Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression
Meghan Hibicke, Alexus N. Landry, Hannah M. Kramer, Zoe K. Talman, Charles D. Nichols
ACS Chemical Neuroscience March 5, 2020 DOI: 10.1021/acschemneuro.9b00493 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Psilocybin Lysergic acid diethylamide (LSD) Ketamine |
| Topics | Anxiety Ketamine LSD Psilocybin Serotonin Depression |
| Keywords | Antidepressant Hallucinogen Pharmacology Depression economics Receptor |
| Citations | 211 |
| Key points | Classic psychedelics may have more persistent antidepressant-like effects than ketamine, and a subjective existential experience may not be necessary for therapeutic effects. |
Abstract
Psilocybin shows efficacy to alleviate depression in human clinical trials for six or more months after only one or two treatments. Another hallucinogenic drug, esketamine, has recently been U.S. Food and Drug Administration (FDA)-approved as a rapid-acting antidepressant. The mechanistic basis for the antidepressant effects of psilocybin and ketamine appear to be conserved. The efficacy of these two medications has not, however, been directly compared either clinically or preclinically. Further, whether or not a profound subjective existential experience is necessary for psilocybin to have antidepressant effects is unknown. To address these questions, we tested psilocybin, lysergic acid diethylamide (LSD), and ketamine in a rat model for depression. As in humans, a single administration of psilocybin or LSD produced persistent antidepressant-like effects in our model. In contrast, ketamine produced only a transient antidepressant-like effect. Our results indicate that classic psychedelics may have therapeutic efficacy that is more persistent than that of ketamine, and also suggest that a subjective existential experience may not be necessary for therapeutic effects.
In the evidence
This study is part of the evidence base for 3 syntheses in the library. Here is how each one recorded it.
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In a rat depression model, ketamine produced only a transient antidepressant-like effect, whereas psilocybin and LSD produced persistent effects.
Synthesized
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A single administration of psilocybin or LSD produced persistent antidepressant-like effects in a rat model, more durable than ketamine.
Synthesized
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A single administration of psilocybin or LSD produced persistent antidepressant-like effects in a rat model, unlike ketamine which produced only transient effects.
Synthesized
Comparable studies
Other preclinical and animal studies on LSD for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Mice and cultured rat cortical neurons | 2023 | Preclinical study | |
| Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling Male rats (olfactory bulbectomised and sham-operated) | 2014 | Animal model study | |
| LSD's rapid antidepressant effects are modulated by 5-HT2B receptors. Naive rats and naive mice | 2025 | Experimental study | |
| 401. Prophylactic effects of LSD on inflammatory rodent model of depression Male mice and male rats | 2026 | Preclinical animal study |