GABA

Both promote calm through different mechanisms

Enhanced relaxation without sedation

⟡ Magnesium

Magnesium is a GABA receptor co-agonist

Supports GABA function and relaxation

Top studies from 38+ peer-reviewed papers

📚meta-analysisn=3838

Liu J et al. • The Cochrane database of systematic reviews (2018)

“This review provides moderate-quality evidence that fails to support the use of GABA receptor agonists (chlormethiazole or diazepam) for the treatment of people with acute stroke.”

Key Findings:

The most frequent adverse events related to chlormethiazole were somnolence (RR 4.56, 95% CI 3.50 to 5.95; two trials; 2527 participants; moderate-quality evidence) and rhinitis (RR 4.75, 95% CI 2.67 to 8.46; two trials; 2527 participants; moderate-quality evidence).
This review provides moderate-quality evidence that fails to support the use of GABA receptor agonists (chlormethiazole or diazepam) for the treatment of people with acute stroke.
More well-designed RCTs with large samples of participants with total anterior circulation syndrome are required to determine if there are benefits for this subgroup.
Somnolence and rhinitis are frequent adverse events related to chlormethiazole.

📊rctn=393

Guo X et al. • JAMA network open (2024)

“Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China.”

Key Findings:

Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d.
A total of 644 patients (88.8%) completed the study.
In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common.

📚meta-analysis

Thomson AR et al. • Neuroscience and biobehavioral reviews (2024)

“Data were extracted and grouped by metabolite, brain region and several other factors before calculation of standardised effect sizes.”

Key Findings:

Data were extracted and grouped by metabolite, brain region and several other factors before calculation of standardised effect sizes.
Further analysis found these alterations are most pronounced in autistic children and in limbic brain regions relevant to autism phenotypes.
Additionally, we show how study outcome varies due to demographic and methodological factors , emphasising the importance of conforming with standardised consensus study designs and transparent reporting.

📚meta-analysisn=7993

Nakahara T et al. • Molecular psychiatry (2022)

“Increased glutamatergic metabolite levels and reduced GABA levels indicate that the disruption of excitatory/inhibitory balance may be related to the pathophysiology of schizophrenia-spectrum disorders.”

Key Findings:

In the whole group, Glx levels in the basal ganglia (g = 0.32; 95% CIs: 0.18-0.45) were elevated.
Subgroup analyses showed elevated Glx levels in the hippocampus (g = 0.47; 95% CIs: 0.21-0.73) and dorsolateral prefrontal cortex (g = 0.25; 95% CIs: 0.05-0.44) in unmedicated patients than HC.
GABA levels in the MCC were decreased in the first-episode psychosis group compared with HC (g = -0.40; 95% CIs: -0.62 to -0.17).

📊rctn=150

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Deligiannidis KM et al. • JAMA psychiatry (2021)

“In this randomized clinical trial, zuranolone improved the core symptoms of depression as measured by HAMD-17 scores in women with PPD and was generally well tolerated, supporting further development of zuranolone in the treatment of PPD.”

Key Findings:

Of 153 randomized patients, the efficacy set comprised 150 patients (mean [SD] age, 28.3 [5.4] years), and 148 (98.7%) completed treatment.
Zuranolone demonstrated significant day 15 HAMD-17 score improvements from baseline vs placebo (-17.8 vs -13.6; difference, -4.2; 95% CI, -6.9 to -1.5; P = .003).
Sustained differences in HAMD-17 scores favoring zuranolone were observed from day 3 (difference, -2.7; 95% CI, -5.1 to -0.3; P = .03) through day 45 (difference, -4.1; 95% CI, -6.7 to -1.4; P = .003).

View all 38+ studies

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GABA

amino acid

Gamma-Aminobutyric Acid

Inhibitory neurotransmitter that calms neural activity — may work through the gut-brain axis for acute anxiety and sleep support.

sleepmentalrelaxationanxietycalmstress

38+ studies

Evidence

Reviewed 19 days ago

high

Safety

250-750mg

Dose

1- days

Time to Effect

Capsules or powder

Best Form

Mechanisms of Action

🧠

GABA Receptor Activation

May activate GABA receptors, promoting calm

🔄

Gut-Brain Communication

May signal relaxation through the gut

Biological PathwayBeta

How GABA works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.

Supplement

Molecular Target

Biological Process

Health Outcome

Strong

Moderate

Emerging

strong

moderate

emerging

Tap node to isolate • Pinch to zoom • Tap edge for research

Recommended Dose

250-750mg

100mg1500mg

Optimal Timing

30-60 minutes before desired effect
Before bed for sleep
Before stressful events for anxiety

Can be taken without food

Available Forms

Form	Type
💊Capsules or powder	Recommended
💊Chewables	Alternative
💊Sublingual tablets	Alternative
💊PharmaGABA (fermented form)	Alternative

PharmaGABA is a naturally-produced form that may have better effects. Sublingual may work faster.

Duration

Minimum: 1 days

Optimal: days

Cycling: Best used as needed rather than daily. Tolerance may develop with chronic use.

Note: Can be taken with or without food. Start with lower doses to assess response. Some take sublingually for faster effects.

😌

Relaxation

Feeling of calm and reduced tension

📅 30-60 minutes

65% of users notice thispositive

😮‍💨

Reduced Anxiety

Less acute stress and worry

📅 30-60 minutes

60% of users notice thispositive

😴

Drowsiness

May cause sleepiness, especially at higher doses

📅 30-60 minutes

40% of users notice thisneutral

High SafetyMax safe dose: Up to 3000mg shown safe acutely, but not necessary

🔴

Pregnant/nursing

Insufficient data; avoid to be safe

🟡

Those on psychiatric medications

Consult doctor before use

Who Should NOT Take This

Those taking sedatives or anti-anxiety medications (without doctor approval)

Drug Interactions

Benzodiazepinesmoderate

May have additive sedative effects

Blood pressure medicationsmild

GABA may lower blood pressure

Alcoholmoderate

Additive sedative effects

Possible Side Effects

Drowsiness

mildcommon

Tip: Reduce dose; don't drive after taking

Tingling/flushing

milduncommon

Tip: Usually harmless and temporary

Shortness of breath (at very high doses)

moderateuncommon

Tip: Reduce dose significantly

Warnings

May cause drowsiness — don't drive or operate machinery
Scientific debate exists about whether oral GABA crosses blood-brain barrier
Avoid combining with alcohol or sedatives

⟡ L-Theanine

Both promote calm through different mechanisms

Enhanced relaxation without sedation

⟡ Magnesium

Magnesium is a GABA receptor co-agonist

Supports GABA function and relaxation

Top studies from 38+ peer-reviewed papers

📚meta-analysisn=3838

Liu J et al. • The Cochrane database of systematic reviews (2018)

“This review provides moderate-quality evidence that fails to support the use of GABA receptor agonists (chlormethiazole or diazepam) for the treatment of people with acute stroke.”

Key Findings:

The most frequent adverse events related to chlormethiazole were somnolence (RR 4.56, 95% CI 3.50 to 5.95; two trials; 2527 participants; moderate-quality evidence) and rhinitis (RR 4.75, 95% CI 2.67 to 8.46; two trials; 2527 participants; moderate-quality evidence).
This review provides moderate-quality evidence that fails to support the use of GABA receptor agonists (chlormethiazole or diazepam) for the treatment of people with acute stroke.
More well-designed RCTs with large samples of participants with total anterior circulation syndrome are required to determine if there are benefits for this subgroup.
Somnolence and rhinitis are frequent adverse events related to chlormethiazole.

📊rctn=393

Guo X et al. • JAMA network open (2024)

“Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China.”

Key Findings:

Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d.
A total of 644 patients (88.8%) completed the study.
In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common.

📚meta-analysis

Thomson AR et al. • Neuroscience and biobehavioral reviews (2024)

“Data were extracted and grouped by metabolite, brain region and several other factors before calculation of standardised effect sizes.”

Key Findings:

Data were extracted and grouped by metabolite, brain region and several other factors before calculation of standardised effect sizes.
Further analysis found these alterations are most pronounced in autistic children and in limbic brain regions relevant to autism phenotypes.
Additionally, we show how study outcome varies due to demographic and methodological factors , emphasising the importance of conforming with standardised consensus study designs and transparent reporting.

📚meta-analysisn=7993

Nakahara T et al. • Molecular psychiatry (2022)

“Increased glutamatergic metabolite levels and reduced GABA levels indicate that the disruption of excitatory/inhibitory balance may be related to the pathophysiology of schizophrenia-spectrum disorders.”

Key Findings:

In the whole group, Glx levels in the basal ganglia (g = 0.32; 95% CIs: 0.18-0.45) were elevated.
Subgroup analyses showed elevated Glx levels in the hippocampus (g = 0.47; 95% CIs: 0.21-0.73) and dorsolateral prefrontal cortex (g = 0.25; 95% CIs: 0.05-0.44) in unmedicated patients than HC.
GABA levels in the MCC were decreased in the first-episode psychosis group compared with HC (g = -0.40; 95% CIs: -0.62 to -0.17).

📊rctn=150

Compare with Others Find Based on Your Goals

Deligiannidis KM et al. • JAMA psychiatry (2021)

“In this randomized clinical trial, zuranolone improved the core symptoms of depression as measured by HAMD-17 scores in women with PPD and was generally well tolerated, supporting further development of zuranolone in the treatment of PPD.”

Key Findings:

Of 153 randomized patients, the efficacy set comprised 150 patients (mean [SD] age, 28.3 [5.4] years), and 148 (98.7%) completed treatment.
Zuranolone demonstrated significant day 15 HAMD-17 score improvements from baseline vs placebo (-17.8 vs -13.6; difference, -4.2; 95% CI, -6.9 to -1.5; P = .003).
Sustained differences in HAMD-17 scores favoring zuranolone were observed from day 3 (difference, -2.7; 95% CI, -5.1 to -0.3; P = .03) through day 45 (difference, -4.1; 95% CI, -6.7 to -1.4; P = .003).

View all 38+ studies

What would you like to do next?

Related Supplements

Lth9.0

L-Theanine

9/10

Tea-derived amino acid that boosts alpha brain waves for calm, focused alertness — synergizes with caffeine to reduce jitteriness.

Htp8.5

5-HTP

Direct serotonin precursor that may support mood, sleep, and appetite control, but requires caution with certain medications.

Mg8.5

Magnesium