Clinical trials available on 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 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.

CompoundCohortRegimenResearch Question/Main FindingsStatusReference
LSDMajor depressive disorderFirst session: 25 or 100 μg, orally; second session: 25, 100, or 200 μg, orallyAssess the benefits of LSD-assisted psychotherapy in patients with identifier: NCT03866252
LSDMajor depressive disorderFirst session: 25 or 100 μg, orally; second session: 25, 100, or 200 μg, orallyAssess antidepressant and anxiolytic effects of LSD in patients with identifier: NCT03866252
LSDIllness-related anxiety20 or 200 μg, orally, onceLSD 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 identifier: NCT00920387 (Gasser et al., 2014, 2015)
LSDHealthy volunteers100–200 µg, orally, onceLSD 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 identifier: NCT01878942 (Dolder et al., 2015; Schmid et al., 2015a; Strajhar et al., 2016)
LSDHealthy volunteers100–200 µg, orally, onceLSD 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 identifier: NCT02308969 (Dolder et al., 2016, 2017b; Liechti et al., 2017; Mueller et al., 2017)
LSDHealthy volunteers100 µg, orally, onceChanges 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 identifier: NCT02451072 (Preller et al., 2018, 2019; Holze et al., 2019; Pokorny et al., 2019)
LSDHealthy volunteers100 µg, orally, onceLSD 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 identifier: NCT03019822 (Holze et al., 2020)
LSDHealthy volunteers75 µg by i.v. injection, onceLSD enhances suggestibility, and this effect could be harnessed in psychotherapeutic settingsCompletedCarhart-Harris et al., 2015
LSDHealthy volunteers75 µg by i.v. injection, onceLSD administration modulates learning adaptive mechanisms and attenuates top-down suppression of prediction errorCompletedTimmermann et al., 2018
LSDHealthy volunteers40–80 µg by i.v. injection, onceLSD 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 LSDCompletedKaelen et al., 2015
LSDHealthy volunteers75 µg by i.v. injection, onceLSD 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 dissolutionCompletedCarhart-Harris et al., 2016c
LSDHealthy volunteers75 µg by i.v. injection, onceLSD increases brain entropy. Entropy increases are greatest while listening to music and experiencing ego dissolutionCompletedLebedev et al., 2016
LSDHealthy volunteers25–50–100–200 µg, orally, once per dose5-HT2A receptor involvement in LSD consciousness-altering effects (using the 5-HT2A antagonist ketanserin before LSD) identifier: NCT03321136
LSDHealthy volunteers100–200 µg, orally, once per doseCompare the acute effects of LSD and identifier: NCT03604744
LSDHealthy volunteers6.5–13–26 µg, orally, once per doseLSD 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 identifier: NCT03790358 (Bershad et al., 2019, 2020)
LSDHealthy volunteers13 µg, orally, onceAssess the effects of repeated very low doses of LSD on mood in individuals with negative identifier: NCT03934710
LSDHealthy volunteers100 µg, orally, onceComparative acute effects of LSD, psilocybin, and mescaline (Five Dimensions of Altered States of Consciousness and resting state fMRI)Not yet identifier: NCT04227756