J Altern Complement Med. 2008 (Jul); 14 (6): 707–713 ~ FULL TEXT
Carlo Calabrese, N.D., M.P.H., William L. Gregory, Ph.D., Michael Leo, Ph.D.,
Dale Kraemer, Ph.D., Kerry Bone, F.N.I.M.H., F.N.H.A.A., and Barry Oken, M.D.
Helfgott Research Institute,
National College of Natural Medicine,
Portland, OR 97201, USA.
OBJECTIVES: Study aims were to evaluate effects of Bacopa monnieri whole plant standardized dry extract on cognitive function and affect and its safety and tolerability in healthy elderly study participants.
DESIGN: The study was a randomized, double-blind, placebo-controlled clinical trial with a placebo run-in of 6 weeks and a treatment period of 12 weeks.
SETTING/LOCATION: Volunteers were recruited from the community to a clinic in Portland, Oregon by public notification.
SUBJECTS: Fifty-four (54) participants, 65 or older (mean 73.5 years), without clinical signs of dementia, were recruited and randomized to Bacopa or placebo. Forty-eight (48) completed the study with 24 in each group.
INTERVENTIONS: Standardized B. monnieri extract 300 mg/day or a similar placebo tablet orally for 12 weeks.
OUTCOME MEASURES: The primary outcome variable was the delayed recall score from the Rey Auditory Verbal Learning Test (AVLT). Other cognitive measures were the Stroop Task assessing the ability to ignore irrelevant information, the Divided Attention Task (DAT), and the Wechsler Adult Intelligence Scale (WAIS) letter-digit test of immediate working memory. Affective measures were the State-Trait Anxiety Inventory, Center for Epidemiologic Studies Depression scale (CESD)-10 depression scale, and the Profile of Mood States. Vital signs were also monitored.
RESULTS: Controlling for baseline cognitive deficit using the Blessed Orientation-Memory-Concentration test, Bacopa participants had enhanced AVLT delayed word recall memory scores relative to placebo. Stroop results were similarly significant, with the Bacopa group improving and the placebo group unchanged. CESD-10 depression scores, combined state plus trait anxiety scores, and heart rate decreased over time for the Bacopa group but increased for the placebo group. No effects were found on the DAT, WAIS digit task, mood, or blood pressure. The dose was well tolerated with few adverse events (Bacopa n = 9, placebo n = 10), primarily stomach upset.
CONCLUSIONS: This study provides further evidence that B. monnieri has potential for safely enhancing cognitive performance in the aging.
From the FULL TEXT Article:
Aging is frequently associated with cognitive decline even in the otherwise healthy. The present increase in the aging demographic in many countries represents an emerging public health problem in terms of disability and economic impact. Safe agents that enhance cognition in the elderly may mitigate the social and personal losses associated with cognitive decline.
Bacopa monnieri (L.) Pennel has been used for centuries in Ayurvedic medicine, either alone or in combination with other herbs, as a memory and learning enhancer, sedative, and anti-epileptic.  It grows in wet tropical environments, and, under its common English name of water hyssop, is a popular aquarium plant. It has drawn the interest of phytotherapists and pharmacologists, [2–4] and an Australian survey showed it to be one of the most popular aid for memory among 60–64-year-old consumers there. 
Animal studies of B. monnieri whole plant or alcohol extracts have reported cognition-enhancing effects including improved motor learning  and acquisition, consolidation, and retention of memory in rats.  Memory-enhancing effects have been attributed to saponins (bacosides, bacopasides, or bacopasaponins). Bacopasaponin constituents have been shown to facilitate mental retention in avoidance response in rats,  and to reverse amnesic effects of neurotoxin, scopolamine, phenytoin, electroshock, and immobilization stress. [9–11] Hypothesized mechanisms of action include cholinergic upregulation,  ?-aminobutyric acid–ergic modulation,  antioxidant effects, [13, 14] protein synthesis in the brain,  5-HT agonism,  and modulation of brain stress hormones.  Bacopa extracts have also ameliorated neurotoxic effects of nicotine  and aluminum  and reduced ?-amyloid levels in the brain of a doubly transgenic mouse model of rapid amyloid deposition (PSAPP mice), suggesting mechanisms of action relevant to Alzheimer's disease. [19, 20]
Bacopa alcohol extract has shown memory-enhancing effects in three double-blind, randomized, placebo-controlled studies. A trial in 46 healthy volunteers 18–60 years old by Stough et al. evaluated their performance on a battery of cognitive tests after 5 weeks and after 12 weeks of 300 mg of B. monnieri extract daily.  The investigators reported significant improvements in measures of the Rey Auditory Verbal Learning Test (AVLT)  and in State Anxiety. Another 3–month study in 76 healthy adults, 40–65 years old, showed an effect of Bacopa on the retention of new information in delayed recall of word pairs.  A third trial in those over 55 with age-associated memory impairment, again with 3 months of treatment, showed more improvements at 12 weeks on subsets of the Wechsler Memory Scale with no loss of the cognitive gains 4 weeks after ending active treatment.  Conversely, in a single dose study of Bacopa extract in which neuropsychological testing was performed 2 hours after administration, no differences were found between groups.  A study by the same investigators with 4 weeks' treatment by a combination of Gingko biloba (maidenhair tree) 120 mg and Bacopa 300 mg in 85 healthy participants also did not show cognitive enhancement.  Stough's study showed effects at 12 weeks but not at 5 weeks, suggesting that cognitive effects with Bacopa may take months to appear. Two uncontrolled trials have reported memory- and learning-enhancing effects of Bacopa with long-term dosing in children  and in patients with anxiety neurosis. 
Chemical characterizations of the plant have been carried out by many investigators. [29–40] There are no data currently available on the pharmacokinetics of Bacopa or its saponins. Phase I clinical studies confirmed the safety of bacosides in healthy male volunteers at both single and chronic dosing administered over a period of 4 weeks  and 6 weeks with a dose of up to 450 mg of dried water extract.  A water extract of Bacopa given orally up to a dose of 5 g/kg did not show toxicity in rats. The LD50 of an alcoholic extract given orally was 17 g/kg.  In the trials cited, total adverse events (AE) were similar in placebo and treatment groups.
Using a rigorous design, the results demonstrate that Bacopa has positive benefits on multiple measures of cognitive performance and affect. Bacopa recipients improved in delayed recall memory and Stroop task reaction times over the course of the study while placebo recipients remained stable on both. Bacopa recipients displayed a decrease in depression and combined state plus trait anxiety scores with the placebo recipients increasing on both. Participants also had slightly lower heart rates after taking Bacopa while those taking the placebo displayed an increase in heart rate. No effects were shown on the immediate recall task, divided attention task, the WAIS digit span task, mood states, blood pressure, and body temperature.
The benefits of B. monnieri for both the delayed recall task and anxiety replicate the findings of Stough et al. and Roodenrys et al. in normal adults but in an elderly population, and reflect the findings of Raghav et al. in an elderly population with cognitive impairments. [21, 23, 24] In all four studies, participants received Bacopa for 12 weeks. Nathan et al. failed to find benefits of Bacopa after 2 hours and 4 weeks. [25, 26]
These data extend the demonstrated benefits of Bacopa to another cognitive task, the Stroop test, and to depression scores and heart rate. Given the purported anxiolytic properties of Bacopa,  it is possible that the increased depression scores and increased heart rate in the placebo group may reflect frustration with the repeated visits in which the same tasks are performed, rather than an actual increase in depression. On the other hand, Bacopa has shown evidence of antidepressant activity in two mouse models.  Insulation against such frustration may be a benefit of Bacopa, leading to better (or less impaired) task performance.
This study provides further evidence that standardized extracts of B. monnieri have potential for safely enhancing cognitive performance in aging, an indication that is closely comparable to the traditional uses of the herb. Whether this effect is due to a direct mechanism in which the active agents in B. monnieri act upon brain chemistry to influence memory processes or to greater tolerance for frustration, or due to decreasing the performance-degrading effects of arousal on complex tasks, or yet some other mechanism, remains to be explored.