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Indolethylamine-N-methyltransferase Polymorphisms: Genetic and Biochemical Approaches for Study of Endogenous N,N,-dimethyltryptamine

/ DMT, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Psychotic Disorders, Publications / /

Abstract

N,N-dimethyltryptamine (DMT) is a powerful serotonergic psychedelic whose exogenous administration elicits striking psychedelic effects in humans. Studies have identified DMT and analogous compounds (e.g., 5-hydroxy-DMT, 5-methoxy-DMT) alongside of an enzyme capable of synthesizing DMT endogenously from tryptamine, indolethylamine-N-methyltransferase (INMT), in human and several other mammalian tissues. Subsequently, multiple hypotheses for the physiological role of endogenous DMT have emerged, from proposed immunomodulatory functions to an emphasis on the overlap between the mental states generated by exogenous DMT and naturally occurring altered states of consciousness; e.g., schizophrenia. However, no clear relationship between endogenous DMT and naturally occurring altered states of consciousness has yet been established from in vivo assays of DMT in bodily fluids. The advent of genetic screening has afforded the capability to link alterations in the sequence of specific genes to behavioral and molecular phenotypes via expression of identified single nucleotide polymorphisms (SNPs) in cell and animal models. As SNPs in INMT may impact endogenous DMT synthesis and levels via changes in INMT expression and/or INMT structure and function, these combined genetic and biochemical approaches circumvent the limitations of assaying DMT in bodily fluids and may augment data from prior in vitro and in vivo work. Therefore, all reported SNPs in INMTwere amassed from genetic and biochemical literature and genomic databases to consolidate a blueprint for future studies aimed at elucidating whether DMT plays a physiological role.

Dean, J. G. (2018). Indolethylamine-N-methyltransferase polymorphisms: genetic and biochemical approaches for study of endogenous N, N,-dimethyltryptamine. Frontiers in neuroscience, 12.,  10.3389/fnins.2018.00232
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Palliative Nursing and Sacred Medicine: A Holistic Stance on Entheogens, Healing, and Spiritual Care

/ Ayahuasca, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , ,

Abstract

The fields of palliative and holistic nursing both maintain a commitment to the care of the whole person, including a focus on spiritual care. Advanced serious illness may pose a plethora of challenges to patients seeking to create meaning and purpose in their lives. The purpose of this article is to introduce scholarly dialogue on the integration of entheogens, medicines that engender an experience of the sacred, into the spiritual and holistic care of patients experiencing advanced serious illness. A brief history of the global use of entheogens as well as a case study are provided. Clinical trials show impressive preliminary findings regarding the healing potential of these medicinal agents. While other professions, such as psychology, pharmacy, and medicine, are disseminating data related to patient outcomes secondary to entheogen administration, the nursing literature has not been involved in raising awareness of such advancements. Research is illustrating their effectiveness in achieving integrative experiences for patients confronting advanced serious illness and their ability to promote presence, introspection, decreased fear, and increased joy and acceptance. Evidence-based knowledge surrounding this potentially sensitive topic is necessary to invite understanding, promote scientific knowledge development, and create healing environments for patients, nurses, and researchers alike.
Rosa, W. E., Hope, S., & Matzo, M. (2018). Palliative Nursing and Sacred Medicine: A Holistic Stance on Entheogens, Healing, and Spiritual Care. Journal of Holistic Nursing, 0898010118770302.
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Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications / / , , , , , ,

Abstract

OBJECTIVES:
Extant evidence indicates that ketamine exerts rapid antidepressant effects in treatment-resistant depressive (TRD) symptoms as a part of major depressive disorder (MDD) and bipolar disorder (BD). The identification of depressed sub-populations that are more likely to benefit from ketamine treatment remains a priority. In keeping with this view, the present narrative review aims to identify the pretreatment predictors of response to ketamine in TRD as part of MDD and BD.
METHOD:
Electronic search engines PubMed/MEDLINE, ClinicalTrials.gov, and Scopus were searched for relevant articles from inception to January 2018. The search term ketamine was cross-referenced with the terms depression, major depressive disorder, bipolar disorder, predictors, and response and/or remission.
RESULTS:
Multiple baseline pretreatment predictors of response were identified, including clinical (i.e., Body Mass Index (BMI), history of suicide, family history of alcohol use disorder), peripheral biochemistry (i.e., adiponectin levels, vitamin B12 levels), polysomnography (abnormalities in delta sleep ratio), neurochemistry (i.e., glutamine/glutamate ratio), neuroimaging (i.e., anterior cingulate cortex activity), genetic variation (i.e., Val66Met BDNF allele), and cognitive functioning (i.e., processing speed). High BMI and a positive family history of alcohol use disorder were the most replicated predictors.
CONCLUSIONS:
A pheno-biotype of depression more, or less likely, to benefit with ketamine treatment is far from complete. Notwithstanding, metabolic-inflammatory alterations are emerging as possible pretreatment response predictors of depressive symptom improvement, most notably being cognitive impairment. Sophisticated data-driven computational methods that are iterative and agnostic are more likely to provide actionable baseline pretreatment predictive information.
Rong, C., Park, C., Rosenblat, J. D., Subramaniapillai, M., Zuckerman, H., Fus, D., … & Cha, D. S. (2018). Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder. International journal of environmental research and public health, 15(4), 771. 10.3390/ijerph15040771
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The early use of MDMA (‘Ecstasy’) in psychotherapy (1977–1985)

/ MDMA, Papers, Psychology, Publications / /

Abstract

3,4-Methylenedioxymethamphetamine (MDMA), also known as ecstasy, was first synthesized in 1912 but first reached widespread popularity as a legal alternative after the much sought-after recreational drug 3,4-methylenedioxy-amphetamine (MDA) was made illegal in 1970. Because of its benign, feeling-enhancing, and nonhallucinatory properties, MDMA was used by a few dozen psychotherapists in the United States between 1977 and 1985, when it was still legal. This article looks into the contexts and practices of its psychotherapeutic use during these years. Some of the guidelines, recommendations, and precautions developed then are similar to those that apply to psychedelic drugs, but others are specific for MDMA. It is evident from this review that the therapists pioneering the use of MDMA were able to develop techniques (and indications/counterindications) for individual and group therapy that laid the groundwork for the use of MDMA in later scientific studies. In retrospect, it appears that the perceived beneficial effects of MDMA supported a revival of psycholytic/psychedelic therapy on an international scale.
Passie, T. (2018). The early use of MDMA (‘Ecstasy’) in psychotherapy (1977–1985). Drug Science, Policy and Law, 4, 2050324518767442., 10.1177/2050324518767442
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Hypothesis: The Psychedelic Ayahuasca Heals Traumatic Memories via a Sigma 1 Receptor-Mediated Epigenetic-Mnemonic Process

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

Abstract

Ayahuasca ingestion modulates brain activity, neurotransmission, gene expression and epigenetic regulation. N,N-Dimethyltryptamine (DMT, one of the alkaloids in Ayahuasca) activates sigma 1 receptor (SIGMAR1) and others. SIGMAR1 is a multi-faceted stress-responsive receptor which promotes cell survival, neuroprotection, neuroplasticity, and neuroimmunomodulation. Simultaneously, monoamine oxidase inhibitors (MAOIs) also present in Ayahuasca prevent the degradation of DMT. One peculiarity of SIGMAR1 activation and MAOI activity is the reversal of mnemonic deficits in pre-clinical models. Since traumatic memories in post-traumatic stress disorder (PTSD) are often characterised by “repression” and PTSD patients ingesting Ayahuasca report the retrieval of such memories, it cannot be excluded that DMT-mediated SIGMAR1 activation and the concomitant MAOIs effects during Ayahuasca ingestion might mediate such “anti-amnesic” process. Here I hypothesise that Ayahuasca, via hyperactivation of trauma and emotional memory-related centres, and via its concomitant SIGMAR1- and MAOIs- induced anti-amnesic effects, facilitates the retrieval of traumatic memories, in turn making them labile (destabilised). As Ayahuasca alkaloids enhance synaptic plasticity, increase neurogenesis and boost dopaminergic neurotransmission, and those processes are involved in memory reconsolidation and fear extinction, the fear response triggered by the memory can be reprogramed and/or extinguished. Subsequently, the memory is stored with this updated significance. To date, it is unclear if new memories replace, co-exist with or bypass old ones. Although the mechanisms involved in memory are still debated, they seem to require the involvement of cellular and molecular events, such as reorganisation of homo and heteroreceptor complexes at the synapse, synaptic plasticity, and epigenetic re-modulation of gene expression. Since SIGMAR1 mobilises synaptic receptor, boosts synaptic plasticity and modulates epigenetic processes, such effects might be involved in the reported healing of traumatic memories in PTSD patients. If this theory proves to be true, Ayahuasca could come to represent the only standing pharmacological treatment which targets traumatic memories in PTSD. Lastly, since SIGMAR1 activation triggers both epigenetic and immunomodulatory programmes, the mechanism here presented could help understanding and treating other conditions in which the cellular memory is dysregulated, such as cancer, diabetes, autoimmune and neurodegenerative pathologies and substance addiction.
Inserra, A. (2018). Hypothesis: The Psychedelic Ayahuasca Heals Traumatic Memories via a Sigma 1 Receptor-Mediated Epigenetic-Mnemonic Process. Frontiers in pharmacology, 9, 330. 10.3389/fphar.2018.00330
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Psychological variables implied in the therapeutic effect of ayahuasca: A contextual approach

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

Abstract

Ayahuasca is a psychedelic decoction originating from Amazonia. The ayahuasca-induced introspective experience has been shown to have potential benefits in the treatment of several pathologies, to protect mental health and to improve neuropsychological functions and creativity, and boost mindfulness. The underlying psychological processes related to the use of ayahuasca in a psychotherapeutic context are not yet well described in the scientific literature, but there is some evidence to suggest that psychological variables described in psychotherapies could be useful in explaining the therapeutic effects of the brew. In this study we explore the link between ayahuasca use and Decentering, Values and Self, comparing subjects without experience of ayahuasca (n = 41) with subjects with experience (n = 81). Results confirm that ayahuasca users scored higher than non-users in Decentering and Positive self, but not in Valued living, Life fulfillment, Self in social relations, Self in close relations and General self. Scores in Decentering were higher in the more experienced subjects (more than 15 occasions) than in those with less experience (less than 15 occasions). Our results show that psychological process variables may explain the outcomes in ayahuasca psychotherapy. The introduction of these variables is warranted in future ayahuasca therapeutic studies.
Franquesa, A., Sainz-Cort, A., Gandy, S., Soler, J., Alcázar-Córcoles, M. Á., & Bouso, J. C. (2018). Psychological variables implied in the therapeutic effect of ayahuasca: A contextual approach. Psychiatry research, 264, 334-339. 10.1016/j.psychres.2018.04.012
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A role for enhanced functions of sleep in psychedelic therapy?

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

Abstract

After a hiatus of several decades, there has been a resurgence of studies into the therapeutic potential of serotonergic psychedelics. When administered in controlled settings, they have been reported to induce a wide variety of long-lasting positive psychological changes. However, the mechanisms by which psychedelics impart these long-lasting benefits remain poorly understood. Here, we highlight one possibility that has remained underexplored: a beneficial interaction with the self-optimizing functions of sleep.
Froese, T., Leenen, I., & Palenicek, T. (2018). A role for enhanced functions of sleep in psychedelic therapy?. Adaptive Behavior, 26(3), 129-135. 10.1177%2F1059712318762735
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Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy.

/ Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , , , , , ,

Abstract

A growing body of evidence shows that existential and spiritual well-being in cancer patients is associated with better medical outcomes, improved quality of life, and serves as a buffer against depression, hopelessness, and desire for hastened death. Historical and recent research suggests a role for psilocybin-assisted psychotherapy in treating cancer-related anxiety and depression. A double-blind controlled trial was performed, where 29 patients with cancer-related anxiety and depression were randomly assigned to treatment with single-dose psilocybin (0.3 mg/kg) or niacin in conjunction with psychotherapy. Previously published results of this trial demonstrated that, in conjunction with psychotherapy, moderate-dose psilocybin produced rapid, robust, and enduring anxiolytic, and anti-depressant effects. Here, we illustrate unique clinical courses described by four participants using quantitative measures of acute and persisting effects of psilocybin, anxiety, depression, quality of life, and spiritual well-being, as well as qualitative interviews, written narratives, and clinician notes. Although the content of each psilocybin-assisted experience was unique to each participant, several thematic similarities and differences across the various sessions stood out. These four participants’ personal narratives extended beyond the cancer diagnosis itself, frequently revolving around themes of self-compassion and love, acceptance of death, and memories of past trauma, though the specific details or narrative content differ substantially. The results presented here demonstrate the personalized nature of the subjective experiences elicited through treatment with psilocybin, particularly with respect to the spiritual and/or psychological needs of each patient.
Malone, T. C., Mennenga, S. E., Guss, J., Podrebarac, S. K., Owens, L. T., Bossis, A. P., … & Ross, S. (2018). Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy. Frontiers in pharmacology, 9, 256, 10.3389/fphar.2018.00256
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Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine

/ Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / / , ,

Abstract

Opioid use disorder (OUD) is currently an epidemic in the United States (US) and ibogaine is reported to have the ability to interrupt opioid addiction by simultaneously mitigating withdrawal and craving symptoms. This study examined opioid withdrawal and drug craving scores in 50 participants with OUD undergoing a week-long detoxification treatment protocol with ibogaine. The Addiction Severity Index (ASI) was used for baseline characterization of participants’ OUD. Clinical Opioid Withdrawal Scale (COWS), Subjective Opioid Withdrawal Scale (SOWS), and Brief Substance Craving Scale (BSCS) scores were collected at 48 and 24 hours prior to ibogaine administration, as well as 24 and 48 hours after ibogaine administration. At 48 hours following ibogaine administration, withdrawal and craving scores were significantly lowered in comparison to baseline: 78% of patients did not exhibit objective clinical signs of opioid withdrawal, 79% reported minimal cravings for opioids, and 68% reported subjective withdrawal symptoms in the mild range. Ibogaine appears to facilitate opioid detoxification by reducing opioid withdrawal and craving in participants with OUD. These results warrant further research using rigorous controlled trials.
Malcolm, B. J., Polanco, M., & Barsuglia, J. P. (2018). Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine. Journal of psychoactive drugs, 1-10. 10.1080/02791072.2018.1447175
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Ceremonial ‘Plant Medicine’ use and its relationship to recreational drug use: an exploratory study

/ Ayahuasca, Biology & Ethnobotany, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / / , ,

Abstract

Background: The ceremonial use of psychoactive/hallucinogenic plant based drugs, such as ayahuasca, psilocybin and others, is a growing trend in the United States (US) and globally. To date, there has been little research documenting how many people are using psychoactive substances in this context, who the users are, what benefits/risks exist in the use of these drugs and the relationship between ceremonial drug use and recreational drug use.
In this paper we describe a cohort of plant medicine facilitators in the US and explore how they differentiate plant medicine use from recreational drug use.
Methods: Using modified ethnography, individual interviews were conducted in 2016 with 15 participants who are currently facilitating plant medicine ceremonies in the US. Descriptive content analysis was performed to discover themes and to inform a larger mixed-method study.
Results: Ceremonial drug use was seen by participants as a natural healing and treatment modality used in the context of community and ritual. Three main themes were identified relating to participants’ differentiation between ceremonial plant medicine use and recreational drug use: (1) participants see a clear delineation between plant medicine use and recreational drug use; (2) plant medicine is seen as a potential treatment for addiction, but concerns exist regarding potential interference with recovery; and (3) plant medicine use may influence recreational use.
Conclusions: More research is needed on who is using plant medicine, motivators for use, perceived and real risks and benefits of plant medicine use and harm reduction techniques regarding safe ingestion.
Dorsen, C., Palamar, J., & Shedlin, M. G. (2018). Ceremonial ‘Plant Medicine’use and its relationship to recreational drug use: an exploratory study. Addiction Research & Theory, 1-8. 10.1080/16066359.2018.1455187
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Journal Club #28: Efficacy and Safety of Psilocybin in Treatment-Resistant Depression: Results of the EPIsoDE Trial - October 6

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