Psychedelic Research Papers

This retrospective analysis (n=100) of the effectiveness of ketamine (35mg/70kg) for borderline personality disorder (BPD) in those with treatment-resistant depression (TRD) finds that intravenous ketamine significantly reduces symptoms of depression, borderline personality, suicidality, and anxiety in patients with comorbid BPD and TRD. Both BPD-positive and BPD-negative groups showed significant improvements in the primary outcome measures, with no significant difference between groups.

This review (2022) makes the cases for using MDMA-assisted therapy (MDMA-AT) in the treatment of borderline personality disorder (BPD). The authors draw parallels between using MDMA-AT to treat disorders similar to BPD, such as PTSD, and provide considerations for designing future clinical trials.

This observational study (n=45) suggests that ayahuasca may have a beneficial effect on psychological functioning by improving mindfulness-related capacities. The authors suggest that ayahuasca-assisted therapy could play a role in treating those with borderline personality disorder (BPD) traits.

This randomized controlled trial (n=22) is the first to study ketamine (35mg/70kg) in Borderline (BPD) in a placebo-controlled study. The study didn't report statistically significant differences between the ketamine and midazolam (active placebo) groups, though it did show a positive trend.

This case study (n=1) examines the therapeutic use of ayahuasca in a woman in her late thirties suffering from complex trauma, bipolar disorder, borderline personality disorder, and suicidality. Participation in multiple ayahuasca ceremonies led to significant alleviation of distress, resolution of suicidality, and recognition of her bipolar disorder diagnosis, though core trauma remained partially unresolved. A subsequent follow-up showed continued reduction in dissociative symptoms and noted positive effects of ayahuasca on other instances of psychosis and bipolar disorder. The study contributes to a better understanding of ayahuasca's potential in treating bipolar disorder and severe traumatization.

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.

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=20) found that dosages of psilocybin (10, 25mg) in a supportive setting, for those with treatment-resistant depression (TRD), changed their personality. At 3-month follow-up, Neuroticism was decreased, Extraversion and Openness were increased. The changes were similar (but more pronounced) to changes after conventional antidepressant treatment.

This placebo-controlled, double-blind study, phase 3 study (n=226) compared esketamine (84mg, nasal, 2xp/w for 4w) with a placebo spray and found esketamine to be effective in lowering depression scores (MADRS) for those suffering from depression (MDD) and suicidal ideation (SI). Scores on a measure of SI was, however, not significantly different between the two groups.

This open-label feasibility study (n=17) showed that psilocybin-assisted group therapy (21-25mg/70kg) was safe and effective for the treatment of demoralization in older long-term AIDS survivors.

This review article (2018) looks at the pre- and post-prohibition clinical studies on psychedelics and offers strategic advice on the legal and regulatory hurdles.

This preprint (2022) reviews the use of neuroimaging techniques in the development of psychedelic therapy using existing data and suggests that the modern development of psychedelic therapy has benefitted greatly from these techniques. It is suggested that current knowledge gaps in the field could be addressed using combined Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) methods, plus other adjunct techniques.

This meta-analysis (n=423) of studies before prohibition (1949-73) of treating unipolar mood disorders (depression) showed that, besides the many flaws of the studies, the results were positive (79% of participants showed improvements, few side-effects).

This (2021) review presents the neurobiological therapeutic mechanisms by which psychedelics work, with a focus on outcomes on 1) neuroplasticity, 2) immune system, and 3) effects on neurotransmitter (-modulator) systems.

This analysis of a double-blind, parallel-arm, randomized placebo-controlled trial (n=29) investigates the impact of ayahuasca on suicidality (SI) in individuals with treatment-resistant depression (TRD). It found that ayahuasca may show potential as a fast-acting and innovative intervention for SI but didn't find significant results (only a trend with a large effect size). This is the first study to investigate ayahuasca for SI.

This review article (2020) argues that mindfulness meditation (MM) and psilocybin may work through similar mechanisms and may be complementary.

This review (2015) discusses data from controlled laboratory studies that highlight MDMA altering social feelings, information processing, and behavior in humans, and social behavior in rodents. The findings are consistent with earlier studies that show that laboratory administration of MDMA strongly alters social processing in humans and increases social approach in humans as well as animals and that neurobiologically complex prosocial effects contribute towards its recreational use.

This review (1998) looks at the history of LSD as a possible treatment for alcoholism (AUD). It highlights the research that had been done and how psychedelics were subsequently relabelled as drugs of abuse.

This pilot RCT study (n=27) investigated the potential of a single ketamine infusion (35mg/70kg), followed by brief exposure therapy, to enhance the extinction of trauma memories in individuals diagnosed with PTSD. Participants were randomly assigned to receive either ketamine or midazolam after retrieval of the traumatic memory, and underwent trauma-focused psychotherapy 24 hours later for four days. While PTSD symptoms improved equally in both groups, post-treatment ketamine recipients showed lower amygdala and hippocampus reactivation to trauma memories than midazolam recipients, suggesting that ketamine may enhance the post-retrieval extinction of trauma memories.

This paper (2020) reviews the safety and efficacy of psilocybin- and MDMA-assisted therapies and argues that it can be rational for some patients to try compassionate psychedelic therapy, notwithstanding the uncertainty of outcomes, as the expected value of psychotherapy can outweigh the expected value of routine care, palliative care, or no care at all. They also address the epistemic risk carried by the notion that psychedelics are philosophically deceptive given that the subjective effects may often feel more real than normal consciousness, but the authors argue that it is not known how classical psychedelics influence one’s beliefs or whether they make one metaphysically irrational, and assert that metaphysics should be ignored in medicine as much as possible. While acknowledging that there are suboptimal uses of psychedelics, the authors see no ethical barriers for their compassionate use in palliative care.

This analysis of an RCT (n=59) investigates the impact of psilocybin-assisted therapy (PAT) and escitalopram on personality traits in patients with moderate-to-severe major depressive disorder over a 6-week trial period. Significant decreases in neuroticism, introversion, disagreeableness, and impulsivity, and increases in absorption, conscientiousness, and openness were observed in the PAT group, while similar changes were seen in the escitalopram group.

This pre-print open-label trial (n=14) organised by ATMA Journey Centers finds psilocybin to be safe, with peak systolic (146) and diastolic (94) blood pressures to be within acceptable ranges. Secondary analyses find a significant decrease in depression (QIDS-SR16) and high mysticism scores (MEQ-30).

This article discusses the therapeutic potential of psychedelic-assisted group psychotherapy (PAGP), which has received less attention than individual psychedelic-assisted psychotherapy models. The authors analyse current literature and use Irvin Yalom's 11 therapeutic factors of group therapy as a framework to discuss the benefits of PAGP, including increased group connectedness and interpersonal learning.

This theory-building article (2023) proposes a model of psychotherapeutic processes associated with ayahuasca consumption. It identifies five key effects: somatic effects, introspection and emotional processing, increased self-connection, increased spiritual connection, and gaining of insights and new perspectives.

This prospective survey study (n=247) finds that those who microdose psychedelics to manage ADHD symptoms experience benefits from it. Participants scored higher on well-being after two and four weeks. The study design, a prospective survey, makes it possible to draw causal inferences (microdosing causing the improvement), but the study had a large drop-out rate (n=46 at 4 weeks).

This trial (n=59) assessed the relationships between therapeutic alliance and rapport, the quality of the acute psychedelic experience and treatment outcomes. Following psilocybin administration at a second session, the therapeutic alliance had a direct impact on final depression scores, not mediated by the acute experience, with a weaker alliance ahead of the second psilocybin session predicting higher absolute depression scores at the endpoint.

This review used the 8 factors of the Controlled Substance Act (CSA) to assess recently published literature involving kratom. It was found that public health would be better served by assuring continued access to kratom and that placing kratom in the CSA would criminalize consumers, impede research and have dangerous public health consequences. Regulation to minimize risks of contaminated, adulterated, and inappropriately marketed products is recommended.

This study analysed data from participants (n=142) in clinical trials who had received LSD and psilocybin to assess the prevalence of recurring drug-like experiences after administration of these substances. 13 participants (9%) reported recurring drug-like experiences (LSD: 7, psilocybin: 2, both: 4) which were considered mild and perceived as neutral to pleasant. No reports met the criteria for hallucinogen-persisting perception disorder (HPPD).

This hypothesis paper (2021) puts forth several solutions to the challenges of psychedelic-assisted therapy. Whitfield builds further on Acceptance and Commitment Therapy (ACT) and Contextual Behavioural Science (CBS). The various constructs of 'Self' or self-models and ways of integrating new perspectives on this concept are discussed.

This review (2022) investigates the neural mechanisms, 5HT2A receptor agonism at the top of the cortical hierarchy, that lead to ego dissolution and long-term neural plasticity. This study uses the hierarchical predictive coding framework to understand the neural mechanisms of consciousness (and psychedelics to test the model).