Lysergic Acid Diethylamide (LSD) for the Treatment of Anxiety Disorders: Preclinical and Clinical Evidence.
Antonio Inserra, Alexandre Piot, Danilo de Gregorio, Gabriella Gobbi
CNS Drugs September 1, 2023 DOI: 10.1007/s40263-023-01008-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Peer reviewed |
|---|---|
| Intervention | Lysergic acid diethylamide (LSD) |
| Topics | Anxiety LSD |
| Keywords | Psychedelics Clinical research Therapeutic drugs Mental health Anxiety treatment |
| Citations | 17 |
| Key findings | LSD induces long-lasting anxiolytic effects despite acutely exacerbating anxiety, with only two randomized controlled trials showing good safety and persistent decreases in anxiety outcomes. |
Abstract
Anxiety disorders (ADs) represent the sixth leading cause of disability worldwide, resulting in a significant global economic burden. Over 50% of individuals with ADs do not respond to standard therapies, making the identification of more effective anxiolytic drugs an ongoing research priority. In this work, we review the preclinical literature concerning the effects of lysergic acid diethylamide (LSD) on anxiety-like behaviors in preclinical models, and the clinical literature on anxiolytic effects of LSD in healthy volunteers and patients with ADs. Preclinical and clinical findings show that even if LSD may exacerbate anxiety acutely (both in "microdoses" and "full doses"), it induces long-lasting anxiolytic effects. Only two randomized controlled trials combining LSD and psychotherapy have been performed in patients with ADs with and without life-threatening conditions, showing a good safety profile and persisting decreases in anxiety outcomes. The effect of LSD on anxiety may be mediated by serotonin receptors (5-HT1A/1B, 5-HT2A/2C, and 5-HT7) and/or transporter in brain networks and circuits (default mode network, cortico-striato-thalamo-cortical circuit, and prefrontal cortex-amygdala circuit), involved in the modulation of anxiety. It remains unclear whether LSD can be an efficacious treatment alone or only when combined with psychotherapy, and if "microdosing" may elicit the same sustained anxiolytic effects as the "full doses". Further randomized controlled trials with larger sample size cohorts of patients with ADs are required to clearly define the effective regimens, safety profile, efficacy, and feasibility of LSD for the treatment of ADs.
Comparable studies
Other narrative reviews on LSD for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Modern Clinical Research on LSD | 2017 | Review | |
| Ayahuasca: Pharmacology, neuroscience and therapeutic potential | 2016 | Review | |
| Psychedelic Drugs in Biomedicine | 2017 | Review | |
| Studies on Lysergic Acid Diethylamide (LSD-25) Nonpsychotic subjects | 1956 | Review | |
| The Past and Future of Psychedelic Science: An Introduction to This Issue | 2019 | Review |
Citations in the library
Cited by 5
- Psychedelics as an intervention for psychological, existential distress in terminally ill patients: A systematic review and network meta-analysis Journal of Psychopharmacology December 10, 2024
- Psychedelic use and bipolar disorder - An investigation of recreational use and its impact on mental health. Journal of Affective Disorders March 15, 2025
- Clinical Research on Lysergic Acid Diethylamide (LSD) in Psychiatry and Neuroscience. Pharmaceuticals (Basel, Switzerland) March 29, 2025
- Psychedelics in developmental stuttering to modulate brain functioning: a new therapeutic perspective? Front Hum Neurosci June 19, 2024
- The Selective Serotonin 5-HT2A Receptor Agonist (S)-3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine (LPH-5) Induces Persistent and Robust Antidepressant-Like Effects in Rodents ACS Pharmacology & Translational Science May 29, 2025
Cites 15
- Lysergic Acid Diethylamide-Assisted Therapy in Patients With Anxiety With and Without a Life-Threatening Illness: A Randomized, Double-Blind, Placebo-Controlled Phase II Study. Biological Psychiatry February 1, 2023
- Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects. Neuroimage August 1, 2019
- Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects Neuropsychopharmacology November 16, 2019
- Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects Neuropsychopharmacology October 15, 2020
- Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects Neuropsychopharmacology February 25, 2022
and 10 more in the library