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MDMA

A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy

June 12, 2020 / Ayahuasca, DMT, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

After a two-decade hiatus in which research on psychedelics was essentially halted, placebo-controlled clinical trials of psychedelic-assisted therapy for mental health conditions have begun to be published. We identified nine randomized, placebo-controlled clinical trials of psychedelic-assisted therapy published since 1994. Studies examined psilocybin, LSD (lysergic acid diethylamide), ayahuasca (which contains a combination of N,N-dimethyltryptamine and harmala monoamine oxidase inhibitor alkaloids), and MDMA (3,4-methylenedioxymethamphetamine). We compared the standardized mean difference between the experimental and placebo control group at the primary endpoint. Results indicated a significant mean between-groups effect size of 1.21 (Hedges g), which is larger than the typical effect size found in trials of psychopharmacological or psychotherapy interventions. For the three studies that maintained a placebo control through a follow-up assessment, effects were generally maintained at follow-up. Overall, analyses support the efficacy of psychedelic-assisted therapy across four mental health conditions – post-traumatic stress disorder, anxiety/depression associated with a life-threatening illness, unipolar depression, and social anxiety among autistic adults. While study quality was high, we identify several areas for improvement regarding the conduct and reporting of trials. Larger trials with more diverse samples are needed to examine possible moderators and mediators of effects, and to establish whether effects are maintained over time.
Luoma, J. B., Chwyl, C., Bathje, G. J., Davis, A. K., & Lancelotta, R. (2020). A Meta-analysis of Placebo-controlled Trials of Psychedelic-assisted Therapy. Journal of Psychoactive Drugs, 1-11., https://doi.org/10.1080/02791072.2020.1769878
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Mystical Experiences in Retrospective Reports of First Times Using a Psychedelic in Finland

June 8, 2020 / Ayahuasca, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications, Salvia / Salvinorin A / By / , ,

Abstract

Despite their acutely inebriating and sometimes unpleasant effects, some people report positive changes in life satisfaction, well-being, or mental health after taking psychedelic drugs. One explanation may be the ability of psychedelics to trigger mystical-type experiences. We examined the validity, reliability, and factor structure of a novel Finnish translation of the Revised Mystical Experiences Questionnaire (MEQ30) among 288 people retrospectively reporting on their first time using a psychedelic. We found evidence for internal consistency reliability and preliminary evidence for criterion and discriminant validity of the Finnish MEQ30. A four-factor structure with factors for mystical qualities, positive mood, transcendence, and ineffability had the best, fair to reasonable fit to the data. MEQ30 scores and having a full mystical experience were highly associated with describing the experience as mystical, spiritual, or religious, and as personally significant, and somewhat associated with the experience being sad or difficult. Mystical experiences were especially associated with positive changes in relationships with nature and oneself and in creativity. Mystical experiences were more common with larger doses. Increasing research suggests mystical-type experiences to relate to positive changes after taking psychedelics. The Finnish MEQ30 is able to tap into relevant information about this aspect of people’s psychedelic experiences.
Kangaslampi, S., Hausen, A., & Rauteenmaa, T. (2020). Mystical Experiences in Retrospective Reports of First Times Using a Psychedelic in Finland. Journal of Psychoactive Drugs, 1-10. https://doi.org/10.1080/02791072.2020.1767321
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Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials

January 3, 2022 / Anxiety Disorders / PTSD, MDMA, Papers / Leave a Comment / By / , , , , , , ,

Abstract

Rationale: Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negative effects on an individual’s health and interpersonal relationships. Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD.

Objectives: To examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD.

Methods: Participants received two to three active doses of MDMA (75-125 mg) during blinded or open-label psychotherapy sessions with additional non-drug therapy sessions. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM IV (CAPS-IV) at baseline, 1 to 2 months after the last active MDMA session (treatment exit), and at least 12 months post final MDMA session (LTFU). A mixed-effect repeated-measures (MMRM) analysis assessed changes in CAPS-IV total severity scores. The number of participants who met PTSD diagnostic criteria was summarized at each time point. Participants completed a long-term follow-up questionnaire.

Results: There was a significant reduction in CAPS-IV total severity scores from baseline to treatment exit (LS mean (SE) = – 44.8 (2.82), p < .0001), with a Cohen’s d effect size of 1.58 (95% CI = 1.24, 1.91). CAPS-IV scores continued to decrease from treatment exit to LTFU (LS mean (SE) = – 5.2 (2.29), p < .05), with a Cohen’s d effect size of 0.23 (95% CI = 0.04, 0.43). The number of participants who no longer met PTSD criteria increased from treatment exit (56.0%) to LTFU (67.0%). The majority of participants reported benefits, including improved relationships and well-being, and a minority reported harms from study participation.

Conclusions: PTSD symptoms were reduced 1 to 2 months after MDMA-assisted psychotherapy, and symptom improvement continued at least 12 months post-treatment. Phase 3 trials are investigating this novel treatment approach in a larger sample of participants with chronic PTSD.

Jerome, L., Feduccia, A. A., Wang, J. B., Hamilton, S., Yazar-Klosinski, B., Emerson, A., Mithoefer, M. C., & Doblin, R. (2020). Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology, 237(8), 2485–2497. https://doi.org/10.1007/s00213-020-05548-2

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MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD: what it is and what it isn’t

May 12, 2020 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By /

Abstract

Background

PTSD is a chronic condition with high rates of comorbidity, but current treatment options are limited and not always effective. One novel approach is MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD, where MDMA is used as a catalyst to facilitate trauma processing during psychotherapy. The aim was to review all current research into MDMA-assisted psychotherapy for PTSD.

Methods

Articles were identified through PubMed and Science Direct for items published up to 31st March 2019 using terms “treatments for PTSD”, “drug treatments for PTSD”, “MDMA”, “MDMA pathway”, “MDMA-assisted psychotherapy” and “MDMA-assisted psychotherapy for PTSD”. Articles were identified through Google Scholar and subject-specific websites. Articles and relevant references cited in those articles were reviewed.

Results

Small-scale studies have shown reduced psychological trauma, however there has been widespread misunderstanding of the aims and implications of this work, most commonly the notion that MDMA is a ‘treatment for PTSD’, which to date has not been researched. This has harmful consequences, namely dangerous media reporting and impeding research progression in an already controversial field.

Conclusions

MDMA-assisted psychotherapy may help people who have experienced psychological trauma and who have not been able to resolve their problems through existing treatments, however more research is needed. If this is to get appropriate research attention, we must report this accurately and objectively.
Morgan, L. (2020). MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD: what it is and what it isn’t. Annals of General Psychiatry, 19, 1-7., https://doi.org/10.1186/s12991-020-00283-6
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Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD: A Longitudinal Pooled Analysis of Six Phase 2 Trials

May 11, 2020 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Rationale: Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negative effects on an individual’s health and interpersonal relationships. Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD.
Objectives: To examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD.
Methods: Participants received two to three active doses of MDMA (75-125 mg) during blinded or open-label psychotherapy sessions with additional non-drug therapy sessions. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM IV (CAPS-IV) at baseline, 1 to 2 months after the last active MDMA session (treatment exit), and at least 12 months post final MDMA session (LTFU). A mixed-effect repeated-measures (MMRM) analysis assessed changes in CAPS-IV total severity scores. The number of participants who met PTSD diagnostic criteria was summarized at each time point. Participants completed a long-term follow-up questionnaire.
Results: There was a significant reduction in CAPS-IV total severity scores from baseline to treatment exit (LS mean (SE) = – 44.8 (2.82), p < .0001), with a Cohen’s d effect size of 1.58 (95% CI = 1.24, 1.91). CAPS-IV scores continued to decrease from treatment exit to LTFU (LS mean (SE) = – 5.2 (2.29), p < .05), with a Cohen’s d effect size of 0.23 (95% CI = 0.04, 0.43). The number of participants who no longer met PTSD criteria increased from treatment exit (56.0%) to LTFU (67.0%). The majority of participants reported benefits, including improved relationships and well-being, and a minority reported harms from study participation.
Conclusions: PTSD symptoms were reduced 1 to 2 months after MDMA-assisted psychotherapy, and symptom improvement continued at least 12 months post-treatment. Phase 3 trials are investigating this novel treatment approach in a larger sample of participants with chronic PTSD.

Jerome, L., Feduccia, A. A., Wang, J. B., Hamilton, S., Yazar-Klosinski, B., Emerson, A., … & Doblin, R. (2020). Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology., https://doi.org/10.1007/s00213-020-05548-2
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Chronic pain and psychedelics: a review and proposed mechanism of action

May 4, 2020 / Ayahuasca, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , ,

Abstract

The development of chronic pain is a complex mechanism that is still not fully understood. Multiple somatic and visceral afferent pain signals, when experienced over time, cause a strengthening of certain neural circuitry through peripheral and central sensitization, resulting in the physical and emotional perceptual chronic pain experience. The mind-altering qualities of psychedelics have been attributed, through serotonin 2A (5-HT2A) receptor agonism, to ‘reset’ areas of functional connectivity (FC) in the brain that play prominent roles in many central neuropathic states. Psychedelic substances have a generally favorable safety profile, especially when compared with opioid analgesics. Clinical evidence to date for their use for chronic pain is limited; however, several studies and reports over the past 50 years have shown potential analgesic benefit in cancer pain, phantom limb pain and cluster headache. While the mechanisms by which the classic psychedelics may provide analgesia are not clear, several possibilities exist given the similarity between 5-HT2A activation pathways of psychedelics and the nociceptive modulation pathways in humans. Additionally, the alterations in FC seen with psychedelic use suggest a way that these agents could help reverse the changes in neural connections seen in chronic pain states. Given the current state of the opioid epidemic and limited efficacy of non-opioid analgesics, it is time to consider further research on psychedelics as analgesics in order to improve the lives of patients with chronic pain conditions.
Castellanos, J. P., Woolley, C., Bruno, K. A., Zeidan, F., Halberstadt, A., & Furnish, T. (2020). Chronic pain and psychedelics: a review and proposed mechanism of action. Regional Anesthesia & Pain Medicine., http://dx.doi.org/10.1136/rapm-2020-101273
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Psychedelics and Psychedelic-Assisted Psychotherapy

May 1, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

Objective: The authors provide an evidenced-based summary of the literature on the clinical application of psychedelic drugs in psychiatric disorders.
Methods: Searches of PubMed and PsycINFO via Ovid were conducted for articles in English, in peer-reviewed journals, reporting on “psilocybin,” “lysergic acid diethylamide,” “LSD,” “ayahuasca,” “3,4-methylenedioxymethamphetamine,” and “MDMA,” in human subjects, published between 2007 and July 1, 2019. A total of 1,603 articles were identified and screened. Articles that did not contain the terms “clinical trial,” “therapy,” or “imaging” in the title or abstract were filtered out. The 161 remaining articles were reviewed by two or more authors. The authors identified 14 articles reporting on well-designed clinical trials investigating the efficacy of lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and ayahuasca for the treatment of mood and anxiety disorders, trauma and stress-related disorders, and substance-related and addictive disorders as well as in end-of-life care.
Results: The most significant database exists for MDMA and psilocybin, which have been designated by the U.S. Food and Drug Administration (FDA) as “breakthrough therapies” for posttraumatic stress disorder (PTSD) and treatment-resistant depression, respectively. The research on LSD and ayahuasca is observational, but available evidence suggests that these agents may have therapeutic effects in specific psychiatric disorders.
Conclusions: Randomized clinical trials support the efficacy of MDMA in the treatment of PTSD and psilocybin in the treatment of depression and cancer-related anxiety. The research to support the use of LSD and ayahuasca in the treatment of psychiatric disorders is preliminary, although promising. Overall, the database is insufficient for FDA approval of any psychedelic compound for routine clinical use in psychiatric disorders at this time, but continued research on the efficacy of psychedelics for the treatment of psychiatric disorders is warranted.

Keywords: Ayahuasca; Drug-Psychotherapy Combination; Lysergic Acid Diethylamide; MDMA; Psilocybin; Psychedelics.
Reiff, C. M., Richman, E. E., Nemeroff, C. B., Carpenter, L. L., Widge, A. S., Rodriguez, C. I., … & Work Group on Biomarkers and Novel Treatments, a Division of the American Psychiatric Association Council of Research. (2020). Psychedelics and psychedelic-assisted psychotherapy. American Journal of Psychiatry, 177(5), 391-410., https://doi.org/10.1176/appi.ajp.2019.19010035
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Psychedelic Psychiatry’s Brave New World

April 2, 2020 / LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

After a legally mandated, decades-long global arrest of research on psychedelic drugs, investigation of psychedelics in the context of psychiatric disorders is yielding exciting results. Outcomes of neuroscience and clinical research into 5-Hydroxytryptamine 2A (5-HT2A) receptor agonists, such as psilocybin, show promise for addressing a range of serious disorders, including depression and addiction.

Nutt, D., Erritzoe, D., & Carhart-Harris, R. (2020). Psychedelic Psychiatry’s Brave New World. Cell, 181(1), 24-28.
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Experience of Music Used With Psychedelic Therapy: A Rapid Review and Implications.

March 30, 2020 / Ayahuasca, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Bonny Method of Guided Imagery and Music emerged following discontinuation of psychedelic therapy research in the early 1970s, but psychedelic therapy research has since revived. Music remains a vital component. This study examined participants’ experiences of music in psychedelic therapy research. A rapid review of qualitative and quantitative journal articles in four major databases was conducted in February to April, 2019, using the terms hallucinogens, psychedelic, “lysergic acid diethylamide,” psilocybin, ayahuasca, music, and/or “music therapy.” Of 406 articles retrieved, 10 were included (n = 180; 18-69 years old). Participants had varied backgrounds. Music was widely considered integral for meaningful emotional and imagery experiences and self-exploration during psychedelic therapy. Music transformed through its elicitation of anthropomorphic, transportive, synesthetic, and material sensations. Music could convey love, carry listeners to other realms, be something to “hold,” inspire, and elicit a deep sense of embodied transformation. Therapeutic influence was especially evident in music’s dichotomous elicitations: Music could simultaneously anchor and propel. Participant openness to music and provision of participant-centered music were associated with optimal immediate and longer-term outcomes. Many studies reported scarce details about the music used and incidental findings of music experienced. Further understanding of participants’ idiosyncratic and shared responses to music during drug therapy phases will inform optimal development of flexible music protocols which enhance psychedelic therapy. Music therapists could be involved in the psychedelic therapy research renaissance through assisting with research to optimize music-based protocols used. If psychedelics become approved medicines, music therapists may be involved in offering psychedelic therapy as part of therapeutic teams.

O’Callaghan, C., Hubik, D. J., Dwyer, J., Williams, M., & Ross, M. (2020). Experience of Music Used With Psychedelic Therapy: A Rapid Review and Implications. Journal of Music Therapy., https://doi.org/10.1093/jmt/thaa006
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Reviewing the Potential of Psychedelics for the Treatment of PTSD.

March 14, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , ,

Abstract

There are few medications with demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD). Treatment guidelines have unequivocally designated psychotherapy as a first line treatment for PTSD. Yet, even after psychotherapy, PTSD often remains a chronic illness, with high rates of psychiatric and medical comorbidity. Meanwhile, the search and development of drugs with new mechanisms of action has stalled. Therefore, there is an urgent need to explore not just novel compounds, but novel approaches for the treatment of PTSD. A promising new approach involves the use of psychedelic drugs. Within the past few years, two psychedelics have received breakthrough designations for psychiatric indications from the US Food and Drug Administration, and several psychedelics are currently being investigated for the treatment of PTSD. This review discusses four types of compounds: 3,4-methylenedioxymethamphetamine (MDMA), ketamine, classical psychedelics (e.g. psilocybin and LSD) and cannabinoids. We describe the therapeutic rationale, the setting in which they are being administered, and their current state of evidence in the treatment of PTSD. Each compound provides unique qualities for the treatment of PTSD, from their use to rapidly target symptoms, to their use as adjuncts to facilitate psychotherapeutic treatments. Several questions are formulated that outline an agenda for future research.
Krediet, E., Bostoen, T., Breeksema, J., van Schagen, A., Passie, T., & Vermetten, E. (2020). Reviewing the Potential of Psychedelics for the Treatment of PTSD. International Journal of Neuropsychopharmacology., https://doi.org/10.1093/ijnp/pyaa018
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