Cannabidiol exhibits anxiolytic-like effects and antipsychotic-like effects in mice models.
Guangzhao Shu, Yang He, Jin Suo, Chunhui Wu, Xu-Bin Gong, Ya-juan Xiang, Wenjiao Yang, Jiaxin Cheng, Yu Wang, Weiming Chen, Jing-Shan Shen
Neuroscience Letters March 1, 2024 DOI: 10.1016/j.neulet.2024.137723 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study (in vitro and in vivo animal study) Peer reviewed |
|---|---|
| Population | CHO cells expressing human 5-HT1A receptors, rats, and mice |
| Interventions | Cannabidiol (CBD) WAY-100635 Phencyclidine (PCP) |
| Dose | CBD 3 mg/kg; CBD 100 mg/kg |
| Measures | Lower lip retraction test (LLR), stress-induced hyperthermia (SIH), forced swim test (FST), tail suspension test (TST), LC-MS/MS neurotransmitter measurement |
| Topics | CBD |
| Key findings | CBD acted as a 5-HT1A receptor agonist in vitro (EC50 = 1.75 μM) and produced 5-HT1A-mediated effects in rats; at 3 mg/kg it reduced stress-induced hyperthermia in mice, an effect abolished by the 5-HT1A antagonist WAY-100635. Chronic CBD at 100 mg/kg reduced phencyclidine-induced immobility and altered hippocampal GABA and norepinephrine levels. The authors conclude that the 5-HT1A receptor mediates CBD's anxiolytic-like effects, while its effects on negative schizophrenia-like symptoms may involve hippocampal GABA and norepinephrine. |
Abstract
Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has been confirmed to induce anxiolytic-like and antipsychotic-like effects. However, the exact mechanisms remain unclear. This study substantiated CBD's interaction with the 5-HT1A receptor (5-HT1AR) in vitro (CHO cells expressing human 5-HT1AR) and in vivo (rat lower lip retraction test, LLR test). We then assessed the impact of CBD in mice using the stress-induced hyperthermia (SIH) model and the phencyclidine (PCP)-induced negative symptoms of schizophrenia model, respectively. Concurrently, we investigated whether WAY-100635, a typical 5-HT1AR antagonist, could attenuate these effects. Furthermore, the neurotransmitter changes through high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were studied. Results revealed that CBD exhibits selective 5-HT1AR agonists-mediated effects in the rat lower lip retraction test, aligning with the robust agonistic (EC50 = 1.75 μM) profile observed in CHO cells. CBD at 3 mg/kg significantly reduced SIH (ΔT), a response that WAY-100635 abolished. Chronic administration of CBD at 100 mg/kg mitigated the increase in PCP-induced immobility time in the forced swim test (FST) and tail suspension test (TST). Moreover, it induced significant alterations in gamma-aminobutyric acid (GABA) and norepinephrine (NE) levels within the hippocampus (HPC). Thus, we concluded that the 5-HT1AR mediates CBD's anxiolytic-like effects. Additionally, CBD's effects on the negative symptoms of schizophrenia may be linked to changes in GABA and NE levels in the hippocampus. These findings offer novel insights for advancing the exploration of CBD's anxiolytic-like and antipsychotic-like effects.