flavonoids and Harmalin concentrations were assessed to investigate phytochemical properties of the extract. Our data showed the inhibitory effect of the extract on growth of all strains of Mycobacterium tuberculosis even on drug resistant strains. Cytokines production in culture media showed the anti-inflammatory activity of the extract. The antioxidant (IC50 (DPPH assay) was 53.6 ± 0.50 mg/L. The amount of total phenolic and flavonoids components was 61.5 ± 0.80 gGAE/kg and 42.20 ± 0.60 respectively. These findings revealed the potential ability of the Peganum harmala s seed as a complementary medicine to treat tuberculosis.
Davoodi, H., Ghaemi, E., Mazandarani, M., Shakeri, F., Javid, S. N., & Klishadi, M. (2015). Anti-mycobacterial and anti-inflammatory activity of Peganum harmala. Journal of Chemical & Pharmaceutical Research, 7(4).
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