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In our literature study we came across the following studies of note. Browse the meta, review, commentary articles for an overview. Check out the individual studies for specific experiments and observations.
Psilocybin and MDMA for the treatment of trauma-related psychopathology
2021 | Bird, C. I. V., Modlin, N. L., Rucker, J.
This review (2021) investigates the therapeutic rationale behind the use of psilocybin and MDMA in the treatment of PTSD and depression. Both compounds and the possible treatment modalities (the combination with talk therapy) are discussed. A combination of first MDMA-assisted therapy, followed by psilocybin-assisted therapy is also presented.
Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder: A systematic review and meta-analysis
2020 | Bahji, A., Forsyth, A., Groll, D., Hawken, E. R.
This systematic review and meta-analysis (2020) found 5 trials (n=106) that found large reductions in PTSD symptoms after MDMA-assisted psychotherapy. The studies showed large improvements, but were only moderate in quality.
Registered clinical studies investigating psychedelic drugs for psychiatric disorders
2021 | Gill, H., Lipsitz, O., Lui, L. M. W., McIntyre, R. S., Rosenblat, J. D., Siegel, A. N., Teopiz, K. M.
This review (2021) summarizes the study characteristics of all ongoing registered clinical trials investigating psychedelic drugs for psychiatric disorders and identifies that their majority focuses on investigating MDMA and psilocybin for treating depression or PTSD, while only 30% of their results are published.
Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine
2018 | Andrews, A. M., Dunlap, L. E., Olsen, D. E.
This review (2018) examines the synthesis of MDMA as well as its pharmacology, metabolism, adverse effects, and potential use in medicine.
Psychedelics and reconsolidation of traumatic and appetitive maladaptive memories: focus on cannabinoids and ketamine
2017 | Chiamulera, C., Fattore, L., Fumagalli, G., Piva, A., Zanda, M. T.
This study (2017) reviews the clinical and preclinical data concerning cannabinoids and ketamine as they relate to possible reconsolidation processes of maladaptive memories.
Making a medicine out of MDMA
2015 | Nutt, D. J., Sessa, B.
This commentary (2015) examines how inappropriate, non-evidence-based, legislative restrictions of MDMA have failed to mitigate the harms of recreational ecstasy use but have effectively halted clinical research for therapeutic use. They urge the regulatory authorities to re-schedule MDMA and promote research for therapeutic uses within psychiatry.
Psychedelic-Assisted Psychotherapy: A Paradigm Shift in Psychiatric Research and Development
2018 | Schenberg, E. E.
This theoretical commentary (2018) highlights the paradigm-shifting implications of psychedelic-assisted psychotherapy in light of a triple crisis within contemporary psychiatry, concerning the lack of reliable therapeutics, a heterogeneity of diagnoses, and a reductionist understanding of mental disorders that explains away the psyche by reducing it to underlying brain processes, whereas the new paradigm aims to incorporate these dimensions in a holistic understanding of human beings and the social factors of their culture and environment.
Ketamine For Post-Traumatic Stress Disorders And Its Possible Therapeutic Mechanism
2021 | Asim, M., Hao, B., Wang, B., Wang, X.
This review (2021) investigates the possibility of ketamine being used to treat Post-Traumatic Stress Disorder (PTSD).
MDMA and PTSD treatment: “PTSD: from novel pathophysiology to innovative therapeutics”
2016 | Sessa, B.
This article (2016) reviews the history and current state of MDMA as a potential treatment for PTSD.
Ketamine as treatment for post-traumatic stress disorder: a review
2019 | Hatten, C., Liriano, F., Schwartz, T. M.
This review (2019) examines the lack of efficient treatment options for patients suffering from PTSD and explores the viability of ketamine for patients who do not respond to conventional treatment. It is thought that ketamine might reverse some of the damage caused by chronic stress, by means of upregulating BDNF and antagonizing NMDA. The review also notes that the deterrent of dissociative side-effects may be less common than previously reported and point to early evidence which supports that ketamine may yield a near-complete resolution of traumatic symptoms, albeit only over a short-term of 1-2 weeks.
Potential Psychiatric Uses for MDMA
2016 | Mithoefer, M. C., Yazar-Klosinski, B.
This commentary (2016) highlights the psychiatric framework of MDMA-assisted psychotherapy, whereby the substance catalyzes the therapeutic treatment window, thus enabling processes such as psychoeducation, distress management, cognitive restructuring, emotion regulation, and interpersonal regulation to continue in the subsequent integration sessions. It also emphasizes the set and setting biological mechanisms underlying MDMA's therapeutic action, and provides recommendations to boost the credibility of researching these outcomes and mechanisms for the purposes of gaining FDA-approval.
Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy
2016 | Amoroso, T., Workman, M.
This meta-analysis (2016) examines the effect sizes of interventions aimed at treating posttraumatic stress disorder with MDMA-assisted psychotherapy and comparing it to the efficacy of prolonged exposure therapy. Results indicated that both therapy options exhibit large effect sizes in outcome measures related to both clinician-observed PTSD symptoms and self-reported symptoms. While both of these therapies are efficient means to treat PTSD, exposure therapy induces a considerably higher state of arousal within a much shorter therapy session, and MDMA-assisted therapy offers a more patient-centered approach that leaves more time to explore different aspects of trauma, in contrast.
The potential use of N-methyl-3,4-methylenedioxyamphetamine (MDMA) assisted psychotherapy in the treatment of eating disorders comorbid with PTSD
2020 | Brewerton, T. D., Lafrance, A., Mithoefer, M. C.
This hypothesis paper (2020) makes the case for treating eating disorders (EDs) comorbid with posttraumatic stress disorder (PTSD).
Can MDMA Play a Role in the Treatment of Substance Abuse?
2013 | Jerome, L., Schuster, S., Yazar-Klosinski, B.
This review (2013) evaluates the potential of MDMA to treat substance abuse and dependence. The authors provide evidence that MDMA may have potential as a treatment for these morbidities, but also highlight that classical psychedelics have a better risk:benefit ratio.
Breakthrough for trauma treatment: safety and efficacy of MDMA-assisted psychotherapy compared to paroxetine and sertraline
2019 | Doblin, R., Emerson, A., Feduccia, A. A., Jerome, L., Mithoefer, M. C., Yazar-Klosinski, B.
This review (2019) details the potential superiority of MDMA-assisted psychotherapy as a treatment for PTSD compared to the conventional treatment options paroxetine and sertraline.
Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin
2020 | Forbes, D., Gibson, K., Varker, T., Watson, L.
This review (9 studies) investigated the therapeutic potential of MDMA, ketamine, LSD, and psilocybin as a therapeutic agent for PTSD. However, only studies concerning ketamine and MDMA were found and included in the review, and it is suggested that MDMA-assisted psychotherapy holds moderate promise.
A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses
2020 | Chi, T., Gold, J. A.
This review (2020) presents modern human studies into psychedelic drugs, including psilocybin, LSD, MDMA, and ayahuasca in the treatment of various psychiatric illnesses, including treatment-resistant depression, post-traumatic stress disorder, end-of-life anxiety, and substance use disorders. Safety and efficacy data are also presented, from both human and animal studies.
MDMA-assisted psychotherapy for PTSD: are memory reconsolidation and fear extinction underlying mechanisms?
2018 | Feduccia, A. A., Mithoefer, M. C.
This review (2018) suggests how memory reconsolidation and fear extinction may play a significant role in the potent therapeutic effects of MDMA in the treatment of PTSD.
The Emerging Role of Psilocybin and MDMA in the Treatment of Mental Illness
2020 | Cha, D. S., Chen-Li, D., El-Halabi, S., Gill, B., Gill, H., Ho, R., Lee, Y., Lipsitz, O., Majeed, A., Mansur, R. B., McIntyre, R. S., Nasri, F., Rodrigues, N. B., Rosenblat, J. D.
This narrative review (2020) evaluates the therapeutic potential of psilocybin and MDMA for the treatment of major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and anxiety. The review explains the need for effective mental health treatments and highlights the lack of dose-response studies in placebo-controlled settings with a real-world clinical population.
Reviewing the potential of psychedelics for the treatment of PTSD
2020 | Bostoen, T., Breeksema, J. J., Krediet, E., Passie, T., van Schagen, A., Vermetten, E.
This review (2020) discusses the potential of MDMA, ketamine, classical psychedelics, and cannabinoids as potential treatments for PTSD.
A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis
2020 | Duffy, J. M. N., Illingworth, B. J. G., Jelen, L. A., Lambarth, A. T., Lewis, D. J., Rucker, J.
This systematic review and meta-analysis (2020) of MDMA-assisted therapy for PTSD, found that over four RCT's (n=67), PTSD scores (CAPS-IV) were lower in the 75mg and 125mg groups (not 100mg), and depression scores (BDI) only in the 75mg group.
The cost-effectiveness of MDMA-assisted psychotherapy for the treatment of chronic, treatment-resistant PTSD
2020 | Doblin, R., Kahn, J. G., Marseille, E., Yazar-Klosinski, B.
This study (2020) on the costs (and benefits) of MDMA-assisted therapy for PTSD finds it to be more cost-effective than other treatments. It's based on the data from six double-blind, placebo-controlled phase II trials (n=105) done by MAPS.
A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy
2020 | Bathje, G. J., Chwyl, C., Davis, A. K., Lancelotta, R., Luoma, J. B.
This meta-analysis of nine placebo-controlled trials (n=211) showed a very large effect size (g=1.21) of treatment on four mental health conditions (PTSD, end-of-life anxiety, depression, social anxiety among autistic adults).
Increases in Psychological Flexibility Mediate Relationship Between Acute Psychedelic Effects and Decreases in Racial Trauma Symptoms Among People of Color
2021| Davis, A. K., Garcia-Romeu, A., Sepeda, N. D., Williams, M. T., Xin, Y.
This survey study (n=313) found that psychological flexibility mediated the relationship between acute psychedelic effects (acute insight & challenging experiences) and decreases in racial trauma among BIPOC.
Neuroimaging correlates and predictors of response to repeated-dose intravenous ketamine in PTSD: preliminary evidence
2021| Brallier, J., Charney, D. S., Collins, A. B., Collins, K. A., Corniquel, M. A., Costi, S., Feder, A., Glasgow, A. M., Horn, S. R., Jha, M. K., Kautz, M., Murrough, J. W., Rutter, S. B., Shin, L. M.
This preregistered randomized double-blind active placebo-controlled between-subjects study (n=21) measured brain activity while viewing facial stimuli in response to repeated and acute administration of ketamine (35mg/70kg) and midazolam (3.15mg/70kg), among patients with severe PTSD. Both midazolam and ketamine improved symptoms, which were most reliably predicted by the reduced excitation of the amygdala and ventromedial prefrontal cortex (vmPFC) during the processing of socio-emotional threat signals, but only ketamine-related improvement was associated with increased top-down inhibition of the amygdala by the vmPFC.
Ketamine accelerates fear extinction via mTORC1 signaling
2017| Duman, R. S., Ghosal, S., Girgenti, M. J., LoPresto, D., Taylor, J. R.
This rat study explores the mechanisms underlying the actions of ketamine in fear conditioning, extinction, and renewal. The study found that ketamine produces long-lasting positive changes in fear extinction, through mTORC1/protein synthesis in the medial prefrontal cortex. This offers more evidence for why and how ketamine may be a potential approach for the treatment of PTSD.
MDMA does not alter responses to the Trier Social Stress Test in humans
2017| Bershad, A. K., de Wit, H., Miller, M. A.
This randomized, double-blind, placebo-controlled, between-subjects study (n=39) assessed the effects of MDMA (35mg and 70mg/70kg) or placebo on physiological and subjective responses to a public speaking task under stressful and non-stressful conditions. Contrary to their initial hypothesis of dampening stress reactions, MDMA produced stress-like effects on both physiological (heart rate, blood pressure, cortisol) and subjective (ratings of stress, tension, and insecurity) ratings on both the stress and no-stress sessions.
Using Psychedelics With Therapeutic Intent Is Associated With Lower Shame and Complex Trauma Symptoms in Adults With Histories of Child Maltreatment
2021| Healy, C. J., Lee, K. A.
This survey study (n=166) investigates whether psychedelic use moderates the relationships between child maltreatment, self-concept, social cognition, and posttraumatic stress symptoms. Results indicate that using psychedelic drugs with therapeutic intent is associated with lower levels of complex posttraumatic stress symptoms and internalized shame in individuals with histories of child maltreatment.
MDMA, cannabis, and cocaine produce acute dissociative symptoms
2015| Bosker, W. M., Giesbrecht, T., Kuypers, K. P. C., Merckelbach, H., Ramaekers, J. G., Spronk, D. B., Theunissen, E. L., van Heugten-Van der Kloet, D., van Wel, J. H. P., Verkes, R. J.
This randomized, double-blind, placebo-controlled, four-way, cross-over study (n=37) investigated the acute dissociative effects of MDMA (25, 50, and 100 mg), cannabis (THC 21mg/70kg), and cocaine (300 mg) and compared them to data of schizophrenia patients, Special Forces soldiers, and ketamine users. Results indicate that MDMA, cannabis, and (to a lesser extent) cocaine can produce dissociative symptoms that are similar to dissociative pathology.
MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD: what it is and what it isn’t
2020| Morgan, L.
This review (2020) discusses current research into MDMA-assisted psychotherapy for patients with treatment-resistant PTSD. It proposed that while MDMA-assisted psychotherapy may help people who have experienced PTSD, the potential of MDMA has to be thoroughly investigated to pit MDMA as a ‘treatment for PTSD’.
Mental health of a self-selected sample of psychedelic users and self-medication practices with psychedelics
2018| Kuypers, K. P. C., Mason, N. L.
The observational survey study (n=1,967) investigated the frequency and efficacy of self-medication practices amongst psychedelic users and found that the prevalence of lifetime psychopathologies amongst psychedelic users was higher than in the general population. Although psychedelics were seldom used for self-medication, those who did use psychedelics in this manner reported it to be more effective than the current lines of treatment for mental illness.
In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation
2020| Berquist, M. D., Fantegrossi, W. E., Kristensen, J. L., Leth-Petersen, S.
This animal study (n=41) compared the hyperthermic side effects of MDMA ( and a deuterium-substituted analog d2-MDMA in rats and found that d2-MDMA produced increases in body temperature that were shorter-lasting and of lower magnitude compared to equivalent doses of MDMA.
3,4-Methylenedioxymethamphetamine facilitates fear extinction learning
2015| Andero, R., Howell, L. L., Ressler, K. J., Young, M. B.
This rodent study appraises the psychotherapeutic gains facilitated by MDMA and investigates its effects on fear extinction learning, which is a key process in exposure-based therapies for PTSD. The authors propose that MDMA improves fear memory extinction via a BDNF-dependent mechanism. The study highlighted the potential of MDMA as a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders marked by altered fear learning.
Relational and Growth Outcomes Following Couples Therapy With MDMA for PTSD
2021| Liebman, R. E., Mithoefer, A. T., Mithoefer, M. C., Monson, C. M., Wagner, A. C.
This open-label study (n=12, 6 couples) examines the secondary outcomes (up to 6 months later) of Cognitive Behavioral Conjoint Therapy (CBCT) where one partner was suffering from PTSD. There were improvements for both partners on post-traumatic growth, relational support, social intimacy, empathic concern, and less conflict.
The Impact of Childhood Maltreatment on Intravenous Ketamine Outcomes for Adult Patients with Treatment-Resistant Depression
2019| Lijffijt, M., Mathew, S. J., O'Brien, B., Swann, A. C., Wells, A.
This open-label study (n=115) found that ketamine improved depression (TRD) symptoms and especially for those with childhood trauma. It is hypothesized that the ability of ketamine to block trauma-associated behavioral sensitization is the mechanism through which this happens.
Participant Reports of Mindfulness, Posttraumatic Growth, and Social Connectedness in Psilocybin-Assisted Group Therapy: An Interpretive Phenomenological Analysis
2021| Agin-Liebes, G. I., Anderson, B. T., Ekman, E., Haas, A., Malloy, M., Woolley, J. D.
This interview study (n=9) of gay men with AIDS, who participated in group therapy with psilocybin, found two major thematic change processes. The first was breaking free from 'autopilot' and becoming more mindful and thus allowing for better emotional processing. The second was meaning-making and posttraumatic growth.
High-dose ketamine infusion for the treatment of posttraumatic stress disorder in combat veterans.
2019| Bonnett, C. J., Jain, R., Ross, C., Wolfson, P. E.
This open-label study (n=30) found that ketamine (6 infusions) reduced PTSD symptoms in combat veterans.
Combining Cognitive-Behavioral Conjoint Therapy for PTSD with 3,4-Methylenedioxymethamphetamine (MDMA): A Case Example
2019| Mithoefer, A. T., Mithoefer, M. C., Monson, C. M., Wagner, A. C.
This case study (n=2) describes the treatment methodology of MDMA (112.5mg) -assisted Cognitive-Behavioral Conjoint Therapy administered to a PTSD patient in conjunction with his romantic partner. Through the therapeutic context, set, and setting that entailed multiple days of participant engagement and the empathy-inducing effects of the MDMA, the procedure created strong therapeutic bonds between the couple and the therapists and facilitated the resolution of PTSD symptoms and improvement in relationship satisfaction.
Sleep Quality Improvements After MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder
2021| Feduccia, A. A., Hamilton, S., Jerome, L., Mithoefer, M. C., Ponte, L., Vermetten, E., Yazar-Klosinski, B.
This analysis of the Phase 2 MDMA trial data (n=63) found that sleep quality improved significantly more in the group that received MDMA (75-125mg) than the placebo/control (0-40mg) group. The sleep quality kept improving and was significantly better at the 12-month follow-up.
Cross-sectional associations between lifetime use of psychedelic drugs and psychometric measures during the COVID-19 confinement: A transcultural study
2021| Alcázar-Córcoles, M. A., Bouso, J. C., Dos Santos, R. G., Hallak, J. E., Ona, G., Révész, D., Rocha, J. M., Rossi, G. N.
This survey study (n=2,974) investigated the relationship between lifetime psychedelic use, personality traits, and mental health during the COVID-19 confinement, and found that regular use was associated with less psychological distress, less peritraumatic stress, and more social support. Psychedelic drug users also scored higher on the novelty-seeking and self-transcendence scales, but lower on cooperativeness.
An analog of psychedelics restores functional neural circuits disrupted by unpredictable stress
2021| Cameron, L. P., Cao, B., Chen, L., Lu, J., Lukasiewicz, K., Mullen, B., Olson, D. E., Shah-Morales, S., Tjia, M., Weiser, S., Zuo, Y.
This animal study (n=76) tested the rescue effects of a single dose of the ibogaine-analog tabernanthalog (10 mg/kg) administered after mild exposure to unpredictable mild stress in mice and found that it restored deficits in dendritic spine structural dynamics, neuronal activities, and the bottom-up processing of novel contextual information.
Effects of ketamine, dexmedetomidine and propofol anesthesia on emotional memory consolidation in rats: Consequences for the development of post-traumatic stress disorder
2017| Berardi, A., Campolongo, P., Morena, M., Palmery, M., Peloso, A., Schelling, G., Trezza, V., Valeri, D.
This animal study (n=160) investigated the effects of ketamine (125 mg/kg) on the formation of traumatic memories in rats and found that it increased the retention of fearful memories when administered in close proximity to stress exposure.
Ketamine anesthesia enhances fear memory consolidation via noradrenergic activation in the basolateral amygdala
2021| Campolongo, P., Colucci, P., De Castro, V., Mancini, G. F., Peloso, A., Schelling, G.
This animal study (n=206) investigated the effects of ketamine (125 mg/kg) on fearful memory consolidation associated with traumatic events and found that ketamine enhances the formation of these memories only when administered in close proximity to the trauma, partially via sympathetic stimulation which releases noradrenaline.
Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy prolong the therapeutic effects of single ketamine infusion on post-traumatic stress disorder and comorbid depression: a pilot randomized, placebo-controlled, crossover clinical trial
2017| Goldberg, M., Moaddel, R., Parikh, T., Pradhan, B. K., Pumariega, A. J., Sabia, M., Torjman, M. C., Wainer, I. W.
This randomized, placebo-controlled, cross-over clinical pilot study (n=10) investigated the antidepressant efficacy of ketamine (35mg/70kg) infusion combined with Mindfulness Based Extinction and Reconsolidation (TIMBER) psychotherapy for patients with PTSD. Ketamine-assisted TIMBER therapy increased the duration of the sustained antidepressant response, as evidenced by improvement of depressive symptoms after switching from the placebo into ketamine condition.
Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic
2017| Abdallah, C. G., Averill, L. A., Duman, R. S., Harpaz-Rotem, I., Kelmendi, B., Krystal, J. H., Sanacora, G., Southwick, S. M.
This review (2017) examines synaptic deficits associated with chronic stress and persisting symptoms of PTSD and characterizes the rapid efficacy of ketamine via mechanisms that open up a window of increased neuroplasticity and enable cognitive and behavioral therapies to treat patients more effectively.
Relational Processes in Ayahuasca Groups of Palestinians and Israelis
2021| Carhart-Harris, R. L., Doblin, R., Ginsberg, N., Karkabi, N., Luan, L., Ron, Y., Roseman, L., Saca, A.
This qualitative interview study (n=31) examined whether ayahuasca group rituals can promote reconciliation between Arab Palestinians and Jewish Israelis, and identified relational processes that can potentially contribute to peacebuilding. Group members felt connected either through a sense of shared humanity based on universal similarities, through the recognition of their intercultural differences, or through conflict-related revelations associated with collective pain and trauma.
Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)
2017| Dunlop, B. W., Howell, L. L., Jovanovic, T., Khoury, L. M., Norrholm, S. D., Rauch, S. A. M., Reiff, C. M., Rothbaum, B. O., Young, M. B.
This vehicle-controlled animal study (n=360) investigated the role of serotonergic neurotransmission in MDMA's (7.8 mg/kg) ability to extinguish fearful memories in mice and found that the selective inhibition of serotonin release via 5-HTT and the inhibition of neurotransmission via 5-HT2A receptors diminished this effect.
A retrospective study of ketamine administration and the development of acute or post-traumatic stress disorder in 274 war-wounded soldiers
2017| Granier, C., Hoffmann, C., Masson, J. L., Mion, G.
This retrospective cohort study (n=274) investigated whether PTSD prevalence amongst wounded French war veterans was linked to ketamine administration during anesthesia, but found no evidence to support such a relationship.
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study
2021| Amar, S., Amiaz, R., Bogenschutz, M. P., Brown, R., Carlin, S. C., Coker, A., de Boer, A., Doblin, R., Emerson, A., Garas, W., Gelfand, Y., Gorman, I., Hamilton, S., Hapke, E., Harrison, C., Klaire, S. S., Kleiman, S., Lilienstein, A., Marta, C. J., Matthews, R., Mitchell, J., Mithoefer, A. T., Mithoefer, M. C., Nicholas, C. R., Ot’alora G, M., Paleos, C., Parker-Guilbert, K., Poulter, B., Quevedo, S., Shannon, S., Tzarfaty, K., van der Kolk, B., Wallach, Y., Wang, J. B., Wells, G., Woolley, J. D., Worthy, R., Yazar-Klosinski, B.
This double-blind, placebo-controlled study (n=90) finds that MDMA-assisted therapy (8-120mg) is effective (d=.91, large effect size) in the treatment of PTSD. 67% of those in the MDMA-group no longer qualified for PTSD (vs 32% for the therapy-only group). This study is part of the Phase 3 trial to get MDMA approved by the FDA.
Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder
2014| Feder, A., Murrough, J. W., Parides, M. K.
This randomized, double-blind, active placebo-controlled study compared the efficacy of ketamine (35mg/70kg) and midazolam (3.15mg/70kg) for the treatment of patients with depressive symptoms associated with chronic PTSD. They found a rapid reduction in symptom severity following intravenous ketamine infusion.
The correlation between ketamine and posttraumatic stress disorder in burned service members
2008| Black, I. H., Garza, T. H., Gaylord, K. M., Maani, C. V., McGhee, L. L.
This observational study (n=241) investigated the prevalence of PTSD with respect to perioperative low-dose ketamine use in burned soldiers undergoing surgery. Results indicate that PTSD was less prevalent amongst soldiers who were treated with ketamine, despite having larger burns, higher injury severity score, undergoing more operations, and spending more time in the ICU compared to soldiers who did not receive it as a treatment.
Acute cognitive effects of single-dose intravenous ketamine in major depressive and posttraumatic stress disorder
2021| Davis, M. T., DellaGiogia, N., Esterlis, I., Maruff, P., Pietrzak, R. H.
This open-label study (n=58) compared the effects of a single dose of ketamine (35-56.7mg/70kg) on the cognitive effects of those suffering from depression (MDD; n=14) or PTSD (n=15) and healthy control subjects (n=29). The study found acute declines in attention, executive function, and verbal memory. Only the effect on attention was larger in the patient groups. The baseline cognitive function of participants didn't predict clinical outcomes.
Naturalistic Use of Mescaline Is Associated with Self-Reported Psychiatric Improvements and Enduring Positive Life Changes
2021| Agin-Liebes, G. I., Davis, A. K., Lancelotta, R., Ramaekers, J. G., Uthaug, M. V.
This survey study (n=452) found that the use of mescaline led to improvements in scores on clinical conditions for those suffering from clinical conditions (anxiety 80%, depression 86%, PTSD & AUD 76%). Those who scored higher on acute mystical experience (MEQ30), ego dissolution, and psychological insight had larger improvement than those who scored lower.
Ayahuasca: pharmacology, neuroscience and therapeutic potential
2016| Álvarez, E., de la Fuente Revenga, M., Domínguez-Clavé, E., Elices, M., Feilding, A., Friedlander, P., Pascual, J. C., Riba, J., Soler, J.
This review (2016) examines the pharmacology and neuroscience of ayahuasca, and preliminary findings which indicate the psychological mechanisms associated with its therapeutic benefits are similar to those of mindfulness-based therapy. Ayahuasca appears to enhance self-acceptance and decentering, which converges on evidence from neuroimaging studies that show activation in areas associated with emotional processing and memory formation, thereby enabling individuals to review emotional events with increased vividness and a heightened sense of “reality”. This suggests potential to treat trauma-related conditions and other disorders like borderline personality disorder.
3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil
2020| Chaves, B. D. R., da Silveira, D. X., Doblin, R., Jardim, A. V., Jardim, D. V., Mithoefer, M. C., Ot’alora G, M., Ribeiro, S., Schenberg, E. E., Steglich, M., Tófoli, L.F.
This open-label clinical pilot study (n=3) investigated the efficacy of MDMA-assisted psychotherapy (75 mg in the 1st session, 75 or 125 mg in the 2nd and 3rd sessions) for patients suffering from severe post-traumatic stress disorder due to sexual abuse. One showed small but clinically significant improvement, one showed moderate improvement, and one showed strong improvement, with regard to diagnostic symptoms for PTSD.
The Potential Dangers of Using MDMA for Psychotherapy
2014| Parrott, A. C.
This review (2014) examines both the negative and positive aspects of using MDMA for psychotherapy, with specific regard to its neurohormonal profile, the effects of serotonergic depletion, and neurotoxicity of repeated usage. The most critical issues are related to the release of difficult feelings and memories and the lack of control thereof due to heightened environmental sensitivity, as well as the risk that negative mood states predominating the phase of neurochemical recovery amongst certain individuals.
People of color in North America report improvements in racial trauma and mental health symptoms following psychedelic experiences
2020| Davis, A. K., Grigas, P. C., Haeny, A. M., Sepeda, N. D., Sinnott, S., Williams, T. M., Xin, Y.
This survey study (n=313) suggests that psychedelic experiences (MDMA, LSD, psilocybin) could reduce symptoms of racial trauma. The participant, 30 days later, slowed moderate reductions in traumatic stress, depression, anxiety, and stress.
Ketamine-Assisted Psychotherapy for PTSD Related to Racial Discrimination
2021| Halstead, M., Krause, R., Reed, S., Williams, M. T.
This case study of ketamine (4x) in combination with psychotherapy (mindfulness-based cognitive therapy, MBCT) describes how it was used to treat PTSD symptoms. The study shows initial success, but also remission at 6-month follow-up.
Posttraumatic Stress Disorder After a Psychedelic Experience, a Case Report
2020| Hassan, A. N., Le Foll, B., Rubin-Kahana, D. S.
This study (2020) presents a case report of a man who developed PTSD after an experience with LSD and DMT.
Posttraumatic Growth After MDMA‐Assisted Psychotherapy for Posttraumatic Stress Disorder
2020| Belser, A. B., Emerson, A., Feduccia, A. A., Gorman, I., Hamilton, S., Hennigan, C., Jerome, L., Shechet, B., Yazar-Klosinski, B.
This study (n=60) pooled participants from three Phase 2 clinical studies using MDMA (75-125 mg) for PTSD and found that posttraumatic growth (PTG) may be a promising new mechanism of action.
Perceived benefits of MDMA-assisted psychotherapy beyond symptom reduction: qualitative follow-up study of a clinical trial for individuals with treatment-resistant PTSD
2019| Barone, W., Beck, J., Mitsunaga-Whitten, M., Perl, P.
This long-term follow-up study (n=24) applied qualitative interviews, an interpretative phenomenological analysis, and quantitative questionnaires to assess the perceived benefits of MDMA-assisted psychotherapy, following a two-year period after the completion of a Phase II clinical trial. Participant depictions of their experience before, during, and in the year after the treatment provide a rich context that demonstrates how MDMA-assisted psychotherapy can impact important areas of functioning as well as the overall quality of life, regardless of changes to PTSD symptoms.
A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder
2021| Bevilacqua, L., Brallier, J., Charney, D. S., Collins, A. B., Collins, K. A., Corniquel, M. A., Costi, S., Feder, A., Glasgow, A. M., Govindarajulu, U., Horn, S. R., Jha, M. K., Kautz, M., Murrough, J. W., Peitrzak, R. H., Rutter, S. B.
This first double-blind (active) placebo-controlled study (n=30) of repeated ketamine (6x, 35mg/70kg) infusions found it to be effective as a treatment for PTSD (67% clinical response), but this response faded (on average) within a month.
3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial
2018| Doblin, R., Emerson, A., Feduccia, A. A., Hamilton, S., Holland, J., Jerome, L., Mithoefer, A. T., Mithoefer, M. C., Wagner, M. T., Wymer, J., Yazar-Klosinski, B.
This Phase II clinical trial (n=26) finds that MDMA-assisted psychotherapy (75-125 mg) led to significant and sustained decreases in PTSD (CAPS-IV) scores as compared to an active placebo (30 mg).
Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study
2012| Doblin, R., Jerome, L., Martin, S. F., Michel, Y., Mithoefer, A. T., Mithoefer, M. C., Wagner, M. T., Yazar-Klosinski, B.
This study presents follow-up data (17-74 months; n=19) on a trial using MDMA-assisted psychotherapy to treat PTSD and found that most participants had maintained their therapeutic benefit over time.
Therapeutic effect of increased openness: investigating mechanism of action in MDMA-assisted psychotherapy
2017| Doblin, R., Jerome, L., MacAulay, R. K., Mithoefer, A. T., Mithoefer, M. C., Wagner, M. T., Yazar-Klosinski, B.
This follow-up study (n=20) finds that Openness (but not Neuroticism) plays a moderating role in the relationship between PTSD reduction following MDMA-assisted psychotherapy treatment.
MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial
2020| Doblin, R., Emerson, A., Feduccia, A. A., Jerome, L., Liebman, R. E., Mithoefer, A. T., Mithoefer, M. C., Monson, C. M., Wagner, A. C., Yazar-Klosinski, B.
This open-label study (n=12, 6 couples) describes the safety, tolerability, and efficacy of MDMA in combination with cognitive-behavioral conjoint therapy (CBCT) where one half of the couple was battling with PTSD.
Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy
2020| Feduccia, A. A., Holland, J., Jerome, L., Mithoefer, M. C.
A pooled analysis of participants (n=50) in Phase II MDMA-trials for PTSD found that recent tapering off SSRIs may reduce treatment response (CAPS-IV score).
MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials
2019| Doblin, R., Emerson, A., Feduccia, A. A., Hamilton, S., Jerome, L., Mithoefer, A. T., Mithoefer, M. C., Wagner, M. T., Walsh, Z., Yazar-Klosinski, B.
This largest double-blind, placebo-controlled study to date (2019) on MDMA-assisted therapy for PTSD finds significant improvements (Cohen's d=0.8) and no significant adverse effects. This study is on the pooled (n=105) data of MAPS' phase II FDA trials.
3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: a randomized phase 2 controlled trial
2018| Doblin, R., Emerson, A., Feduccia, A. A., Giron, S. G., Grigsby, J., Hamilton, S., Jerome, L., Mithoefer, M. C., Ot’alora G, M., Poulter, B., Van Derveer, III, J. W., Yazar-Klosinski, B.
This double-blind, between-subjects study (n=28) on the treatment of Posttraumatic stress disorder (PTSD) compared the effectiveness of two higher (100-125mg) with one lower dose (40mg) of MDMA in combination with psychotherapy. One month after two sessions, the higher doses of MDMA showed the largest reduction on a PTSD Scale. At the 12-month follow-up, PTSD symptoms remained lower than baseline with 75% of the participants not meeting PTSD criteria.
The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study
2010| Doblin, R., Jerome, L., Mithoefer, A. T., Mithoefer, M. C., Wagner, M. T.
This first placebo-controlled study (n=20) showed that 83% of participants in the active treatment group didn't qualify for PTSD anymore (CAPS score). This study was the one that highlighted the promise of MDMA-assisted psychotherapy for PTSD.
Psychedelic Treatment for Trauma-Related Psychological and Cognitive Impairment Among US Special Operations Forces Veterans
2020| Amoroso, T., Averill, L. A., Barsuglia, J. P., Davis, A. K., Sepeda, N. D.
This survey study (n=51) found very large effects on mental health for special forces veterans after ibogaine and 5-MeO-DMT treatment.
Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD: A Longitudinal Pooled Analysis of Six Phase 2 Trials
2020| Doblin, R., Emerson, A., Feduccia, A. A., Hamilton, S., Jerome, L., Mithoefer, M. C., Wang, J. B., Yazar-Klosinski, B.
MDMA-assisted psychotherapy showed a very large effect (d=1.58, 56% no longer met PTSD criteria) which improved at 12-months follow-up (d=0.43, 67%).
A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)- assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD)
2012| Oehen, P., Schnyder, U., Traber, R., Widmer, V.
Three doses of MDMA (125mg) showed the most promise in this pilot study (n=12) of MDMA psychotherapy for PTSD. The CAPS score (PTSD measure) was just shy of significance, self-reported improvement was significant.
This section compares the research with psychedelics to other therapies, medicines, or treatments.
This section highlights the various measures used and their use in research.
Who are the top researches in this area, the ones who have done the groundbreaking research.
What do we not know at this time? Where are the gaps in our knowledge and are we closing it?
The companies that are actively engaged in researching this topic or (planning to) provide therapy focussed on this topic.
This section highlights everything done outside of academia, from popular press to books and non academic research.