Acute Ultra Low Dose THC Attenuates Anxiety-Like Behavior in a Mouse Model for Major-Depressive Disorder
Meitar Grad, Hadas Volkov, Noam Shomron
Journal of Molecular Neuroscience October 12, 2026 DOI: 10.1007/s12031-026-02597-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Chronic mild stress mouse model for major depressive disorder |
| Dose | 0.002 mg/kg |
| Topics | Anxiety Cannabis Depression |
| Key points | Acute ultra-low-dose THC (0.002 mg/kg) reduced anxious behavior in a chronic mild stress mouse model, and the authors identify Elmod1 as a molecular mediator of this anxiolytic effect, with glucocorticoid-related mRNAs also implicated. The treatment altered mRNAs related to neuronal differentiation and synaptic plasticity. |
Abstract
Abstract Major depressive disorder (MDD) is a prevalent psychiatric disorder, and is a leading cause of disability worldwide. Current treatments for MDD entail many side effects, and include a lag until the onset of therapeutic effects. The current hypotheses as for the etiology of MDD revolve around the monoamine hypothesis and the plasticity and neurodegeneration hypothesis. According to the latter, employing a neuroprotective treatment may help ameliorate depressive symptoms. Δ 9 -Tetrahydrocannabinol (THC) is the primary psychoactive component of the cannabis sativa plant. THC interacts with the endocannabinoid system, which was shown to be involved in the regulation of emotional states (e.g. anxiety) and stress through modulation of synaptic plasticity. Here, we show the potential of acute, ultra-low dose (0.002 mg/kg) THC in ameliorating anxious behavior in a chronic mild stress mouse model for MDD. We utilize next generation sequencing techniques to show the treatment’s effect on neuronal differentiation and synaptic plasticity-related mRNAs, and specify Elmo domain containing 1 ( Elmod1 ) as a molecular mediator of the observed anxiolytic effects. Moreover, we show the involvement of glucocorticoids-related mRNAs in the observed anxiolytic effect of acute, ultra-low dose THC.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Acute ultra-low-dose THC (0.002 mg/kg) reduced anxiety-like behavior, with Elmod1 and glucocorticoid-related mRNAs implicated as mediators.
Synthesized
Comparable studies
Other preclinical and animal studies on cannabis for anxiety, most cited first.
Citations in the library
Cites 11
- Beyond the serotonin deficit hypothesis: communicating a neuroplasticity framework of major depressive disorder. Molecular Psychiatry December 1, 2024
- Functional effects of synthetic cannabinoids versus Δ9 -THC in mice on body temperature, nociceptive threshold, anxiety, cognition, locomotor/exploratory parameters and depression. Addiction Biology May 1, 2019
- Hippocampal differential expression underlying the neuroprotective effect of delta-9-tetrahydrocannabinol microdose on old mice. Frontiers in Neuroscience July 18, 2023
- Differential effects of Δ9-tetrahydrocannabinol dosing on correlates of schizophrenia in the sub-chronic PCP rat model. PLoS One 2020
- Cannabis effects on brain structure, function, and cognition: considerations for medical uses of cannabis and its derivatives The American Journal of Drug and Alcohol Abuse July 31, 2019
and 6 more in the library