Psychedelic Research Papers

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.

This randomised, double-blind, placebo-controlled clinical trial (n=16) examines MDMA's (80-120mg) effects on neural circuits in individuals with subthreshold PTSD symptoms and early life trauma. The study finds that participants with higher baseline amygdala reactivity (emotional experiences) showed significant reductions in amygdala and sgACC (emotional processing) activity, increased sgACC-amygdala connectivity, and increased likability of threat expressions after 120mg MDMA compared to those with lower baseline reactivity.

This real-world study (n=185) found that oral esketamine (35-210mg/70kg; 6w; 12x) was effective and well-tolerated in severely treatment-resistant depression (TRD) patients, showing significant symptom improvement with minimal dropouts (7.6%), suggesting it could be a viable alternative to intranasal or intravenous administration.

This open-label fixed-order dose-escalation trial (n=14) evaluated inhaled DMT (15mg & 60mg) for treatment-resistant depression (TRD) for the first time. Results showed rapid and sustained antidepressant effects with a 21-point reduction on the Montgomery-Asberg Depression Rating Scale by day 7 (p<0.001), an 86% response rate, and a 57% remission rate lasting up to 3 months, with significant decreases in suicidal ideation (SI).

This multicenter, randomised, placebo-controlled clinical trial (n=236) investigates the efficacy and safety of esketamine (ESK) (8x35mg) for smoking cessation in patients with lung cancer and major depressive disorder (MDD). Eight weekly intranasal ESK sessions significantly improved both self-reported (44.1%) and biologically verified (28.8%) smoking abstinence at 6-month follow-up, alongside reductions in depression, anxiety, nicotine dependence, and respiratory symptoms.

This multi-dataset observational study (n=5 nationally representative surveys) quantifies changes in psilocybin use and healthcare utilisation in the United States between 2014 and 2023. It finds that adult lifetime use increased from 10.0% (25 million) in 2019 to 12.1% (31.3 million) in 2023, while adolescent use rose modestly from 1.1% to 1.3% during the same period.

This secondary analysis of a randomised trial (n=41) found that while psilocybin therapy (2x25 mg, three weeks apart) maintained emotional responses to musical surprises and increased activation in prefrontal and sensory brain regions. Escitalopram reduced surprise-related affective responses and increased activation in memory and emotional processing areas, suggesting distinct neurological mechanisms between these treatments for depression.

This exploratory observational study (n=14) examines the phenomenological and neuronal effects of 5-MeO-DMT through micro-phenomenological interviews, psychometric questionnaires, and EEG recordings in naturalistic ceremonial settings. The findings reveal that 5-MeO-DMT induces variable experiences of visual imagery, bodily and narrative self-disruption, and reduced phenomenal distinctions, with EEG showing alpha and beta power reductions suggesting inhibited top-down processing.

This prospective cohort study (n=654 start, n=212 end) investigated delusional ideation, magical thinking, and HPPD symptoms in participants before and after planned psychedelic use. Results showed reduced delusional ideation after one month, no changes in magical thinking, and HPPD-like effects in 30% of participants (though rarely distressing at <1%), with younger age, female gender, psychiatric history, and baseline trait absorption predicting HPPD-like effects.

This observational study (n=343) of terrorist attack survivors found that those under the influence of classic psychedelics during the traumatic event reported lower anxiety and post-traumatic symptoms compared to MDMA users or non-users, particularly when psychedelics were taken alone.

This re-analysis of a Phase I RCT (n=80) examines the pharmacokinetics (how the body affects a drug) of LSD microdosing (10µg; 14x; 6w) in healthy adult males. The study established a one-compartment pharmacokinetic model showing an elimination half-life of 3.08h, found minimal physiological effects (<15% change in heart rate), noted possible influence of CYP enzymes on drug metabolism, and reported no changes in peripheral BDNF levels.

This re-analysis (n=14) applies a receptor-informed network control theory framework to investigate the effects of DMT on the brain's control energy landscape. It reveals that DMT, like LSD and psilocybin, reduces global control energy, with these trajectories correlating with EEG signal diversity and subjective intensity ratings. Furthermore, the regional effects of DMT correlate with serotonin 2a receptor density, demonstrating a potential proof-of-concept for predicting pharmacological intervention effects on brain dynamics using control models.