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 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 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 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 open-label waitlist trial (n=30) assessed the feasibility of psilocybin-assisted psychotherapy (PAP/PAT) in a complex population with treatment-resistant depression (TRD), including major depressive and bipolar II disorders, baseline suicidality, and significant comorbidity. Participants received one, two, or three sessions of PAP with psilocybin (25mg), accompanied by preparation and integration psychotherapy sessions. Immediate treatment showed greater reductions in depression severity (MADRS) compared to the waitlist period, with a large effect size (g = 1.07, p < 0.01). Repeated doses were associated with further reductions in depression severity. Adverse events were transient, and the study demonstrated feasibility, preliminary antidepressant efficacy, safety, and tolerability in this population.

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 prospective observational study (n=807) analysed negative psychological responses to psychedelics, defining it as a clinically meaningful decline in mental health four weeks post-use. They found that 16% of participants experienced negative responses, with a notably higher prevalence (31%) among those with a prior diagnosis of personality disorder. The study implies that individuals with a history of personality disorder might face elevated risks with psychedelic use, emphasizing the need for enhanced psychological support and therapeutic alliance in this population.

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 (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 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 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 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 preprint (n=58) assessed the association between participation in an ayahuasca retreat in a traditional indigenous Amazonian context and how it is related to nature-relatedness. Retreat participation was associated with increases in nature-relatedness, mindfulness and improvements in depression and anxiety.

This paper is the most comprehensive review of psychedelics research up to 2016 by the eminent David E. Nichols.

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 double-blind placebo-controlled microdosing study (n=75) showed that psilocybin microdoses (0.7g dried truffles, 15mg psilocybin, about 1/10th a high dose) didn't alter self-awareness or modulate emotion processing. The confirmatory analysis also found no effects, but an exploratory analysis showed some reduction of depression and stress in only the first block.

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).

This pooled-data study (n=409) looks at the non-pharmacological influences on the psychedelic experience. This includes the current mood state, drug pre-experiences, expectancies, and social and environmental variables. The drug dosage, personality trait absorption, and being emotionally excitable were the top predictors of pleasant and peak/mystical experiences.

This preprint meta-analysis (n=175) of three double-blind placebo-controlled longitudinal experiments investigated the effects of microdosing psilocybin (0.74 - 1.71mg) on creativity and found that it increased the originality of their ideas while generating novel applications for ordinary things (divergent thinking). However, it did not increase the number of novel ideas, or their ability to detect features that are common across multiple things (convergent thinking).

This positron emission tomography (PET) study (n=45) assessed the differential effects of MDMA and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin 2A receptor binding. The authors found evidence that MDMA, but not hallucinogen, use is associated with changes in the cerebral presynaptic serotonergic transmitter system.