Psychedelic Research Papers

This pre-print re-analysis of an RCT of MDMA-assisted therapy for PTSD finds that study participants (n=90) had significant improvements in the measures of self-experience (e.g. alexithymia - the inability to identify & describe emotions experienced by oneself). The change in scores of self-experience correlate with recovery from PTSD.

This theory-building article (2022) proposes a nuanced mechanism through which MDMA alleviates the symptoms of PTSD. This mechanism relates to the increase of brain-derived neurotrophic factor (BDNF) in fear memory learning pathways which act together with MDMA's pro-social effects to explain the therapeutic effects of MDMA.

This follow-up analysis (n=9), of fMRI data from veterans and first responders who underwent MDMA-assisted therapy (3x 100-125mg) for PTSD, finds a correlation between reductions in PTSD and 1) increased amygdala-hippocampal connectivity, and 2) reduced amygdala-precuneus connectivity during memory recall.

This case study (n=1) describes how a teenager self-treated their psychosis (accompanied by complex PTSD and suicidal ideations) through high-dose LSD and low-dose DMT sessions. The hypothesis argues that psychedelics were able to break down the defensive system and allow for the integration of traumatic memories.

This review (2022) assessed the literature on the basic and clinical neuroscience of the interactions between the class of antidepressants known as SSRIs and MDMA. SSRIs could dampen the therapeutic effects of MDMA-assisted therapy for PTSD. Further research is needed to elucidate the biological mechanisms underlying these interactions.

This double-blind placebo-controlled study (n=30) found that MDMA (125mg), administrated to healthy subjects, helped reduce fear conditioning in a lab test (versus the placebo). The results were not dependent on the level of oxytocin (which MDMA increased fourfold).

This paper (2022) revies the historical perspective of psychedelic research and practices, as well as the intersection of historical trauma adverse childhood experience, PTSD, and substance use disorder (SUDs) through the lens of New Mexic, a state with a high population of Indigenous and Hispanic peoples as well as high rates of trauma, PTSD, and SUDs. The paper discusses the importance of community-based participatory approaches that are more inclusive and respectful of Indigenous and other minority communities.

This study (2022) analysed data from two Phase II and one Phase III trials from MAPS where MDMA-assisted therapy (MDMA-AT) was used to treat PTSD in order to compare the efficacy and safety of MDMA-AT between Black, Indigenous, and People of Color (BIPOC) and non-Hispanic White participants. No significant ethnoracial difference in CAPS-5 scores was observed while BIPOC participants trended toward greater reductions following MDMA-AT.

This paper (2022) reviews the neurocognitive effects of subanesthetic doses of intravenous ketamine in pharmacological studies among healthy subjects and patients with PTSD or depression. No significant impairment in cognitive function was found in patients with depression and possible in those with PTSD. In contrast, immediate cognitive dysfunction was found in healthy subjects.

This study (2022) examines the group therapy model used in MDMA and LSD therapy in private practice in Switzerland. The majority of patients suffered from PTSD with psychedelic therapy addressing symptoms like regulation of emotions and impulses, negative self-perception, alterations in relationships with others, as well as meaning, recall, and processing of traumatic memories. MDMA was most often used in the first phase to enhance motivation to change while LSD was introduced to intensify and deepen the therapeutic process.

This open-label study (n=15) assessed the effectiveness of six ketamine infusions (35mg/70kg) over a 12-day period on neurocognitive function in veterans with comorbid PTSD and major depressive disorder (MDD). Significant improvement was observed in working memory following completion of the infusion series while greater improvements in PTSD and MDD symptoms were associated with lower working memory, slower processing speed and faster set-shifting at baseline.

This trial (n=90) used the Eating Attitudes Test (EAT-26) to assess the impact MDMA-assisted therapy has on symptoms of eating disorders (ED) in participants with PTSD. There was a significant reduction in total EAT-26 scores in the total group of PTSD participants following MDMA-AT versus placebo (p = .03). Overall, MDMA-AT significantly reduced ED symptoms compared to therapy with placebo among participants with severe PTSD.

This study (2022) uses a decision-analytic model to assess the cost and health benefits of expanded access to MDMA-assisted therapy (MDMA-AT) in the phase III clinical trials from MAPS. Expanding access to MDMA-AT to 25-75% of eligible patients was projected to avert 43,618-106,932 deaths and gain 3.3-8.2 million quality-adjusted life-years (QALYs).

This study (2022) builds on previous research assessing the cost-effectiveness of MDMA-assisted therapy (MDMA-AT) for the treatment of PTSD by assessing the data from a recent phase III trial. MDMA-AT as conducted in the phase III trial costs $11,537 per patient. Compared to the standard of care for 1,000 patients, MDMA-AT generates discounted net health care savings of $132.9 million over 30 years. Ultimately, MDMA-AT for severe or chronic PTSD is cost-saving while delivering substantial clinical benefit.

This paper (2022) makes the case for using psychedelics to treat fear-related disorders such as phobias and PTSD. The authors propose that combing the current gold standard for treating these disorders, extinction-based exposure therapy (ET), with psychedelics could enhance therapeutic outcomes. MDMA and ketamine are proposed as being the most effective therapeutic and their potential mechanisms of action are discussed.

This double-blind placebo-controlled trial (n=34) assessed the effects of MDMA (100mg) following a fear acquisition session, an extinction training session and retention in healthy subjects. There was no difference between extinction training and retention between groups. However, significantly more participants in the MDMA group retained extinction learning compared to the placebo group (p = 0.007).

This trial (n=90) assessed patterns of alcohol and substance use in patients receiving MDMA-assisted therapy. MDMA was associated with a significant reduction in Alcohol Use Disorder Identification Test (AUDIT) scores when compared to placebo. Changes in Drug Use Disorder Identification Test (DUDIT) scores did not significantly differ between groups.

This case study (2022), documented improvements in PTSD symptoms and carried out an interpretative phenomenological analysis (IPA) of the effects and mechanisms of a participant of colour from an open-label trial of MDMA-assisted therapy (AT) for PTSD to provide a culturally-informed lens of symptoms recovery. Recommendations for attuning to culturally relevant material during MDMA-AT were provided.

This study retrospectively analyzed clinical outcomes in 15 veterans with comorbid treatment-resistant depression (TRD) and PTSD who initially received intranasal ketamine treatment before sitting to treatment with IV racemic ketamine. Both treatments led to significant reductions in measures of TRD and PTSD however, treatment with IV racemic ketamine led to greater reductions, suggesting that off-label use of IV racemic ketamine may be useful for those who do not respond adequately to FDA-approved intranasal ketamine.

This double-blind RCT (n=158) assessed 8 repeated doses of intravenous ketamine administered twice weekly at a low dose (0.2 mg/kg; n = 53), standard dose (0.5 mg/kg; n = 51) ketamine or placebo (n=54) in veterans and service members with PTSD. It was found that the standard dose of ketamine reduced MADRS scores significantly more than placebo. However, the trial failed to find a significant dose-related effect of ketamine on PTSD symptoms measured using the CAPS-5.

This meta-analysis (2021) assessed the literature regarding the possibilities of using ketamine to treat anxiety disorders. Six RCTs investigating various disorders were included. Ketamine was associated with treatment response for social anxiety disorder but not for PTSD. Doses of >0.5 mg/kg were associated with a greater reduction in scores of anxiety and these anxiolytic effects could be sustained.

This is the first open-label study (2018) to assess the effects of repeated ketamine infusions in the treatment of comorbid PTSD and treatment-resistant depression (TRD) (n=15). Participants received six IV ketamine infusions (0.5 mg/kg) on a Monday-Wednesday-Friday schedule over a 12-day period. Ketamine significantly reduced measures of symptoms change for both disorders (MADRS & PTSD Checklist for DSM-V) and the remission rate for PTSD and TRD were 80% and 93.3%, respectively.

This survey study (n=51) examined the correlation between psychedelic treatment and changes in alcohol misuse among trauma-exposed US Special Operations Forces Veterans (SOFV). Participants underwent treatment with either ibogaine or 5-MeO-DMT at a clinic in Mexico. Treatment led to reductions in alcohol misuse, PTSD symptoms as well as increasing psychological flexibility.

This systematic review (2021) entails a meta-analysis of the current literature on MDMA-assisted therapy for the treatment of PTSD. It was found that MDMA significantly reduced CAPS scores and is generally safe and well tolerated although side effects such as headache and nausea are commonly reported.

This survey study (n=121) explored the co-occurrence of PTSD in patients with a substance use disorder (SUD). It was found that SUD patients with PTSD were more likely to use MDMA than those without PTSD and MDMA use was associated with avoidance symptoms. The authors conclude that MDMA use might reflect an attempt to self-medicate to deal with avoidance symptoms however, it may also be the case that MDMA use led to more severe avoidance symptoms.

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.

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.

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.

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’.

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.