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Psychedelic Psychotherapy Insights From 25 Years of Research

Abstract

Presented at a conference titled “Psychedelic Science 2013,” highlighting the resumption of investigations with psychedelic substances (i.e., psilocybin, DMT, LSD, MDMA, etc.) in the United States and Europe after a dormant period of more than two decades, the author presents insights and perspectives gleaned from his 25 years of clinical research experience. After acknowledging the vastness and potential significance of this research frontier, the article focuses on the “cartography of inner space”; the unique therapeutic potential of transcendental states of consciousness; the entelechy of the interpersonally grounded psyche; the importance of integration in drug-free therapy sessions; the roles of expectation, religious education and faith; the role of music; and future research directions.

Richards, W. A. (2016). Psychedelic Psychotherapy Insights From 25 Years of Research. Journal of Humanistic Psychology, 0022167816670996.
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Abraham Maslow’s Interest in Psychedelic Research: A Tribute

In this brief tribute to Abraham Maslow, a founder of the Journal of Humanistic Psychology, his interests in psychedelic research are described by the author who served as his research assistant from 1966 to 1967.
Richards, W. A. (2016). Abraham Maslow’s Interest in Psychedelic Research: A Tribute. Journal of Humanistic Psychology, 0022167816670997.
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A Case of 3,4-Dimethoxyamphetamine (3,4-DMA) and 3,4 Methylendioxymethamphetamine (MDMA) Toxicity with Possible Metabolic Interaction

Abstract

BACKGROUND: We present a case of “ecstasy” ingestion revealing 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-dimethoxyamphetamine (3,4-DMA) and absence of cytochrome P450 (CYP)-2D6 MDMA metabolites.

CASE REPORT: A 19-year-old presented following a seizure. Initial vital signs were normal. Laboratories were normal with the exception of sodium 127 mEq/L and urine drugs of abuse screen positive for amphetamines. Twelve hours later, serum sodium was 114 mEq/L and a second seizure occurred. After receiving hypertonic saline (3%), the patient had improvement in mental status and admitted to taking “ecstasy” at a rave prior to her initial presentation. Liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS) of serum and urine revealed MDMA, 3,4-DMA, and the CYP-2B6 MDMA metabolites 3,4-methylendioxyamphetamine (MDA) and 4-hydroxy-3-methoxyamphetamine (HMA). The CYP2D6 metabolites of MDMA, 3,4-dihydromethamphetamine (HHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), were detected at very low levels.

CONCLUSION: This case highlights the polypharmacy which may exist among users of psychoactive illicit substances and demonstrates that concurrent use of MDMA and 3,4-DMA may predispose patients to severe toxicity. Toxicologists and other healthcare providers should be aware of this potential toxicity.

Darracq, M. A., Thornton, S. L., Minns, A. B., & Gerona, R. R. (2016). A Case of 3, 4-Dimethoxyamphetamine (3, 4-DMA) and 3, 4 Methylendioxymethamphetamine (MDMA) Toxicity with Possible Metabolic Interaction. Journal of Psychoactive Drugs, 1-4. 10.1080/02791072.2016.1225324
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Ayahuasca and Sumak Kawsay: Challenges to the Implementation of the Principle of “Buen Vivir,” Religious Freedom, and Cultural Heritage Protection

Abstract

The current environmental crisis can be approached, through many perspectives, as a civilizational crisis. Alternatives of human transcendence are identified in the Inca civilization to compensate for the malaise that characterizes the actual crisis. There is a multicultural dimension to the manifestations of Hoasca (or Ayahuasca) occurring in Amazonian countries. As employed by the Beneficent Spiritist Center União do Vegetal (UDV) in a religious context, it can contribute to the reconstruction of buen vivir (or in Quechua, sumak kawsay, meaning complete wellness), which served as the principle of the civilizations that preceded the colonization of the Americas by Europeans. Today, the State openly confronts the manifestation of the constitutional principles of buen vivir, religious freedom, and the protection of this cultural heritage. Here, the implications of the civilizational crisis and ways of overcoming it are approached from the standpoint of deep ecology, but the implications also reflect the doctrinal vision of the UDV to which the authors are affiliated.

Irigaray, C. T. J., Girard, P., Irigaray, M., & Silva, C. J. (2016). Ayahuasca and Sumak Kawsay: Challenges to the Implementation of the Principle of “Buen Vivir,” Religious Freedom, and Cultural Heritage Protection. Anthropology of Consciousness, 27(2), 204-225. 10.1111/anoc.12057
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Ayahuasca Treatment Center Safety for the Western Seeker

Abstract

Ayahuasca, an ancient Amazonian psychedelic tea traditionally used ceremonially among indigenous peoples, has recently become known as a possible treatment for a wide range of disorders. The awareness of this sacred medicine has grown exponentially over the past decade, attracting westerners from a wide variety of backgrounds, hoping to find treatment for a myriad of emotional and physical illnesses, as well as spiritual needs. In the wake of the commercialization and westernization of the use of ayahuasca, and the subsequent proliferation of ayahuasca treatment centers, this paper examines the benefits and possible risks of this form of therapy in an effort to create a safety protocol for Westerners in this context. The most practical approach to increasing safety for Westerners attending these Amazonian treatment centers is to educate the seeker prior to treatment and to provide access to specialized therapeutic aftercare services.

Ray, R. R., & Lassiter, K. S. (2016). Ayahuasca Treatment Center Safety for the Western Seeker. Anthropology of Consciousness, 27(2), 121-150. 10.1111/anoc.12060
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The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells

Abstract

N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper, we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, iPSCs), monocyte-derived macrophages (moMACs), and dendritic cells (moDCs). Results showed that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2) through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1) suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.

Szabo, A., Kovacs, A., Riba, J., Djurovic, S., Rajnavolgyi, E., & Frecska, E. (2016). The Endogenous Hallucinogen and Trace Amine N, N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells. Frontiers in Neuroscience, 10, 423. http://dx.doi.org/10.3389/fnins.2016.00423
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Psychological and neuropsychological assessment of regular hoasca users

Abstract

BACKGROUND: Hoasca (also called ayahuasca) is a N,N-dimethyltryptamine (DMT) – containing psychedelic brew originally used for magico-religious purposes by Amerindian populations of the Amazon Basin. Recently, Brazilian syncretic churches have helped spread the ritual use of hoasca to Western societies. The aim of this study was to evaluate substance use, and neuropsychological and psychological functioning of regular hoasca users within a religious setting.

METHODS: Assessment of socio-economic status, mood, personality traits, impulsiveness, drug use, quality of life, extrinsic and intrinsic religiosity, and neuropsychological function was performed on 30 volunteers from a U.S. branch of União do Vegetal (UDV), a Brazilian religion which uses hoasca ritually. We also assessed 27 non-hoasca-using control subjects matched by socio-demographic profile and church attendance. Mann-Whitney U, chi-squared and Fisher tests were used to analyze differences between groups. Spearman’s association and simple logistic regression tests were used to analyze the impact of frequency of hoasca use on dependent variables.

RESULTS: Relative to the control group, the UDV group demonstrated lower scores for depression (p=0.043, r=.27) and confusion (p=0.032, r=.29) as assessed by the Profile of Mood States (POMS); higher scores on the instrument Big Five Inventory (BFI) for the personality traits agreeableness (p=0.028, r=.29) and openness (p=0.037, r=.28); higher scores on the quality life domain role limitations due to physical health as determined by the instrument Medical Outcomes Study Short Form-36 – SF-36 (p=0.035, r=.28); less recent use of alcohol (p<0.001, φc=.57), greater past use of alcohol to intoxication (p=0.007, φc=.36) and past use of cannabis (p=0.001, φc=.45) as measured by the Addiction Severity Index (ASI), 5th edition; better score on a measure of memory vulnerability to proactive interference as measured by the California Verbal Learning Test – CVLT (p=0.040, r=.27). Lifetime use of hoasca was positively correlated with role limitations due to physical health (p=0.032, rs=.39) and negatively associated with lifetime heavy alcohol use (p=0.034, OR=0.979).

CONCLUSIONS: The findings indicate that religious use of hoasca does not adversely affect neuropsychological functioning and may have positive effects on substance abuse and mood.

Barbosa, P. C. R., Strassman, R. J., da Silveira, D. X., Areco, K., Hoy, R., Pommy, J., … & Bogenschutz, M. (2016). Psychological and neuropsychological assessment of regular hoasca users. Comprehensive Psychiatry, 71, 95-105. 0.1016/j.comppsych.2016.09.003

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Clinical and biological predictors of ketamine response in treatment-resistant major depression: Review

Abstract

OBJECTIVE: The aim of this review was to determine the clinical and biological predictors of the ketamine response.

METHODS: A systematic research on PubMed and PsycINFO database was performed without limits on year of publication.

RESULTS: The main predictive factors of ketamine response, which were found in different studies, were (i) a family history of alcohol dependence, (ii) unipolar depressive disorder, and (iii) neurocognitive impairments, especially a slower processing speed. Many other predictive factors were identified, but not replicated, such as personal history of alcohol dependence, no antecedent of suicide attempt, anxiety symptoms. Some biological factors were also found such as markers of neural plasticity (slow wave activity, brain-derived neurotrophic factor Val66Met polymorphism, expression of Shank 3 protein), other neurologic factors (anterior cingulate activity, concentration of glutamine/glutamate), inflammatory factors (IL-6 concentration) or metabolic factors (concentration of B12 vitamin, D- and L-serine, alterations in the mitochondrial β-oxidation of fatty acids). This review had several limits: (i) patients had exclusively resistant major depressive episodes which represent a sub-type of depression and not all depression, (ii) response criteria were more frequently assessed than remission criteria, it was therefore difficult to conclude that these predictors were similar, and finally (iii) many studies used a very small number of patients.

CONCLUSIONS: In conclusion, this review found that some predictors of ketamine response, like basal activity of anterior cingulate or vitamin B12 concentration, were identical to other therapeutics used in major depressive episode. These factors could be more specific to the major depressive episode and not to the ketamine response. Others, like family history of alcohol dependence, body mass index, or D- and L-serine were different from the other therapeutics. Neurocognitive impairments like slower speed processing or alterations in attention tests were also predictive to a good response. These predictive factors could be more specific to ketamine. With these different predictor factors (clinical and biological), it could be interesting to develop clinical strategies to personalize ketamine’s administration.

Romeo, B., Choucha, W., Fossati, P., & Rotge, J. Y. (2016). [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][Clinical and biological predictors of ketamine response in treatment-resistant major depression: Review]. L’Encephale. 10.1016/j.encep.2016.06.005
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Ketamine Treatment and Global Brain Connectivity in Major Depression

Abstract

Capitalizing on recent advances in resting state functional connectivity magnetic resonance imaging (rs-fcMRI) and the distinctive paradigm of rapid mood normalization following ketamine treatment, the current study investigated intrinsic brain networks in major depressive disorder (MDD) during a depressive episode and following treatment with ketamine. Medication-free patients with MDD and healthy control subjects (HC) completed baseline rs-fcMRI. MDD patients received a single infusion of ketamine and underwent repeated rs-fcMRI at 24 h post-treatment. Global brain connectivity with global signal regression (GBCr) values were computed as the average of correlations of each voxel with all other gray matter voxels in the brain. MDD group showed reduced GBCr in the prefrontal cortex (PFC), but increased GBCr in the posterior cingulate, precuneus, lingual gyrus, and cerebellum. Ketamine significantly increased GBCr in the PFC and reduced GBCr in the cerebellum. At baseline, 2174 voxels of altered GBCr were identified, but only 310 voxels significantly differed relative to controls following treatment (corrected α<0.05). Responders to ketamine showed increased GBCr in the lateral PFC, caudate, and insula. Followup seed-based analyses illustrated a pattern of dysconnectivity between the PFC/subcortex and the rest of the brain in MDD, which appeared to normalize post-ketamine. The extent of the functional dysconnectivity identified in MDD and the swift and robust normalization following treatment, suggest that GBCr may serve as a treatment response biomarker for the development of rapid acting antidepressants. The data also identified unique prefrontal and striatal circuitry as putative marker of successful treatment and target for antidepressants development.

Abdallah, C. G., Averill, L. A., Collins, K. A., Geha, P., Schwartz, J., Averill, C., … & Iosifescu, D. V. (2016). Ketamine Treatment and Global Brain Connectivity in Major Depression. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. 10.1038/npp.2016.186

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Ketamine: Future Treatment For Unresponsive Depression?

Abstract

Major Depressive Disorder (MDD) is a debilitating mental health condition which accounts for a significant portion of worldwide disability. Historically, the suggested pharmacotherapy to treat MDD have been monoaminergic-acting antidepressants, such as SSRIs or SNRIs. These drugs can provide relief, but often take weeks to noticeably improve depressive symptoms and are not always effective, leading to a condition known as Treatment-Resistant Depression (TRD). It is believed that 50% MDD sufferers in Ireland suffer from TRD, and thus the development of improved pharmacotherapies is necessary. One emerging therapy is low dose, intravenous (R-S)-Ketamine (ketamine). While the molecular basis of ketamine’s therapeutic effect has not been fully determined, it has shown to effectively and swiftly mitigate the symptoms of TRD. Barriers do exist preventing the legal prescription of ketamine, including its questionable safety profile and risk of inducing dependence. Despite this, ketamine remains a promising pharmacotherapy for TRD and further investigation is required.

Frere, M., & Tepper, J. (2016). Ketamine: Future Treatment For Unresponsive Depression?. Irish Medical Journal. 10147/620895
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