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Home/Research/LSD/Depressive Disorders

LSD for Depressive Disorders

159 papers and 12 clinical trials exploring lsd as a treatment for depressive disorders.

Compoundclassic psychedelic

LSD

LSD is a classic psychedelic ergoline with high potency at microgram doses and an 8-12 hour duration of action, mediated primarily via 5-HT2A receptor agonism. Modern Phase IIb data in generalised anxiety disorder and FDA Breakthrough Therapy Designation for MM120 have reignited clinical development.

Full LSD profile
IndicationApproximately 260 million people worldwide are affected by depression.

Depressive Disorders

Depressive disorders, particularly major depressive disorder (MDD), are significant contributors to global mental health issues. Research into the therapeutic potential of psychedelics, such as psilocybin and ketamine, offers promising avenues for treatment, especially for cases that are resistant to conventional therapies.

Full Depressive Disorders profile

Academic Research

159 papers
Open Accessindividual

Psychedelic-assisted therapy: a survey on the clinical methods of Swiss physicians

This survey study (n=41) examined how Swiss physicians provide psychedelic-assisted therapy under legal exemptions, mainly for depression, anxiety, PTSD and chronic pain. It found wide variation in practice, with psilocybin, MDMA and LSD commonly used, music often played during sessions, and adverse effects usually including disorientation, feeling cold, anxiety and nausea.

Published
May 20, 2026
Journal
Therapeutic Advances in Psychopharmacology
Authors
Beichmann, K., Catzeflis, P., Aicher, H. D., Seragnoli, F., Calder, A., Amrani, A., Hasler, G.
Open Accessindividual

Neuroplastic white matter changes in patients with major depression following lysergic acid diethylamide treatment

This randomised clinical trial (n=61) in people with major depressive disorder compared low-dose LSD (2 × 25 μg) with moderate-to-high-dose LSD (100 μg then 200 μg) and found that the higher-dose group showed white matter changes on brain scans linked with later improvements in depressive symptoms.

Published
May 7, 2026
Journal
Cell Reports
Authors
Avram, M., Menegaux, A., Müller, F., Zaczek, H., Korda, A., Rogg, H., Becker, A. M., Ley, L., Liechti, M. E., Borgwardt, S.
Open Accessindividual

Age moderates the relationship between psychedelics use and mental health in naturalistic settings

This cross-sectional survey (n=1,088) found that age significantly moderates the relationship between lifetime psychedelic use and mental health, with classic psychedelics such as psilocybin being associated with lower depression and anxiety in younger adults, but these benefits diminish with age and even reverse for anxiety in older participants.

Published
March 10, 2026
Journal
Research Square
Authors
Gregorio, G. D., Basset, S., Manmohan, H., Nixon, W. C., Pogaku, A., Zhou, J., Sanderson, D. J., Lengieza, M. L., Bocchio, M.
Open Accessindividual

LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial

This open-label trial (n=19) found that repeated microdosed LSD (8 to 20 μg) was associated with short-term improvements in daily mood, but not same-day changes in self-reported depression, in people with major depressive disorder. It also provided pharmacokinetic data for sublingual LSD and found no evidence of tolerance or sensitisation across the 8-week dosing regimen.

Published
March 1, 2026
Journal
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Authors
Daldegan-Bueno, D., Donegan, C. J., Sumner, R., Forsyth, A., Jeong, S. H., Evans, W., Alshakhouri, M., Murphy, R. J., Reynolds, L., Hoeh, N., Allen, N., Sundram, F., Menkes, D. B., Muthukumaraswamy, S.
Open Accessindividual

It's all about the relationship: The caregiver experience of supporting a person with advanced cancer going through an LSD microdosing trial

This secondary analysis of an RCT (n=15 interviews) found that caregivers of people with advanced cancer were generally supportive of participation in an LSD microdosing plus meaning-centred psychotherapy trial, though some were initially hesitant. It highlighted the bidirectional nature of patient-caregiver well-being, with the intervention seen as offering hope, easing existential distress, and strengthening their relationship.

Published
February 26, 2026
Journal
Palliative & Supportive Care
Authors
Cottam, F., Wells, A., Clayden, C., Reynolds, L.
Open Accessindividual

Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD A Randomized Clinical Trial

In a multicentre, double‑blind, placebo‑controlled phase 2 trial of 65 adults with chronic PTSD, once‑weekly oral TSND‑201 produced significantly greater reductions in clinician‑rated PTSD severity (CAPS‑5; LS mean difference 9.64, P = .01) and improvements in self‑reported symptoms, functioning and depression versus placebo. TSND‑201 was generally well tolerated — common adverse events included headache, decreased appetite, nausea, dizziness and transient blood‑pressure increases — supporting its potential as a rapid‑acting, durable treatment for PTSD.

Published
February 18, 2026
Journal
JAMA Psychiatry
Authors
Jones, A., Warner-Schmidt, J., Kwak, H., Stogniew, M., Mandell, B., Ching, T. H., Stein, M. B., Kelmendi, B.

Clinical Trials

12 trials
Not yet recruitingPhase I

Shortened LSD Intervention for Major Depressive Disorder

This Phase I, open-label, single-group trial (n=10) will evaluate the safety and potential clinical effectiveness of a shortened LSD experience in adults with major depressive disorder (MDD). Participants will receive oral LSD hemi-L-tartrate 250 µg followed 45 minutes later by oral risperidone 1 mg, with the aim of assessing whether risperidone can abbreviate the subjective effects of LSD while still offering possible antidepressant benefit. The study will enrol adults aged 21 to 70 years with DSM-5 MDD and a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 28 at screening. Participants will be monitored for 10.5 hours after dosing and assessed at several time points for subjective effects and discharge readiness. The primary outcome is change in MADRS at 1 month.

Started
July 1, 2026
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT07503002
RecruitingPhase III

A Phase 3 Trial of DT120 for Major Depressive Disorder (Ascend)

This Phase III, randomised, double-blind, placebo-controlled trial (n=165) will evaluate the efficacy and safety of oral DT120 (LSD) in adults aged 18 to 74 years with major depressive disorder (MDD). Participants will be assigned to placebo, 50µg DT120 or 100µg DT120, with the main efficacy measure being change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6. The study includes a 12-week single-dose treatment period in Part A, followed by a 40-week open-label extension in Part B. Adults must have a DSM-5-confirmed diagnosis of MDD, a current major depressive episode lasting 8 weeks to 24 months, a MADRS score of at least 26 and a Clinical Global Impression-Severity (CGI-S) score of at least 4 at screening and baseline. During the extension phase, participants may receive open-label retreatment with DT120 based on pre-specified safety and symptom severity criteria, and will be monitored for efficacy and safety.

Started
May 10, 2026
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT07592689
Active not recruitingPhase III

A Phase 3 Trial of MM120 for Major Depressive Disorder (Emerge)

This randomised, double-blind, placebo-controlled Phase III trial (n=140) will evaluate the efficacy and safety of a single oral dose of MM120 (100 µg LSD D-tartrate) for the treatment of major depressive disorder (MDD).

Started
April 14, 2025
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT06941844
CompletedPhase NA

Salivary Oxytocin as a Biomarker in Psychedelic Assisted Psychotherapy (PAP_OXT)

This observational pilot study (n=10) will examine salivary oxytocin levels during a single dose of LSD as part of psychedelic-assisted psychotherapy (PAP) for anxiety disorders or depression.

Started
August 5, 2024
Type
observational
Randomized
No
Registry ID
NCT06557239
Not yet recruitingPhase II

Assessing the effects of Lysergic acid diethylamide (LSD) microdosing in people experiencing depression (LSDDEP2)

Randomised, double-dummy, triple-blind, placebo-controlled, parallel groups trial (n=90) investigating sublingual LSD microdosing (2–20 µg, start 8 µg) twice weekly for 8 weeks versus active placebo (caffeine or methylphenidate) in people with MDD.

Started
March 11, 2024
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
ACTRN12624000128594
RecruitingPhase II

Lysergic Acid Diethylamide (LSD) in Palliative Care (LPC)

Randomised, quadruple-blind, active-placebo controlled parallel trial (n=60) testing two oral LSD sessions (100 µg then 100/200 µg) versus low-dose LSD active-placebo (25 µg ×2) for psychosocial distress in patients with end-stage disease.

Started
September 1, 2023
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT05883540

Explore further

Search all LSD papers Search all Depressive Disorders trials Full LSD profile Full Depressive Disorders profile