Can melatonin cause anxiety
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Can Melatonin Cause Anxiety?
Introduction to Melatonin and Anxiety
Melatonin, a hormone produced by the pineal gland, is widely recognized for its role in regulating sleep-wake cycles. It has also been explored for its potential therapeutic effects on anxiety. Anxiety disorders are prevalent mental health conditions that can significantly impact daily life. Understanding whether melatonin can cause or alleviate anxiety is crucial for its safe and effective use.
Melatonin's Anxiolytic Effects
Preoperative and Postoperative Anxiety
Several studies have investigated melatonin's effects on anxiety in surgical settings. A comprehensive review of 27 randomized controlled trials (RCTs) involving 2319 participants found that melatonin likely reduces preoperative anxiety compared to placebo, with a mean difference of -11.69 on a visual analogue scale (VAS) . Additionally, melatonin may reduce immediate postoperative anxiety, although the effect is smaller and of uncertain clinical relevance . Another systematic review of 12 RCTs with 774 patients supported these findings, showing that melatonin can reduce preoperative anxiety and may be as effective as midazolam, a commonly used benzodiazepine .
Anxiety in Animal Models
Preclinical studies have also demonstrated melatonin's anxiolytic effects. In a mouse model of sleep deprivation, melatonin supplementation was found to suppress anxiety-like behaviors and reduce corticosterone levels, a stress hormone . Similarly, in rats exposed to chronic unpredictable mild stress, melatonin treatment improved anxiety-like behaviors and increased hippocampal dopamine content, suggesting a role in modulating the dopaminergic system .
Mechanisms of Action
Oxidative Stress and Neuroinflammation
Melatonin's anxiolytic effects may be attributed to its antioxidant properties. In sleep-deprived rats, melatonin prevented anxiety-like behavior by reducing oxidative stress and maintaining a balance between GABAergic and glutamatergic transmission . Another study found that melatonin alleviated anxiety-like behaviors in a traumatic brain injury model by activating the protein kinase A/cAMP-response element-binding protein (PKA/CREB) signaling pathway and reducing neuroinflammation .
Neuroprotective Effects
Melatonin's neuroprotective capabilities also play a role in its anxiolytic effects. In a study on Alzheimer's disease (AD) mice, melatonin treatment ameliorated anxiety and depression-like behaviors, potentially through modulating the expression of anxiety-associated proteins such as glutathione S-transferase P 1 (GSTP1) .
Clinical Implications
Safety and Tolerability
Melatonin is generally well-tolerated with few adverse effects. In clinical trials, common side effects included nausea, sleepiness, dizziness, and headache, but no serious adverse events were reported . This favorable safety profile makes melatonin an attractive option for managing anxiety, especially in comparison to benzodiazepines, which are associated with higher risks of sedation and cognitive impairment .
Potential for Anxiety Reduction
Given the evidence, melatonin appears to have a beneficial effect on anxiety, particularly in preoperative and postoperative settings, as well as in animal models of stress and neurodegenerative diseases. Its anxiolytic effects are likely mediated through its antioxidant properties, modulation of neurotransmitter systems, and neuroprotective actions.
Conclusion
Current research suggests that melatonin does not cause anxiety; rather, it may have significant anxiolytic effects. These effects are supported by both clinical and preclinical studies, highlighting melatonin's potential as a safe and effective treatment for anxiety. Further research is needed to fully understand the mechanisms and optimize its use in various anxiety-related conditions.
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