OPEN Foundation

Author name: OPEN Foundation

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

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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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Harm Reduction or Psychedelic Support?

Abstract

Many of the EDM events known as “transformational festivals” provide psychedelic support spaces: volunteer projects caring for festivalgoers undergoing difficult drug experiences. Mostly drawn from the festival community, many volunteer carers (“sitters”) subscribe to psychedelic culture discourse which frames these substances as aids to personal growth if handled appropriately. However, within the dominant paradigm of international drug prohibition, support projects must employ the contrasting discourse of harm reduction in order to gain access to events, visibility to festivalgoers, and integration with other support staff. Harm reduction, a paradigm for the care of drug users which began as a grassroots heroin addict advocacy movement, has since become associated with neoliberal, medicalised views of drugs, drug users and the self. his article considers how psychedelic support workers negotiate this discourse dichotomy in the course of caregiving, within differing national and local drug policy climates. Early findings are presented from ethnographic fieldwork as a psychedelic support volunteer with three organisations at seven festivals, combining participant observation and in-depth interviews with nineteen support workers. Events in the UK, the US and Portugal were studied due to these countries’ contrasting policy regimes. Points of conflict between the psychedelic and harm reduction discourses were found to create tensions both within the support organisations and in their relations with on-site medics, security guards, festival organisers and police. he findings suggest that mainstream harm reduction discourses may be a poor it for psychedelics and that risks inhere in their adoption by festival support spaces, such as abjection of drug users in difficulty which may create a trust-damaging divide between users and workers.

Ruane, D. (2015). Harm Reduction or Psychedelic Support?. Dancecult: Journal of Electronic Dance Music Culture, 7(1) http://dx.doi.org/10.12801/1947-5403.2015.07.01.03

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MDMA for the treatment of mood disorder: all talk no substance?

Abstract

BACKGROUND:

Unipolar depression is the third highest contributor to the global burden of disease, yet current pharmacotherapies typically take about 6 weeks to have an effect. A rapid-onset agent is an attractive prospect, not only to alleviate symptoms before first-line antidepressants display therapeutic action, but as a further treatment option in nonresponsive cases. It has been suggested that 3,4-methylene-dioxymethamphetamine (MDMA) could play a part in the treatment of depression, either as a rapid-onset pharmacological agent or as an adjunct to psychotherapy. Whilst these hypotheses are in keeping with the monoamine theory of depression and the principles surrounding psychotherapy, explicit experimental evidence of an antidepressant effect of MDMA has rarely been established.

AIMS:

To address the hypothesis surrounding MDMA as a rapid-onset antidepressant by examining pharmacological, psychological and behavioural studies. We consider whether this therapy could be safe by looking at the translation of neurotoxicity data from animals to humans.

METHOD:

A literature review of the evidence supporting this hypothesis was performed.

CONCLUSIONS:

The pharmacology of MDMA offers a promising target as a rapid-onset agent and MDMA is currently being investigated for use in psychotherapy in anxiety disorders; translation from these studies for use in depression may be possible. However, experimental evidence and safety analysis are insufficient to confirm or reject this theory at present.

Patel, R., & Titheradge, D. (2015). MDMA for the treatment of mood disorder: all talk no substance?. Therapeutic Advances in Psychopharmacology, 2045125315583786. https://dx.doi.org/10.1177/2045125315583786
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Breath and Body: Scientific and Experiential Perspectives on Breathwork - September 23rd