Psychedelic Research Papers

This systematic review (n=93 cases) found that psychedelic-induced psychosis, primarily caused by LSD and MDMA, lasted an average of 1.8 weeks and responded much better to second-generation antipsychotics (91% response rate) than first-generation antipsychotics (27% response rate), though one-third of patients later developed schizophrenia spectrum disorders.

This pre-print simultaneous PET-MRI study (first of its kind) demonstrates that LSD increases global cerebral blood flow and internal carotid artery flow without affecting artery diameter (opposite to psilocybin's effects), while decreasing global connectivity (particularly in visual networks) and increasing network entropy and spatial complexity, with researchers also observing an anticlockwise hysteresis loop (dynamic lag between an input and an output) between plasma levels and subjective effects that challenges existing hypotheses about psychedelic mechanisms of action.

This mixed-methods analysis (n=973 across multiple cohorts) examines how psychedelic experiences influence “meaning in life” using the Meaning in Life Questionnaire (MLQ) across three contexts: a psilocybin clinical trial for depression, a single-arm healthy volunteer study, and a naturalistic retreat-based study. It finds strong increases in the “presence of meaning” subscale and modest decreases in “search for meaning,” with enhancements linked to improvements in mental health and to the intensity of mystical, ego-dissolution, and emotional breakthrough experiences.

This double-blind, placebo-controlled, cross-over study (n=40) found that two doses of psilocybin (18.2mg/70kg) administered at least 56 days apart (avg. 15 months) produced positive lasting effects in healthy individuals regardless of previous psychedelic experience, sex, or setting, with challenging experiences in controlled environments not causing adverse outcomes, supporting psilocybin's psychological safety for repeated use.

This data analysis of three studies (n=84) validates a three-item Peak Experience Scale (PES) for rapidly assessing 5-MeO-DMT experiences, demonstrating that the scale shows strong internal consistency (Cronbach's α=0.896), correlates highly with established psychedelic experience measures (MEQ-30, EDI, 5D-ASC), and could effectively guide dosing regimens for rapid-acting psychedelics.

This secondary analysis of a randomised, double-blind, placebo-controlled trial (n=31) demonstrated that an ayahuasca-inspired DMT/harmine formulation significantly enhanced mindfulness and compassion (both self-compassion and compassion for others) one day post-treatment, with more pronounced effects in high-sensitivity participants.

This analysis of fMRI data (n=15) examined how LSD (75μg) affects local brain activity and connectivity, finding that LSD decreased both measures in somatosensory/visual areas, with additional activity decreases in Default Mode and Fronto-Parietal networks and connectivity decreases in subcortical regions, with these changes occurring primarily in brain regions with high densities of D2 and 5HT1a receptors, suggesting complex neurobiological mechanisms underlying LSD's effects.

This pre-print reports an observational pilot study (n=12) examining salivary oxytocin ('love/bonding hormone') dynamics during LSD-assisted psychotherapy (100-150μg) for treatment-resistant depression (TRD), finding significant time-dependent variations in both oxytocin levels and subjective drug intensity ratings, suggesting oxytocin may serve as a potential biomarker for psychedelic therapy.

This Phase II trial long-term follow-up (n=30) found that a single dose of psilocybin (25mg) combined with psychological support provided sustained benefits for cancer patients with depression, with 54% showing significant depression reduction (50% remission) and 46% experiencing reduced anxiety at 2 years' follow-up, suggesting a potential paradigm shift in depression treatment for cancer patients compared to traditional daily antidepressants.

This first RCT (n=25) of vaporised DMT (60mg) demonstrated that DMT significantly increased subjective experience measures while causing only transient, safe physiological changes and predominantly mild adverse events. This suggests that inhaled DMT is safe, well-tolerated, and effective at inducing profound altered states of consciousness. Significant correlations were observed between physiological responses and subjective experiences.

This secondary analysis of an RCT comparing psilocybin therapy to escitalopram in MDD patients (n=59) found that psilocybin produced superior improvements in cognitive biases. Psilocybin significantly increased self-reported optimism (d=1.1) and optimistic beliefs about desirable life events (d=1.1), while improving all three domains of dysfunctional attitudes (achievement, dependency, and self-control). Escitalopram showed more modest effects, reducing pessimism about negative events and improving only the achievement domain of dysfunctional attitudes.

This secondary analysis of an open-label feasibility study (n=14) of MDMA-assisted psychotherapy for alcohol use disorder (AUD) found, through Bayesian analysis, a 55-63% probability of achieving a 2-level reduction in WHO drinking risk at 3 months follow-up, with preliminary evidence suggesting reductions in alcohol craving and improvements in sleep and psychosocial functioning compared to baseline.

This economic analysis comparing esketamine nasal spray (plus oral antidepressant) versus quetiapine extended release (plus oral antidepressant) for treatment-resistant depression (TRD) found esketamine achieved higher remission rates at 32 weeks (50% vs 33%) and lower cost-per-remitter in both commercial ($3,102 lower) and Medicaid ($456 lower) settings, with even greater cost savings in scenarios where non-responders received transcranial magnetic stimulation.

This randomised cross-over study (n=7) used precision functional mapping with high-resolution multi-echo fMRI to characterise psilocybin (25mg) versus methylphenidate effects on brain networks, revealing decreased network modularity during psilocybin exposure and reproducible network changes. Participants showed unique brain configurations and reported stronger mystical experiences with psilocybin compared to methylphenidate.

This double-blind controlled trial (n=61) found that high-dose LSD-assisted therapy (100μg + 200μg) reduced depression symptoms more than low-dose LSD (25μg + 25μg) in patients with moderate-to-severe major depressive disorder (MDD), with benefits lasting up to 12 weeks and similar side effects between groups.

This pre-print pre-registered meta-analysis (s=24) comparing psychedelic-assisted therapy (PAT) and open-label traditional antidepressants (tAD) for major depression found no significant difference in effectiveness between the two approaches, with both producing clinically meaningful improvements, challenging previous assumptions about PAT's superiority when accounting for the unblinding effect present in psychedelic trials.

This open-label follow-up study (n=10) of Veterans with severe treatment-resistant depression (TRD) found that a single dose of psilocybin (25mg) significantly reduced depression for up to 12 months, though effects began to wane after 6 months, with 40% maintaining response and 30% maintaining remission at the 12-month follow-up.

This secondary analysis of an RCT (n=15) investigates the acute effects of MDMA (100mg) on anterior pituitary function in healthy adults. It finds that MDMA significantly activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing both ACTH and cortisol levels. No significant effects were observed on other anterior pituitary hormones, though prolactin showed a mild, non-significant increase.

This Delphi consensus study (n=89) involved psychedelic researchers, clinicians, and past trial participants across 17 countries to develop reporting standards for extra-pharmacological variables in psychedelic clinical trials. It resulted in the ReSPCT guidelines, a 30-item framework covering physical environment, session procedures, therapeutic protocol, and subjective experiences, aiming to standardise how “set and setting” are documented in future research.

This randomised, waitlist-controlled exploratory study (n=29) of psychedelic-naïve clergy delivered two supported psilocybin sessions (20mg/70kg followed a month later by 20-30mg/70kg). Six months after screening (and still evident 16 months later) the psilocybin group showed sustained improvements in religious practice, leadership effectiveness and overall well-being, with 96 % ranking at least one session among their five most spiritually significant life events and no serious adverse events despite 46 % describing the experience as among their five most challenging.

This cost-utility analysis, alongside a randomized controlled trial (n=174), compared subcutaneous ketamine (twice-weekly for 4 weeks) with midazolam in treatment-resistant depression. Including midazolam costs, ketamine raised QALYs (0.435 vs 0.352) and was dominant with an 89–91 % chance of costing < $50 000/QALY, but once these comparator costs were excluded ketamine was no longer cost-effective (ICER ≈ $108 500–$251 250/QALY, ≤ 5 % probability).

This case study (n=2) of an open-label pilot study (n=10) explores psilocybin-assisted psychotherapy for women with anorexia nervosa (AN or partial remission). Two participants experienced the therapeutic emergence of previously dissociated traumatic memories, leading to remission of AN symptoms and meaningful weight gain at 3-month follow-up.

This population-level Markov simulation study (n=350,000 initial patients + 11,296 annually) models the economic impacts of intravenous ketamine versus ECT for treatment-resistant depression over 5 years. The model projects annual societal savings of $828.2 million ($95.3M to patients, $743.7M to payers) with expanded ketamine access, though with an added $10.8M annual caregiver burden.

This pharmacovigilance analysis (n=751) examines suspected adverse reactions (SARs) to esketamine nasal spray (Spravato) reported in the EudraVigilance database across European countries. The study identifies increased blood pressure (15.4%) and dissociation (15%) as the most common SARs, with data suggesting a potentially higher risk of suicidality with esketamine compared to fluoxetine and venlafaxine, prompting recommendations for careful monitoring of patients with a history of suicidal ideation.

This randomized, double-blind, placebo-controlled crossover study (n=20) tests the bioequivalence and oral bioavailability of LSD base and tartrate in various formulations (ethanolic solution, watery solution, dissolvable tablet, and IV). All oral formulations were bioequivalent with 80% absolute oral bioavailability. IV LSD produced stronger subjective effects, including more ego dissolution and anxiety.

This randomised, double-blind, placebo-controlled single ascending dose study (n=29) tested prolonged intravenous DMT administration (30-s bolus (1.5-7.5mg) + 6-h infusion (4.4-33.3nl/ml)) in healthy volunteers. It found the treatment to be safe, with only mild, self-limiting adverse events, and observed mild psychedelic effects, reduced attention and stability, and decreased occipital alpha EEG power at higher doses, supporting further investigation in stroke recovery contexts.

This secondary analysis (n=82) of a Phase III RCT of MDMA-assisted therapy found significant improvements in both uncompassionate self-responding and compassionate self-responding across all six Self-Compassion Scale subscales, most with large effect sizes. Changes in self-compassion fully mediated the reductions in PTSD severity and depressive symptoms observed with MDMA-AT versus placebo plus therapy, though no significant effects were seen for alcohol or substance use outcomes.

This Phase III open-label extension study (n=1148) evaluates the long-term safety and efficacy of esketamine nasal spray combined with oral antidepressants in treatment-resistant depression (TRD) patients who previously participated in other Phase III trials. The study involved flexible dosing of intranasal esketamine (twice-weekly during induction, then weekly to monthly during maintenance) with direct staff supervision, with participants either entering through a 4-week induction phase (n=458) or directly into maintenance (n=690) based on their previous response.

This secondary analysis of an RCT (n=59) investigates the impact of psilocybin-assisted therapy (PAT) and escitalopram (SSRI) on responsiveness to emotional stimuli in patients with moderate-to-severe major depressive disorder over a 6-week trial period. Responses to emotional faces were reduced in the SSRI group, not the psilocybin group at the follow-up.

This secondary analysis of an RCT brain imaging (EEG) study (n=30) examines how DMT/HAR and Harmine alone affect face recognition and self-processing in healthy males using a visual oddball task. It finds DMT/HAR enhanced early visual processing while reducing neural differentiation between self and other faces at posterior sites, suggesting psychedelics reshape rather than erase self-boundaries while preserving socially meaningful representations.