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Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases
Open accessAbstract
A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.
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“After crossover, 12 months later (n = 9), both groups reported a decrease in anxiety.”
From Psychedelics for the treatment of depression, anxiety, and existential distress in patients with a terminal illness: a systematic review (2022) · cites this paper as Gasser et al., 2014
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“Psychedelic-assisted therapy (PAT) with psilocybin and lysergic acid diethylamide (LSD) has demonstrated efficacy in the treatment of depression, anxiety, and some other neuropsychiatric disorders”
From Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response (2024) · cites this paper as Gasser et al., 2014
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“More modern trials have assessed the efficacy of psychedelics to reduce anxiety symptoms among patients with a life-threatening illness, and have demonstrated large significant reductions in ratings of anxiety, with a response rate of 60–80% (defined as >50% decrease in measure relative to baseline), sustained over the course of 6–12 months post treatment (15–17)”
From Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees (2022) · cites this paper as [15]
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In the citing paper
“The remaining 7 SAEs occurred in 2 studies20,27 and were deemed unrelated to LSD: 2 pregnancies followed by spontaneous abortion; a planned nasal surgery; a radial fracture at a personal event unrelated to the study procedures; a suspected transient ischemic attack (2 weeks following LSD dose in a participant with Marfan syndrome and at least 4 prior suspected transient ischemic attack episodes);”
From Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis (2024) · cites this paper as [27]
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“No drug-related severe adverse events were reported.”
From Psychedelics for the treatment of depression, anxiety, and existential distress in patients with a terminal illness: a systematic review (2022) · cites this paper as Gasser et al., 2014
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“As macrodoses have been found to be effective in the treatment of anxiety (Gasser et al. 2014;Griffiths et al. 2016;Grob et al. 2011;Ross et al. 2016) and treatment resistant depression (Carhart-Harris et al. 2018, 2016;Osório et al. 2015)”
From Psychedelic Microdosing, Mindfulness, and Anxiety: A Cross-Sectional Mediation Study (2023) · cites this paper as Gasser et al. 2014
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“Several studies disclosed deaths occurring after study completion; this practice is atypical, and as such, they are not tabulated in Table 1. However, for completeness, these deaths included: 3 deaths in a study of LSD for anxiety27 and 30 deaths across 3 studies of psilocybin for anxiety and mood disorders in participants with life-threatening cancer diagnoses during a period of up to”
From Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis (2024) · cites this paper as [27]
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“Entactogens and hallucinogens have shown promising results in preliminary clinical trials in disorders also characterized by social impairments such as depression, anxiety, post-traumatic stress disorder (PTSD), and autism spectrum disorders (ASD) (15–19).”
From Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019) · cites this paper as [15]
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Nayak, S., & Johnson, M. W. (2021) · Pharmacopsychiatry · doi:10.1055/a-1312-7297 · Cited by 71
Psychedelic therapy's transdiagnostic effects: A research domain criteria (RDoC) perspective
Kelly, J. R., Gillan, C. M., Prenderville, J., Kelly, C., Harkin, A., Clarke, G., & O'Keane, V. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.800072 · Cited by 69
Giluk (2009) · doi:10.1017/s003329172000389x · Cited by 68
Wolff, M., Mertens, L. J., Walter, M., Enge, S., & Evens, R. (2022) · Journal of Psychopharmacology · doi:10.1177/02698811211073758 · Cited by 58
dos Santos, R. G., Hallak, J. E., Baker, G., & Dursun, S. (2021) · Journal of Psychopharmacology · doi:10.1177/0269881120986422 · Cited by 55
Psilocybin for Trauma-Related Disorders
Khan, A. J., Bradley, E., O’Donovan, A., & Woolley, J. (2022) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2022_366 · Cited by 67
Luoma, J. B., Sabucedo, P., Eriksson, J., Gates, N., & Pilecki, B. C. (2019) · Journal of Contextual Behavioral Science · doi:10.1016/j.jcbs.2019.10.003 · Cited by 56
Metabolism of lysergic acid diethylamide (LSD): an update
Libânio Osório Marta, R. F. (2019) · Drug Metabolism Reviews · doi:10.1080/03602532.2019.1638931 · Cited by 54
Husain, M. I., Ledwos, N., Fellows, E., Baer, J., Rosenblat, J. D., Blumberger, D. M., Mulsant, B. H., & Castle, D. J. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1076459 · Cited by 50
Studies with psychedelic drugs in human volunteers
Sellers, E. M., Romach, M. K., & Leiderman, D. B. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.029 · Cited by 42
Lafrance, A., Strahan, E., Bird, B. M., St. Pierre, M., & Walsh, Z. (2021) · Journal of Humanistic Psychology · doi:10.1177/00221678211048049 · Cited by 40
Historic psychedelic drug trials and the treatment of anxiety disorders.
Weston, N. M., Gibbs, D., Bird, C. I. V., Daniel, A., Jelen, L. A., Knight, G., Goldsmith, D., Young, A. H., & Rucker, J. J. (2020) · Depression and Anxiety · doi:10.1002/da.23065 · Cited by 38
Kiraga, M. K., Kuypers, K. P. C., Uthaug, M. V., Ramaekers, J. G., & Mason, N. L. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.883869 · Cited by 26
“Recently, there has been a resurgence of interest regarding the therapeutic potential of these substances, including psilocybin, ayahuasca, and LSD, in treating an array of different mental health disorders (10–14).”
BackgroundInfluentialEpigenetic Mechanisms of Rapid-Acting Antidepressants
Inserra, A., Campanale, A., Rezai, T., Romualdi, P., & Rubino, T. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03055-y · Cited by 27
Calder, A. E., Rausch, B., Liechti, M. E., Holze, F., & Hasler, G. (2024) · Journal of Psychopharmacology · doi:10.1177/02698811241278873 · Cited by 20
“…therapy (PAT) with psilocybin and lysergic acid diethylamide (LSD) has demonstrated efficacy in the treat-ment of depression, anxiety, and some other neuropsychiatric disorders (Gasser et al., 2014; Goodwin et al., 2022; Holze et al., 2023b; Raison et al., 2023; von Rotz et al., 2023).”
BackgroundPharmacotherapy for Anxiety Disorders.
O’Leary, K. B., & Khan, J. S. (2024) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2024.04.012 · Cited by 22
Naturalizing psychedelic spirituality
Letheby, C. (2017) · Zygon: Journal of Religion and Science · doi:10.1111/zygo.12353 · Cited by 18
Blinding and expectancy confounds in psychedelic randomised controlled trials
Muthukumaraswamy, S., Forsyth, A., & Lumley, T. (2021) · doi:10.31234/osf.io/q2hzm · Cited by 15
Barnett (2024) · doi:10.1089/psymed.2023.0010 · Cited by 13
Psychedelic Microdosing, Mindfulness, and Anxiety: A Cross-Sectional Mediation Study
Hartong, V., & van Emmerik, A. (2023) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2022.2080616 · Cited by 11
“ment of anxiety in patients with life threatening diseases (Gasser et al. 2014; Griffiths et al. 2016; Grob et al. 2011; Ross et al. 2016) and treatment resistant depression (Carhart-Harris et al.”
BackgroundInfluentialSelf-Care Practices with Psychedelics–A Qualitative Study of Users’ Perspectives
Soares, C. M., Leite, Â., & Pinto, M. (2023) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2022.2071134 · Cited by 10
Psychoanalyst attitudes towards psychedelic-assisted therapy
Kraiem, E., Diener, M., Guss, J., Mavrides, L., & Saban, S. (2025) · Drugs Education Prevention and Policy · doi:10.1080/09687637.2024.2359444 · Cited by 4
Could psychedelics treat personality disorders
(2022) · Journal of Addiction Science · doi:10.17756/jas.2022-057 · Cited by 3
Metadata
- Authors
- Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R.
- Affiliations
- University of Bern (CH)
- Multidisciplinary Association for Psychedelic Studies (US)
- Harvard University (US)
- Corresponding author
- Gasser, Peter
- Venue
- Journal of Nervous & Mental Disease
- Published
- 2014-07
- Volume
- 202
- Issue
- 7
- Pages
- 513-520
- ISSN
- 0022-3018 (ISSN-L)
- PMC
- PMC4086777
- OpenAlex
- W2078821747
- Cited by
- 750
- References
- 32
- Citations by year
- 2026: 47 · 2025: 72 · 2024: 113 · 2023: 74 · 2022: 89 · 2021: 109 · 2020: 63 · 2019: 34 · 2018: 41 · 2017: 37 · 2016: 38 · 2015: 20 · 2014: 11
- FWCI
- 41.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- The Journal of Nervous and Mental Disease (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- BORIS (University Library Bern) (submittedVersion, cc-by-nc-nd)
- Open Access CRIS of the University of Bern
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Social Sciences › Psychology › Social Psychology › Music Therapy and Health
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- lysergic acid diethylamide, anxiety, life-threatening illness, terminal illness, trait anxiety, state anxiety, drug safety, psychedelic therapy
- MeSH terms
- Adult, Anxiety, Anxiety Disorders, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Lysergic Acid Diethylamide, Male, Middle Aged, Neoplasms, Pilot Projects, Placebos, Psychiatric Status Rating Scales, Psychotherapy, Serotonin Antagonists, Treatment Outcome, Cross-Over Studies
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