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It’s Tea Time: Interference of Ayahuasca Brew on Discriminative Learning in Zebrafish

/ Ayahuasca, Neuroscience, Papers, Psychology, Publications / / , , , , ,

Abstract

Ayahuasca is a psychoactive brew traditionally used in shamanistic and vegetalistic rituals and has recently received lot of attention due to potential cognitive benefits. Ayahuasca effects are caused by the synergistic interaction of β-carbolines (harmine, harmaline and tetrahydroarmine) contained in Banisteriopsis caapi stalks combined with the N,N-dimethyltryptamine (DMT) from Psychotria viridis leaves, a potent agonist to serotonin (5-HT) receptors. The present study approaches the effects of chronic and acute exposure to two Ayahuasca concentrations (0.1 and 0.5 ml/L) on the cognitive ability to discriminate objects in a one-trial learning task in zebrafish. Based on the combination of concentrations and exposure regimens, we divided adult zebrafish in five treatment groups: acute 0.1 and 0.5 ml/L, chronic 0.1 and 0.5 ml/L, and control 0.0 (n = 20 for each group). Then we tested them in a memory task of object discrimination. Acute Ayahuasca exposed groups performed similarly to the control group, however chronically treated fish (13 days) presented both impaired discriminative performance and locomotor alterations. Overall, these results indicate that Ayahuasca is a potent psychoactive drug that, in chronic exposure, negatively affects mnemonic parameters in zebrafish. In single exposure it does not affects cognitive performance, but the higher concentration (0.5) affected locomotion. Moreover, we reinforce the importance of the zebrafish for behavioral pharmacological studies of drug screening, in special to psychedelic drug research.

Eduardo-da-Silva, P., Lobao-Soares, B., Amarilha, H., Pinheiro-da-Silva, J., Silva, P. F., & Luchiari, A. C. (2018). It’s tea time: Interference of Ayahuasca brew on discriminative learning in zebrafish. Frontiers in behavioral neuroscience, 12, 190., 10.3389/fnbeh.2018.00190

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The influence of therapists’ first-hand experience with psychedelics on psychedelic-assisted psychotherapy research and therapist training

/ MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / / ,

Abstract

Clinical research on psychedelic-assisted psychotherapy is rapidly advancing in the USA, with two drugs, psilocybin and MDMA, progressing through a structure of FDA-approved trials on a trajectory toward Drug Enforcement Agency rescheduling for therapeutic use. Researcher’s and clinician’s personal use of psychedelics was cited as a potential confound in psychedelic research studies conducted in the 1950s and 1960s, a concern which contributed to the cessation of this research for some 20 years. Currently, there is no empirical research on personal use of psychedelics by current academic researchers and clinicians; its influence is undocumented, unknown, and undertheorized. This paper explores the history of personal use of psychedelics by clinicians and researchers, the potential impact of personal use on psychedelic-assisted psychotherapy and research, and the rationale for opening an academic discussion and program of research to investigate the role of personal use. We propose that there are factors unique to psychedelic-assisted therapy such that training for it cannot neatly fit into the framework of modern psychopharmacology training, nor be fully analogous to psychotherapy training in contemporary psychological and psychiatric settings. We argue that scientific exploration of the influence of therapists’ first-hand experience of psychedelics on psychedelic-assisted therapy outcomes is feasible, timely, and necessary for the future of clinical research.
Nielson, E. M., & Guss, J. (2018). The influence of therapists’ first-hand experience with psychedelics on psychedelic-assisted psychotherapy research and therapist training. Journal of Psychedelic Studies, 1-10. 10.1556/2054.2018.009
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Legitimate Medicine in the Age of Consumerism

/ Anthropology & Sociology, Papers, Psychiatry & Medicine, Psychology, Publications / /

Abstract

From the opioid epidemic and medical marijuana to abortion restrictions and physician-assisted suicide, disputes over the proper uses of medicine loom large in American life. Nowhere is this conflict more apparent than in federal drug control policy, which is premised on a clear distinction between legitimate “medical” uses and illicit “abuse.” Yet the Controlled Substances Act defines neither of these foundational concepts. While it is tempting to imagine medicine’s scope is limited to treating or preventing disease – rendering nontherapeutic drug use “abuse” – in fact medical practice has always included interventions that are not aimed at healing. This trend has only accelerated as medical practice has become increasingly consumer-oriented. From Adderall to Xanax, patients now routinely seek prescriptions not to treat diagnosable illnesses, but to relieve stress, improve productivity, and otherwise enhance quality of life.

As physicians increasingly prescribe psychoactive drugs to help healthy people obtain desirable mental states, distinguishing legitimate drug use from recreational abuse becomes ever more difficult. Having failed to acknowledge this challenge, the DEA, courts, and scholars have not offered a principled way to make this distinction, rendering drug control policy increasingly incoherent. As a result, doctors face criminal prosecution without clear standards governing prescribing, potentially valuable interventions are arbitrarily barred from the market, and millions seek the benefits of drugs without professional medical guidance to mitigate their risks.

Rather than being limited to therapeutic aims, medicine is better understood as the application of a loosely-defined set of knowledge and interventions that the law entrusts to specific professionals, with accompanying duties to use these tools to benefit patients. Medical practice includes treating and preventing illnesses, but can also include enhancing social and cognitive functioning and promoting the well-being of people whose challenges do not rise to the level of disorders. Discarding a narrow conception of medicine does not require abandoning the enforcement of drug laws or the policing of doctors. But acknowledging the expansiveness of medicine’s domain does argue for clarifying the scope of physicians’ criminal liability and pursuing new strategies for harnessing drugs’ benefits while mitigating their risks.

Lamkin, M. (2018). Legitimate Medicine in the Age of Consumerism., 10.2139/ssrn.3228692
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DMT Models the Near-Death Experience

/ DMT, Papers, Psychology, Publications / / , , , , , ,

Abstract

Near-death experiences (NDEs) are complex subjective experiences, which have been previously associated with the psychedelic experience and more specifically with the experience induced by the potent serotonergic, N,N-Dimethyltryptamine (DMT). Potential similarities between both subjective states have been noted previously, including the subjective feeling of transcending one’s body and entering an alternative realm, perceiving and communicating with sentient ‘entities’ and themes related to death and dying. In this within-subjects placebo-controled study we aimed to test the similarities between the DMT state and NDEs, by administering DMT and placebo to 13 healthy participants, who then completed a validated and widely used measure of NDEs. Results revealed significant increases in phenomenological features associated with the NDE, following DMT administration compared to placebo. Also, we found significant relationships between the NDE scores and DMT-induced ego-dissolution and mystical-type experiences, as well as a significant association between NDE scores and baseline trait ‘absorption’ and delusional ideation measured at baseline. Furthermore, we found a significant overlap in nearly all of the NDE phenomenological features when comparing DMT-induced NDEs with a matched group of ‘actual’ NDE experiencers. These results reveal a striking similarity between these states that warrants further investigation.
Timmermann, C., Roseman, L., Williams, L., Erritzoe, D., Martial, C., Cassol, H., … & Carhart-Harris, R. (2018). DMT models the near-death experience. Frontiers in psychology, 9, 1424., 10.3389/fpsyg.2018.01424
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Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews

/ Ayahuasca, Depressive Disorders, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / / , , ,

Abstract

Mood, anxiety, and substance-use disorders are among the most prevalent psychiatric disorders in the population. Although several pharmacological treatments are available, they are not effective for a significant proportion of patients and are associated with several adverse reactions. Therefore, new treatments should be explored. Recent studies suggest that serotonergic hallucinogens/psychedelics including ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) have anxiolytic, antidepressive, and antiaddictive effects. Areas Covered: A systematic review of systematic reviews assessing the efficacy, safety, and tolerability of serotonergic hallucinogens/psychedelic was performed using the PubMed data base until 11 April 2018. Systematic reviews with or without meta-analysis were analyzed, but only reviews that described at least one randomized controlled trial (RCT) were included. Expert Commentary: Psilocybin and LSD reduced anxiety and depression in cancer patients and symptoms of alcohol and tobacco dependence, and ayahuasca reduced depression symptoms in treatment-resistant depression. Although the results are promising, several studies were open label, and only few were RCTs, and most had small sample sizes and a short duration. Single or few doses of these drugs seem to be well tolerated, but long-term studies are lacking. New RCTs with bigger samples and longer duration are needed to replicate these findings.

dos Santos, R. G., Bouso, J. C., Alcázar-Córcoles, M. Á., & Hallak, J. E. (2018). Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: A systematic review of systematic reviews. Expert review of clinical pharmacology, 11(9), 889-902., 10.1080/17512433.2018.1511424
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Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress

/ Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Psychology, Publications / /

Abstract

Cancer is highly prevalent and one of the leading causes of global morbidity and mortality. Psychological and existential suffering is common in cancer patients, associated with poor psychiatric and medical outcomes. Promising early-phase clinical research (1960s to early 1970s) suggested a therapeutic signal for serotoninergic psychedelics (e.g. psilocybin, LSD) in treating cancer-related psychiatric distress. After several decades of quiescence, research on psychedelic-assisted therapy to treat psychiatric disorders in cancer patients has resumed within the last 2 decades in the US and Europe. This review article is based on a systematic search of clinical trials from 1960–2018 researching the therapeutic use of psychedelic treatment in patients with serious or terminal illnesses and related psychiatric illness. The search found 10 eligible clinical trials, with a total of 445 participants, with the vast majority of the patients having advanced or terminal cancer diagnoses. Six open label trials, published between 1964 and 1980 (n = 341), suggested that psychedelic therapy (mostly with LSD) may improve cancer-related depression, anxiety, and fear of death. Four RCTs trials were published between 2011 and 2016 (n = 104), mostly with psilocybin treatment (n = 92), and demonstrated that psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress.
Ross, S. (2018). Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress. International Review of Psychiatry, 30(4), 317-330., 10.1080/09540261.2018.1482261
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Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution

/ Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / / , , , , , ,

Abstract

Rationale

Ayahuasca is a psychotropic plant tea from South America used for religious purposes by indigenous people of the Amazon. Increasing evidence indicates that ayahuasca may have therapeutic potential in the treatment of mental health disorders and can enhance mindfulness-related capacities. Most research so far has focused on acute and sub-acute effects of ayahuasca on mental health-related parameters and less on long-term effects.

Objectives

The present study aimed to assess sub-acute and long-term effects of ayahuasca on well-being and cognitive thinking style. The second objective was to assess whether sub-acute and long-term effects of ayahuasca depend on the degree of ego dissolution that was experienced after consumption of ayahuasca.

Results

Ayahuasca ceremony attendants (N = 57) in the Netherlands and Colombia were assessed before, the day after, and 4 weeks following the ritual. Relative to baseline, ratings of depression and stress significantly decreased after the ayahuasca ceremony and these changes persisted for 4 weeks. Likewise, convergent thinking improved post-ayahuasca ceremony up until the 4 weeks follow-up. Satisfaction with life and several aspects of mindfulness increased the day after the ceremony, but these changes failed to reach significance 4 weeks after. Changes in affect, satisfaction with life, and mindfulness were significantly correlated to the level of ego dissolution experienced during the ayahuasca ceremony and were unrelated to previous experience with ayahuasca.

Conclusion

It is concluded that ayahuasca produces sub-acute and long-term improvements in affect and cognitive thinking style in non-pathological users. These data highlight the therapeutic potential of ayahuasca in the treatment of mental health disorders, such as depression.

Uthaug, M. V., van Oorsouw, K., Kuypers, K. P. C., van Boxtel, M., Broers, N. J., Mason, N. L., … & Ramaekers, J. G. (2018). Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution. Psychopharmacology, 235(10), 2979-2989., 10.1007/s00213-018-4988-3
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Psychedelics as anti-inflammatory agents

/ Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Publications / / ,

Abstract

Serotonin (5-hydroxytryptamine, 5-HT)2A receptor agonists have recently emerged as promising new treatment options for a variety of disorders. The recent success of these agonists, also known as psychedelics, like psilocybin for the treatment of anxiety, depression, obsessive-compulsive disorder (OCD), and addiction, has ushered in a renaissance in the way these compounds are perceived in the medical community and populace at large. One emerging therapeutic area that holds significant promise is their use as anti-inflammatory agents. Activation of 5-HT2A receptors produces potent anti-inflammatory effects in animal models of human inflammatory disorders at sub-behavioural levels. This review discusses the role of the 5-HT2A receptor in the inflammatory response, as well as highlight studies using the 5-HT2A agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] to treat inflammation in cellular and animal models. It also examines potential mechanisms by which 5-HT2A agonists produce their therapeutic effects. Overall, psychedelics regulate inflammatory pathways via novel mechanisms, and may represent a new and exciting treatment strategy for several inflammatory disorders.

Flanagan, T. W., & Nichols, C. D. (2018). Psychedelics as anti-inflammatory agents. International Review of Psychiatry, 30(4), 363-375., 10.1080/09540261.2018.1481827

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Iterative l-Tryptophan Methylation in Psilocybe Evolved by Subdomain Duplication

/ Biology & Ethnobotany, Mushrooms / Psilocybin, Neuroscience, Papers, Pharmacology & Chemistry, Publications / / , , , ,

Abstract

Psilocybe mushrooms are best known for their l-tryptophan-derived psychotropic alkaloid psilocybin. Dimethylation of norbaeocystin, the precursor of psilocybin, by the enzyme PsiM is a critical step during the biosynthesis of psilocybin. However, the “magic” mushroom Psilocybe serbica also mono- and dimethylates l-tryptophan, which is incompatible with the specificity of PsiM. Here, a second methyltransferase, TrpM, was identified and functionally characterized. Mono- and dimethylation activity on l-tryptophan was reconstituted in vitro, whereas tryptamine was rejected as a substrate. Therefore, we describe a second l-tryptophan-dependent pathway in Psilocybe that is not part of the biosynthesis of psilocybin. TrpM is unrelated to PsiM but originates from a retained ancient duplication event of a portion of the egtDB gene that encodes an ergothioneine biosynthesis enzyme. During mushroom evolution, this duplicated gene was widely lost but re-evolved sporadically and independently in various genera. We propose a new secondary metabolism evolvability mechanism, in which weakly selected genes are retained through preservation in a widely distributed, conserved pathway.

Blei, F., Fricke, J., Wick, J., Slot, J. C., & Hoffmeister, D. (2018). Iterative l‐Tryptophan Methylation in Psilocybe Evolved by Subdomain Duplication. ChemBioChem, 19(20), 2160-2166., 10.1002/cbic.201800336.
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N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function

/ DMT, Neuroscience, Papers, Publications / /

Abstract

This report provides a historical overview of research concerning the endogenous hallucinogen N, N-dimethyltryptamine (DMT), focusing on data regarding its biosynthesis and metabolism in the brain and peripheral tissues, methods and results for DMT detection in body fluids and brain, new sites of action for DMT, and new data regarding its possible physiological and therapeutic roles. Research that further elaborates its consideration as a putative neurotransmitter is also addressed. Taking these studies together, the report proposes several new directions and experiments to ascertain the role of DMT in the brain, including brain mapping of enzymes responsible for the biosynthesis of DMT, further studies to elaborate its presence and role in the pineal gland, a reconsideration of binding site data, and new administration and imaging studies. The need to resolve the “natural” role of an endogenous hallucinogen from the effects observed from peripheral administration are also emphasized.

Barker, S. A. (2018). N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present and Future Research to Determine Its Role and Function. Frontiers in neuroscience, 12, 536., 10.3389/fnins.2018.00536
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