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A Model of Enlightened/Mystical/Awakened Experience.

/ Papers, Psychology, Publications / /

Abstract

Awakening experiences are powerful and transcendent experiences that profoundly affect the individual. There appears to be an essential core experience of oneness. It is experienced as a completely subjective phenomenon where awareness contains reality and the notions of an external reality and a separate self are perceived as delusions. A model is presented of awakening experiences that postulates 3 layers of processing, sensory, perceptual, and cognitive, that separate external energy from awareness. The model hypothesizes that awakening experiences results from the progressive removal of the cognitive, perceptual, and sensory layers of information processing. This to some extent returns awareness to a primal state that was present before the development of neural information processing. The model simplifies, summarizes, and explains awakening experiences and is consistent with neural system activity observed during contemplative practice, transcendent states, and hallucinatory drug use and with the effects of changes in the neural systems on experiences.

de Castro, J. M. (2015). A Model of Enlightened/Mystical/Awakened Experience. http://dx.doi.org/10.1037/rel0000037
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Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder

/ Depressive Disorders, Neuroscience, Papers, Psychology, Publications / / ,

Abstract

Depression is a devastating disorder that places a significant burden on both the individual and society. As such, the discovery of novel therapeutics and innovative treatments—especially for treatment-resistant depression (TRD)—are essential. Research into antidepressant therapies for TRD has evolved from explorations of antidepressants with primary mechanisms of action on the monoaminergic neurotransmitter system to augmentation agents with primary mechanisms both within and outside of the serotonin/norepinephrine system. Now the field of antidepressant research has changed trajectories yet again; this time, compounds with primary mechanisms of action on the glutamatergic, cholinergic and opioid systems are in the forefront of antidepressant exploration. In this review, we will discuss the most recent research surrounding these novel compounds. In addition, we will discuss novel device-based therapeutics, with a particular focus on transcranial magnetic stimulation. In many cases of antidepressant drug discovery, the role of serendipity coupled with meticulous clinical observation in drug development in medicine was crucial. Moving forward, we must look toward the combination of innovation plus improvements on the remarkable discoveries thus far to advance the field of antidepressant research.

Papakostas, G. I., & Ionescu, D. F. (2015). Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder. Molecular psychiatry. https://dx.doi.org/10.1038/mp.2015.92
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Perceptual distortions and delusional thinking following ketamine administration are related to increased pharmacological MRI signal changes in the parietal lobe

/ Ketamine, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / / , , , , ,

Abstract

Ketamine produces effects in healthy humans that resemble the positive, negative and cognitive symptoms of schizophrenia. We investigated the effect of ketamine administration on brain activity as indexed by blood-oxygen-level-dependent (BOLD) signal change response, and its relationship to ketamine-induced subjective changes, including perceptual distortion. Thirteen healthy participants volunteered for the study. All underwent a 15-min functional MRI acquisition with a ketamine infusion commencing after 5 min (approx 0.26 mg/kg over 20s followed by an infusion of approx. 0.42 mg/kg/h). Following the scan, participants self-rated ketamine-induced effects using the Psychotomimetic States Inventory. Ketamine led to widespread cortical and subcortical increases in BOLD response (FWE-corrected p < 0.01). Self-rated perceptual distortions and delusional thoughts correlated with increased BOLD response in the paracentral lobule (FWE-corrected p < 0.01). The findings suggest that BOLD increases in parietal cortices reflect ketamine effects on circuits that contribute to its capacity to produce perceptual alterations and delusional interpretations.

Stone, J., Kotoula, V., Dietrich, C., De Simoni, S., Krystal, J. H., & Mehta, M. A. (2015). Perceptual distortions and delusional thinking following ketamine administration are related to increased pharmacological MRI signal changes in the parietal lobe. Journal of Psychopharmacology, 0269881115592337. https://dx.doi.org/10.1177/0269881115592337
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Therapy with Substance: Psycholytic psychotherapy in the twenty first century

/ Publications /

Therapy with substance“A unique account and the definitive guide for a future generation of psychedelic psychotherapists. Therapy with Substance is a comprehensive guide for the medical use of psychedelic substances in the therapy of emotional and psychosomatic disorders based on years of work that she had conducted with her clients without official permission. It describes in clear and articulate language everything that is necessary to know for effective and safe use of this treatment modality and for work with non-ordinary states of consciousness in general.”

Stanislav Grof (from the foreword)

In this groundbreaking book, Doctor Friederike Meckel Fischer explores how the skillful use of psychedelic substances in psycholytic psychotherapy can cause dramatic breakthroughs for people who have not responded to traditional methods of psychotherapy. Her extraordinary conclusion is that psycholytic psychotherapy is the only method that reaches the depth of the psyche required to resolve and heal our deepest wounds. Psychedelic drugs were routinely used in clinical research and psychotherapy until the 1960s. Since then they have been illegal except for a short period in the 1990s in Switzerland. During this window of opportunity, Dr Fischer developed her unique method using these substances to assist the progress of those of her patients who were “stuck”.  This book is a description of her use of psychedelic-assisted psychotherapy; the group work, the family constellation work, the body work, the spiritual experiences, how to work with the substances themselves, together with moving accounts of her patients and their stories. This is a unique account and the definitive guide for the new generation of psychedelic psychotherapists.

Dr Meckel is a medical doctor who has trained in individual, group and family psychotherapy and, with Stanislav Grof, in transpersonal psychotherapy.

Therapy with Substance: Psycholytic psychotherapy in the twenty first century, by Friederike Meckel Fischer, Muswell Hill Press, 244 pages.
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Ayahuasca Alters Structural Parameters of the Rat Aorta

/ Ayahuasca, Papers, Psychiatry & Medicine, Publications / / , , , , , ,

Abstract

Ayahuasca is a hallucinogenic brew traditionally used by Northwestern Amazonian indigenous groups for therapeutic purposes. It is prepared by the decoction of Banisteriopsis caapi with the leaves of Psychotria viridis. Banisteriopsis caapi contains β-carbolines that are inhibitors of monoamine oxidase and P. viris is rich in dimethyltryptamine, a 5-HT1A/2A/2C agonist. Acute ayahuasca administration produces moderate cardiovascular effects in healthy volunteers, but information regarding long-term use is lacking. This study investigated the effects of ayahuasca (2–4 mL/kg) in the rat aorta after acute and chronic (14 days) administration. Ayahuasca caused flattening and stretching of vascular smooth muscle cells and changes in the arrangement and distribution of collagen and elastic fibers. Chronic treatment with the higher dose significantly increased media thickness and the ratio of media thickness to lumen diameter. More research is needed on the cardiovascular function of long-term ayahuasca consumers.

Pitol, D. L., Siéssere, S., Dos Santos, R. G., Nunes, M. R. M., Cecilio, H. J., Scalize, P. H., … & Hallak, R. S. (2015). Ayahuasca alters structural parameters of the rat aorta. Journal of cardiovascular pharmacology. http://dx.doi.org/10.1097/FJC.0000000000000243
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Psychedelics and creativity: a review of the quantitative literature

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

Abstract

After a 40-year hiatus, the question of whether psychedelics can increase creativity is being asked with renewed vigor. This article critically reviews the conceptual issues of studying psychedelic-induced creativity by summarizing the limited evidence on the question and suggesting two broader frameworks. There are two important challenges to researchers on this topic. One is to separate creativity from other effects of the drug that may be mistaken for creativity. The second is to develop operational measures to quantify it. This article reviews the major studies assessing creativity (or related constructs) induced by psychedelics, including a reanalysis of raw data from one study. Results are modest and inconclusive but are consistent with reports that psychedelics give rise to unusual or novel thoughts. Given the lack of robust changes in creativity measures, I suggest creativity may be too specific of a construct to accurately and fully characterize the putatively beneficial cognitive changes that psychedelic users report. Feelings of creativity may be an inconsistent result of a more general effect of these drugs, such as alterations in availability of mental representations or changes in Bayesian inference. Ultimately, creativity may not be a sufficiently creative construct to capture the beneficial effects of psychedelics.

Baggott, M. J. (2015). Psychedelics and creativity: a review of the quantitative literature. PeerJ PrePrints, 3, e1468. https://dx.doi.org/10.7287/peerj.preprints.1202v1
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Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications, Substance Use Disorder / / , , , , ,

Abstract

Objective The authors conducted a systematic review and meta-analysis of ketamine and other N-methyl-d-aspartate (NMDA) receptor antagonists in the treatment of major depression.

Method Searches of MEDLINE, PsycINFO, and other databases were conducted for placebo-controlled, double-blind, randomized clinical trials of NMDA antagonists in the treatment of depression. Primary outcomes were rates of treatment response and transient remission of symptoms. Secondary outcomes included change in depression symptom severity and the frequency and severity of dissociative and psychotomimetic effects. Results for each NMDA antagonist were combined in meta-analyses, reporting odds ratios for dichotomous outcomes and standardized mean differences for continuous outcomes.

Results Ketamine (seven trials encompassing 147 ketamine-treated participants) produced a rapid, yet transient, antidepressant effect, with odds ratios for response and transient remission of symptoms at 24 hours equaling 9.87 (4.37–22.29) and 14.47 (2.67–78.49), respectively, accompanied by brief psychotomimetic and dissociative effects. Ketamine augmentation of ECT (five trials encompassing 89 ketamine-treated participants) significantly reduced depressive symptoms following an initial treatment (Hedges’ g=0.933) but not at the conclusion of the ECT course. Other NMDA antagonists failed to consistently demonstrate efficacy; however, two partial agonists at the NMDA coagonist site, d-cycloserine and rapastinel, significantly reduced depressive symptoms without psychotomimetic or dissociative effects.

Conclusions The antidepressant efficacy of ketamine, and perhaps D-cycloserine and rapastinel, holds promise for future glutamate-modulating strategies; however, the ineffectiveness of other NMDA antagonists suggests that any forthcoming advances will depend on improving our understanding of ketamine’s mechanism of action. The fleeting nature of ketamine’s therapeutic benefit, coupled with its potential for abuse and neurotoxicity, suggest that its use in the clinical setting warrants caution.

Newport, D. J., Carpenter, L. L., McDonald, W. M., Potash, J. B., Tohen, M., & Nemeroff, C. B. (2015). Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. American Journal of Psychiatry, 172(10), 950-966. http://dx.doi.org/10.1176/appi.ajp.2015.15040465

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Howard Becker in Hyperspace: Social Learning in an On-Line Drug Community

/ Anthropology & Sociology, Papers, Publications / / ,

Abstract

Analyzing on-line drug communities provides important insights into the connection between computer-mediated communication and drug use in contemporary society. Drawing on social learning theory, we analyze conversations within the on-line community DMT-Nexus. We find that the on-line context affects the social learning process concerning drug use in distinct ways and identify how users gain relevant knowledge and interpretive strategies and acquire credibility. Based on these findings, we propose an expansion of Becker’s social learning model of drug use reflecting the unique constraints and opportunities of on-line contexts including the importance of vivid textual descriptions and modes of communication.

Rosino, M., & Linders, A. (2015). Howard Becker in Hyperspace: Social Learning in an On-Line Drug Community. Deviant Behavior, (ahead-of-print), 1-15. https://dx.doi.org/10.1080/01639625.2014.977114
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Paclitaxel combined with harmine inhibits the migration and invasion of gastric cancer cells through downregulation of cyclooxygenase‑2 expression

/ Papers, Psychiatry & Medicine, Publications / / , ,

Abstract

Cyclooxygenase‑2 (COX‑2) has a critical role in the invasiveness and metastasis of gastric cancer. In addition, paclitaxel (PTX) and harmine (HM) were reported to be potential therapeutic drug candidates for cancer therapy; however, the synergistic antitumor effect of PTX and HM combined treatment on the human gastric cancer cells remains to be elucidated. The aim of the present study was to evaluate the effects of PTX and/or HM on the cell migration and invasion in two human gastric cancer cell lines, SGC‑7901 and MKN‑45. MTT assay was used to detect the growth inhibition induced by PTX and HM . The Transwell assay was employed to assess the effects of PTX and HM on the cell migration and invasion. The expression levels of COX-2 and matrix metalloproteinase-9 (MMP-9) were analyzed by western blot analysis. The results demonstrated that PTX and HM inhibited cell proliferation in a dose‑dependent manner. Individually PTX and HM were able to inhibit the migration and invasion of two human gastric cancer cells; however, the combination of PTX and HM exerted synergistic effects on migration and invasion inhibition, with downregulation of COX‑2 and matrix metalloproteinase (MMP)‑9. In conclusion, the results of the present study indicated that combination chemotherapy using PTX with HM exerted an antitumor effect, which may be implicated for the treatment of gastric cancer. Of note, the combination of the two drugs inhibited migration and invasion more effectively compared with each drug alone, the mechanism of which proceeded via the downregulation of COX‑2 expression.

Sun, K., Tang, X. H., & Xie, Y. K. (2015). Paclitaxel combined with harmine inhibits the migration and invasion of gastric cancer cells through downregulation of cyclooxygenase‑2 expression. Oncology Letters, 10(3), 1649-1654. https://dx.doi.org/10.3892/ol.2015.3425
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Pharmacokinetics and concentration-effect relationship of oral LSD in humans

/ LSD, Neuroscience, Papers, Psychiatry & Medicine, Publications / / , , , ,

Abstract

Background: The pharmacokinetics of oral lysergic acid diethylamide (LSD) are unknown, despite its common recreational use and renewed interest in its use in psychiatric research and practice.

Methods: We characterized the pharmacokinetic profile, pharmacokinetic-pharmacodynamic relationship, and urine recovery of LSD and its main metabolite after administration of a single oral dose of LSD (200 μg) in eight male and eight female healthy subjects.

Results: Plasma LSD concentrations were quantifiable (> 0.1 ng/ml) in all of the subjects up to 12 h after administration. Maximal concentrations of LSD (mean ± SD: 4.5 ± 1.4 ng/ml) were reached (median, range) 1.57 (0.5-4) h after administration. Concentrations then decreased following first-order kinetics with a half-life of 3.6 ± 0.9 h up to 12 h and slower elimination thereafter with a terminal half-life of 8.9 ± 5.9 h. One percent of the orally administered LSD was eliminated in urine as LSD, and 14% was eliminated as 2-oxo-3-hydroxy-LSD within 24 h. No sex differences were observed in the pharmacokinetic profiles of LSD. The acute subjective and sympathomimetic responses to LSD lasted up to 12 h and were closely associated with the concentrations in plasma over time and exhibited no acute tolerance.

Conclusions: These first data on the pharmacokinetics and concentration-effect relationship of oral LSD are relevant for further clinical studies and serve as a reference for the assessment of intoxication with LSD.

Dolder, P. C., Schmid, Y., Haschke, M., Rentsch, K. M., & Liechti, M. E. (2015). Pharmacokinetics and concentration-effect relationship of oral LSD in humans. International Journal of Neuropsychopharmacology, pyv072.

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