Nootropics is a term used to describe those agents that improve cognition, memory, creativity or motivation. Nootropic substances can be as common as everyday caffeine and nicotine, or stimulants such as amphetamine and methylphenidate or many prescription items including levodopa. Nootropic agents can also include plants, vitamins or other dietary supplements. Bacopa monnieri is one of the most significant current botanicals used for their nootropic effects.
Bacopa monnieri
Bacopa monnieri is a well-known herb native to Australia and India. While it is commonly found as a weed in rice fields, it also grows throughout East Asia and even the United States. It has a long historical use in Ayurvedic medicine in areas of memory and intelligence. The entire plant can be used as medicine. The main nootropic constituents of bacopa are believed to be of triterpenoid saponins known as bacosides, with jujubogenin or pseudo-jujubogenin moieties as aglycone units.[i] There are 12 bacopasides analogs called bacopasides I–XII that have been identified.[ii], [iii], [iv] There are several alkaloids including brahmine, nicotine, and herpestine as well as d-mannitol, apigenin, hersaponin, monnierasides I–III, cucurbitacins and plantainoside B. The constituent most studied and as a whole plant extract has been bacoside A.
While many of the pharmaceutical nootropics are potentially addictive (ex/ caffeine, nicotine and psychostimulants), bacopa appears to nourish rather than deplete neurons. Historically, bacopa was used by Vedic scholars to help them memorize lengthy hymns and scriptures and many ancient texts refer to the herb’s ability to sharpen intellect and improve mental deficits. It is often found in many Ayurvedic preparations for cognitive dysfunction.
There is conflicting evidence as to the effects of bacopa on cognitive function, but there are possible mechanisms for cognitive improvement include modulation of acetylcholine release, choline acetylase activity, and muscarinic cholinergic receptor binding. In the laboratory, bacopa inhibits acetylcholinesterase activity and may also have neuroprotective effects including the ability to protect neurons from beta-amyloid-induced cell death.
At least six high-quality randomized, double-blind, placebo-controlled human trials have been conducted. Pase et al. conducted a systematic review, finding some evidence that bacopa could be used as a memory enhancer even in individuals without dementia.[v] These same 6 studies met the final inclusion criteria and were included in the systematic review. All the trials were conducted over 12 weeks. Not all the trials used the same dosage and 3 different Bacopa extracts were used at dosages of 300-450 mg extract per day. All the reviewed trials evaluated the effects of Bacopa on memory, and other cognitive function tests were less well studied. Across all the studies, Bacopa improved performance on 9 of 17 tests in memory free recall. There was no real evidence of any other cognitive domain enhancement.
In a meta-analysis, Neale et al. compared the nootropic effects of Bacopa monnieri to Panax ginseng and modafinil (an eugeroic-wakefulness drug).[vi] Chronic bacopa use produced the most consistent and largest effect sizes of the three. Bacopa showed small- to medium-effect sizes for attention and information processing tasks. Larger-effect sizes were evident for auditory verbal learning tasks, including delayed word pair memory, delayed word recall and for protection from proactive interference during delayed memory. The highest effect sizes for cognitive outcomes were 0.77 for modafinil (visuospatial memory accuracy), 0.86 for Ginseng (simple reaction time) and 0.95 for Bacopa (delayed word recall). These findings support the use of bacopa, particularly in measures of verbal recall.
Highlighting a couple of the individual studies, Stough et al. conducted a randomized double blind placebo controlled trial in 46 healthy adults, examining the effects of bacopa on cognitive function in healthy individuals, using a bacopa supplement of 300 mg/day standardized to 55% bacosides for 12 weeks.[vii] A battery of eight tests was taken at 5 weeks and 12 weeks post administration, finding significantly improved speed of visual information processing, learning rate, memory consolidation, and state anxiety compared to placebo, with maximal effects evident after 12 weeks.
A study conducted in Portland, Oregon evaluated the effects of Bacopa monnieri whole plant standardized dry extract on cognitive function in healthy elderly participants.[viii] This randomized, double-blind, placebo-controlled clinical trial had a treatment period of 12 weeks. Fifty four men 65 or older (mean of 73.5 years) without dementia were enrolled and randomized to bacopa or placebo. Forty-eight (48) completed the study with 24 in each group. Participants were given Standardized B. monnieri extract 300 mg/day or a similar placebo tablet orally for 12 weeks.
Bacopa participants had enhanced Rey Auditory Verbal Learning Test (AVLT) delayed word recall memory scores relative to placebo. Other cognitive measures such as the Stroop task results were similarly significant, with the Bacopa group improving and the placebo group unchanged. Depression and anxiety scores and heart rate decreased over time for the Bacopa group but increased for the placebo group. No effects were found on the Divided Attention Task (DAT), and the Wechsler Adult Intelligence Scale (WAIS) letter-digit test of immediate working memory. Overall, the study provided further evidence that bacopa could enhance cognitive performance in aging individuals.
Bacopa has also been studied in children for effects on cognition and learning. A systematic overview published in 2017 gives a good insight into the research and potential.[ix] Nine trials met the inclusion criteria and five studies reported sufficient data for effect size analysis. Most of the improvements reported were in behavioral outcomes. Cognitive abilities and behavioral outcomes were reviewed in six studies, with visual perception, impulsivity, and attention demonstrating the greatest improvements.
Dosages, Side Effects, Toxicity, Contraindications:
Bacopa has been used safely in children and adults in studies up to 6 months in duration. Common dosages range from 350-640mg/day; Part used is the leaf.
Drug Interactions that are moderate and thus caution should be considered include:
-Acetylcholinasterase inhibitors
– Anticholinergics
– Cholinergics
– Cytochrome p450 1A2 substrates
– Cytochrome p450 2C19 substrates
– Cytochrome p450 2C9 substrates
– Cytochrome p450 3A4 substrates
Minor drug interactions include:
-Thyroid hormones
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels and have cholinergic effects, and thus should be used with caution in those individuals with bradycardia (slow heart rate) , gastrointestinal or urogenital obstruction, peptic ulcer disease, asthma and chronic obstructive pulmonary disease. Thyroid drugs might also increase thyroxine levels.
Bacopa is generally well tolerated but there are reports of increased stool frequency, nausea and abdominal cramps. Less common side effects could include dry mouth, muscle fatigue, flatulence, bloating, decreased appetite, headache, palpitations, drowsiness, sleep issues, and vivid dreams.
References
[i] Sivaramakrishna C. Rao CV. Trimurtulu G. Vanisree M. Subbaraju GV. Triterpenoid glycosides from Bacopa monnieri. Phytochemistry. 2005;66:2719–2728.
[ii] . Chakravarty AK. Sarkar T. Masuda K. Shiojima K. Nakane T. Kawahara N. Bacopaside I and II: two pseudojujubogenin glycosides from Bacopa monniera. Phytochemistry. 2001;58:553–556.
[iii] Chakravarty A.K. Garai S. Masuda K. Nakane T. Kawahara N. Bacopasides III–V: Three new triterpenoid glycosides from Bacopa monniera. Chem Pharm Bull. 2003;51:215–217.
[iv] Garai S. Mahato SB. Ohtani K. Yamasaki K. Dammarane-type triterpenoid saponins from Bacopa monniera. Phytochemistry. 1996;42:815–820.
[v] Pase MP. Kean J. Sarris J. Neale C. Scholey AB. Stough C. The cognitive-enhancing effects of Bacopa monnieri: A systematic review of randomized, controlled human clinical trials. J Altern Complement Med. 2012;18:1–6
[vi] Neale C, Camfield D, Reay J, et al. Cognitive effects of two nutraceuticals Ginseng and Bacopa benchmarked against modafinil: a review and comparison of effect sizes. Br J Clin Pharmacol. 2013 Mar;75(3):728-37.
[vii] Stough C1, Lloyd J, Clarke J, Downey LA, Hutchison CW, Rodgers T, Nathan PJ.The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berl). 2015 Jul;232(13):2427.
[viii] Calabrese C, Gregory W, Leo M, et al. Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial. J Altern Complement Med. 2008 Jul;14(6):707-13.
[ix] Kean J, Downey L, Stough C. Systematic Overview of Bacopa monnieri (L.) Wettst. Dominant Poly-Herbal Formulas in Children and Adolescents. Medicines 2017; 4(4): 86
