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Our vision is that psychedelics can be used worldwide to better the lives of as many as 450 million people who suffer from mental health problems. Our information hopes to make that vision come to life just a little faster.
Here will be a narrative, readable, summary of the research.
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.
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., 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).
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, M. C., Mithoefer, A. T., 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.
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, M. C., Mithoefer, A. T., 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, M. C., Mithoefer, A. T., 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, M. C., Mithoefer, A. T., 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, M. C., Mithoefer, A. T., 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).
The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories
2014| Bloomfield, M., Bolstridge, M., Carhart-Harris, R. L., Curran, H. V., De Meer, I., Erritzoe, D., Feilding, A., Ferguson, B., Kaelen, M., Moran, R. J., Newbould, R. D., Nutt, D. J., Stewart, L., Tanner, M., Wall, M. B., Williams, T. M.
This double-blind, placebo-controlled, within-subjects fMRI study (n=19) investigated the effect of MDMA on the recollection of favorite and worst autobiographical memories (AMs). Positive memories were rated as more positive and negative memories as less negative after MDMA use. Several brain regions were found to be active during AM recollection and related to memory valance.
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, M. C., Mithoefer, A. T., 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, M. C., Mithoefer, A. T., 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.