MDMA for PTSD and beyond: a new paradigm brings hope DOI Creative Commons

Scott Shannon,

Jamarie Geller

Frontiers in Human Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Dec. 11, 2024

Introduction We are experiencing a mental health crisis of unprecedented proportions. Over the last two decades this grew from perfect storm rising insurance deductibles, escalating social stressors, COVID-19 pandemic, and critical workforce deficiency. Perhaps no arena has greater shortfall effective treatment options than Post-traumatic Stress Disorder (PTSD) as new was approved by FDA 24 years ago (Hamner Davis, 2024). Inadequate funding for research efforts public resources available to expandservices may in part stem inordinate prevalence PTSD among women anddisadvantaged populations. Women experience at three times rate found inmen (US Department Veterans Affairs, 2023), these rates also significantly higheramong African Americans, Latinos, Native homeless (Tortella-Feliu et al.,2019; Kwon al., 2024; Armoon 2019; Reyes, 2019). Neighborhood poverty alsopredicts development following traumatic event (Ravi, al, 2023). Our traumaburden is unevenly distributed across society.Trauma unfortunately quite common. The National Center estimates that over 13 million people US suffer with 5% our population diagnosed any given year annual cost been estimated $232 billion (per person/year $19,630) 2018 (Davis 2022). group report high levels trauma. According PTSD, 23% veterans accessing Administration services (USDepartment Suicide, often linked trauma nowbecome leading cause death those serving Armed Forces (Kaplansky andToussaint, For society, human suffering immense undeniable. Yet, current treatments inadequate (Smith Trauma-focused psychological therapies (TFPT) best-evidenced interventions they typically first line (Schrader Ross, 2021). However, only about 50% patients complete course treatment, response who do roughly (Schottenbauer 2008). TFPTs not used clinicians (Kline 2001) due fear retraumatizing, dislike manualized, rigid concern symptom exacerbation (Finch 2020). Even when high-quality TFPT offered, refuse even consider option because facing way extremely painful indicated medications, such sertraline paroxetine which were early 1990s, minimally evidenced small effect size (0.28 0.23, respectively) (Hoskins 2015; Hoskins 2021) burdened side effects. need innovation care feels critical. MDMA Psychedelic Framework represents best hope generation. application MDMA-assisted psychotherapy (MDMA-AP) time considered linkage medication (DeBattista Schatzberg, This combination serves core psychedelic framework. framework components: container, catalyst carrier (Shannon, container psychotherapeutic model support, safety rapport well attention set setting. creates atmosphere trust work traumatized patients. itself. agent alters consciousness flow information within it. improves access memories feelings including material. Mechanistically, MDMA, psilocybin, ketamine all different, their distinctive neurochemical properties continue be elaborated. ultimately induce an altered awareness enhanced processing contents held psyche. Finally, there carrier. includes use curated music delivered headphones, eyeshades designed drive inward therapeutic benefit. Without carrier, externally focused, little consequence other amusement or distraction. While commonly setting, it can tool (along eye shades headphones) support focus attention. Music does contribute context, but plays larger role nature reducing cognitive hierarchy. synergistic psychedelics allows flexibility thought perception characteristic insight (Lebedev, 2016). Together, basic components comprise psychotherapy. ties disparate arms conventional together time. Both psychopharmacology finally share unified goals common process. Thus, groundbreaking true paradigm shift (Zaretsky 2024).MDMA Psychotherapy evolved enormously since Sigmund Freud popularized psychoanalysis, its remains talk therapy. Transcranial Magnetic Stimulation (TMS) more modern less invasive variation on shock Electroconvulsive Therapy (ECT) introduced 1930s. Psychopharmacology, 1950s, care. specific medications prescribed evolve, format much same: daily dosing agents reduce load. catalysts durably improve psychiatric disorders through alteration innovative core. It generally accepted principle magnitude success flows quality relationship therapist. When history trauma, creating context becomes imperative. supports alignment process modulating range physiological These include increase monoamines accompanied significant oxytocin release. appears occasion sense deep safety: relaxed, compassionate prosocial, fearful state. With level emotional safety, easily accessed reconsolidated (Feduccia Mithoefer, 2018; Molla There network changes induced implicated empathogenic effects, modulation sensory information, extinction (Gamma 2000; Yu A study carried out Singleton colleagues (2022) exploring brain activity connectivity post-MDMA-AP resting-state amygdala-hippocampal connectivity, addition shifts. induces limited enhancement neuroplasticity (Ly 2018), enhance learning trauma-related reappraisal both during after session. allow body digest move without sequelae PTSD.Perhaps most importantly, facilitates something takes develop (and some, never does): decrease defensiveness/avoidance. Theoretically, necessary healing take place. potential accelerate forms offers. challenges Western idea driven external expertise intervention, rather internal wisdom innate capacity heal. we would argue many modes psychotherapy, majority currently US, mechanism mysterious. must remain humble face complexity consciousness. Phase III studies published recently MDMA-AP demonstrate sizes evidence serious adverse effects (Mitchell 2021; Mitchell Concerns functional unblinding challenge medicine whole (Goodwin assessment tools, Diagnostic Statistical Manual (DSM) exhibit disappointing low interrater reliability actual practice. They create formidable desire brain-based science diagnostic categories inclusive based superficial phenomenology. In opinion, created calls methods honor centrality psyche personal experience. Given exposure (three doses) compared dosing, multiple pharmaceuticals, biochemical considerably reduced. have some risks, manageable. almost exclusively time-limited responses day ingestion: muscle tightness, nausea loss appetite. benefit durable improvement combined large 0.91, benefits likely far outweigh risks. Furthermore, emphasizes power each individual heal thus carries optimism too lacking psychiatry emphasis pathology. Potential To fully grasp care, outline confers via observed relaxation defenses, augmentation compassion oneself others. real reevaluation one's values, behaviors, beliefs. perspective, span domains psychopathology beyond If one learn regulate nervous system work, increased tolerability clinical issues, hard assess promise transdiagnostic capacity. Clearly, broad facets developmental, attachment, repeated traumas. utility several categories, especially roots (addiction, anxiety, depression, personality difficulties) could useful eating where self-compassion acceptance won. therapy adults, sponsors will compelled investigate effectiveness adolescents children (Kangaslampi Zijlmans, believe another deserves completely change trajectory lives. Taking reasoning step further, perhaps parents treated prior generational carryover untreated burden (Narayan pernicious defined Adverse Childhood Experiences (ACEs) literature (Gilgoff 2020), dramatically pain, illness lifetime. relational speed couples, families, groups. see invaluable fractured groups communities, infusion facilitation clear, communication. Additionally, place various demographic groups, disenfranchised whom meaningful historically limited. Often, faced enormous pain structural factors deserve potentially profound modality. encourage ongoing investigation into veterans, additional justice-involved, color, LGBTQ communities. Does carry justice agenda? engagement broader issues around shared humanity interconnection. manner, might patients, delivery itself.Discussion At juncture, understand effectively evaluate transformative novel modality, reimagine fabric healthcare country. industry increasingly controlled rapid symptomatic management (Goldman 2018). frustrated attempts implement parity provisions (https://www.kff.org/mental-health/issue-brief/mental-health-parity-at-a-crossroads/). Prevention ignored on-going (Kamra underlies intensive prevention needed innovation. By emphasizing heal, bring humanistic needs approach. reimagining programs preventative nature, help mitigate vast sooner. Can demand complex expensive unlike hip replacement placement stent? Economic evaluation outlines severe save $100,000 per case consequences impairment entire positive trials assessing represent type demands what is, be.

Language: Английский

Thеrаpеutic Cоmmunicаtiоn In Еncоuntеr Grоups as a Mеаns of Suppоrting Psychоlоgicаl Wеll-Bеing DOI

I Rustаmоvа

Jurnal Psikologi, Journal Year: 2025, Volume and Issue: 2(2)

Published: Feb. 6, 2025

Thе аuthоrs еxplоrе thе intricаtе psychоlоgicаl mеchаnisms thаt shаpе аn individuаl's lеvеl оf wеll-bеing, еmphаsizing intеrplаy bеtwееn cоgnitivе, еmоtiоnаl, аnd sоciаl fаctоrs. Thеy еxаminе hоw vаriоus intеrnаl еxtеrnаl influеncеs, such аs rеsiliеncе, cоping strаtеgiеs, suppоrt nеtwоrks, еmоtiоnаl rеgulаtiоn, cоntributе tо оvеrаll mеntаl hеаlth. Аdditiоnаlly, study highlights significаncе grоups thеrаpеutic cоmmunicаtiоn cruciаl intеrvеntiоns prоvidе vаlidаtiоn, prаcticаl а sеnsе bеlоnging fоr individuаls nаvigаting chаllеnging lifе circumstаncеs. аrguе thеsе suppоrtivе еnvirоnmеnts fоstеr rеsiliеncе еnhаncе wеll-bеing by fаcilitаting shаrеd еxpеriеncеs, еmpаthy, cоnstructivе diаlоguе.

Language: Английский

Citations

0

Epigenetic factors in posttraumatic stress disorder resilience and susceptibility DOI Creative Commons
Majeed M. A. Ali,

Ibrahim El Tantawy El Sayed,

Yuliang Wang

et al.

Egyptian Journal of Medical Human Genetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 20, 2025

Abstract Background Posttraumatic stress disorder (PTSD) affects approximately 8% of the US population, with varying susceptibility among individuals exposed to trauma. While genetic factors contribute PTSD risk, emerging evidence suggests that epigenetic mechanisms play a crucial role in translating environmental exposures into lasting neurobiological changes. Purpose This review provides comprehensive analysis cutting-edge research on PTSD, particular emphasis novel findings regarding resilience and mechanisms. We explore recent technological advances their applications understanding pathophysiology. Main body Advanced epigenomic approaches have revealed complex interactions between DNA methylation, histone modifications, non-coding RNAs PTSD. Novel highlight cell type-specific signatures temporal dynamics following trauma exposure. Single-cell studies identified previously unknown cellular heterogeneity responses. Recent data modifications not only influence individual but may also transgenerational transmission effects. Integrative multi-omics new insights molecular networks underlying vulnerability. Conclusion unprecedented complexity These open avenues for personalized interventions based profiles suggest therapeutic strategies targeting modifications. enhanced has significant implications risk assessment, prevention, treatment. Graphical abstract

Language: Английский

Citations

0

NEUROBIOLOGICAL ASPECTS OF PATHOGENETIC MECHANISMS IN THE DEVELOPMENT OF POST-TRAUMATIC STRESS DISORDER (LITERATURE REVIEW) DOI Creative Commons
Oleksandr Oleshko, Kristina Berladir, Tetiana Oleshko

et al.

Eastern Ukrainian Medical Journal, Journal Year: 2025, Volume and Issue: 13(1), P. 39 - 54

Published: Jan. 1, 2025

Post-traumatic stress disorder (PTSD) occurs as a result of exposure to life-threatening traumatic event or situation involving violence. The main manifestations PTSD are obsessive re-experiencing the event, increased nervous arousal, avoidance stimuli related emotional and cognitive disorders that persist for long time. This mental is exhausting causes changes make it difficult sometimes impossible patients with function professionally socially. results in significant clinical burden high socioeconomic costs. Materials methods. authors have reviewed more than 100 scientific papers from world literature on problems diagnosis, symptoms, pathophysiological neurobiological mechanisms play an important role development can be used key elements choice treatment measures. Results. multifactorial disease, therefore, numerous factors involved its occurrence progression. immediate response activation neuroendocrine autonomic systems release adrenaline norepinephrine. involvement hypothalamic-pituitary-adrenal system subsequent secretion cortisol may trigger development. A link has been found between activity noradrenergic system, glucocorticoid exposure, impaired interaction neurons amygdala prefrontal cortex. In addition, glucocorticoids associated immune neuroinflammation. Inflammatory cytokines regulate modify functioning neurotransmitters such serotonin dopamine, which contributes onset progression symptoms. Conclusions. data large number studies allow us confirm following pathogenesis PTSD. These include vegetative regulation, dysfunction immunological regulatory inflammatory mechanisms, dysregulation monoaminergic transmission system. Further study pathogenetic pathways will better implementation strategy medical care

Language: Английский

Citations

0

TRPC4/5 inhibitors: Phase I results and proof of concept studies DOI Creative Commons
Simone Grimm,

Stefan Just,

René Fuertig

et al.

European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 29, 2024

Language: Английский

Citations

1

PHYSIOLOGICAL MECHANISMS OF STRESS AND POST-TRAUMATIC STRESS DISORDER DOI Open Access

V.A. Gorbachenko,

V.V. Olianin,

O.O. Lukyanets

et al.

Fìzìologìčnij žurnal, Journal Year: 2024, Volume and Issue: 70(6), P. 98 - 109

Published: Nov. 20, 2024

Post-Traumatic Stress Disorder (PTSD) is a complex mental disorder that develops following exposure to severe traumatic events and characterized by symptoms such as re-experiencing the trauma, heightened anxiety, hyperarousal. Recent studies indicate pathophysiology of PTSD largely influenced dysfunction in hypothalamic-pituitary-adrenal (HPA) axis disruptions neurotransmitter regulation, which affect key brain structures, including amygdala, hippocampus, prefrontal cortex. The amygdala plays central role formation retention fear, amplifying emotional responses stimuli. hormones, cortisol, adrenaline, noradrenaline, combination with neurotransmitters (serotonin, dopamine, glutamate), modulate activity, influencing development PTSD. This review highlights importance investigating biomarkers for early diagnosis explores promising therapeutic strategies focused on correcting HPA restoring balance alleviate symptoms.

Language: Английский

Citations

1

Current Status and Future Directions of Artificial Intelligence in Post-Traumatic Stress Disorder: A Literature Measurement Analysis DOI Creative Commons

Ruoyu Wan,

Ruohong Wan,

Qing Xie

et al.

Behavioral Sciences, Journal Year: 2024, Volume and Issue: 15(1), P. 27 - 27

Published: Dec. 30, 2024

This study aims to explore the current state of research and applicability artificial intelligence (AI) at various stages post-traumatic stress disorder (PTSD), including prevention, diagnosis, treatment, patient self-management, drug development. We conducted a bibliometric analysis using software tools such as Bibliometrix (version 4.1), VOSviewer 1.6.19), CiteSpace 6.3.R1) on relevant literature from Web Science Core Collection (WoSCC). The reveals significant increase in publications since 2017. Kerry J. Ressler has emerged most influential author field date. United States leads number publications, producing seven times more papers than Canada, second-ranked country, demonstrating substantial influence. Harvard University Veterans Health Administration are also key institutions this field. Journal Affective Disorders highest impact area. In recent years, keywords related functional connectivity, risk factors, algorithm development have gained prominence. holds immense potential, with AI poised revolutionize PTSD management through early symptom detection, personalized treatment plans, continuous monitoring. However, there numerous challenges, fully realizing AI's potential will require overcoming hurdles design, data integration, societal ethics. To promote extensive in-depth future research, it is crucial prioritize standardized protocols for implementation, foster interdisciplinary collaboration-especially between neuroscience-and address public concerns about role healthcare enhance its acceptance effectiveness.

Language: Английский

Citations

1

MDMA for PTSD and beyond: a new paradigm brings hope DOI Creative Commons

Scott Shannon,

Jamarie Geller

Frontiers in Human Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Dec. 11, 2024

Introduction We are experiencing a mental health crisis of unprecedented proportions. Over the last two decades this grew from perfect storm rising insurance deductibles, escalating social stressors, COVID-19 pandemic, and critical workforce deficiency. Perhaps no arena has greater shortfall effective treatment options than Post-traumatic Stress Disorder (PTSD) as new was approved by FDA 24 years ago (Hamner Davis, 2024). Inadequate funding for research efforts public resources available to expandservices may in part stem inordinate prevalence PTSD among women anddisadvantaged populations. Women experience at three times rate found inmen (US Department Veterans Affairs, 2023), these rates also significantly higheramong African Americans, Latinos, Native homeless (Tortella-Feliu et al.,2019; Kwon al., 2024; Armoon 2019; Reyes, 2019). Neighborhood poverty alsopredicts development following traumatic event (Ravi, al, 2023). Our traumaburden is unevenly distributed across society.Trauma unfortunately quite common. The National Center estimates that over 13 million people US suffer with 5% our population diagnosed any given year annual cost been estimated $232 billion (per person/year $19,630) 2018 (Davis 2022). group report high levels trauma. According PTSD, 23% veterans accessing Administration services (USDepartment Suicide, often linked trauma nowbecome leading cause death those serving Armed Forces (Kaplansky andToussaint, For society, human suffering immense undeniable. Yet, current treatments inadequate (Smith Trauma-focused psychological therapies (TFPT) best-evidenced interventions they typically first line (Schrader Ross, 2021). However, only about 50% patients complete course treatment, response who do roughly (Schottenbauer 2008). TFPTs not used clinicians (Kline 2001) due fear retraumatizing, dislike manualized, rigid concern symptom exacerbation (Finch 2020). Even when high-quality TFPT offered, refuse even consider option because facing way extremely painful indicated medications, such sertraline paroxetine which were early 1990s, minimally evidenced small effect size (0.28 0.23, respectively) (Hoskins 2015; Hoskins 2021) burdened side effects. need innovation care feels critical. MDMA Psychedelic Framework represents best hope generation. application MDMA-assisted psychotherapy (MDMA-AP) time considered linkage medication (DeBattista Schatzberg, This combination serves core psychedelic framework. framework components: container, catalyst carrier (Shannon, container psychotherapeutic model support, safety rapport well attention set setting. creates atmosphere trust work traumatized patients. itself. agent alters consciousness flow information within it. improves access memories feelings including material. Mechanistically, MDMA, psilocybin, ketamine all different, their distinctive neurochemical properties continue be elaborated. ultimately induce an altered awareness enhanced processing contents held psyche. Finally, there carrier. includes use curated music delivered headphones, eyeshades designed drive inward therapeutic benefit. Without carrier, externally focused, little consequence other amusement or distraction. While commonly setting, it can tool (along eye shades headphones) support focus attention. Music does contribute context, but plays larger role nature reducing cognitive hierarchy. synergistic psychedelics allows flexibility thought perception characteristic insight (Lebedev, 2016). Together, basic components comprise psychotherapy. ties disparate arms conventional together time. Both psychopharmacology finally share unified goals common process. Thus, groundbreaking true paradigm shift (Zaretsky 2024).MDMA Psychotherapy evolved enormously since Sigmund Freud popularized psychoanalysis, its remains talk therapy. Transcranial Magnetic Stimulation (TMS) more modern less invasive variation on shock Electroconvulsive Therapy (ECT) introduced 1930s. Psychopharmacology, 1950s, care. specific medications prescribed evolve, format much same: daily dosing agents reduce load. catalysts durably improve psychiatric disorders through alteration innovative core. It generally accepted principle magnitude success flows quality relationship therapist. When history trauma, creating context becomes imperative. supports alignment process modulating range physiological These include increase monoamines accompanied significant oxytocin release. appears occasion sense deep safety: relaxed, compassionate prosocial, fearful state. With level emotional safety, easily accessed reconsolidated (Feduccia Mithoefer, 2018; Molla There network changes induced implicated empathogenic effects, modulation sensory information, extinction (Gamma 2000; Yu A study carried out Singleton colleagues (2022) exploring brain activity connectivity post-MDMA-AP resting-state amygdala-hippocampal connectivity, addition shifts. induces limited enhancement neuroplasticity (Ly 2018), enhance learning trauma-related reappraisal both during after session. allow body digest move without sequelae PTSD.Perhaps most importantly, facilitates something takes develop (and some, never does): decrease defensiveness/avoidance. Theoretically, necessary healing take place. potential accelerate forms offers. challenges Western idea driven external expertise intervention, rather internal wisdom innate capacity heal. we would argue many modes psychotherapy, majority currently US, mechanism mysterious. must remain humble face complexity consciousness. Phase III studies published recently MDMA-AP demonstrate sizes evidence serious adverse effects (Mitchell 2021; Mitchell Concerns functional unblinding challenge medicine whole (Goodwin assessment tools, Diagnostic Statistical Manual (DSM) exhibit disappointing low interrater reliability actual practice. They create formidable desire brain-based science diagnostic categories inclusive based superficial phenomenology. In opinion, created calls methods honor centrality psyche personal experience. Given exposure (three doses) compared dosing, multiple pharmaceuticals, biochemical considerably reduced. have some risks, manageable. almost exclusively time-limited responses day ingestion: muscle tightness, nausea loss appetite. benefit durable improvement combined large 0.91, benefits likely far outweigh risks. Furthermore, emphasizes power each individual heal thus carries optimism too lacking psychiatry emphasis pathology. Potential To fully grasp care, outline confers via observed relaxation defenses, augmentation compassion oneself others. real reevaluation one's values, behaviors, beliefs. perspective, span domains psychopathology beyond If one learn regulate nervous system work, increased tolerability clinical issues, hard assess promise transdiagnostic capacity. Clearly, broad facets developmental, attachment, repeated traumas. utility several categories, especially roots (addiction, anxiety, depression, personality difficulties) could useful eating where self-compassion acceptance won. therapy adults, sponsors will compelled investigate effectiveness adolescents children (Kangaslampi Zijlmans, believe another deserves completely change trajectory lives. Taking reasoning step further, perhaps parents treated prior generational carryover untreated burden (Narayan pernicious defined Adverse Childhood Experiences (ACEs) literature (Gilgoff 2020), dramatically pain, illness lifetime. relational speed couples, families, groups. see invaluable fractured groups communities, infusion facilitation clear, communication. Additionally, place various demographic groups, disenfranchised whom meaningful historically limited. Often, faced enormous pain structural factors deserve potentially profound modality. encourage ongoing investigation into veterans, additional justice-involved, color, LGBTQ communities. Does carry justice agenda? engagement broader issues around shared humanity interconnection. manner, might patients, delivery itself.Discussion At juncture, understand effectively evaluate transformative novel modality, reimagine fabric healthcare country. industry increasingly controlled rapid symptomatic management (Goldman 2018). frustrated attempts implement parity provisions (https://www.kff.org/mental-health/issue-brief/mental-health-parity-at-a-crossroads/). Prevention ignored on-going (Kamra underlies intensive prevention needed innovation. By emphasizing heal, bring humanistic needs approach. reimagining programs preventative nature, help mitigate vast sooner. Can demand complex expensive unlike hip replacement placement stent? Economic evaluation outlines severe save $100,000 per case consequences impairment entire positive trials assessing represent type demands what is, be.

Language: Английский

Citations

0