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The cost-effectiveness of MDMA-assisted psychotherapy for the treatment of chronic, treatment-resistant PTSD

January 7, 2022 / Anxiety Disorders / PTSD, MDMA, Papers, Psychiatry & Medicine / Leave a Comment / By / , , ,

Abstract

Background: Chronic posttraumatic stress disorder (PTSD) is a disabling condition that generates considerable morbidity, mortality, and both medical and indirect social costs. Treatment options are limited. A novel therapy using 3,4-methylenedioxymethamphetamine (MDMA) has shown efficacy in six phase 2 trials. Its cost-effectiveness is unknown.

Methods and findings: To assess the cost-effectiveness of MDMA-assisted psychotherapy (MAP) from the health care payer’s perspective, we constructed a decision-analytic Markov model to portray the costs and health benefits of treating patients with chronic, severe, or extreme, treatment-resistant PTSD with MAP. In six double-blind phase 2 trials, MAP consisted of a mean of 2.5 90-minute trauma-focused psychotherapy sessions before two 8-hour sessions with MDMA (mean dose of 125 mg), followed by a mean of 3.5 integration sessions for each active session. The control group received an inactive placebo or 25-40 mg. of MDMA, and otherwise followed the same regimen. Our model calculates net medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Efficacy was based on the pooled results of six randomized controlled phase 2 trials with 105 subjects; and a four-year follow-up of 19 subjects. Other inputs were based on published literature and on assumptions when data were unavailable. We modeled results over a 30-year analytic horizon and conducted extensive sensitivity analyses. Our model calculates expected medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Future costs and QALYs were discounted at 3% per year. For 1,000 individuals, MAP generates discounted net savings of $103.2 million over 30 years while accruing 5,553 discounted QALYs, compared to continued standard of care. MAP breaks even on cost at 3.1 years while delivering 918 QALYs. Making the conservative assumption that benefits cease after one year, MAP would accrue net costs of $7.6 million while generating 288 QALYS, or $26,427 per QALY gained.

Conclusion: MAP provided to patients with severe or extreme, chronic PTSD appears to be cost-saving while delivering substantial clinical benefit. Third-party payers are likely to save money within three years by covering this form of therapy.

Marseille, E., Kahn, J. G., Yazar-Klosinski, B., & Doblin, R. (2020). The cost-effectiveness of MDMA-assisted psychotherapy for the treatment of chronic, treatment-resistant PTSD. PloS one, 15(10), e0239997. https://doi.org/10.1371/journal.pone.0239997

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DMT alters cortical travelling waves

November 26, 2021 / DMT, Neuroscience, Papers / Leave a Comment / By / , , , ,

Abstract

Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) can rapidly induce an extremely immersive state of consciousness characterized by vivid and elaborate visual imagery. Here, we investigated the electrophysiological correlates of the DMT-induced altered state from a pool of participants receiving DMT and (separately) placebo (saline) while instructed to keep their eyes closed. Consistent with our hypotheses, results revealed a spatio-temporal pattern of cortical activation (i.e. travelling waves) similar to that elicited by visual stimulation. Moreover, the typical top-down alpha-band rhythms of closed-eyes rest were significantly decreased, while the bottom-up forward wave was significantly increased. These results support a recent model proposing that psychedelics reduce the ‘precision-weighting of priors’, thus altering the balance of top-down versus bottom-up information passing. The robust hypothesis-confirming nature of these findings imply the discovery of an important mechanistic principle underpinning psychedelic-induced altered states.

Alamia, A., Timmermann, C., Nutt, D. J., VanRullen, R., & Carhart-Harris, R. L. (2020). DMT alters cortical travelling waves. eLife, 9, e59784. https://doi.org/10.7554/eLife.59784

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The effectiveness of intravenous ketamine in adults with treatment-resistant major depressive disorder and bipolar disorder presenting with prominent anxiety: Results from the Canadian Rapid Treatment Center of Excellence

November 26, 2021 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, Papers, Psychology / Leave a Comment / By / , , , , , , , , , , , ,

Abstract

Background: Individuals meeting criteria for treatment-resistant depression (TRD) are differentially affected by high levels of anxiety symptoms.

Aims: There is a need to identify the efficacy of novel rapid-onset treatments in adults with mood disorders and comorbid anxious-distress.

Methods: This study included patients with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD) who were receiving intravenous (IV) ketamine treatment at a community-based clinic.Anxious-distress was proxied using items from the Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS-SR16) and Generalized Anxiety Disorder 7-item (GAD7) scales. The difference in QIDS-SR16 total score, QIDS-SR16 suicidal ideation (SI) item and GAD7 score were analyzed between groups.

Results: A total of 209 adults with MDD (n = 177) and BD (n = 26) were included in this analysis. From this sample, 94 patients (mean = 45 ± 13.9 years) met the criteria for anxious-distress. Individuals meeting the criteria for anxious-distress exhibited a significantly greater reduction in QIDS-SR16 total score following four infusions (p = 0.02) when compared with patients not meeting the anxious-distress criteria. Both anxious-distressed and low-anxiety patients exhibited a significant reduction in SI (p < 0.0001) following four infusions.Finally, there was a significantly greater reduction in anxiety symptoms in the anxious-distress group compared with the non-anxious distress group following three (p = 0.02) and four infusions (p < 0.001).

Conclusion: Patients with TRD and prominent anxiety receiving IV ketamine exhibited a significant reduction in depressive, SI and anxiety symptoms.

McIntyre, R. S., Rodrigues, N. B., Lipsitz, O., Nasri, F., Gill, H., Lui, L. M., Subramaniapillai, M., Kratiuk, K., Teopiz, K., Ho, R., Lee, Y., Mansur, R. B., & Rosenblat, J. D. (2021). The effectiveness of intravenous ketamine in adults with treatment-resistant major depressive disorder and bipolar disorder presenting with prominent anxiety: Results from the Canadian Rapid Treatment Center of Excellence. Journal of psychopharmacology (Oxford, England), 35(2), 128–136. https://doi.org/10.1177/0269881120954048

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Acute subjective effects in LSD- and MDMA-assisted psychotherapy

March 16, 2022 / LSD, MDMA, Papers / Leave a Comment / By / , , ,

Abstract

Background: Lysergic acid diethylamide (LSD) and 3,4-methylenedioxymethamphetamine (MDMA) were used in psychotherapy in the 1960s-1980s, and are currently being re-investigated as treatments for several psychiatric disorders. In Switzerland, limited medical use of these substances is possible in patients not responding to other treatments (compassionate use).

Methods: This study aimed to describe patient characteristics, treatment indications and acute alterations of mind in patients receiving LSD (100-200 µg) and/or MDMA (100-175 mg) within the Swiss compassionate use programme from 2014-2018. Acute effects were assessed using the 5 Dimensions of Altered States of Consciousness scale and the Mystical Experience Questionnaire, and compared with those in healthy volunteers administered with LSD or MDMA and patients treated alone with LSD in clinical trials.

Results: Eighteen patients (including 12 women and six men, aged 29-77 years) were treated in group settings. Indications mostly included posttraumatic stress disorder and major depression. Generally, a drug-assisted session was conducted every 3.5 months after 3-10 psychotherapy sessions. LSD induced pronounced alterations of consciousness on the 5 Dimensions of Altered States of Consciousness scale, and mystical-type experiences with increases in all scales on the Mystical Experience Questionnaire. Effects were largely comparable between patients in the compassionate use programme and patients or healthy subjects treated alone in a research setting.

Conclusion: LSD and MDMA are currently used medically in Switzerland mainly in patients with posttraumatic stress disorder and depression in group settings, producing similar acute responses as in research subjects. The data may serve as a basis for further controlled studies of substance-assisted psychotherapy.

Schmid, Y., Gasser, P., Oehen, P., & Liechti, M. E. (2021). Acute subjective effects in LSD- and MDMA-assisted psychotherapy. Journal of psychopharmacology (Oxford, England), 35(4), 362–374. https://doi.org/10.1177/0269881120959604

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Microdosing psychedelics: Subjective benefits and challenges, substance testing behavior, and the relevance of intention

February 6, 2022 / Microdosing, Papers / Leave a Comment / By / , , , , ,

Abstract

Background: Microdosing psychedelics is the practice of taking small, sub-hallucinogenic doses of lysergic acid diethylamide or psilocybin-containing mushrooms. Despite its surging popularity, little is known about the specific intentions to start microdosing and the effects of this practice.

Aims: First, we aimed to replicate previous findings regarding the subjective benefits and challenges reported for microdosing. Second, we assessed whether people who microdose test their substances before consumption. Third, we examined whether having an approach-intention to microdosing was predictive of more reported benefits.

Methods: The Global Drug Survey runs the world’s largest online drug survey. Participants who reported last year use of lysergic acid diethylamide or psilocybin in the Global Drug Survey 2019 were offered the opportunity to answer a sub-section on microdosing.

Results: Data from 6753 people who reported microdosing at least once in the last 12 months were used for analyses. Our results suggest a partial replication of previously reported benefits and challenges among the present sample often reporting enhanced mood, creativity, focus and sociability. Counter to our prediction, the most common challenge participants associated with microdosing was ‘None’. As predicted, most participants reported not testing their substances. Counter to our hypothesis, approach-intention – microdosing to approach a desired goal – predicted less rather than more benefits. We discuss alternate frameworks that may better capture the reasons people microdose.

Conclusion: Our results suggest the perceived benefits associated with microdosing greatly outweigh the challenges. Microdosing may have utility for a variety of uses while having minimal side effects. Double-blind, placebo-controlled experiments are required to substantiate these reports.

Petranker, R., Anderson, T., Maier, L. J., Barratt, M. J., Ferris, J. A., & Winstock, A. R. (2022). Microdosing psychedelics: Subjective benefits and challenges, substance testing behavior, and the relevance of intention. Journal of psychopharmacology (Oxford, England), 36(1), 85–96. https://doi.org/10.1177/0269881120953994

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Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans

February 6, 2022 / Mushrooms / Psilocybin, Neuroscience, Papers / Leave a Comment / By / , , , , , , ,

Abstract

Background: Psilocybin is a serotonergic psychedelic with psychoactive effects mediated by serotonin 2A receptor (5-HT2AR) activation. It produces an acute psychedelic altered state of consciousness with a unique phenomenology that can be temporally characterized by three intensity phases: onset of psychoactive effect, a peak plateau and return to normal consciousness.

Aims: We evaluated whether pre-drug brain 5-HT2AR binding predicted the three phases of psilocybin subjective drug intensity (SDI) and retrospective self-report of mystical type experiences in healthy individuals.

Method: Sixteen participants completed a pre-drug [11C]Cimbi-36 positron emission tomography scan to assess 5-HT2AR binding. On a separate day, participants completed a single psilocybin session (oral dose range 0.2-0.3 mg/kg), during which SDI was assessed every 20 min. The Mystical Experience Questionnaire (MEQ) was completed at the end of the session. The three SDI phases were modelled using segmented linear regressions. We evaluated the associations between neocortex 5-HT2AR binding and SDI/MEQ outcomes using linear regression models.

Results: Neocortex 5-HT2AR was statistically significantly negatively associated with peak plateau duration and positively with time to return to normal waking consciousness. It was also statistically significantly negatively associated with MEQ total score.

Conclusion: This is the first study to investigate how individual brain 5-HT2AR binding predicts subjective effects of a single dose of psilocybin. Our findings reinforce the role of cerebral 5-HT2AR in shaping the temporal and mystical features of the psychedelic experience. Future studies should examine whether individual brain levels of 5-HT2AR have an impact on therapeutic outcomes in clinical studies.

Stenbæk, D. S., Madsen, M. K., Ozenne, B., Kristiansen, S., Burmester, D., Erritzoe, D., Knudsen, G. M., & Fisher, P. M. (2021). Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans. Journal of psychopharmacology (Oxford, England), 35(4), 459–468. https://doi.org/10.1177/0269881120959609

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Polypharmacology or “Pharmacological Promiscuity” In Psychedelic Research: What Are We Missing?

November 26, 2021 / Ayahuasca, Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry / Leave a Comment / By / , , ,

Abstract

Research with psychedelic drugs has mainly focused on isolated compounds. However, this approach is challenged by the “polypharmacology” paradigm. In this Viewpoint, we suggest that we may be missing something if we do not use the whole product in the case of ayahuasca or Psilocybe mushrooms. After describing how research on psychedelic drugs can be effectively combined with the polypharmacology paradigm, ethical issues are also briefly discussed.

Ona, G. S., Dos Santos, R. G., Hallak, J., & Bouso, J. C. (2020). Polypharmacology or “Pharmacological Promiscuity” In Psychedelic Research: What Are We Missing?. ACS chemical neuroscience, 11(20), 3191–3193. https://doi.org/10.1021/acschemneuro.0c00614

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Potential safety, benefits, and influence of the placebo effect in microdosing psychedelic drugs: A systematic review

November 26, 2021 / LSD, Microdosing, Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / By / ,

Abstract

Microdosing psychedelic drugs-that is, taking sub-behavioral doses of lysergic acid diethylamide (LSD) or psilocybin-is a growing practice in Western societies. Taken mainly for creative or mood-enhancing purposes, thousands of users are increasingly being exposed to (micro)doses of psychedelic drugs. In this systematic review, we searched the available evidence from human studies, focusing our results in terms of three main axes: efficacy, safety, and the influence of the placebo effect in microdosing practices. While the available evidence has some strengths (e.g. large sample sizes, robust methodologies) there are also remarkable limitations (e.g. gender bias, heterogeneity of dosing schedules and drugs used). Highly contradictory results have been found, showing both the benefits and detriments of microdosing in terms of mood, creative processes, and energy, among other regards. This review provides a general overview of the methods and approaches used, which could be useful for improving future studies.

Ona, G., & Bouso, J. C. (2020). Potential safety, benefits, and influence of the placebo effect in microdosing psychedelic drugs: A systematic review. Neuroscience and biobehavioral reviews, 119, 194–203. https://doi.org/10.1016/j.neubiorev.2020.09.035

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The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain

November 26, 2021 / Neuroscience, Papers, Salvia / Salvinorin A / Leave a Comment / By / , , , , , , ,

Abstract

Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum. Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first time to explore the effects of inhaled SA on strength, variability, and entropy of functional connectivity (static, dynamic, and entropic functional connectivity, respectively, or sFC, dFC, and eFC). SA tended to decrease within-network sFC but increase between-network sFC, with the most prominent effect being attenuation of the default mode network (DMN) during the first half of a 20-min scan (i.e., during peak effects). SA reduced brainwide dFC but increased brainwide eFC, though only the former effect survived multiple comparison corrections. Finally, using connectome-based classification, most models trained on dFC network interactions could accurately classify the first half of SA scans. In contrast, few models trained on within- or between-network sFC and eFC performed above chance. Notably, models trained on within-DMN sFC and eFC performed better than models trained on other network interactions. This pattern of SA effects on human brain function is strikingly similar to that of other hallucinogens, necessitating studies of direct comparisons.

Doss, M. K., May, D. G., Johnson, M. W., Clifton, J. M., Hedrick, S. L., Prisinzano, T. E., Griffiths, R. R., & Barrett, F. S. (2020). The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain. Scientific reports, 10(1), 16392. https://doi.org/10.1038/s41598-020-73216-8

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The emerging role of psilocybin and MDMA in the treatment of mental illness

November 26, 2021 / MDMA, Mushrooms / Psilocybin, Papers, Psychology / Leave a Comment / By / , , , , , , , , , , , , ,

Abstract

Introduction: Mental illness has a chronic course of illness with a number of clinical manifestations. Affected individuals experience significant functional, emotional, cognitive, and/or behavioral impairments. The growing prevalence of mental illness has been associated with significant social and economic costs. Indeed, the economic burden of mental illness is estimated to exceed $1.8 trillion USD over the next 30 years. A significant number of individuals affected by mental illness fail to respond to first-line treatment options. Therefore, there remains an unmet need for rapidly attenuating therapeutic options for mental health disorders with minimal social and economic burden.

Areas covered: The paucity of novel treatment options warrants a renewed investigation of psychedelic-based psychotherapy. Herein, the authors will evaluate the therapeutic potential of traditional psychedelics, psilocybin, and MDMA, in the treatment of mental illness with a narrative review of available literature.

Expert opinion: Psychedelics, such as psilocybin and MDMA, offer an alternative avenue of therapy for many mental health disorders. Available evidence indicates that psychedelics may offer a single-dose, rapid effect model that have robust effects with treatment-resistant mental disorders and a unique advantage as a possible monotherapy for mental illness. Novel clinical trials that evaluate the safety, tolerability, and efficacy in clinically representative populations are warranted.

Gill, H., Gill, B., Chen-Li, D., El-Halabi, S., Rodrigues, N. B., Cha, D. S., Lipsitz, O., Lee, Y., Rosenblat, J. D., Majeed, A., Mansur, R. B., Nasri, F., Ho, R., & McIntyre, R. S. (2020). The emerging role of psilocybin and MDMA in the treatment of mental illness. Expert review of neurotherapeutics, 20(12), 1263–1273. https://doi.org/10.1080/14737175.2020.1826931

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