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Production Options for Psilocybin: Making of the Magic

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

Abstract

The fungal genus Psilocybe and other genera comprise numerous mushroom species that biosynthesize psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine). It represents the prodrug to its dephosphorylated psychotropic analogue, psilocin. The colloquial term “magic mushrooms” for these fungi alludes to their hallucinogenic effects and to their use as recreational drugs. However, clinical trials have recognized psilocybin as a valuable candidate to be developed into a medication against depression and anxiety. We here highlight its recently elucidated biosynthesis, the concurrently developed concept of enzymatic in vitro and heterologous in vivo production, along with previous synthetic routes. The prospect of psilocybin as a promising therapeutic may entail an increased demand, which can be met by biotechnological production. Therefore, we also briefly touch on psilocybin’s therapeutic relevance and pharmacology.

Fricke, J., Lenz, C., Wick, J., Blei, F., & Hoffmeister, D. (2018). Production Options for Psilocybin: Making of the Magic. Chemistry–A European Journal., 10.1002/chem.201802758

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Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine

/ Humanities & Art, MDMA, Neuroscience, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Psychology, Publications / / , ,

Abstract

Better known as “ecstasy”, 3,4-methylenedioxymethamphetamine (MDMA) is a small molecule that has played a prominent role in defining the ethos of today’s teenagers and young adults, much like lysergic acid diethylamide (LSD) did in the 1960s. Though MDMA possesses structural similarities to compounds like amphetamine and mescaline, it produces subjective effects that are unlike any of the classical psychostimulants or hallucinogens and is one of the few compounds capable of reliably producing prosocial behavioral states. As a result, MDMA has captured the attention of recreational users, the media, artists, psychiatrists, and neuropharmacologists alike. Here, we detail the synthesis of MDMA as well as its pharmacology, metabolism, adverse effects, and potential use in medicine. Finally, we discuss its history and why it is perhaps the most important compound for the future of psychedelic science-having the potential to either facilitate new psychedelic research initiatives, or to usher in a second Dark Age for the field.

Dunlap, L. E., Andrews, A. M., & Olson, D. E. (2018). Dark classics in chemical neuroscience: 3, 4-Methylenedioxymethamphetamine. ACS chemical neuroscience, 9(10), 2408-2427., 10.1021/acschemneuro.8b00155
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Ketamine normalizes brain activity during emotionally valenced attentional processing in depression

/ Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Publications / / , , , , ,

Abstract

BACKGROUND:

An urgent need exists for faster-acting pharmacological treatments in major depressive disorder (MDD). The glutamatergic modulator ketamine has been shown to have rapid antidepressant effects, but much remains unknown about its mechanism of action. Functional MRI (fMRI) can be used to investigate how ketamine impacts brain activity during cognitive and emotional processing.

METHODS:

This double-blind, placebo-controlled, crossover study of 33 unmedicated participants with MDD and 26 healthy controls (HCs) examined how ketamine affected fMRI activation during an attentional bias dot probe task with emotional face stimuli across multiple time points. A whole brain analysis was conducted to find regions with differential activation associated with group, drug session, or dot probe task-specific factors (emotional valence and congruency of stimuli).

RESULTS:

A drug session by group interaction was observed in several brain regions, such that ketamine had opposite effects on brain activation in MDD versus HC participants. Additionally, there was a similar finding related to emotional valence (a drug session by group by emotion interaction) in a large cluster in the anterior cingulate and medial frontal cortex.

CONCLUSIONS:

The findings show a pattern of brain activity in MDD participants following ketamine infusion that is similar to activity observed in HCs after placebo. This suggests that ketamine may act as an antidepressant by normalizing brain function during emotionally valenced attentional processing.

CLINICAL TRIAL:

NCT#00088699: https://www.clinicaltrials.gov/ct2/show/NCT00088699.

Reed, J. L., Nugent, A. C., Furey, M. L., Szczepanik, J. E., Evans, J. W., & Zarate Jr, C. A. (2018). Ketamine normalizes brain activity during emotionally valenced attentional processing in depression. NeuroImage: Clinical, 20, 92-101., 10.1016/j.nicl.2018.07.006
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Psychedelic-Assisted Psychotherapy: A Paradigm Shift in Psychiatric Research and Development.

/ Iboga / Ibogaine, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / /

Abstract

Mental disorders are rising while development of novel psychiatric medications is declining. This stall in innovation has also been linked with intense debates on the current diagnostics and explanations for mental disorders, together constituting a paradigmatic crisis. A radical innovation is psychedelic-assisted psychotherapy (PAP): professionally supervised use of ketamine, MDMA, psilocybin, LSD and ibogaine as part of elaborated psychotherapy programs. Clinical results so far have shown safety and efficacy, even for “treatment resistant” conditions, and thus deserve increasing attention from medical, psychological and psychiatric professionals. But more than novel treatments, the PAP model also has important consequences for the diagnostics and explanation axis of the psychiatric crisis, challenging the discrete nosological entities and advancing novel explanations for mental disorders and their treatment, in a model considerate of social and cultural factors, including adversities, trauma, and the therapeutic potential of some non-ordinary states of consciousness.

Schenberg, E. E. S. (2018). Psychedelic-assisted psychotherapy: a paradigm shift in psychiatric research and development. Frontiers in pharmacology, 9, 733., 10.3389/fphar.2018.00733
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Rapid antidepressant effect of S-ketamine in schizophrenia.

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

Abstract

Rapid anti-suicidal and antidepressant effects of ketamine have repeatedly been confirmed in unipolar and bipolar depression. Although meaningful antidepressant efficacy of ketamine has also been shown in depressed patients with a history of psychotic symptoms, its administration in psychotic disorders has largely been neglected due to its potential to exacerbate dissociative or psychotic symptoms. Presenting a case of a young female inpatient suffering from schizophrenia with a severe post-psychotic depression, we demonstrate a robust anti-suicidal and antidepressant effect of S-ketamine infusions administered thrice weekly for 3 weeks in total. Importantly, no relevant psychotic or dissociative symptoms occurred during the whole augmentation treatment period leading to a sustained remission of depressive symptoms and suicidality. Our safe and effective experience with intravenous S-ketamine might encourage researchers and clinicians to widen its administration range beyond the diagnosis of depression to enrich the current knowledge of ketamine effects in psychotic disorders.
Bartova, L., Papageorgiou, K., Milenkovic, I., Dold, M., Weidenauer, A., Willeit, M., … & Kasper, S. (2018). Rapid antidepressant effect of S-ketamine in schizophrenia. European Neuropsychopharmacology, 28(8), 980-982., 10.1016/j.euroneuro.2018.05.007
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Positive psychology in the investigation of psychedelics and entactogens: A critical review

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

Abstract

RATIONALE:
We reviewed the concepts and empirical findings in studies with psychedelics and entactogens related to positive psychology – the study of healthy human functioning, well-being and eudaemonia. It is an unresolved question how beneficial effects of psychedelics and entactogens are related to the potential risks of these substances – particularly in non-clinical settings.
METHODS:
We searched in PubMed, PsychINFO and the Cochrane Library for controlled clinical and epidemiological studies which applied concepts from positive psychology. We included N = 77 eligible studies with 9876 participants published before November 1st, 2017: (1) quantitative studies (N = 54), (2) preliminary or exploratory studies and reviews not including meta-analyses (N = 17), and (3) studies evidencing primarily negative results (N = 6).
RESULTS:
Positive psychology concepts have been applied for measuring effects of clinical trials, recreational and ceremonial use of psychedelics and entactogens. Psychedelics and entactogens were shown to produce acute and long-term effects on mood, well-being, prosocial behaviours, empathy, cognitive flexibility, creativity, personality factors like openness, value orientations, nature-relatedness, spirituality, self-transcendence and mindfulness-related capabilities.
CONCLUSIONS:
There is preliminary evidence for beneficial effects of psychedelics and entactogens on measures of positive psychology in clinical and healthy populations, however their sustainability remains largely unresolved. The reported results must be considered preliminary due to methodological restrictions. Since longitudinal data on both positive and adverse effects of psychedelics are lacking, more rigorous and standardized measures from positive psychology should be applied in less biased populations with prospective longitudinal designs to carefully assess the benefit-risk-ratio.
Jungaberle, H., Thal, S., Zeuch, A., Rougemont-Bücking, A., von Heyden, M., Aicher, H., & Scheidegger, M. (2018). Positive psychology in the investigation of psychedelics and entactogens: A critical review. Neuropharmacology. 10.1016/j.neuropharm.2018.06.034
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High dose psilocybin is associated with positive subjective effects in healthy volunteers

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

Abstract

AIM:
The aim of the current study was to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects.
METHODS:
Healthy participants ( n=12) were given three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or (18.8-36.6 mg; 27.1-54.0 mg; 36.3-59.2 mg) a minimum of four weeks apart in a supervised setting. Blood and urine samples, vital signs, and electrocardiograms were obtained. Subjective effects were assessed using the Mystical Experience Questionnaire and Persisting Effects Questionnaire.
RESULTS:
There was a significant linear dose-related response in Mystical Experience Questionnaire total score and the transcendence of time and space subscale, but not in the rate of a complete mystical experience. There was also a significant difference between dose 3 compared to dose 1 on the transcendence of time and space subscale, while no dose-related differences were found for Mystical Experience Questionnaire total scores or rate of a mystical experience. Persisting Effects Questionnaire positive composite scores 30 days after completion of the last dose were significantly higher than negative composite scores. Persisting Effects Questionnaire results revealed a moderate increase in sense of well-being or life satisfaction on average that was associated with the maximum Mystical Experience Questionnaire total score. Pharmacokinetic measures were associated with dose but not with Mystical Experience Questionnaire total scores or rate of a mystical experience.
CONCLUSIONS:
High doses of psilocybin elicited subjective effects at least as strong as the lower doses and resulted in positive persisting subjective effects 30 days after, indicating that a complete mystical experience was not a prerequisite for positive outcomes.
Nicholas, C. R., Henriquez, K. M., Gassman, M. C., Cooper, K. M., Muller, D., Hetzel, S., … & Hutson, P. R. (2018). High dose psilocybin is associated with positive subjective effects in healthy volunteers. Journal of Psychopharmacology, 0269881118780713.
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Mental health of a self-selected sample of psychedelic users and self-medication practices with psychedelics

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

Abstract

Background

A substantial number of people worldwide suffer from mental health problems during their lifetime. First-line treatments are not effective for everybody. Recent studies suggest that psychedelic drugs have high therapeutic potential for a variety of mental disorders.

Aims

This survey study aimed to assess the tendency of psychedelic users to self-medicate with psychedelics and to compare the effectiveness of self-administered psychedelics to treat their disorder and the treatment offered by a medical professional.

Methods and results

In total, 1,967 respondents consented were ≥18 years and completed the questionnaire. The mean (±SD) age was 25.9 (8.7); 79% were males, 20% females, and 1% classified themselves as “other.” Almost half of the respondents (46%) indicated to have suffered/to be suffering from a mental disorder, with 77% being diagnosed by a medical professional. In 99% of the diagnosed cases, the treatment was offered; 77% searched for treatments outside a medical professional’s recommendation with 81% who had used/were using psychedelics to treat/cure symptoms. Self-administered psychedelic treatment had a higher likelihood of being efficacious, with higher symptoms reduction and larger quality of life improvement compared to treatment offered by a medical professional.

Conclusions

Lifetime prevalence of psychopathologies in the current sample of psychedelic drug users seemed to be higher than in the general population. Self-medication with psychedelics was not highly frequent; although when it occurred, it was rated as significantly more effective as treatment offered by a medical professional. Current findings support research exploring the potential of psychedelics in the treatment of psychopathologies.

Mason, N. L., & Kuypers, K. P. (2018). Mental health of a self-selected sample of psychedelic users and self-medication practices with psychedelics. Journal of Psychedelic Studies, 2(1), 45-52. 10.1556/2054.2018.006
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Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts

/ Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / / , , , ,

Abstract

Background:

Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilitated addiction treatment interventions. Fifteen participants completed a psilocybin-facilitated smoking cessation pilot study between 2009 and 2015.

Aims:

The aims of this study were as follows: (1) to identify perceived mechanisms of change leading to smoking cessation in the pilot study; (2) to identify key themes in participant experiences and long-term outcomes to better understand the therapeutic process.

Methods:

Participants were invited to a retrospective follow-up interview an average of 30 months after initial psilocybin sessions. Semi-structured interviews were conducted with 12 of the 15 participants. Data were analysed using thematic analysis.

Results:

Participants reported gaining vivid insights into self-identity and reasons for smoking from their psilocybin sessions. Experiences of interconnectedness, awe, and curiosity persisted beyond the duration of acute drug effects. Participants emphasised that the content of psilocybin experiences overshadowed any short-term withdrawal symptoms. Preparatory counselling, strong rapport with the study team, and a sense of momentum once engaged in the study treatment were perceived as vital additional factors in achieving abstinence. In addition, participants reported a range of persisting positive changes beyond smoking cessation, including increased aesthetic appreciation, altruism, and pro-social behaviour.

Conclusions:

The findings highlight the value of qualitative research in the psychopharmacological investigation of psychedelics. They describe perceived connections between drug- and non-drug factors, and provide suggestions for future research trial design and clinical applications.

Noorani, T., Garcia-Romeu, A., Swift, T. C., Griffiths, R. R., & Johnson, M. W. (2018). Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts. Journal of Psychopharmacology, 32(7), 756-769. 10.1177%2F0269881118780612
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Breath and Body: Scientific and Experiential Perspectives on Breathwork - September 23rd

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