Clinical trials available on ClinicalTrials.gov investigating the use of LSD as a potential therapeutic approach for MDD, anxiety, and other psychiatric disorders
For completed trials, the references of published work were added if available either from the ClinicalTrials.gov web site or PubMed upon searching the NCT identifier. If information was available on the main findings of the study, it was added. If the trial was not completed or it was completed but no information was available in the form of a published original manuscript, we reported the main research question(s) the study aims to address.
| Compound | Cohort | Regimen | Research Question/Main Findings | Status | Reference |
| LSD | Major depressive disorder | First session: 25 or 100 μg, orally; second session: 25, 100, or 200 μg, orally | Assess the benefits of LSD-assisted psychotherapy in patients with MDD | Recruiting | ClinicalTrials.gov identifier: NCT03866252 |
| LSD | Major depressive disorder | First session: 25 or 100 μg, orally; second session: 25, 100, or 200 μg, orally | Assess antidepressant and anxiolytic effects of LSD in patients with MDD | Recruiting | ClinicalTrials.gov identifier: NCT03866252 |
| LSD | Illness-related anxiety | 20 or 200 μg, orally, once | LSD reduces anxiety. Sustained anxiolytic effects and increased quality of life over a 12-mo period. Facilitated access to emotions and confrontation with previously unknown anxieties. The experience leads to a restructuring of the person’s emotional trust, situational understanding, habits, and world view. No adverse reactions. LSD can be safe and generate lasting benefits in patients with a life-threatening disease | Completed | ClinicalTrials.gov identifier: NCT00920387 (Gasser et al., 2014, 2015) |
| LSD | Healthy volunteers | 100–200 µg, orally, once | LSD induces visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization phenomena. Increased subjective well-being, happiness, closeness to others, and openness. LSD breaks down hippocampal-prefrontal cortex–mediated inhibitory processing, which might be involved in the formation of LSD-induced visual imageries. LSD increases blood pressure, heart rate, body temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine. No severe acute adverse effects. LSD detected in all subjects up to 12 h after administration. Maximal LSD plasma concentrations reached 0.5–4 h after administration. Half-life of 2.5–4.5 h up to 12 h and slower elimination after. No sex differences in pharmacokinetics. Acute effects up to 12 h. LSD induces fewer mystical experiences than psilocybin. LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 µg compared with 100 µg. Feelings of ego dissolution at 100 µg correlated to LSD plasma levels | Completed | ClinicalTrials.gov identifier: NCT01878942 (Dolder et al., 2015; Schmid et al., 2015a; Strajhar et al., 2016) |
| LSD | Healthy volunteers | 100–200 µg, orally, once | LSD impairs fear recognition and enhances emotional empathy and sociality. Maximum mean plasma concentration of 1.3 and 3.1 ng/ml reached 1.4 and 1.5 h after administration of 100 and 200 µg LSD, respectively. Mean plasma half-life 2.6 h. Subjective effects last 8.2 ± 2.1 h for the 100-µg and 11.6 ± 1.7 h for the 200-µg dose, respectively. Subjective peak effects reached 2.8 and 2.5 h after administration of LSD 100 and 200 µg, respectively. LSD reduces left amygdala and right medial prefrontal cortex activity during the presentation of fearful faces. Negative correlation between LSD-induced amygdala response to fearful stimuli and LSD-induced subjective drug effects | Completed | ClinicalTrials.gov identifier: NCT02308969 (Dolder et al., 2016, 2017b; Liechti et al., 2017; Mueller et al., 2017) |
| LSD | Healthy volunteers | 100 µg, orally, once | Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to 5-HT2A. LSD impairs working memory, executive functions, and cognitive flexibility but not risk-based decision-making. 5-HT2A signaling underlies LSD-induced alteration of the neural response to dynamic changes in music. LSD decreases striatothalamic functional connectivity independently of 5-HT2A and increases thalamo-PCC connectivity in a 5-HT2A–dependent fashion | Completed | ClinicalTrials.gov identifier: NCT02451072 (Preller et al., 2018, 2019; Holze et al., 2019; Pokorny et al., 2019) |
| LSD | Healthy volunteers | 100 µg, orally, once | LSD compared with MDMA produces greater subjective drug effects, ego dissolution, introversion, emotional excitation, anxiety, and inactivity. LSD produces greater impairments in concentration, sense of time, and speed of thinking. LSD does not increase oxytocin levels. Acute LSD does not affect circulating BDNF | Completed | ClinicalTrials.gov identifier: NCT03019822 (Holze et al., 2020) |
| LSD | Healthy volunteers | 75 µg by i.v. injection, once | LSD enhances suggestibility, and this effect could be harnessed in psychotherapeutic settings | Completed | Carhart-Harris et al., 2015 |
| LSD | Healthy volunteers | 75 µg by i.v. injection, once | LSD administration modulates learning adaptive mechanisms and attenuates top-down suppression of prediction error | Completed | Timmermann et al., 2018 |
| LSD | Healthy volunteers | 40–80 µg by i.v. injection, once | LSD enhances the emotional response to music. Increased functional connectivity between parahippocampal-visual cortex and increased parahippocampal-visual cortex information flow in the interaction between music and LSD | Completed | Kaelen et al., 2015 |
| LSD | Healthy volunteers | 75 µg by i.v. injection, once | LSD increases blood flow to the visual cortex and decreases alpha power, and these effects predict the magnitude of visual hallucinations. LSD decreases DMN integrity and delta and alpha power in the PCC, and these effects correlate with ego dissolution | Completed | Carhart-Harris et al., 2016c |
| LSD | Healthy volunteers | 75 µg by i.v. injection, once | LSD increases brain entropy. Entropy increases are greatest while listening to music and experiencing ego dissolution | Completed | Lebedev et al., 2016 |
| LSD | Healthy volunteers | 25–50–100–200 µg, orally, once per dose | 5-HT2A receptor involvement in LSD consciousness-altering effects (using the 5-HT2A antagonist ketanserin before LSD) | Completed | ClinicalTrials.gov identifier: NCT03321136 |
| LSD | Healthy volunteers | 100–200 µg, orally, once per dose | Compare the acute effects of LSD and psilocybin | Recruiting | ClinicalTrials.gov identifier: NCT03604744 |
| LSD | Healthy volunteers | 6.5–13–26 µg, orally, once per dose | LSD microdosing produces dose-related subjective effects across the three doses. Microdoses increased ratings of vigor and slightly decreased positivity ratings of images with positive emotional content at 26 µg. Other mood, cognition, and physiological measures were unaffected. Low-dose LSD (13 µg) increases amygdala connectivity with the right angular gyrus, right middle frontal gyrus, and the cerebellum and decreases amygdala connectivity with the superior temporal gyrus. Effects on mood positively correlated with the increase in amygdala-middle frontal gyrus connectivity | Recruiting | ClinicalTrials.gov identifier: NCT03790358 (Bershad et al., 2019, 2020) |
| LSD | Healthy volunteers | 13 µg, orally, once | Assess the effects of repeated very low doses of LSD on mood in individuals with negative mood | Recruiting | ClinicalTrials.gov identifier: NCT03934710 |
| LSD | Healthy volunteers | 100 µg, orally, once | Comparative acute effects of LSD, psilocybin, and mescaline (Five Dimensions of Altered States of Consciousness and resting state fMRI) | Not yet recruiting | ClinicalTrials.gov identifier: NCT04227756 |
NCT, ClinicalTrials.gov identifier.