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Psychoactive substances as a last resort—a qualitative study of self-treatment of migraine and cluster headaches

/ Anthropology & Sociology, Headache Pain and Neurological Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology / / , ,

Abstract

Background

Treatment resistant cluster headache and migraine patients are exploring alternative treatments online. The aim of this study was to improve comprehension regarding the use of non-established or alternative pharmacological treatments used by sufferers of cluster headaches and migraines.

Methods

A qualitative thematic analysis of the users’ own accounts presented in online forum discussions were conducted. The forum boards https://shroomery.org/, http://bluelight.org, and https://clusterbusters.org/ met the inclusion criteria and were used for the study.

Results

The analysis resulted in six themes: a desperate need for effective treatments; the role of the forum—finding alternative treatments and community support; alternative treatment substances; dosage and regimens; effects and treatment results; and adverse effects. The results provide an insight into why, how, and by which substances and methods sufferers seek relief from cluster headache and migraines.

Conclusions

These patients are in a desperate and vulnerable situation, and illicit psychoactive substances are often considered a last resort. There appeared to be little or no interest in psychoactive effects per se as these were rather tolerated or avoided by using sub-psychoactive doses. Primarily, psilocybin, lysergic acid diethylamide, and related psychedelic tryptamines were reportedly effective for both prophylactic and acute treatment of cluster headache and migraines. Treatment results with cannabis were more unpredictable. No severe adverse events were reported, but it was observed how desperation sometimes spurred risky behavior when obtaining and testing various treatment alternatives. The forum discourse mainly revolved around maximizing treatment results and minimizing potential harms.

Andersson, M., Persson, M., & Kjellgren, A. (2017). Psychoactive substances as a last resort—a qualitative study of self-treatment of migraine and cluster headaches. Harm Reduction Journal, 14(1), 60. 10.1186/s12954-017-0186-6

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Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors

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

Abstract

Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level (“standard”) support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning.
Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., Jesse, R., MacLean, K. A., … & Klinedinst, M. A. (2017). Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors. Journal of Psychopharmacology, 0269881117731279.
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First Time View on Human Metabolome Changes after a Single Intake of 3,4-Methylenedioxymethamphetamine in Healthy Placebo-Controlled Subjects

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

Abstract

3,4-Methylenedioxymethamphetamine (MDMA; “ecstasy”) is widely consumed recreationally. Little is known about its effects on the human metabolome. Mapping biochemical changes after drug exposure can complement traditional approaches by revealing potential biomarkers of organ toxicity or discovering new metabolomic features in a time- and dose-dependent manner. We aimed to analyze for the first time plasma samples from a randomized, double-blind, placebo-controlled crossover study in healthy adults to explore changes in endogenous plasma metabolites following a single intake of MDMA. Plasma samples from 15 subjects taken at four different time points were analyzed with the commercially available AbsoluteIDQ kit (Biocrates). Time series analysis revealed a total of nine metabolites, which showed a significant concentration change after MDMA administration compared with placebo. Paired t tests of the single time points showed statistically significant concentration changes mainly of glycerophospholipids and the metabolic ratio of methionine-sulfoxide over methionine. Changes of this metabolic ratio may be indicative for changes in systemic oxidative stress levels, and the increased amount of glycerophospholipids could be interpreted as an upregulation of energy production. Baseline samples within the experimental study design were crucial for evaluation of metabolomics data as interday individuality within subjects was high otherwise resulting in overestimations of the findings.
Boxler, M. I., Liechti, M. E., Schmid, Y., Kraemer, T., & Steuer, A. E. (2017). First Time View on Human Metabolome Changes after a Single Intake of 3, 4-Methylenedioxymethamphetamine in Healthy Placebo-Controlled Subjects. Journal of proteome research, 16(9), 3310-3320. 10.1021/acs.jproteome.7b00294
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Developing Guidelines and Competencies for the Training of Psychedelic Therapists

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

Abstract

Research since the 1950s has shown that psychedelic-assisted psychotherapy has had significant positive effects in reductions of specific clinical symptoms and increases in quality of life as measured on a variety of indices. The intensity of focus on evidence-based outcomes, however, has resulted in a paucity of active discussions and research on the core competencies of the therapists themselves. The context of the history of psychedelic research reveals how this neglect of therapist variables occurred. With current discussions of Phase 3 and expanded access research programs for psilocybin-assisted and MDMA-assisted psychotherapies, there will be a great need for competent therapists trained in this clinical specialty. This is particularly the case if less restricted, legal medical use is approved within the next 6 to 10 years. This article is the first review and compilation of psychedelic therapist competencies derived from the psychedelic literature. These six therapist competencies are empathetic abiding presence; trust enhancement; spiritual intelligence; knowledge of the physical and psychological effects of psychedelics; therapist self-awareness and ethical integrity; and proficiency in complementary techniques. A further contribution of this review is a delineation of the 12 fundamental curricular domains of study for the training and development of these therapist competencies. As current legal restrictions evolve, aspects of these training guidelines will develop accordingly.
Phelps, J. (2017). Developing Guidelines and Competencies for the Training of Psychedelic Therapists. Journal of Humanistic Psychology, 57(5), 450-487. 10.1177/0022167817711304
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Assessing the psychedelic “after-glow” in ayahuasca users: post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities

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

Abstract

BACKGROUND:
Ayahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures.
METHODS:
Using 1H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose.
RESULTS:
Magnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the “nonjudging” subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later.
CONCLUSIONS:
These results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca.
Sampedro, F., de la Fuente Revenga, M., Valle, M., Roberto, N., Domínguez-Clavé, E., Elices, M., … & Friedlander, P. (2017). Assessing the psychedelic “after-glow” in ayahuasca users: post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities. International Journal of Neuropsychopharmacology. 10.1093/ijnp/pyx036
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Serotonin and brain function: a tale of two receptors

/ Neuroscience, Papers, Psychology, Publications / / ,

Abstract

Previous attempts to identify a unified theory of brain serotonin function have largely failed to achieve consensus. In this present synthesis, we integrate previous perspectives with new and older data to create a novel bipartite model centred on the view that serotonin neurotransmission enhances two distinct adaptive responses to adversity, mediated in large part by its two most prevalent and researched brain receptors: the 5-HT1A and 5-HT2A receptors. We propose that passive coping (i.e. tolerating a source of stress) is mediated by postsynaptic 5-HT1AR signalling and characterised by stress moderation. Conversely, we argue that active coping (i.e. actively addressing a source of stress) is mediated by 5-HT2AR signalling and characterised by enhanced plasticity (defined as capacity for change). We propose that 5-HT1AR-mediated stress moderation may be the brain’s default response to adversity but that an improved ability to change one’s situation and/or relationship to it via 5-HT2AR-mediated plasticity may also be important – and increasingly so as the level of adversity reaches a critical point. We propose that the 5-HT1AR pathway is enhanced by conventional 5-HT reuptake blocking antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), whereas the 5-HT2AR pathway is enhanced by 5-HT2AR-agonist psychedelics. This bipartite model purports to explain how different drugs (SSRIs and psychedelics) that modulate the serotonergic system in different ways, can achieve complementary adaptive and potentially therapeutic outcomes.
Carhart-Harris, R. L., & Nutt, D. J. (2017). Serotonin and brain function: a tale of two receptors. Journal of Psychopharmacology (Oxford, England), 31(9), 1091. 10.1177/0269881117725915
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Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic

/ Anxiety Disorders / PTSD, Ketamine, Neuroscience, Papers, Psychology, Publications / / , , , , , ,

Abstract

PURPOSE OF REVIEW:
Studies of the neurobiology and treatment of PTSD have highlighted many aspects of the pathophysiology of this disorder that might be relevant to treatment. The purpose of this review is to highlight the potential clinical importance of an often-neglected consequence of stress models in animals that may be relevant to PTSD: the stress-related loss of synaptic connectivity.
RECENT FINDINGS:
Here, we will briefly review evidence that PTSD might be a “synaptic disconnection syndrome” and highlight the importance of this perspective for the emerging therapeutic application of ketamine as a potential rapid-acting treatment for this disorder that may work, in part, by restoring synaptic connectivity. Synaptic disconnection may contribute to the profile of PTSD symptoms that may be targeted by novel pharmacotherapeutics.
Krystal, J. H., Abdallah, C. G., Averill, L. A., Kelmendi, B., Harpaz-Rotem, I., Sanacora, G., … & Duman, R. S. (2017). Synaptic loss and the pathophysiology of PTSD: implications for ketamine as a prototype novel therapeutic. Current Psychiatry Reports, 19(10), 74. 10.1007/s11920-017-0829-z
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Enzymatic synthesis of psilocybin

/ Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry / / , ,

Abstract

Psilocybin is the psychotropic tryptamine-derived natural product of Psilocybe carpophores, the so-called “magic mushrooms”. Although its structure has been known for 60 years, the enzymatic basis of its biosynthesis has remained obscure. We characterized four psilocybin biosynthesis enzymes, namely i) PsiD, which represents a new class of fungal l-tryptophan decarboxylases, ii) PsiK, which catalyzes the phosphotransfer step, iii) the methyltransferase PsiM, catalyzing iterative N-methyl transfer as the terminal biosynthetic step, and iv) PsiH, a monooxygenase. In a combined PsiD/PsiK/PsiM reaction, psilocybin was synthesized enzymatically in a step-economic route from 4-hydroxy-l-tryptophan. Given the renewed pharmaceutical interest in psilocybin, our results may lay the foundation for its biotechnological production.
Fricke, J., Blei, F., & Hoffmeister, D. (2017). Enzymatic synthesis of psilocybin. Angewandte Chemie International Edition. 10.1002/anie.201705489
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Psychedelic Drugs as Therapeutics: No Illusions About the Challenges

/ Mushrooms / Psilocybin, Papers, Psychology / / ,

Abstract

Interest in the potential therapeutic benefits of psychedelic agents has recently increased. In addition to psilocybin, a wide variety of agents with psychedelic properties have been proposed and partially tested. However, the challenges of obtaining approval to market a restricted psychotomimetic agent are formidable.
Sellers, E. M., & Leiderman, D. B. (2017). Psychedelic Drugs as Therapeutics: No Illusions About the Challenges. Clinical Pharmacology & Therapeutics. 10.1002/cpt.776
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Functional Mushrooms: Ecological Allies for Whole-Body Health - February 18

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