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Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

August 17, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

Introduction: Interest in the use of psychedelic substances for the treatment of mental disorders is increasing. Processes that may affect therapeutic change are not yet fully understood. Qualitative research methods are increasingly used to examine patient accounts; however, currently, no systematic review exists that synthesizes these findings in relation to the use of psychedelics for the treatment of mental disorders.

Objective: To provide an overview of salient themes in patient experiences of psychedelic treatments for mental disorders, presenting both common and diverging elements in patients’ accounts, and elucidating how these affect the treatment process.

Methods: We systematically searched the PubMed, MEDLINE, PsycINFO, and Embase databases for English-language qualitative literature without time limitations. Inclusion criteria were qualitative research design; peer-reviewed studies; based on verbalized patient utterances; and a level of abstraction or analysis of the results. Thematic synthesis was used to analyze and synthesize results across studies. A critical appraisal of study quality and methodological rigor was conducted using the Critical Appraisal Skills Programme (CASP).

Results: Fifteen research articles, comprising 178 patient experiences, were included. Studies exhibited a broad heterogeneity in terms of substance, mental disorder, treatment context, and qualitative methodology. Substances included psilocybin, lysergic acid diethylamide (LSD), ibogaine, ayahuasca, ketamine and 3,4-methylenedioxymethamphetamine (MDMA). Disorders included anxiety, depression, eating disorders, post-traumatic stress disorder, and substance use disorders. While the included compounds were heterogeneous in pharmacology and treatment contexts, patients reported largely comparable experiences across disorders, which included phenomenological analogous effects, perspectives on the intervention, therapeutic processes and treatment outcomes. Comparable therapeutic processes included insights, altered self-perception, increased connectedness, transcendental experiences, and an expanded emotional spectrum, which patients reported contributed to clinically and personally relevant responses.

Conclusions: This review demonstrates how qualitative research of psychedelic treatments can contribute to distinguishing specific features of specific substances, and carry otherwise undiscovered implications for the treatment of specific psychiatric disorders.

Breeksema, J. J., Niemeijer, A. R., Krediet, E., Vermetten, E., & Schoevers, R. A. (2020). Psychedelic treatments for psychiatric disorders: a systematic review and thematic synthesis of patient experiences in qualitative studies. CNS drugs, 1-22; 10.1007/s40263-020-00748-y

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The impact of 3,4-methylendioxymetamphetamine (MDMA) abstinence on seeking behavior and the expression of the D 2-like and mGlu 5 receptors in the rat brain using saturation binding analyses

January 27, 2022 / MDMA, Neuroscience, Papers, Substance Use Disorder / Leave a Comment / By / , , , , , ,

Abstract

The abundance of research indicates that enriched environment acts as a beneficial factor reducing the risks of relapse in substance use disorder. There is also strong evidence showing the engagement of brain dopaminergic and glutamatergic signaling through the dopamine D2-like and metabotropic glutamate type 5 (mGlu5) receptors, respectively, that has a direct impact on drug reward and drug abstinence. The present study involved 3,4-methylendioxymethamphetamine (MDMA) self-administration with the yoked-triad procedure in rats kept under different housing conditions during abstinence – enriched environment (EE) or isolation cage (IC) conditions – aimed at evaluating changes in brain receptors affecting drug-seeking behavior as well as density and affinity of the D2-like and mGlu5 receptors in several regions of the animal brain. Our results show that exposure to EE conditions strongly reduced active lever presses during cue-induced drug-seeking. At the neurochemical level, we demonstrated marked decreases of D2-like receptor affinity in the dorsal striatum in rats previously self-administering MDMA under EE and increases in density under IC conditions. Moreover, we found the increases in the density and decreases in the affinity of the D2-like receptor in the prefrontal cortex and nucleus accumbens provoked by IC conditions. The mGlu5 receptor density decreased only in the prefrontal cortex after IC and EE abstinence. Moreover, our study has revealed a clear decrease in mGlu5 receptor density in the nucleus accumbens in the group actively administering MDMA only under EE conditions. This study demonstrates that housing conditions have impact on drug-seeking behavior in rats during abstinence from MDMA self-administration. The observed changes in the dopamine D2-like and mGlu5 receptor Bmax and/or Kd values were brain-region specific and related to either pharmacological and/or motivational features of MDMA.

Frankowska, M., Miszkiel, J., Pomierny-Chamiolo, L., Pomierny, B., Celeste Borelli, A., Suder, A., & Filip, M. (2020). The impact of 3,4-methylendioxymetamphetamine (MDMA) abstinence on seeking behavior and the expression of the D2-like and mGlu5 receptors in the rat brain using saturation binding analyses. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 71(4), 10.26402/jpp.2020.4.09. https://doi.org/10.26402/jpp.2020.4.09

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[Psychedelics for existential distress in terminally ill patients]

August 1, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Existential distress in patients with a terminal illness is often associated with (symptoms of) anxiety and depression. Psychotherapeutic interventions seem effective but effects are short-lived. There are no proven effective pharmacological interventions.<br/> AIM: To present an overview of literature on psychedelic treatment of existential distress in patients with terminal illness.<br/> METHOD: Literature research in PubMed/Medline databases, supplemented with cross-references.<br/> RESULTS: 14 clinical studies have been conducted: 6 with classic psychedelics between 1960 and 1980, and 8 with classic psychedelics and ketamine after 2000. Results of early pre-post studies are promising but have serious methodological limitations. Recent clinical research with LSD, psilocybin and ketamine are also promising although limited in terms of research design and generalizability. Overall, studies show a positive effect on existential and spiritual well-being, quality of life, acceptance and (symptoms of) anxiety and depression. Mystical experiences are correlated with positive outcomes. Few adverse effects are reported.<br/> CONCLUSION: Treatment of existential distress using classical psychedelics or ketamine in patients with terminal illness seems auspicious. Larger clinical studies in a more diverse patient population with fewer methodological limitations are needed to draw conclusions about efficacy and generalizability.
Schimmel, N., Breeksema, J. J., Veraart, J. K. E., van den Brink, W., & Schoevers, R. A. (2020). Psychedelics for existential distress in terminally ill patients. Tijdschrift Voor Psychiatrie, 62(8), 659-668., https://europepmc.org/article/med/32816294
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[Psychedelics in the treatment of PTSD]

August 1, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, LSD, MDMA, Papers, Psychology, Publications / By / , , , , ,

Abstract

Posttraumatic stress disorder (PTSD) is often a chronic condition, despite the availability of various evidence-based treatment options. Psychedelics offer new treatment opportunities.<br/> AIM: An overview of the current evidence, therapeutic context, and possible mechanisms of action of different types of psychedelics in the treatment of PTSD.<br/> METHOD: A scoping review of the available literature.<br/> RESULTS: MDMA-assisted psychotherapy has shown to produce lasting reductions in PTSD symptoms in multiple RCTs. Based on a small number of studies, ketamine administration appears to lead to temporary symptom relief. Current studies are investigating whether the use of ketamine in combination with psychotherapy can lead to lasting reductions in PTSD symptoms. Classical psychedelics (such as psilocybin and LSD) induce psychoactive effects (on behavior or experience) that could contribute to the psychotherapeutic treatment of PTSD but have not yet been investigated in controlled studies. Reported positive effects extend beyond PTSD symptoms only.<br/> CONCLUSION: Psychedelics may have potential to serve as a catalyst for the psychotherapeutic treatment of PTSD. Most evidence exists for MDMA-supported psychotherapy; relatively little research is available on ketamine and classical psychedelics. Future research needs to show whether the use of psychedelics can be integrated into available treatment options for PTSD.
Vermetten, E., Krediet, E., Bostoen, T., Breeksema, J. J., Schoevers, R. A., & van den Brink, W. (2020). Psychedelics in the treatment of PTSD. Tijdschrift Voor Psychiatrie, 62(8), 640-649., https://pubmed.ncbi.nlm.nih.gov/32816292/

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3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil

July 3, 2020 / Anxiety Disorders / PTSD, MDMA, Papers, Psychiatry & Medicine, Psychology, Publications / By / , , , , , ,

Abstract

Objective: To conduct Brazil’s first clinical trial employing 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder (PTSD), given its high prevalence resulting from epidemic violence.

Methods: Of 60 volunteers, four matched the inclusion & exclusion criteria. Three patients with PTSD secondary to sexual abuse (diagnosed by the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale for DSMV-4 [CAPS 4]) completed enrollment and treatment, following a standardized Multidisciplinary Association for Psychedelic Studies protocol consisting of 15 weekly therapy sessions: three with orally administered MDMA with concurrent psychotherapy and music, spaced approximately 1 month apart. CAPS-4 scores two months after the final MDMA session were the primary outcome.

Results: No serious adverse events occurred. The most frequent adverse events were somatic pains and anguish. CAPS-4 reductions were always greater than 25 points. The final scores were 61, 27, and 8, down from baseline scores of 90, 78, and 72, respectively. All reductions were greater than 30%, which is indicative of clinically significant improvement. Secondary outcomes included lower Beck Depressive Inventory scores and higher Post-Traumatic Growth Inventory and Global Assessment of Functioning scores.

Conclusions: Considering the current limitations in safe and efficacious treatments for PTSD and recent studies abroad with larger patient samples, MDMA-assisted psychotherapy could become a viable treatment in Brazil.

Jardim, A. V., Jardim, D. V., Chaves, B. R., Steglich, M., Ot’alora G, M., Mithoefer, M. C., … & Doblin, R. (2020). 3, 4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil. Brazilian Journal of Psychiatry, (AHEAD); 10.1590/1516-4446-2020-0980
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The Effects of 3,4-methylenedioxymethamphetamine on Neurogenesis in the Hippocampus of Male Rats

February 6, 2022 / MDMA, Neuroscience, Papers / Leave a Comment / By / , , , , , ,

Abstract

Introduction: The administration of 3,4-methylenedioxymethamphetamine (MDMA) or ecstasy causes memory impairment, whereas neurogenesis improves memory and learning. Hence, this study evaluated the effects of MDMA on neurogenesis in the hippocampus of male rats.

Methods: Adult male Wistar rats received Intraperitoneal (IP) injections of MDMA (10 mg/ kg). We assessed nestin, sex-determining region Y-box 2 (Sox2), and NeuroD expressions according to the immunohistochemistry analyses.

Results: MDMA reduced the expressions of nestin, Sox2, and NeuroD compared with the control groups. The reduction in NeuroD expression was age-related.

Conclusion: MDMA possibly has negative effects on neurogenesis, which specifically results from impaired survival of newborn cells.

Soleimani Asl, S., Ghasemi Moravej, F., Kowsari, G., Farhadi, M. H., Pourhaydar, B., Ghasemi Hamidabadi, H., & Mehdizadeh, M. (2020). The Effects of 3,4-methylenedioxymethamphetamine on Neurogenesis in the Hippocampus of Male Rats. Basic and clinical neuroscience, 11(4), 457–464. https://doi.org/10.32598/bcn.9.10.420

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Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments

June 12, 2020 / Depressive Disorders, Humanities & Art, MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

Introduction: Combinations of psychotherapy with antidepressants are gold-standard psychiatric treatments. They operate through complex and interactional mechanisms, not unlike the reemergent paradigm of psychedelic-assisted psychotherapy, which promising research suggests may also be highly effective in even challenging populations.
Areas covered: We review the therapeutic mechanisms behind both conventional and psychedelic paradigms, including the evolution of this knowledge and the associated explanatory frameworks. We explore how psychedelics have provided insights about psychiatric illnesses and treatments over the past decades. We discuss limitations to early explanatory models while highlighting and comparing the psychological and biological mechanisms underlying many psychiatric treatments.
Methods: A narrative review was conducted based on a search in Medline/Pubmed up to January 1st, 2020, and iterative retrieval of references from recent reviews and clinical trials.
Expert opinion: The contextual model of the common factors of psychotherapy provides a powerful perspective on psychotherapy, antidepressants, and psychedelics, as well as 3,4-methylenedioxymethamphetamine (MDMA) and ketamine. It aligns well with key tenets of psychedelic-assisted psychotherapy. Conventional antidepressants and especially psychedelics may improve the efficacy of psychotherapy via neurochemical changes and increased environmental sensitivity. Combined treatments hold significant promise for advancing the knowledge and treatment of many forms of psychopathology.

Keywords: Psychedelics; antidepressants; ketamine; ketamine-assisted psychotherapy; lsd; mdma; mdma-assisted psychotherapy; psilocybin; psychedelic-assisted psychotherapy; psychiatry; psychotherapy.
Greenway, K. T., Garel, N., Jerome, L., & Feduccia, A. A. (2020). Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments. Expert Review of Clinical Pharmacology, 1-15., https://doi.org/10.1080/17512433.2020.1772054
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Spotlight commentary: REBUS and the anarchic brain

June 12, 2020 / Ayahuasca, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Salvia / Salvinorin A / By / ,

Abstract

In ‘REBUS and the Anarchic Brain: Towards a Unified Model of the Brain Action of Psychedelics’, Carhart-Harris and Friston offer an important analysis of what the predictive processing framework has to offer our understanding of psychedelic experiences, providing an invaluable ground for psychedelic psychiatry. While applauding this, we encourage paying greater attention to contextual factors shaping extreme experiences and their sequalae, and suggest that the authors’ comparisons with certain non-psychedelic altered states may overlook more informative parallels that can be drawn elsewhere. Addressing both points will prove fruitful, ultimately, in identifying the mechanisms of action of greatest interest in psychedelic experiences.
Carhart-Harris, R. L., & Friston, K. J. (2019). REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics. Pharmacological reviews, 71(3), 316-344., https://doi.org/10.1093/nc/niaa007
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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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