Bacopa Herb: Brain and Nervine Tonic Assists Memory and Alertness

Studies show that bacopa has strong antioxidant properties, protects mental function in those with epilepsy who take the drug phenytion, while a study on rats showed bacopa administration improves learning skills.

Countless studies have shown Brahmi helps improve protein activity and protein synthesis, especially in brain cells, which can increase intelligence, longevity and memory and decrease senility and aging. It has tranquilizing effects but, unlike synthetic sedatives which often have side effects of dulling the mind, it actually improves mental clarity. It is also used as an anti-anxiety agent, to calm restlessness in children, and to cure several mental disorders. It is most commonly used as a nervine tonic that enhances learning and academic performance, improves mental aletness, and sharpens short-term and long-term memory

In use for several thousand years in the Indian Ayurvedic tradition as a nerve tonic for the brain, to enhance clear thinking and support memory function, the herb Bacopa monniera has revitalizing effects for memory-function enhancement now being confirmed by scientific research. Most interesting of the many effects of Bacopa is its ability to help increase novelty-seeking behavior, an attribute of intelligence associated with increased mental pleasure and increased lifespan. Literally a brain food, Bacopa is thought to help nourish your neurons as it restores depleted synaptic activity

Bacopa has demonstrated sedative activity (without affecting motor co-ordination), analgesic activity, anxiety reduction and anticonvulsant activity. Bacopa significantly reduced anxiety and improved mental performance and memory in a group with anxiety neurosis. It was accompanied by reduction in mental fatigue, a general feeling of well-being, improved sleep and appetite, and an increase in body weight. Bacopa significantly improved IQ scores in 10-13 year old children. It was particularly effective in improving visual motor function and immediate memory. Another study involving 50 children demonstrated significant improvement in attention.

Bacopa is used as a 'brain tonic' for improving memory, concentration and learning, particularly where stress is also present. It can assist nervous deficit due to injury, stroke and Alzheimer's disease. Bacopa is used for people with nervous breakdown, nervous exhaustion, behavioural disorders, anxiety and conditions where anxiety may play a role, such as irritable bowel syndrome.

Active constituents
Two saponins, designated as bacopaside I and II, are found in Bacopa monniera. Additional phytochemicals betulinic acid, wogonin and oroxindin have been isolated from the aerial parts of Bacopa monniera. Bacopa also has the flavonoids apigenin and luteolin.

The bacosides, are thought responsible for the therapeutic properties of the herb. In animal studies, both purified bacosides and extracts of bacopa standardized for bacosides have been found to enhance several aspects of mental function and learning ability. Additional brain effects of bacopa demonstrated in animal research include reduction of both anxiety and depression. Biochemically, these nervous-system effects have been attributed to an enhancement of the effects of the neurotransmitters acetylcholine and, possibly, serotonin or GABA (gamma aminobutyric acid).
Bacopa extracts also appear to have significant antioxidant activity in the brain, and other effects that may help protect brain cells.

Animal research has also reported that bacopa extracts can relax the muscles that control the blood vessels, the intestine, and the airways of the respiratory system, and can help both prevent and heal ulcers in the stomach.
Bacosides have been shown to alleviate fatigue and increase stamina. Bacosides also enhance the metabolism of neurotransmitters, the chemical messengers between nerve cells, thereby increasing mental function. They also help to keep the toxic effects of stress to a minimum.

Traditional application suggests that Bacopa has a direct effect on improving brain functions, increasing concentration, and in promoting memory functions. Bacosides play a protective role in the synaptic functions of the nerves in the hippocampus, the seat of memory. Nerve impulses are transmitted across the synapses and their degeneration is believed to contribute to impaired memory and cognition.

Bacopa: Ayurvedic Memory Herb
Researchers at the Department of Psychology, University of Wollongong, in Australia, studied the effects of Bacopa on human memory. Seventy-six adults aged between 40 and 65 years took part in a double-blind randomized, placebo control study in which various memory functions were tested and levels of anxiety measured. There were three testing sessions: one prior to the trial, one after three months on the trial, and one six weeks after the completion of the trial. The results showed a significant effect of bacopa monniera on a test for the retention of new information. Follow-up tests showed that the rate of learning was unaffected, suggesting that bacopa decreases the rate of forgetting of newly acquired information.

Additional Benefits of Bacopa
Bacopa moniera has antioxidant properties. One rodent study indicates bacopa to have some potential in helping protect the stomach from ulcer formation.

Bacopa Side Effects
Long term side effects are currently not fully known. As with most herbs, it's best to take breaks from use.

RESEARCH:

Bacopa Human Research Update
Chronic effects of Brahmi (Bacopa monniera) on human memory.
Neuropsychopharmacology. 2002 Aug;27(2):279-81.
A study is reported on the effects of Brahmi (Bacopa monniera) on human memory. Seventy-six adults aged between 40 and 65 years took part in a double-blind randomized, placebo control study in which various memory functions were tested and levels of anxiety measured. There were three testing sessions: one prior to the trial, one after three months on the trial, and one six weeks after the completion of the trial. The results show a significant effect of the Bacopa monniera on a test for the retention of new information. Follow-up tests showed that the rate of learning was unaffected, suggesting that Bacopa monniera decreases the rate of forgetting of newly acquired information. Tasks assessing attention, verbal and visual short-term memory and the retrieval of pre-experimental knowledge were unaffected.

The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects.
Psychopharmacology (Berl) 2001 Aug;156(4):481-4
Extracts of Bacopa monniera have been reported to exert cognitive enhancing effects in animals. However, the effects on human cognition are inconclusive. The current study examined the chronic effects of an extract of bacopa on cognitive function in healthy human subjects. The study was a double-blind placebo-controlled independent-group design in which subjects were randomly allocated to one of two treatment conditions, bacopa (300 mg) or placebo. Neuropsychological testing was conducted pre-(baseline) and at 5 and 12 weeks post drug administration. RESULTS: Bacopa significantly improved speed of visual information processing measured by the IT task, learning rate and memory consolidation compared to placebo, with maximal effects evident after 12 weeks.

CONCLUSIONS: These findings suggest that Bacopa monniera may improve higher order cognitive processes that are critically dependent on the input of information from our environment such as learning and memory.

The acute effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy normal subjects.
Hum Psychopharmacol. 2001 Jun;16(4):345-351.
The Ayurvedic medicine Bacopa monniera (Brahmi) has been shown to exert cognitive enhancing effects in animals. The current study examined the acute effects of an extract of Bacopa monniera on cognitive function in normal healthy human subjects. Subjects were randomly allocated to one of two treatment conditions, Bacopa monniera (300 mg) (n = 18) or placebo (n = 20). Neuropsychological testing was conducted before and 2 h after drug administration. No significant changes were found on any of the tests. The findings suggest that Bacopa monniera, at least for the dose administered, has no acute effects on cognitive functioning in normal healthy subjects.

Bacopa Animal Research Update
Adaptogenic effect of Bacopa monniera (Brahmi).
Pharmacol Biochem Behav. 2003 Jul;75(4):823-30.
We report the investigations on the adaptogenic property of a standardized extract of Bacopa monniera against acute and chronic stress (CS) models in rats. Panax root powder (Panax quinquefolium) was taken as a standard. Male rats exposed to immobilization stress for 150 min once only for acute and for seven consecutive days in CS, were fed with Bacopa monniera or Panax root powder daily for 3 days in acute and for 7 days in CS, 45 min prior to each exposure of stress. Rats were sacrificed immediately after stress, the blood was collected, and the plasma was separated out for biochemical estimation. Adrenals, spleen, and thymus were dissected for organ weight and stomach for ulcer score. Acute exposure significantly increased the ulcer index, adrenal gland weight, plasma glucose, liver enzymes, but significantly decreased the spleen weight. Pretreatment with Bacopa monniera po significantly reduced the acute state-induced increase in the ulcer index, adrenal gland weight, plasma glucose, AST, and CK. A Bacopa monniera dose of 80 mg/kg po significantly reversed the acute state-induced changes in adrenal gland weight, spleen weight, plasma glucose, ALT, and AST. Pretreatment with low dose of Bacopa monniera extract at 40 mg/kg significantly reversed changes in ulcer index and plasma AST only, whereas the pretreatment with higher dose significantly reversed CS-induced changes in ulcer index, adrenal gland weight, CK, and AST. Panax root powder significantly reversed CS-induced increase in ulcer index, adrenal gland weight, CK, and AST. On the basis of our result, it is concluded that the standardized extract of Bacopa monniera possesses a potent adaptogenic activity.

Effect of Bacopa monniera and Azadirachta indica on gastric ulceration and healing in experimental NIDDM rats.
Indian J Exp Biol. 2004 Apr;42(4):389-97.
Gastric ulcers were induced in normal /NIDDM rats by various physical and chemical agents and duodenal ulcer were induced by cysteamine. Ulcer healing activity was studied in gastric ulcers induced by acetic acid and HCI. The result indicated that in both, normal and NIDDM rats, Bacopa monniera extract did not show any significant effect on blood glucose level, while Azadirachta indica significantly decreased it. However, both Bacopa monniera extract and Azadirachta showed significant anti-ulcer and ulcer-healing activities in normal and NIDDM rats. Further, the present results also indicated that the ulcer protective effects of Bacopa monniera extract was more pronounced in non-diabetic, while that of Azadirachta was more in NIDDM rats. The anti-ulcer and ulcer-healing activities of Bacopa monniera extract and Azadirachta may be due to their effects on various mucosal offensive and defensive factors, and correction of blood sugar level by Azadirachta may help to have more ulcer protective effect in NIDDM rats.

Antidepressant activity of standardized extract of Bacopa monniera in experimental models of depression in rats.
Phytomedicine. 2002 Apr;9(3):207-11.
Bacopa monniera is a commonly used Ayurvedic drug for mental disorders. The standardized bacopa extract was reported earlier to have significant anti-oxidant effect, anxiolytic activity and improve memory retention in Alzheimer's disease. Presently, the standardized methanolic extract of Bacopa monniera (bacoside A) was investigated for potential antidepressant activity in rodent models of depression. The effect was compared with the standard antidepressant drug imipramine. The bacopa extract when given in the dose of 20 and 40 mg/kg, orally once daily for 5 days was found to have significant antidepressant activity in forced swim and learned helplessness models of depression and was comparable to that of imipramine.

Bacopa Laboratory Studies

Quantitative determination of the major saponin mixture bacoside A in Bacopa monnieri by HPLC.
Phytochem Anal. 2005 Jan-Feb;16(1):24-9.
Bacoside A, the putative bioactive component of the Indian medicinal plant Bacopa monnieri, was found to be a mixture of saponins with bacoside A3 (1), bacopaside II (2), jujubogenin isomer of bacopasaponin C (3) and bacopasaponin C (4) as major constituents. An HPLC method together with an optimised extraction procedure was developed for the estimation of 1-4 in B. monnieri to enable standardisation of the latter. Two common flavonoids, luteolin and apigenin, were present in all samples of Bacopa monnieri.

Phytotoxic and antimicrobial constituents of Bacopa monnieri and Holmskioldia sanguinea.
Phytother Res. 2004 Feb;18(2):114-7.
The phytochemicals betulinic acid (1), wogonin (2) and oroxindin (3) isolated from the aerial parts of Bacopa monnieri and Holmskioldia sanguinea showed significant antifungal activity against the two fungi Alternaria alternata and Fusarium fusiformis.

Free radical scavenging capacity and protective effect of Bacopa monniera on DNA damage.
Phytother Res. 2003 Sep;17(8):870-5.
Bacopa monniera is an Ayurvedic medicine, clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative. In this work, the free radical scavenging capacity of a methanol extract of Bacopa monniera and the effect on DNA cleavage induced by H2O2 UV-photolysis was investigated. In addition, we examined whether Bacopa monniera extract is capable of reducing the hydrogen peroxide-induced cytotoxicity and DNA damage in human non-immortalized fibroblasts. Bacopa monniera showed a dose-dependent free radical scavenging capacity and a protective effect on DNA cleavage. The antioxidant capacity of Bacopa monniera may explain, at least in part, the reported antistress, immunomodulatory, cognition-facilitating, antiinflammatory and antiaging effects produced by it in experimental animals and in clinical situations and may justify further investigation of its other beneficial properties. Moreover, this experimental evidence suggests that because of its antioxidant activity, Bacopa monniera may be useful in the treatment of human pathologies in which free radical production plays a key role.

In vitro evaluation of Bacopa monniera on anti-Helicobacter pylori activity and accumulation of prostaglandins.
Phytomedicine. 2003;10(6-7):523-7.
Bacopa monniera is an Indian tratidional medicine widely used to improve intellectual functions. Earlier, we had reported the prophylactic and curative effects of standardized extract of Bacopa monniera in various gastric ulcer models. The effect was due to augmentation of the defensive mucosal factors like increase in mucin secretion, life span of mucosal cells and gastric antioxidant effect rather than on the offensive acid-pepsin secretion. The present study includes evaluation of standardized Bacopa monniera on other contributing factors towards ulcerogenesis. Bacopa monniera showed anti-Helicobacter pylori activity in vitro and increased in vitro of prostanoids (PGE and PGI2) in human colonic mucosal incubates. It may be concluded that these factors may contribute to antiulcerogenic activity of Bacopa monniera.

Broncho-vasodilatory activity of fractions and pure constituents isolated from Bacopa monniera.
J Ethnopharmacol. 2003 May;86(1):27-35.
The present study demonstrates that various fractions and sub-fractions isolated from Bacopa monniera produced significant inhibition of carbachol-induced bronchoconstriction, hypotension and bradycardia in anaesthetized rats. Overall bioassay-directed fractionation of Bacopa monniera improved the bronchodilatory activity in various fractions and compound 1 (2-219x) in anaesthetized rats. In vitro, the KCl-induced contraction was equally inhibited by crude Bacopa monniera extract, petroleum ether and methanol fractions on trachea suggesting bronchodilatory activity remained the same in fractions. On pulmonary artery petroleum ether, dichloromethane and methanol fractions produced 2-2.6 times more vasodilatation compared to crude extract of Bacopa monniera. Thus, it may be concluded that various fractions derived from Bacopa monniera possess broncho-vasodilatory activity, which is attributed mainly to inhibition of calcium ions.

Antistress effects of bacosides of Bacopa monnieri
Phytother Res. 2002 Nov;16(7):639-45.
The antistress effect of bacosides of Brahmi (Bacopa monnieri) was -studied in adult male Sprague Dawley rats by administering oral doses of 20 and 40 mg/kg for 7 consecutive days. In half of the animals treated with 20 or 40 mg/kg of bacopa, stress was given 2 h after the last dose. Stress was also administered to the animals treated with distilled water alone. Bacopa, at both doses, did not induce a significant change in the expression of Hsp70 in any brain region studied while stress alone produced a significant increase in the Hsp70 expression in all the brain regions. A significant decrease in the activity of superoxide dismutase (SOD) was evident in the hippocampus with the lower dose of Bacopa and in animals given stress alone, while an increase in the activity of SOD was observed in the brain regions with the higher dose of Bacopa. An increase in the activity of cytochrome P450 (P450) dependent 7-pentoxyresorufin-o-dealkylase (PROD) and 7-ethoxyresorufin-o-deethylase (EROD) was observed in all the brain regions after exposure to stress alone and with both doses of Bacopa although the magnitude of induction of P450 expression was less with a higher dose of Bacopa. Interestingly, stress when given to the animals pretreated with Bacopa for 7 days resulted in a decrease in Hsp70 expression in all the brain regions with a significant decrease occurring only in the hippocampus. Likewise the activity of SOD was found to be further reduced in all the brain regions in the animals treated with the lower dose of Bacopa followed by stress. However, when stress was given to the animals pretreated with the higher dose of Bacopa, a significant increase in the enzyme activity was observed in the cerebral cortex and in the rest of the brain while the activity of SOD was reduced to a much greater extent in the cerebellum and in the hippocampus. Likewise, the activity of P450 enzymes was found to be restored to almost control levels in the animals given stress and pretreated with the higher dose of Bacopa, while a lesser degree of induction, compared with animals treated with Bacopa or stress alone, was observed in the animals pretreated with the lower dose of Bacopa and given stress. The data indicate that Bacopa has potential to modulate the activities of Hsp70, P450 and SOD thereby possibly allowing the brain to be prepared to act under adverse conditions such as stress.

Actions:
Nerve tonic
Adaptogen
Anti-Oxidant
Anti-Microbial
Anti-Fungal
Sedative
Cardio Tonic
Anti-convulsant
Anti-depressant

Studies have indicated that Bacopa may be able to help:
- Improve spatial memory
- Increase learning speed
- Protect the brain from free-radical damage
- Enhance episodic memory
- Alleviate anxiety
- Lower mental fatigue
- Diminish attention-deficit problems
- Handle increasingly difficult tasks
- Promote vigilance
- Inhibit age-related cognitive decline

Active Constituents and Pharmacokinetics
Compounds responsible for the pharmacological effects of Bacopa include alkaloids, saponins, and sterols. Many active constituents--the alkaloids Brahmine and herpestine, saponins d-mannitol and hersaponin, acid A, and monnierin--were isolated in India over 40 years ago. Other active constituents have since been identified, including betulic acid, stigmastarol, beta-sitosterol, as well as numerous bacosides and bacopasaponins. The constituents responsible for Bacopa's cognitive effects are bacosides A and B.5.

Mechanisms of Action
Since Bacopa's primary therapeutic use is to enhance cognitive function, most research has focused on the mechanism behind these properties. The triterpenoid saponins and their bacosides are responsible for Bacopa's ability to enhance nerve impulse transmission. The bacosides aid in repair of damaged neurons by enhancing kinase activity, neuronal synthesis, and restoration of synaptic activity, and ultimately nerve impulse transmission.
Loss of cholinergic neuronal activity in the hippocampus is the primary feature of Alzheimer's disease.  Based on animal study results, bacosides appear to have antioxidant activity in the hippocampus, frontal cortex, and striatum. Animal research has shown Bacopa extracts modulate the expression of certain enzymes involved in generation and scavenging of reactive oxygen species in the brain. In vitro research has shown Bacopa exerts a protective effect against DNA damage in astrocytes  and human fibroblasts.

In animals Bacopa has a relaxant effect on pulmonary arteries, aorta, trachea, and ileal and bronchial tissue, possibly mediated by inhibition of calcium-ion influx into cell membranes.  Bacopa appears to stabilize mast cells in vitro,  and possesses anti-inflammatory activity via inhibition of prostaglandin synthesis and lysosomal membrane stabilization.  In vitro research suggests an anticancer effect for Bacopa extracts, possibly due to inhibition of DNA replication in cancer cell lines.

Clinical Indications: Cognitive Effects
Adults
Bacopa monniera has been studied clinically for its acute and chronic effects on cognitive function. In adults, it appears only chronic administration is associated with cognitive-enhancing effects. In a double-blind, placebo-controlled trial of 38 healthy volunteers (ages 18-60), subjects were given a single dose of 300 mg Bacopa monniera extract (standardized to 55-percent combined bacosides A and B) or placebo. Subjects were tested two hours after drug administration. coinciding with maximum pharmacodynamic effect. Acute administration of this dose of Bacopa extract resulted in no significant changes in cognitive function when compared to baseline values. Parameters assessed included attention, working and short-term memory, verbal learning, decision making, memory consolidation, executive processes, planning and problem solving, speed of information processing, and motor responsiveness.

On the other hand, significant cognitive-enhancing benefits have been demonstrated with more chronic administration of Bacopa extracts. Australian researchers conducted a double-blind, placebo-controlled, 12-week trial utilizing the same patient selection criteria and same dose of Bacopa extract (300 mg daily) containing 55-percent combined bacosides. Forty-six healthy volunteers (ages 18-60) were randomly and evenly divided into treatment and placebo groups. The same series of tests administered in the acute dosage trial were administered at baseline, five, and 12 weeks after treatment began. At the end of the 12-week study, results indicated a significant improvement in verbal learning, memory consolidation, and speed of early information processing in the treatment group compared to placebo. These effects were not observed at baseline or at five weeks. These results may be attributed to Bacopa's antioxidant properties and/or its effect on the cholinergic system.

Children
Bacopa's ability to modulate or enhance cognitive function has also been studied in children. Forty children from rural India (ages 6-8) were divided into treatment and placebo groups of 20 children each. Children in the treatment group received one teaspoon Bacopa syrup (350 mg Bacopa powder/teaspoonful) three times daily for three months. The placebo group received Syrup Simplex (details not available). A series of tests measuring visuomotor and perceptual abilities and memory span were administered at baseline and at the end of treatment. Significant improvements were noted in strengthened exploratory drive (as measured by maze learning), improved perceptual images of patterns, and increased perceptual organization and reasoning ability (as measured by reaction time). This study, however, was not double-blinded. (22)

A double-blind, randomized, placebo-controlled trial of 36 children with diagnosed attention deficit/hyperactivity disorder was conducted over a 16-week period. Nineteen children received an extract of Bacopa (standardized to contain 20-percent bacosides) at a dosage of 50 mg twice daily for 12 weeks, and 17 subjects were given a placebo. The mean age of the children in the two groups was 8.3 years and 9.3 years, respectively. Active drug treatment was followed by four weeks of placebo and the children were evaluated on numerous cognitive function tests at baseline, four, eight, 12, and 16 weeks. A significant benefit was observed in Bacopa-treated subjects at 12 weeks as evidenced by improvement on sentence repetition, logical memory, and paired associate learning tasks. Evaluation showed these improvements were maintained at 16 weeks (after four weeks placebo administration).

Anxiety and Depression
Bacopa's traditional use as an anti-anxiety remedy in Ayurvedic medicine is supported by both animal and clinical research. Research using a rat model of clinical anxiety demonstrated a Bacopa extract of 25-percent bacoside A exerted anxiolytic activity comparable to Lorazepam, a common benzodiazapene anxiolytic drug. Importantly, the Bacopa extract did not induce amnesia, side effects associated with Lorazepam, but instead had a memory-enhancing effect. (24)

A one-month, limited clinical trial of 35 patients with diagnosed anxiety neurosis demonstrated that administration of Brahmi syrup (30 mL daily in two divided doses, equivalent to 12 g dry crude extract of Bacopa) resulted in a significant decrease in anxiety symptoms, level of anxiety, level of disability, and mental fatigue, and an increase in immediate memory span. Other changes noted were increased body weight, decreased respiration rate, and decreased systolic blood pressure.

Epilepsy
Although Bacopa has been indicated as a remedy for epilepsy in Ayurvedic medicine, research in animals shows anticonvulsant activity only at high doses over extended periods of time. Early research in India demonstrated that hersaponin (an active constituent) exhibited protection against seizures in mice. (26) A more recent Indian study also examined the anticonvulsant properties of Bacopa extracts in mice and rats. Researchers determined that intraperitoneal injections of high doses of Bacopa extract (close to 50 percent of LD50) given for 15 days demonstrated anticonvulsant activity. When administered acutely at lower doses (approaching 25 percent of LD50), anticonvulsant activity was not observed.

Bronchitis and Asthma
Animal studies have demonstrated Bacopa extracts have a relaxant effect on chemically-induced bronchoconstriction, probably via inhibition of calcium influx into cell membranes. An earlier in vitro study by Dar and Channa demonstrated the broncho-vasodilatory activity of B. monniera on rabbit and guinea pig trachea, pulmonary artery, and aorta.  A subsequent rat study with Bacopa extracts confirmed the earlier results. Methanol subfractions of Bacopa extracts were given to anesthetized rats prior to induction of bronchoconstriction with carbachol, an acetylcholine analogue. Nearly all of the Bacopa extract subfractions inhibited carbachol-induced bronchoconstriction, hypotension, and bradycardia in this animal model.  An in vitro study also demonstrated a methanol extract of Bacopa possessed potent mast cell stabilizing activity comparable to disodium cromoglycate, a commonly used allergy medication.  These studies indicate the potential usefulness of Bacopa extracts in bronchoconstrictive and allergic conditions, and warrant human studies.

Gastrointestinal Disorders
In vitro, animal, and human studies have investigated the effects of Bacopa extracts on the gastrointestinal tract. In vitro studies  have demonstrated direct spasmolytic activity on intestinal smooth muscle, via inhibition of calcium influx across cell membrane channels. This property suggests Bacopa extracts may be of benefit in conditions characterized by intestinal spasm such as irritable bowel syndrome (IBS).

A double-blind, randomized, placebo-controlled trial of 169 patients with IBS compared the effects of an Ayurvedic preparation containing Bacopa monniera and Aegle marmelos to standard therapy (clidinium bromide, chlordiazepoxide, and psyllium). Subjects were divided into five subgroups based on type of IBS, and randomly assigned to standard drug treatment, botanical treatment, or placebo for six weeks. Treatment was administered orally as 5 g drug, botanical, or placebo three times daily. Data analysis revealed standard drug therapy to be superior to the Ayurvedic preparation, except in patients with IBS characterized by diarrhea. This result was attributed to the Aegle marmelos, a commonly known antidiarrheal in India, although the two botanicals were not given separately, so individual effects cannot be confirmed. Ayurvedic therapy was superior to placebo in all parameters examined, but no benefit could be linked specifically to the Bacopa portion of the Ayurvedic preparation.

Animal and in vitro studies suggest Bacopa may have a protective and curative effect for gastric ulcers. In rats a Bacopa extract standardized for bacoside A was evaluated for its prophylactic and healing effects in five models of gastric ulcers. At a dose of 20 mg/kg for 10 days, Bacopa extract significantly healed penetrating ulcers induced by acetic acid, significantly strengthened the mucosal barrier, and decreased mucosal exfoliation. The extract also alleviated stress-induced ulcers as observed by significant reduction in lipid peroxidation in rat gastric mucosa. Bacopa's antioxidant properties and its ability to balance SOD and catalase levels may account for this effect. (31) A recent in vitro study also demonstrated Bacopa extract's specific anti-microbial activity against Helicobacter pylori, a bacteria associated with chronic gastric ulcers. When the extract was incubated with human colonic muscosal cells and H. pylori it resulted in accumulation of prostaglandin E and prostacycline. prostaglandins known to be protective for gastric mucosa.

Cardiovascular Effects
Use of Bacopa as a "cardiotonic" is frequently mentioned in Ayurvedic medicine texts, but no clinical studies have been conducted. In vitro research using rabbit aorta and pulmonary artery has demonstrated Bacopa extract exerts a vasodilatory effect on calcium chloride-induced contraction in both tissues. It is believed to exert this effect via interference with calcium channel flux in tissue cells.

Hypothyroidism
A study in mice demonstrated high doses (200 mg/kg) of Bacopa extract increased the thyroid hormone. T4, by 41 percent when given orally. T3 was not stimulated, suggesting the extract may directly stimulate synthesis and/or release of T4 at the glandular level, while not affecting conversion of T4 to T3. While this study indicates Bacopa extract does have a stimulatory effect on thyroid function, the doses were very high and the typical 200-400 mg daily dose in humans may not have the same effect.

Protection from Drug Toxicity
In vitro and animal studies have demonstrated Bacopa extracts may have a protective effect against certain drugs and their negative side effects. An in vitro study using guinea pig ileum isolates examined the effect of Bacopa extract on drug-induced morphine withdrawal. Addition of 1,000 [micro]g/mL Bacopa extract to the tissue isolates prior to injection of morphine significantly reduced the naloxone-induced withdrawal effects, an effect that may be attributed to the anticholinergic and calcium antagonistic activity reported by other researchers.

A second study examined the effects of an alcohol extract of Bacopa on morphine-induced hepatotoxicity in rats, as measured by lipid peroxide accumulation and antioxidant enzyme levels. Administration of Bacopa extract with morphine significantly decreased lipid peroxidation and increased levels of antioxidant enzymes and glutathione in rat hepatic tissue, when compared to morphine alone. These results suggest a protective effect for Bacopa on the hepatic antioxidant status in morphine-treated rats.  Some of the same researchers reported a similar effect for brain mitochondrial enzyme activity of morphine-treated rats.

It has also been reported that antiepileptic drugs, such as phenytoin, can result in cognitive impairment. In mice, Bacopa administration with phenytoin significantly reversed phenytoin-induced cognitive impairment, as noted by improved acquisition and retention of memory. These results suggest a potential corrective effect of Bacopa extracts in phenytoin-induced cognitive deficit.

Cancer
In vitro research demonstrated Bacopa saponin fractions have cytotoxic activity for sarcoma-180 cells. It is thought this might be due to Bacopa's inhibition of DNA replication in the cancerous cell line.  Research in humans may be indicated.

Drug/Botanical Interactions
Bacopa has been noted in animal models to decrease the toxicity of morphine  and phenytoin.  It has also been shown, albeit inconsistently, to have a slight sedative effect, so caution is advised in combination with other known sedatives. Also, since it appears to stimulate T4 activity in animals at high doses, it is theorized it may potentiate the activity of thyroid-stimulating drugs or inhibit the effect of thyroid-suppressant drugs.

Side Effects and Toxicity
Therapeutic doses of Bacopa are not associated with any known side effects, and Bacopa has been used safely in Ayurvedic medicine for several hundred years. A double-blind, placebo-controlled clinical trial of healthy male volunteers investigated the safety of pharmacological doses of isolated bacosides over a four-week period. Concentrated bacosides given in single (20-30 mg) and multiple (100-200 mg) daily doses were well tolerated and without adverse effects. The LD50 of Bacopa extracts administered orally to rats was 5 g/kg for aqueous extracts and 17 g/kg of the alcohol extract. Neither extract resulted in gross behavioral changes at these concentrations.

Dosage
Traditional daily doses of Bacopa are 5-10 o of non-standardized powder, 8-16 mL of infusion, and 30 mL daily of syrup (Brahmi). Dosages of a 1:2 fluid extract are 5-12 mL per day for adults and 2.5-6 mL per day for children ages 6-12. For Bacopa extracts standardized to 20-percent bacosides A and B the dosage is 200-400 mg daily in divided doses for adults, and for children, 100-200 mg daily in divided doses.

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Bacopa is said to be toxic at doses given .05 mg per kg. of body weight [1].

Research:
Neurogen Rx
Brain Nutrition

Neurogen Rx is a sophisticated cognitive formula with bacopa and brain herbs and specific homeopathic remedies. It combines a delicate balance of brain circulation agents and neurotransmitter precursors with powerful natural brain chemicals that support healthy:
• Memory and Mood, Concentration as well as Alertness & Focus

This comprehensive brain nutrition formula is designed to provide mental clarity, mental energy, mental strength, stress reduction, improved mood, and improved creativity.
Neurogen Rx helps replenish and provide the nutrients needed for proper brain function. All of lives experiences are enhanced when the human brain is healthy and functioning at its optimum

Formula:
Bacopa Extract, 100 mg,
Ashwagandha, 120 mg
Ginkgo biloba, 95 mg
Phosphorus 9C, Baryta Carbonica 9C, Kali phosphoricum 12C, Phosphoricum acidum 12C, Sulfur 9C, Caladium 9C Anacardium 9C