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Home/Research/LSD/Treatment-Resistant Depression (TRD)

LSD for Treatment-Resistant Depression (TRD)

17 papers and 0 clinical trials exploring lsd as a treatment for treatment-resistant depression (trd).

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
Indication30% of individuals with depression experience treatment-resistant depression.

Treatment-Resistant Depression (TRD)

Research into psychedelics as a treatment for Treatment-Resistant Depression (TRD) is advancing rapidly, with compounds like psilocybin showing particular promise. Approximately 30% of depression sufferers experience TRD, which reflects a significant unmet need in mental health treatment.

Full Treatment-Resistant Depression (TRD) profile

Academic Research

17 papers
Paywallindividual

A qualitative analysis of participant expectations and experiences of psilocybin-assisted psychotherapy for methamphetamine use disorder

Participants in a pilot study of psilocybin‑assisted psychotherapy for methamphetamine use disorder found the intervention acceptable and reported that confronting vividly challenging psychedelic experiences—described as “leaning into the obstacle”—fostered new self‑understandings and shifts in relationships that reduced the salience of methamphetamine. A strong therapeutic alliance, characterised by concentrated attention and intersubjective intimacy, was seen as critical to these positive changes.

Published
December 22, 2025
Journal
Addiction
Authors
Brett, J., Lea, T., Knock, E., Albert, S., Acheson, L., Siefried, K. J., Job, S.
Open Accessindividual

Effects of LSD and Psilocybin on Heart Rate in Patients Receiving Psychedelic Treatment for Depressive and Anxiety Disorders: A Retrospective Observational Study

In this retrospective study of 30 patients receiving LSD or psilocybin for treatment‑resistant depression or anxiety, LSD produced a delayed, sustained increase in heart rate peaking at 3–4 hours while psilocybin showed an earlier decline, with a significant time × substance interaction that persisted after adjusting for age and anxiety and no serious cardiovascular events observed. These preliminary findings suggest distinct temporal cardiovascular profiles for LSD versus psilocybin but should be interpreted cautiously given the retrospective design, small sample and dose imbalance.

Published
December 19, 2025
Journal
Psychology International
Authors
Cheng, M., Aboulafia-Brakha, T., Buchard, A., Boyanova Anastasova, R., Girani, L., Breitenmoser, A., Alaux, S., Mabilais, C., Amberger, C., Seragnoli, F., Furtado, L., Thorens, G., Zullino, D., Penzenstadler, L.
Open Accessmeta

A review of psychedelics trials completed in depression, informed by European regulatory perspectives

This systematic review (s=8) analyses completed controlled trials of psychedelics for depression, including psilocybin, LSD, ayahuasca, and DMT, all in Phase II or I/II. It evaluates methodological patterns against the draft European Medicines Agency guideline revision, highlighting challenges such as unblinding, expectancy, and adverse event characterisation, while calling for larger studies to assess long-term efficacy and safety.

Published
January 1, 2025
Journal
Neuroscience Applied
Authors
Silva, F., Butlen-Ducuing, F., Guizzaro, L., Balabanov, P., Meyer-Lindenberg, A.
Paywallmeta

Quality of reporting on psychological interventions in psychedelic treatments: a systematic review

This systematic review (s=45) on psychedelic-assisted psychotherapy for mental disorders finds that psychological interventions are reported with low completeness and high heterogeneity. It also finds that MDMA studies are more homogeneous, with greater procedural detail.

Published
December 9, 2024
Journal
Lancet
Authors
Seybert, C., Schimmers, N., Silva, L., Breeksema, J. J., Veraart, J. K. E., Bessa, B. S., d'Orsi, D., Schoevers, R. A., Dinis-Oliveira, R. J.
Open Accessmeta

Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies

This systematic review (2024) and meta-analysis (s=131) examines the incidence of psychedelic-induced psychosis, focusing on individuals with schizophrenia. It finds an incidence of 0.002% in population studies, 0.2% in UCTs, and 0.6% in RCTs, with 3.8% of UCT participants with schizophrenia developing long-lasting psychotic symptoms. It also reports that 13.1% of those with psychedelic-induced psychosis later developed schizophrenia.

Published
November 27, 2024
Journal
Molecular Psychiatry
Authors
Sabé, M., Sulstarova, A., Glangetas, A., De Pieri, M., Mallet, L., Curtis, L., Richard-Lepouriel, H., Penzenstadler, L., Seragnoli, F., Thorens, G., Zullino, D., Preller, K., Böge, K., Leucht, S., Correll, C. U., Solmi, M., Kaiser, S., Kirschner, M.
Open Accessindividual

Self-treatment of psychosis and complex post-traumatic stress disorder with LSD and DMT-A retrospective case study

This case study (n=1) describes how a teenager self-treated their psychosis (accompanied by complex PTSD and suicidal ideations) through high-dose LSD and low-dose DMT sessions. The hypothesis argues that psychedelics were able to break down the defensive system and allow for the integration of traumatic memories.

Published
December 1, 2022
Journal
Psychiatry Research
Authors
Turkia, M.

Clinical Trials

0 trials

No clinical trials have been tagged with both LSD and Treatment-Resistant Depression (TRD) yet.

Trials are continuously being added as new studies are registered.

Explore further

Search all LSD papers Search all Treatment-Resistant Depression (TRD) trials Full LSD profile Full Treatment-Resistant Depression (TRD) profile