GABA
GABA/Drug Interactions:
AlcoholAlcohol: Ethanol is known to exert effects through potentiating the GABA(A) receptor (45; 46). Alcohol and GABA supplementation may have synergistic effects. In rodent models of chronic alcohol exposure, ethanol reduced the sensitivity of GABA(A) receptors to benzodiazepines (74). GABA(A) receptor function altered by ethanol may alter the effects of exogenous GABA. Conversely, the GABA analog gabapentin has been shown to ameliorate alcohol-induced sleep disturbances (75). GABA may have similar effects, though this has not been conclusively demonstrated. AnticoagulantsAnticoagulants: In human research, five patients taking GABA and phosphatidylserine had decreased fibrinogen and prothrombin time (12), although the effects of GABA alone were unclear. AnticonvulsantsAnticonvulsants: In animal (59; 81) and human research (12; 13), GABA given with phosphatidylserine had anticonvulsant effects. AntihypertensivesAntihypertensives: In animal research, GABA had antihypertensive effects (25; 82; 28; 27; 83; 84). In dogs, GABA was shown to inhibit the vasoconstrictive effects of angiotensin II at a low dose (50mcg), but not at a high dose (500mcg) (85). AntineoplasticsAntineoplastics: In animal research, GABA reduce chemically induced colonic neoplasias (14; 15). BarbituratesBarbiturates: Barbiturates are known to be allosteric modulators of the GABA(A) receptor and may also act as direct GABA agonists (47). Pentobarbital has been shown to increase the response to exogenous GABA in hippocampal cells (48). BenzodiazepinesBenzodiazepines: Benzodiazepines are known to be allosteric modulators of the GABA(A) receptor (47). GABA is also known to increase the affinity of brain receptors to benzodiazepines (76). In fact, the pharmacological actions of benzodiazepines are produced mostly by enhancing the effects of endogenous and exogenous GABA (77; 78). Studies also suggest that benzodiazepines increase GABA uptake in synapses (17). Beta-carbolinesBeta-carbolines: Beta-carbolines are known to be direct GABA agonists (47). They may enhance the effects of exogenous GABA. Chloride channel blockersChloride channel blockers: Picrotoxin, a chloride channel blocker, has been shown to abolish the effects of exogenous GABA (49). Dopaminergic agentsDopaminergic agents: GABA has been shown to suppress dopamine-induced prolactin secretion when administered together (50mg of GABA and 500mg of dopamine, infused over 60 minutes) (50). It is believed that the stimulatory effects of GABA on prolactin secretion are due to inhibition of endogenous dopamine. GABA transporter (GAT) inhibitorsGABA transporter (GAT) inhibitors: GAT inhibitors, such as the anticonvulsant drug tiagabine, increase the effects of endogenous GABA by blocking transporter-mediated reuptake (47). GAT inhibitors may thus potentiate the effects of exogenous GABA. GABA(A) receptor antagonistsGABA(A) receptor antagonists: Bicuculline, a specific GABA(A) receptor antagonist, has been shown to abolish the effects of exogenous GABA (49). GABAergic drugsGABAergic drugs: Numerous drugs (notably antiepileptic agents) exert effects through GABA receptor-mediated effects (51). These include barbiturates and benzodiazepines, which are known to be allosteric modulators of the GABA(A) receptor (47). Other GABAergic drugs directly act as GABA agonists (including beta-carbolines and barbiturates) or increase endogenous GABA levels and/or neurotransmission (such as gabapentin, pregabalin, valproate, and vigabatrin (47). Exogenous GABA may interact with these agents; however, this is not clear. Some experts recommend that patients taking GABAergic drugs avoid exogenous GABA supplementation. Hepatic agentsHepatic agents: In human research, five patients treated with GABA and phosphatidylserine had slightly increased glutamate pyruvate transaminase (GPT) (12). Neuroactive steroidsNeuroactive steroids: Neuroactive steroids are known to be allosteric modulators of the GABA(A) receptor and may also act as direct GABA agonists (47). Thus, neuroactive steroids may potentially alter the effects of exogenous GABA. PicrotoxinPicrotoxin: Picrotoxin, a chloride channel blocker, has been shown to abolish the effects of exogenous GABA (49). SedativesSedatives
: In human research, oral GABA intake resulted in stress-reducing effects (14; 15) and a lack of alertness (50). However, intravenous doses of GABA (0.1-1.0mg/kg) resulted in anxiety, dysphoria, and mood disturbance in both normal volunteers and euthymic bipolar patients (52). Selective serotonin reuptake inhibitors (SSRIs)Selective serotonin reuptake inhibitors (SSRIs): 5-HTP is a precursor to serotonin, which is known to potentiate GABAergic effects (37). GABA/Herb/Supplement Interactions:
5-HTP5-HTP: 5-HTP is a precursor to serotonin, which is known to potentiate GABAergic effects (37). AnticoagulantsAnticoagulants: In human research, five patients taking GABA and phosphatidylserine had decreased fibrinogen and prothrombin time (12), although the effects of GABA alone were unclear. AnticonvulsantsAnticonvulsants: In animal (59; 81) and human research (12; 13), GABA given with phosphatidylserine had anticonvulsant effects. Antihypertensive herbs and supplementsAntihypertensive herbs and supplements: In animal research, GABA had antihypertensive effects (25; 82; 28; 27; 83; 84). In dogs, GABA was shown to inhibit the vasoconstrictive effects of angiotensin II at a low dose (50mcg), but not at a high dose (500mcg) (85). Antineoplastic herbs and supplementsAntineoplastic herbs and supplements: In animal research, GABA reduce chemically induced colonic neoplasias (14; 15). CoffeeCoffee: Coffee extracts have been shown to inhibit GABA(A) receptor response in cultured oocytes (38). The clinical relevance of this interaction is unclear. GABAergic herbs and supplementsGABAergic herbs and supplements: For many dietary supplements that are used widely for enhancing memory and reducing insomnia, the mechanisms of action are thought to be mediated by endogenous GABA. These include 5-HTP, hop (Humulus lupulus), kava (Piper methysticum), lemon balm (Melissa officinalis), passion flower (Passiflora spp.), skullcap (Scutellaria spp.), and valerian (Valeriana officinalis) (7). These substances may interact with exogenous GABA; however, this is not clear. Some experts recommend that GABA should be taken separately from other dietary supplements. HepaticsHepatics: In human research, five patients treated with GABA and phosphatidylserine had slightly increased glutamate pyruvate transaminase (GPT) (12). L-arginineL-arginine: In electrophysiological experiments, L-arginine increased membrane currents induced by exogenous GABA (39). The clinical relevance of this interaction is unclear. MagnesiumMagnesium: In electrophysiological experiments, magnesium potentiated GABAergic synaptic mediated by GABA(A) receptors (40). Theoretically, magnesium may increase the effects of GABA supplementation, but the clinical relevance of this potential interaction is unclear. PhosphatidylserinePhosphatidylserine: Although endogenous GABA has anticonvulsant effects and GABAergic drugs are used to treat epilepsy (10), exogenous GABA is not an effective anticonvulsant, because when administered orally or systemically, it does not cross the blood-brain barrier (11). In animal research, GABA used in combination with phosphatidylserine (PS) stopped penicillin-induced epileptic activity on the electroencephalogram (EEG), while GABA alone did not (59), and PS been shown to potentiate the anticonvulsant effects of equal amounts of exogenous GABA administered to rats (81). Thus, clinical studies have examined GABA-PS for the treatment of epilepsy (12; 13). SedativesSedatives
: In human research, oral GABA intake resulted in stress-reducing effects (14; 15) and a lack of alertness (50). However, intravenous doses of GABA (0.1-1.0mg/kg) resulted in anxiety, dysphoria, and mood disturbance in both normal volunteers and euthymic bipolar patients (52). Selective serotonin reuptake inhibitors (SSRIs)Selective serotonin reuptake inhibitors (SSRIs): 5-HTP is a precursor to serotonin, which is known to potentiate GABAergic effects (37). TeaTea: In laboratory research, tea fragrance has been shown to enhance the GABA(A) receptor response (86). In laboratory research, green tea, black tea, and oolong tea increased the response produced by GABA, suggesting that these teas contain GABA. However, lipophilic components of green tea extracted by ethyl ether inhibited the GABA(A) receptor response in cultured cells (41). ValerianValerian: The anxiolytic effects of valerian are potentiated by GABAergic mechanisms (42). In rats, administration of valerian extracts with exogenous GABA (3.6mcg/kg) led to increased anxiolytic effects (72). Vitamin B6Vitamin B6: Some GABA supplements are formulated to include vitamin B6, which purportedly decreases drowsiness induced by GABA.ZincZinc: In electrophysiological experiments, zinc inhibited GABAergic synaptic currents, presumably through allosteric modulation of GABA(A) receptor gating (43). Theoretically, zinc may reduce the effects of GABA supplementation, but the clinical relevance of this potential interaction is unclear. GABA/Food Interactions:
GeneralGeneral: Some experts believe that GABA is best absorbed when taken with food. However, other experts have suggested taking GABA on an empty stomach, although the rationale is unclear.AlcoholAlcohol: Ethanol is known to exert effects through potentiating the GABA(A) receptor (45; 46). Alcohol consumption and GABA supplementation may have synergistic effects. In rodent models of chronic alcohol exposure, ethanol reduced the sensitivity of GABA(A) receptors to benzodiazepines (74). Altered GABA(A) receptor function by ethanol may alter the effects of exogenous GABA. Conversely, the GABA analog gabapentin has been shown to ameliorate alcohol-induced sleep disturbances (75). GABA may have similar effects, though this has not been conclusively demonstrated. Fermented foodsFermented foods: GABA was originally identified as a bacterial fermentation product (73) and naturally occurs in a number of fermented food products, including fermented cabbage (kimchi) (29; 30), fermented milk (31), and fermented fruit juice (32). GABA-enriched plant productsGABA-enriched plant products: Several studies have examined growth conditions that maximize GABA biosynthesis and accumulation in plant foods, such as fava beans (23), tomatoes (24; 25), sunflower (26), and soybeans (27). Transgenic rice expressing a seed-specific glutamate decarboxylase (GAD) gene has been developed to produce GABA-enriched rice (28). TeaTea: In laboratory research, tea fragrance has been shown to enhance the GABA(A) receptor response (86). In laboratory research, green tea, black tea, and oolong tea increased the response produced by GABA, suggesting that these teas contain GABA. However, lipophilic components of green tea extracted by ethyl ether inhibited the GABA(A) receptor response in cultured cells (41). GABA/Lab Interactions:
Coagulation panelCoagulation panel: In one study, five patients taking GABA and phosphatidylserine had decreased fibrinogen and prothrombin time (12). Heart rateHeart rate: In healthy young adults, vegetable tablets containing GABA were shown to alter heart rate variability (87). In a human study, GABA resulted in a decrease in heart rate compared to the control group (65) Liver function testsLiver function tests: In one study, five patients treated with GABA and phosphatidylserine had slightly increased glutamate pyruvate transaminase (GPT) (12). ProlactinProlactin: In human research, healthy female patients had a prolactin level increase after a 50mg GABA injection (50).