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Perceived Benefits of MDMA-Assisted Psychotherapy beyond Symptom Reduction: Qualitative Follow-Up Study of a Clinical Trial for Individuals with Treatment-Resistant PTSD.

/ Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / / , , ,

Abstract

We present select findings from a long-term follow-up qualitative study of MDMA-assisted psychotherapy for veterans, firefighters, and police officers suffering from chronic, treatment-resistant PTSD. Semi-structured qualitative interviews were conducted at participants’ one-year follow-up after a recently completed phase 2 clinical trial. Available interviews from 19 of 24 participants were analyzed. This qualitative analysis sought to complement, clarify, and expand upon the quantitative findings obtained from the Clinician Administered PTSD Scale (CAPS-IV) and supported by the Long-Term Follow-Up (LTFU) Questionnaire. Pertinent data from interview transcripts were coded and analyzed using an interpretative phenomenological analysis (IPA) methodological framework. We explore prominent thematic elements from participant accounts to better understand the outcomes experienced in this trial. All participants reported experiencing lasting personal benefits and enhanced quality of life that extend beyond quantifiable symptom reduction. We explore a range of treatment benefits beyond symptom reduction to highlight the utility of qualitative investigations of the process and effects of MDMA-assisted psychotherapy. Limitations and challenges encountered in conducting this study are discussed along with recommendations for improved qualitative research protocols in future clinical trials.
Barone, W., Beck, J., Mitsunaga-Whitten, M., & Perl, P. (2019). Perceived Benefits of MDMA-Assisted Psychotherapy beyond Symptom Reduction: Qualitative Follow-Up Study of a Clinical Trial for Individuals with Treatment-Resistant PTSD. Journal of psychoactive drugs, 1-10., https://doi.org/10.1080/02791072.2019.1580805
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Metabolite Profiling of Antiaddictive Alkaloids from Four Mexican Tabernaemontana Species and the Entheogenic African Shrub Tabernanthe iboga (Apocynaceae)

/ Biology & Ethnobotany, Iboga / Ibogaine, Papers, Pharmacology & Chemistry, Publications, Substance Use Disorder / / , , , ,

Abstract

Ibogaine and other ibogan type alkaloids present anti-addictive effects against several drugs of abuse and occur in different species of the Apocynaceae family. In this work, we used gas chromatography-mass spectrometry (GC/MS) and principal component analysis (PCA) in order to compare the alkaloid profiles of the root and stem barks of four Mexican Tabernaemontana species with the root bark of the entheogenic African shrub Tabernanthe iboga. PCA demonstrated that separation between species could be attributed to quantitative differences of the major alkaloids, coronaridine, ibogamine, voacangine, and ibogaine. While T. iboga mainly presented high concentrations of ibogaine, Tabernaemontana samples either showed a predominance of voacangine and ibogaine, or coronaridine and ibogamine, respectively. The results illustrate the phytochemical proximity between both genera and confirm previous suggestions that Mexican Tabernaemontana species are viable sources of anti-addictive compounds.

Krengel, F., Chevalier, Q., Dickinson, J., Santoyo, J. H., & Reyes-Chilpa, R. (2019). Metabolite Profiling of Antiaddictive Alkaloids from Four Mexican Tabernaemontana Species and the Entheogenic African Shrub Tabernanthe iboga (Apocynaceae). Chemistry & biodiversity., 10.1002/cbdv.201800506
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The effects of ketamine on suicidality across various formulations and study settings

/ Anxiety Disorders / PTSD, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / / ,

Abstract

INTRODUCTION:

Suicidality and self-injurious behavior afflict patients with a wide variety of psychiatric illnesses. Currently, there are few pharmacologic treatments for suicidality and self-injurious behavior and none that treat these conditions emergently. Recently, ketamine has demonstrated efficacy in treating both depression and acute suicidal ideation. An increasing usage of ketamine, of a variety of formulations, has been studied for these indications. This article reviews the evidence for use of ketamine in self-injurious behavior and suicidality.

METHODS:

A review of the MEDLINE database for articles relating to ketamine, self-injurious behavior, suicidality, and self-harm was conducted. Additional articles were assessed via cross-reference.

RESULTS:

A total of 24 articles that included clinical trials, meta-analyses, case series, and case reports were analyzed. The majority of studies of ketamine for suicidal ideation include the intravenous route using a dose of 0.5 mg/kg over 40 minutes. These studies suggest that intravenous ketamine may be effective at reducing suicidal ideation acutely. Data on use of ketamine in the intramuscular, intranasal, and oral forms are limited and of poorer quality. Studies on these formulations contain greater variability of positive and negative results of ketamine for reducing suicidality and self-injurious behavior. The durability of the antisuicidal effects across all formulations is limited.

DISCUSSION:

Ketamine may be an effective option for the treatment of suicidal ideation in patients across inpatient, outpatient, or emergent settings. At this time, more research is needed on the efficacy of ketamine across all formulations being used in clinical practice.

Dadiomov, D., & Lee, K. (2019). The effects of ketamine on suicidality across various formulations and study settings. Mental Health Clinician, 9(1), 48-60., 10.9740/mhc.2019.01.048
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Transformative Psychopharmacology: the Case of 5-Methoxy-N,N-Dimethyltryptamine

/ DMT, Neuroscience, Papers, Publications / /

Abstract

Since the 2nd part of last century neo-shamanic rituals using mind-altering extracts from plants or animals have become increasingly popular in Europe and the USA. The first rituals coming to the west were based on drinking a special Amazonian tea, Ayahuasca, based on 2 different plants, with active compounds belonging to the class of the beta-carbolines (harmala alkaloids) and tryptamines. The use of such compounds will be described from the perspective of the transformative psychopharmacology: that part of psychopharmacology studying the use of psychoactive compounds to achieve a new balance, a transformation or healing and sometimes even leading to a cure. Examples of curing are meanwhile well documented, for instance the positive influence on drug abuse and addiction, alcoholism. The importance of the healing aspects of these rituals however are often neglected or overlooked. For users, these are key however. As medicine becomes more and more personalized and postmodern, it will be relevant to understand why patients and healthy people decide to participate in healing rituals based on psycho-active compounds. We will present the pharmacology, the transformative psychopharmacology, the effects and adverse events of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) and its place in postmodern medicine.

Jan M Keppel Hesselink (2019) Transformative Psychopharmacology: the Case of 5-Methoxy-N,N-Dimethyltryptamine. International Journal of Psychotherapy Practice and Research – 1(3):9-15., 10.14302/issn.2574-612X.ijpr-18-2503
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Microdosing psychedelics: personality, mental health, and creativity differences in microdosers

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

Abstract

RATIONALE:

Microdosing psychedelics-the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin-is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties, microdosing mayprovide complementary clinical benefits using lower-risk, non-hallucinogenic doses.

OBJECTIVES:

This pre-registered study aimed to investigate whether microdosing psychedelics is related to differences in personality, mental health, and creativity.

METHODS:

In this observational study, respondents recruited from online forums self-reported their microdosing behaviors and completed questionnaires concerning dysfunctional attitudes, wisdom, negative emotionality, open-mindedness, and mood. Respondents also performed the Unusual Uses Task to assess their creativity.

RESULTS:

Current and former microdosers scored lower on measures of dysfunctional attitudes (p < 0.001, r = – 0.92) and negative emotionality (p = 0.009, r = – 0.85) and higher on wisdom (p < 0.001, r = 0.88), openmindedness(p = 0.027, r = 0.67), and creativity (p < 0.001, r = 0.15) when compared to non-microdosing controls.

CONCLUSIONS:

These findings provide promising initial evidence that warrants controlled experimental research to directly test safety and clinical efficacy. As microdoses are easier to administer than full-doses, this new paradigm has the exciting potential to shape future psychedelic research.

Anderson, T., Petranker, R., Rosenbaum, D., Weissman, C. R., Dinh-Williams, L. A., Hui, K., … & Farb, N. A. (2018). Microdosing Psychedelics: Personality, mental health, and creativity differences in microdosers. Psychopharmacology, 1-10., 10.1007/s00213-018-5106-2
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Microdosing psychedelics: personality, mental health, and creativity differences in microdosers.

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

Abstract

RATIONALE:
Microdosing psychedelics-the regular consumption of small amounts of psychedelic substances such as LSD or psilocybin-is a growing trend in popular culture. Recent studies on full-dose psychedelic psychotherapy reveal promising benefits for mental well-being, especially for depression and end-of-life anxiety. While full-dose therapies include perception-distorting properties, microdosing mayprovide complementary clinical benefits using lower-risk, non-hallucinogenic doses.
OBJECTIVES:
This pre-registered study aimed to investigate whether microdosing psychedelics is related to differences in personality, mental health, and creativity.
METHODS:
In this observational study, respondents recruited from online forums self-reported their microdosing behaviors and completed questionnaires concerning dysfunctional attitudes, wisdom, negative emotionality, open-mindedness, and mood. Respondents also performed the Unusual Uses Task to assess their creativity.
RESULTS:
Current and former microdosers scored lower on measures of dysfunctional attitudes (p < 0.001, r = – 0.92) and negative emotionality (p = 0.009, r = – 0.85) and higher on wisdom (p < 0.001, r = 0.88), openmindedness(p = 0.027, r = 0.67), and creativity (p < 0.001, r = 0.15) when compared to non-microdosing controls.
CONCLUSIONS:
These findings provide promising initial evidence that warrants controlled experimental research to directly test safety and clinical efficacy. As microdoses are easier to administer than full-doses, this new paradigm has the exciting potential to shape future psychedelic research.

Anderson, T., Petranker, R., Rosenbaum, D., Weissman, C. R., Dinh-Williams, L. A., Hui, K., … & Farb, N. A. (2019). Microdosing Psychedelics: Personality, mental health, and creativity differences in microdosers. Psychopharmacology, 236(2), 731-740., https://doi.org/10.1007/s00213-018-5106-2
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[Off-label ketamine treatment for treatment-resistant depression: win-win?]

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

Smith-Apeldoorn, S. Y., Veraart, J. K. E., & Schoevers, R. A. (2019). Off-label ketamine treatment for treatment-resistant depression: win-win?., https://europepmc.org/abstract/med/31512733
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How do psychedelics work?

/ Neuroscience, Papers, Publications / /

Abstract

Purpose of review

Psychedelics are reawakening interest from psychiatry, cognitive neuroscience and the general public with impressive outcomes in small-scale clinical trials, intriguing human brain imaging work and high-impact journalism.

Recent findings

This brief opinion piece offers a perspective on how psychedelics work in the brain that may help contextualize these developments. It attempts to link various scales of action, from the molecular (serotonin 2A receptor agonism) through to the anatomical and functional (heightened plasticity) and up to the dynamic (increased brain entropy), systems level (network disintegration and desegregation) and experiential.

Summary

It is proposed that psychedelics initiate a cascade of neurobiological changes that manifest at multiple scales and ultimately culminate in the relaxation of high-level beliefs. The purpose of psychedelic therapy is to harness the opportunity afforded by this belief-relaxation to achieve a healthy revision of pathological beliefs.

Carhart-Harris, R. L. (2019). How do psychedelics work?. Current opinion in psychiatry, 32(1), 16-21.,  10.1097/YCO.0000000000000467
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Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment‐resistant depression

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

Abstract

Objective

To examine the effect of high baseline anxiety on response to ketamine versus midazolam (active placebo) in treatment‐resistant depression (TRD).

Methods

In a multisite, double‐blind, placebo‐controlled trial, 99 subjects with TRD were randomized to one of five arms: a single dose of intravenous ketamine 0.1, 0.2, 0.5, 1.0 mg/kg, or midazolam 0.045 mg/kg. The primary outcome measure was changed in the six‐item Hamilton Rating Scale for Depression (HAMD6). A linear mixed effects model was used to examine the effect of anxious depression baseline status (defined by a Hamilton Depression Rating Scale Anxiety‐Somatization score ≥7) on response to ketamine versus midazolam at 1 and 3 days postinfusion.

Results

N = 45 subjects had anxious TRD, compared to N = 54 subjects without high anxiety at baseline. No statistically significant interaction effect was found between treatment group assignment (combined ketamine treatment groups versus midazolam) and anxious/nonanxious status on HAMD6 score at either days 1 or 3 postinfusion (Day 1: F(1, 84) = 0.02, P = 0.88; Day 3: F(1, 82) = 0.12, P = 0.73).

Conclusion

In contrast with what is observed with traditional antidepressants, response to ketamine may be similar in both anxious and nonanxious TRD subjects. These pilot results suggest the potential utility of ketamine in the treatment of anxious TRD.

Salloum, N. C., Fava, M., Freeman, M. P., Flynn, M., Hoeppner, B., Hock, R. S., … & Mathew, S. J. (2018). Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment‐resistant depression. Depression and anxiety., 10.1002/da.22875
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Role of serotonin transporter and receptor gene variations in the acute effects of MDMA in healthy subjects

/ MDMA, Neuroscience, Papers, Publications / / , ,

Abstract

Methylenedioxymethamphetamine (MDMA; ecstasy) is used recreationally and has been investigated as an adjunct to psychotherapy. Most acute effects of MDMA can be attributed to activation of the serotonin (5-hydroxytryptamine [5-HT]) system. Genetic variants, such as single-nucleotide polymorphisms (SNPs) and polymorphic regions in 5-HT system genes, may contribute to interindividual differences in the acute effects of MDMA. We characterized the effects of common genetic variants within selected genes that encode the 5-HT system (TPH1 [tryptophan 5-hydroxylase 1] rs1800532 and rs1799913, TPH2 [tryptophan 5-hydroxylase 2] rs7305115, HTR1A [5-HT1A receptor] rs6295, HTR1B [5-HT1B receptor] rs6296, HTR2A [5-HT2A receptor] rs6313, and SLC6A4 [serotonin transporter] 5-HTTLPR and rs25531) on the physiological and subjective response to 125 mg MDMA compared with placebo in 124 healthy subjects. Data were pooled from eight randomized, double-blind, placebo-controlled studies that were conducted in the same laboratory. TPH2 rs7305115, HTR2A rs6313, and SLC6A4 5-HTTLPR polymorphisms tended to moderately alter some effects of MDMA. However, after correcting for multiple comparisons, none of the tested genetic polymorphisms significantly influenced the response to MDMA. Variations in genes that encode key targets in the 5-HT system did not significantly influence the effects of MDMA in healthy subjects. Interindividual differences in the 5-HT system may thus play a marginal role when MDMA is used recreationally or therapeutically.

Vizeli, P., Meyer zu Schwabedissen, H. E., & Liechti, M. E. (2018). Role of serotonin transporter and receptor gene variations in the acute effects of MDMA in healthy subjects. ACS chemical neuroscience., 10.1021/acschemneuro.8b00590
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