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Greater subjective effects of a low dose of LSD in participants with depressed mood

Neuropsychopharmacology volume 49, pages 774–781 (2024)Cite this article

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Abstract

Recent studies and anecdotal reports suggest that psychedelics can improve mood states, even at low doses. However, few placebo-controlled studies have examined the acute effects of low doses of LSD in individuals with psychiatric symptoms. In the current study, we examined the acute and sub-acute effect of a low dose of LSD (26 µg) on subjective effects and mood in volunteers with mild depressed mood. The study used a randomized, double-blind, crossover design to compare the effects of LSD in two groups of adults: participants who scored high (≥17; n = 20) or low (<17; n = 19) on the Beck Depression-II inventory (BDI) at screening. Participants received a single low dose of LSD (26 µg) and placebo during two 5-h laboratory sessions, separated by at least one week. Subjective, physiological, and mood measures were assessed at regular intervals throughout the sessions, and behavioral measures of creativity and emotion recognition were obtained at expected peak effect. BDI depression scores and mood ratings were assessed 48-h after each session. Relative to placebo, LSD (26 µg) produced expected, mild physiological and subjective effects on several measures in both groups. However, the high BDI group reported significantly greater drug effects on several indices of acute effects, including ratings of vigor, elation, and affectively positive scales of a measure of psychedelic effects (5D-ASC). The high BDI group also reported a greater decline in BDI depression scores 48-h after LSD, compared to placebo. These findings suggest that an acute low dose of LSD (26 µg) elicits more pronounced positive mood and stimulant-like effects, as well as stronger altered states of consciousness in individuals with depressive symptoms, compared to non-depressed individuals.

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Fig. 1: Subjective effects after LSD in the Low and High BDI groups.
Fig. 2: Acute subjective and mood effects after LSD in the Low and High BDI groups.
Fig. 3: Effects of LSD on the 5-Dimensional Altered States of Consciousness measure in the Low (green) and High (blue) BDI groups.
Fig. 4: Effect of LSD (26 µg) on Beck Depression Inventory-II (BDI) ratings 48 h after drug administration sessions in low BDI (green) and high BDI (blue) groups.

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Acknowledgements

The authors acknowledge the support of the Mass Spectrometry Core in Research Resources Center of University of Illinois at Chicago. Clinical trials registry: Clinicaltrials.gov, Mood Effects of Serotonin Agonists (NCT03790358).

Funding

This work was supported by National Institutes of Health (grant DA02812). HM was supported by T32GM07019.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, 5841 S Maryland Ave MC3077, Chicago, IL, 60637, USA

    Hanna Molla, Royce Lee, Ilaria Tare & Harriet de Wit

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  4. Harriet de Wit
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Contributions

HdW, HM, and RL contributed to the design and implementation of the study. IT carried out the data collection. HM analyzed the data. HdW and HM prepared the manuscript. All authors reviewed and edited the final manuscript.

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Correspondence to Harriet de Wit.

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Competing interests

HdW is on the Board of Directors of PharmAla Biotech and consultant to Awakn Life Sciences and Gilgamesh Pharmaceuticals. These were unrelated to the present research. HM, RL, and IT report no conflicts.

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Molla, H., Lee, R., Tare, I. et al. Greater subjective effects of a low dose of LSD in participants with depressed mood. Neuropsychopharmacol. 49, 774–781 (2024). https://doi.org/10.1038/s41386-023-01772-4

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