Effects of cannabidiol, with and without ∆9-tetrahydrocannabinol, on anxiety-like behavior following alcohol withdrawal in mice.
Mariam Melkumyan, Vibha M Annaswamy, Alexandra M Evans, Opeyemi F Showemimo, Zari E McCullers, Dongxiao Sun, Terrence E Murphy, Kent E Vrana, Amy C Arnold, Wesley M Raup-Konsavage, Yuval Silberman
Frontiers in Neuroscience 2024 DOI: 10.3389/fnins.2024.1375440 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment (mouse study) Peer reviewed |
|---|---|
| Population | Mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure |
| Interventions | Cannabidiol (CBD) CBD:THC (3:1 ratio) |
| Duration | Acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure |
| Measures | open field test, immunohistochemical analysis (S100β and Iba1 cell counts) |
| Topics | Anxiety Cannabis CBD |
| Keywords | Cannabidiol CBD Alcohol withdrawal Astrocytes Microglia Open field test ∆9-Tetrahydrocannabinol THC |
| Key findings | CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-hour withdrawal, whereas at 24 hours CBD alone reduced anxiety-like behaviors and CBD:THC produced mixed effects (increased center time but also increased immobility). Cannabinoids reversed withdrawal-associated decreases in S100β and Iba1 cell counts in the central amygdala seen at 4 hours but not 24 hours. The authors suggest cannabinoid effects on withdrawal anxiety depend on timing of use and may involve central amygdala neuroimmune function. |
Abstract
Alcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate continued alcohol use. Alcohol increases neuroimmune activity in the brain. Our recent evidence indicates that alcohol directly modulates neuroimmune function in the central amygdala (CeA), a key brain region regulating anxiety and alcohol intake, to alter neurotransmitter signaling. We hypothesized that cannabinoids, such as cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), which are thought to reduce neuroinflammation and anxiety, may have potential utility to alleviate alcohol withdrawal-induced stress-sensitivity and anxiety-like behaviors via modulation of CeA neuroimmune function. We tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor. We found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100β and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects.. These results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.