Bacopa

Bacopa, brahmi, was commonly used as a brain tonic and to enhance learning ^{28Reference 28Mukherjee et al. · 1966Clinical trialClinical trial on Brahmi}. Ayurveda classes it as a medhya rasayana, a tonic for the mind, and it has long been used for memory loss ^{10,13Reference 10Prabhakar et al. · 2020RCTEfficacy of Bacopa monnieri (Brahmi) and donepezil in Alzheimer’s disease and mild cognitive impairment — randomised double-blind phase-2b trial (terminated)View study →Reference 13Chaudhari et al. · 2017ReviewNeurocognitive effect of nootropic drug Brahmi (Bacopa monnieri) in Alzheimer’s disease — reviewView study →}.

It was also given for anxiety and epilepsy ^{29Reference 29Chopra · 1958Chopra’s Indigenous Drugs of India}.

A 2014 meta-analysis pooled nine randomised, placebo-controlled trials (518 subjects, all using standardised extracts for at least 12 weeks). It found faster performance on the Trail-Making B test and a shorter choice reaction time, and concluded that the herb improves “speed of attention” in particular ^{1Reference 1Kongkeaw et al. · 2014Meta-analysisMeta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract — systematic review and meta-analysisView study →}.

Individual trials point to memory retention specifically.

In Roodenrys’s double-blind trial of 76 adults aged 40–65, bacopa slowed the forgetting of newly learned information without changing the rate of learning. Attention and short-term memory were unaffected ^{4Reference 4Roodenrys et al. · 2002RCTChronic effects of Brahmi (Bacopa monnieri) on human memory — randomised placebo-controlled trialView study →}.

In Calabrese’s trial in healthy adults aged 65 and over (54 randomised, 48 completed; 300 mg/day for 12 weeks), bacopa improved delayed word recall and Stroop performance ^{2Reference 2Calabrese et al. · 2008RCTEffects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly — randomised, double-blind, placebo-controlled trialView study →}.

In Morgan’s trial in adults over 55 (98 randomised, 81 completed; BacoMind 300 mg/day for 12 weeks), bacopa improved verbal learning, memory acquisition and delayed recall ^{3Reference 3Morgan et al. · 2010RCTDoes Bacopa monnieri improve memory performance in older persons? — randomised, placebo-controlled, double-blind trialView study →}.

A 2026 network meta-analysis of 29 trials (2,107 healthy adults) ranked high-dose brahmi (600 mg/day or more) first for working memory, above ginkgo and placebo. It found no advantage for attention or processing speed ^{6Reference 6Tiemtad et al. · 2026Meta-analysisComparative effects of Bacopa monnieri and Ginkgo biloba on cognitive functions — systematic review and network meta-analysisView study →}.

Gap: the effects are specific to certain measures (retention and attention speed rather than global cognition), and they were shown almost entirely with CDRI 08 and BacoMind. No trial has tested whether a tea or generic powder does the same.

In streptozotocin-diabetic rats, oral bacopa extract restored superoxide dismutase, catalase and glutathione peroxidase activity and reduced lipid peroxidation in brain and kidney ^{7Reference 7Kapoor et al. · 2009AnimalBacopa monnieri modulates antioxidant responses in brain and kidney of diabetic rats — animal modelView study →}.

In prenatally stressed rat offspring, a standardised extract (CDRI 08) reversed oxidative and apoptotic markers alongside memory recovery, acting through BDNF and synaptic-protein signalling ^{9Reference 9Sivasangari et al. · 2020AnimalStandardized Bacopa monnieri extract ameliorates learning and memory impairments through synaptic protein, neurogranin, BDNF signaling, and HPA axis in prenatally stressed rat offspring — animal modelView study →}.

A 2015 review of the ageing brain describes several antioxidant actions, including free-radical scavenging, reduced lipid peroxidation and metal chelation, and notes that the mechanism linking them to human cognitive improvement is still unknown ^{8Reference 8Simpson et al. · 2015ReviewBacopa monnieri as an antioxidant therapy to reduce oxidative stress in the aging brain — reviewView study →}.

The bacosides and phenolic constituents are the presumed active antioxidants.

In cell and rodent models bacopa protects cholinergic neurons, reduces β-amyloid deposition, inhibits acetylcholinesterase comparably to donepezil in some assays, and lowers stress-induced hippocampal damage ^{13Reference 13Chaudhari et al. · 2017ReviewNeurocognitive effect of nootropic drug Brahmi (Bacopa monnieri) in Alzheimer’s disease — reviewView study →}.

An ethanolic extract inhibits tau aggregation and tau-mediated toxicity in Neuro2a cells, restoring Nrf2 and reducing GSK-3β phosphorylation ^{12Reference 12Dubey et al. · 2023In vitroBacopa monnieri reduces Tau aggregation and Tau-mediated toxicity in cells — in vitroView study →}.

A 2024 systematic review of 22 clinical and preclinical reports credits bacoside A and betulinic acid with anti-apoptotic, antioxidant and synapse-restoring actions ^{11Reference 11Valotto Neto et al. · 2024Systematic reviewInvestigating the neuroprotective and cognitive-enhancing effects of Bacopa monnieri — systematic reviewView study →}.

A phase-2b trial compared brahmi 300 mg/day with donepezil 10 mg/day for 12 months in Alzheimer’s disease and mild cognitive impairment. It was stopped after recruiting 34 of a planned 48 patients, because of slow recruitment and dropouts. It found no difference between the two on the main cognitive score (ADAS-Cog) at any point, and a difference on one memory scale only at the final visit ^{10Reference 10Prabhakar et al. · 2020RCTEfficacy of Bacopa monnieri (Brahmi) and donepezil in Alzheimer’s disease and mild cognitive impairment — randomised double-blind phase-2b trial (terminated)View study →}.

Gap: the trial was small, unfinished and had no placebo group, so it cannot show whether either treatment helped. Benefit in dementia has not been demonstrated.

Human anxiety findings come from secondary outcomes, not dedicated trials. In Calabrese’s trial in older adults, combined state and trait anxiety scores and heart rate fell in the bacopa group and rose on placebo ^{2Reference 2Calabrese et al. · 2008RCTEffects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly — randomised, double-blind, placebo-controlled trialView study →}. In Roodenrys’s trial in adults aged 40–65, anxiety levels did not change ^{4Reference 4Roodenrys et al. · 2002RCTChronic effects of Brahmi (Bacopa monnieri) on human memory — randomised placebo-controlled trialView study →}.

In an acute, double-blind crossover study, 17 healthy volunteers took CDRI 08 at 320 mg and 640 mg. It produced some positive mood effects and lowered salivary cortisol during a multitasking stress test ^{16Reference 16Benson et al. · 2014RCTAn acute, double-blind, placebo-controlled cross-over study of 320 mg and 640 mg doses of Bacopa monnieri (CDRI 08) on multitasking stress reactivity and mood — randomised controlled trialView study →}.

Preclinically, a standardised extract normalised stress-hormone markers (corticosterone, ACTH) in prenatally stressed rats ^{9Reference 9Sivasangari et al. · 2020AnimalStandardized Bacopa monnieri extract ameliorates learning and memory impairments through synaptic protein, neurogranin, BDNF signaling, and HPA axis in prenatally stressed rat offspring — animal modelView study →}.

Gap: no adequately powered trial with anxiety as the primary outcome. The human evidence is a few secondary endpoints and one small acute crossover.

A 14-week randomised, double-blind, placebo-controlled trial gave CDRI 08 to boys aged 6–14 with inattention and hyperactivity (112 recruited, 93 analysed). It found no difference on behaviour, the primary outcome, but reported gains in cognitive flexibility, executive function, interpersonal problems and sleep routine ^{17Reference 17Kean et al. · 2022RCTEffects of Bacopa monnieri (CDRI 08) in a population of males exhibiting inattention and hyperactivity aged 6 to 14 years — randomised, double-blind, placebo-controlled trialView study →}.

A 2016 systematic review of five studies in children and adolescents found small-to-medium effect sizes (mean d = 0.42), with improvements in language, memory and attention measures. Mild side effects were reported by only 2.3% of participants ^{18Reference 18Kean et al. · 2016Systematic reviewA systematic review of the Ayurvedic medicinal herb Bacopa monnieri in child and adolescent populations — systematic reviewView study →}.

An open-label study of BacoMind 225 mg/day for six months in 31 children with ADHD reported less restlessness and better self-control, but it had no control group ^{19Reference 19Dave et al. · 2014An open-label study to elucidate the effects of standardized Bacopa monnieri extract in the management of symptoms of attention-deficit hyperactivity disorder in childrenView study →}.

Gap: the one blinded trial did not improve behaviour, its primary measure. The benefits appear on secondary cognitive and sleep outcomes and need replication.

In N9 microglial cells, bacopa tea, infusion and alkaloid extracts, and bacoside A, inhibited release of the inflammatory cytokines TNF-α and IL-6. They also inhibited caspase-1, caspase-3 and matrix metalloproteinase-3, enzymes linked to brain inflammation and to tau cleavage in early Alzheimer’s disease ^{14Reference 14Nemetchek et al. · 2017In vitroThe Ayurvedic plant Bacopa monnieri inhibits inflammatory pathways in the brain — in vitro (microglial cell line)View study →}.

In a colchicine-induced rat dementia model, oral extract lowered IL-6, TNF-α, MCP-1, COX-2 and iNOS, reduced BACE-1 activity and amyloid production, and reversed memory deficits ^{15Reference 15Saini et al. · 2019AnimalBacopa monnieri prevents colchicine-induced dementia by anti-inflammatory action — animal modelView study →}.

Gap: cell and rodent work only, with no human inflammatory endpoint.

Triterpene saponins isolated from bacopa, bacopaside I, bacopaside II and bacopasaponin C, reduced immobility in the mouse forced-swim and tail-suspension tests, the standard rodent antidepressant screens ^{20Reference 20Zhou et al. · 2007AnimalTriterpene saponins from Bacopa monnieri and their antidepressant effects in two mice models — animal modelView study →}.

In a reserpine-induced rat depression model, the extract restored serotonin, dopamine, noradrenaline, BDNF and Bcl-2 and lowered pro-apoptotic and inflammatory markers. The authors described the effect as comparable to citalopram ^{21Reference 21Zaazaa et al. · 2022AnimalNeuroprotective role of Bacopa monnieri extract in modulating depression in an experimental rat model — animal modelView study →}.

No human antidepressant trial of bacopa alone exists. Depression scores fell as a secondary outcome in Calabrese’s trial in older adults ^{2Reference 2Calabrese et al. · 2008RCTEffects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly — randomised, double-blind, placebo-controlled trialView study →}.

Gap: the “comparable to citalopram” finding is a rodent comparison, not a clinical one.

In rats with pilocarpine-induced temporal-lobe epilepsy, bacopa and isolated bacoside A reversed the loss of hippocampal GABA and GABA(A) receptors and corrected the accompanying deficits in radial-arm and Y-maze performance ^{22Reference 22Mathew et al. · 2011AnimalBehavioral deficit and decreased GABA receptor functional regulation in the hippocampus of epileptic rats: effect of Bacopa monnieri — animal modelView study →}.

Brahmi has a long history of use in Ayurveda for epilepsy, but there is no controlled human trial. Bacopa has been reported to lower blood levels of the anti-seizure drug phenytoin.

Gap: no controlled human data; the mechanism rests on one rodent model.

Side effects. In trials the most consistent side effects are digestive: more frequent stools, abdominal cramps and nausea ^{2,3Reference 2Calabrese et al. · 2008RCTEffects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly — randomised, double-blind, placebo-controlled trialView study →Reference 3Morgan et al. · 2010RCTDoes Bacopa monnieri improve memory performance in older persons? — randomised, placebo-controlled, double-blind trialView study →}. In a review of studies in children, 2.3% of participants reported mild side effects ^{18Reference 18Kean et al. · 2016Systematic reviewA systematic review of the Ayurvedic medicinal herb Bacopa monnieri in child and adolescent populations — systematic reviewView study →}.

Animal toxicity. In rats, a standardised extract (BacoMind) had a single-dose oral LD50 of 2,400 mg/kg. A 90-day study found no toxicity at up to 500 mg/kg/day, the no-observed-adverse-effect level ^{23Reference 23Joshua Allan et al. · 2007AnimalSafety evaluation of a standardized phytochemical composition extracted from Bacopa monnieri in Sprague–Dawley rats — animal toxicologyView study →}.

Drug-metabolising enzymes. In vitro, a standardised extract inhibited CYP2C19, CYP2C9, CYP1A2 and CYP3A4. At the gut concentration estimated for a 300 mg/day dose it cut CYP3A4, CYP2C9 and CYP2C19 activity to under 10%. The isolated bacosides had almost no effect ^{24Reference 24Ramasamy et al. · 2014In vitroInhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized extract and constituents — in vitroView study →}.

In rats, a week of standardised bacopa extract slowed CYP3A and P-glycoprotein, raising blood levels of carbamazepine about fourfold and digoxin by about a third ^{38Reference 38Singh et al. · 2013AnimalEvaluation of memory enhancing clinically available standardized extract of Bacopa monniera on P-glycoprotein and cytochrome P450 3A in Sprague-Dawley rats — animal modelView study →}. This has not been tested in people, but care is sensible with drugs cleared by these routes.

Phenytoin. Bacopa has been reported to lower blood levels of phenytoin, which matters because of its traditional use in epilepsy.

Cholinergic drugs. A 58-year-old woman taking cevimeline for Sjögren’s syndrome developed sweating, malaise, nausea and a fast heart rate after taking a supplement containing bacopa and phosphatidylserine. She recovered once she stopped the supplement ^{25Reference 25Acquarulo et al. · 2022Case reportSuspected cholinergic toxicity due to cevimeline hydrochloride and Bacopa monnieri interaction — case reportView study →}.

Thyroid. In male mice, a bacopa leaf extract raised T4 by 41%, suggesting a thyroid-stimulating effect. It should be used carefully with thyroid conditions or thyroid medication ^{26Reference 26Kar et al. · 2002AnimalRelative efficacy of three medicinal plant extracts in the alteration of thyroid hormone concentrations in male mice — animal modelView study →}.

No clinical interaction trial has been done.