The Dual Action: How Licorice Affects the Central Nervous System
The sedative effects of licorice are not a simple phenomenon but are rooted in complex biological interactions. The primary active compounds, particularly certain flavonoids, have been found to influence key systems that regulate rest and relaxation in the body.
GABA Receptor Modulation
One of the most significant ways licorice can promote sleepiness is by interacting with the brain's gamma-aminobutyric acid (GABA) system. GABA is the chief inhibitory neurotransmitter in the central nervous system, responsible for reducing neuronal excitability throughout the nervous system. Essentially, GABA helps to calm the nerves and induce a state of relaxation. Several studies have shown how licorice's compounds, such as the flavonoid glabridin, can positively modulate GABAA receptors, amplifying the effects of natural GABA.
- Potentiation: Glabridin from licorice has been shown to potentiate GABA's effects in a dose-dependent manner, similar to prescription hypnotic drugs.
- Regulation: Glycyrrhizin, another key compound, has been found to upregulate the level of GABA and its receptors, further promoting the body's natural calming processes.
This GABAergic action is similar to how benzodiazepine drugs work to induce sedation, explaining why consuming licorice may lead to a feeling of calm and drowsiness. The potentiation of GABAergic inhibition in the brain's dorsal raphe neurons is a scientifically validated mechanism for its hypnotic effects.
Cortisol and Adrenal Function
Licorice's effects are not limited to neurotransmitters. Another crucial mechanism involves its impact on the body's stress hormone, cortisol. The active compound glycyrrhizin, found in non-deglycyrrhizinated licorice, inhibits the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme is responsible for converting active cortisol into its inactive form, cortisone. By inhibiting this conversion, licorice causes a buildup of active cortisol, which can lead to fatigue and lethargy over time despite initial stimulation.
The Licorice-Cortisol Connection Explained:
- Ingestion: You consume licorice containing glycyrrhizin.
- Enzyme Inhibition: Glycyrrhizin blocks the 11β-HSD2 enzyme in the kidneys.
- Cortisol Buildup: This blockage prevents cortisol from being inactivated.
- Hormonal Chaos: High circulating cortisol levels cause mineralocorticoid-like effects, including sodium retention and potassium loss, which can contribute to the feeling of fatigue.
This can create a paradox: initially, licorice might be used as an adrenal tonic for energy support, but with excessive intake, it can disrupt the natural hormonal rhythm and cause a rebound effect of tiredness.
Potential Side Effects and Safety Concerns
While the sedative effects might be welcome for some, licorice can cause a range of adverse effects, especially with chronic or excessive consumption. These side effects are directly related to the dose of glycyrrhizin and its impact on hormonal and electrolyte balance.
The Risk of Hypokalemia
One of the most well-documented side effects of excessive licorice intake is hypokalemia, or low potassium levels. This occurs because the glycyrrhizin-induced hormonal imbalance causes the kidneys to excrete more potassium. Symptoms of low potassium include muscle weakness and lethargy, which can contribute significantly to the feeling of sleepiness or general tiredness. In severe cases, this can lead to irregular heart rhythms and heart failure.
DGL vs. Regular Licorice
Understanding the difference between traditional licorice and its alternative, deglycyrrhizinated licorice (DGL), is crucial for managing these side effects. DGL is processed to remove most of the glycyrrhizin, making it a much safer option for long-term use.
| Feature | Standard Licorice (Glycyrrhiza) | Deglycyrrhizinated Licorice (DGL) | |
|---|---|---|---|
| Glycyrrhizin Content | High | Low (often <3%) | |
| Effect on Cortisol | Inhibits conversion to cortisone, raising active cortisol levels | Minimal to no effect | |
| Effect on Potassium | Can cause low potassium levels (hypokalemia) | Minimal to no effect | |
| Sedative/Hypnotic Effects | Potentiates GABA, potentially causing sleepiness and lethargy | Less likely to cause sleepiness via hormonal pathways | |
| Safety for Long-Term Use | Not recommended due to significant side effects (hypertension, edema) | Considered safer for long-term use | n |
Conclusion: Navigating Licorice and Your Energy Levels
To summarize, licorice can make you sleepy through a dual-action mechanism involving its flavonoid compounds and the active triterpene, glycyrrhizin. Flavonoids like glabridin act directly on the brain's GABA receptors, enhancing their calming effects, while glycyrrhizin disrupts cortisol metabolism and can lead to electrolyte imbalances like hypokalemia, both of which result in lethargy and fatigue. The intensity of these effects largely depends on the amount of glycyrrhizin consumed. For those who experience sleepiness from licorice, particularly from consuming products with high concentrations of glycyrrhizin, moderation is key. A safer alternative for long-term use, especially for those sensitive to glycyrrhizin's effects, is to choose deglycyrrhizinated licorice (DGL). Always be mindful of the quantity you consume, and if you have pre-existing health conditions like heart disease or high blood pressure, consult a healthcare provider before regular consumption. A deeper dive into the science of licorice's hypnotic effects can be found in this study: Potentiating effect of glabridin on GABAA receptor ....
Why Licorice Can Cause Lethargy and Sleepiness
- GABAergic Activity: Flavonoid compounds in licorice, such as glabridin, can boost the activity of the calming neurotransmitter GABA in the brain, promoting sleepiness.
- Cortisol Regulation: Glycyrrhizin inhibits an enzyme that deactivates cortisol, leading to higher active cortisol levels that can disrupt hormonal balance and cause fatigue.
- Electrolyte Imbalance: Excessive intake of glycyrrhizin can cause low potassium (hypokalemia), resulting in muscle weakness and lethargy.
- DGL is Different: Deglycyrrhizinated licorice (DGL) has had the glycyrrhizin removed, making it a safer option for avoiding hormonal and electrolyte side effects associated with fatigue.
- Dosage Matters: The risk of experiencing sleepiness and lethargy is dose-dependent, with high or chronic consumption being more likely to cause adverse effects.
