best-nootropics-to-boost-acetylcholine

Advanced Guide to Acetylcholine Supplements in Nootropic Stacks

David Tomen
Author:
David Tomen
15 minute read

Supplements That Boost Acetylcholine

The neurotransmitter Acetylcholine (ACh) plays a leading role in alertness, focus, memory and mood. ACh also contributes to neuroplasticity that supports long-term potentiation needed to form long-term memory. And for a healthy, optimized brain.

ACh deficiency has been linked to ADHD, Alzheimer’s, dementia, Parkinson’s, and multiple sclerosis.

But you can’t take acetylcholine as a supplement. There is no such thing as “acetylcholine pills”, or “acetylcholine tablets”. But certain foods can help boost acetylcholine (ACh) by providing your brain with the choline it needs to synthesize ACh.

Food sources of choline are egg yolks, liver, milk and other dairy products, certain grains like quinoa and amaranth, bacon, edamame and cruciferous vegetables.

Most of us don’t get enough choline in our diet to produce the acetylcholine we need. And this is particularly true if you’re using any one of the racetam nootropics in your stack.

So many neurohackers use one of the choline supplements we discussed in Part 1 – Advanced Guide to Choline in Nootropic Stacks of this series to boost acetylcholine. Including:

And from our review, we know these nootropics often do so much more than simply increase acetylcholine in our brain.

But we have several other options available to help increase ACh release in the brain, inhibit its breakdown, encourage reuptake, stimulate ACh neuroreceptors, or provide the ingredients needed to create acetylcholine.

These nootropic supplements are considered cholinergic compounds. The following list is a brief description of both natural and synthetic nootropics that help acetylcholine in your brain.

For a more detailed review of each the following nootropics, simply click on the live link associated with that supplement. And you’ll go to a new page which will provide you with the nootropic’s history, mechanism of action, clinical studies, dosage notes, side effects and recommendations.

You can easily find these acetylcholine supplements on Amazon, GNC, The Vitamin Shoppe, Whole Foods and sometimes even Walmart. And the racetams are available at a few trusted online nootropic vendors.

Supplements that Boost Acetylcholine

Acetyl-L-Carnitine (ALCAR)

ALCAR boosts acetylcholine. It is a precursor to the synthesis of acetylcholine in the presence of Coenzyme-A. ALCAR donates a “methyl group” to make acetylcholine.[i]

Alpha-Lipoic Acid

Alpha-Lipoic Acid increases acetylcholine production by activation of choline acetyltransferase and increases glucose uptake. This process supplies more Acetyl-CoA for the production of acetylcholine.[ii]

Ashwagandha

Ashwagandha (Withania somnifera) extract inhibits acetylcholinesterase. The enzyme responsible for breaking down acetylcholine. The result is a boost in cognition, learning and memory.[iii]what foods contain acetylcholine

Researchers at Nizam’s Institute of Medical Sciences in Hyderabad, India gave 20 healthy male volunteers 250 mg capsules of standardized Ashwagandha extract for 14 days.

Significant improvements in reaction times were reported at the end of the trial. The study suggests that Ashwagandha extract improves cognitive and psychomotor (physical reaction) performance even when you’re in the best of health.[iv]

Bacopa Monnieri

Bacopa Monnieri (Brahmi) was given to devotees in ancient India to help memorize long passages of text. And enhance cognition.

As an adaptogen, Bacopa helps balance the neurotransmitters acetylcholine, dopamine, and serotonin. And research shows Bacopa inhibits acetylcholinesterase (the enzyme that breaks down acetylcholine). As well as activates choline acetyltransferase. The enzyme that promotes acetylcholine creation.[v]

Researchers searched clinical studies to compare the cognition enhancing effects of Bacopa Monnieri and Ginseng to the popular smart drug Modafinil.

The team found that both Bacopa and Ginseng worked better than Modafinil for improving accuracy, memory and processing speed.[vi]

DHA

DHA (docosahexaenoic acid) is an omega-3 fatty acid. The highest levels of DHA are found in phosphatidylserine (PS). With lower levels in phosphatidylcholine (PC).

PS and PC are called phospholipids. And make up much of the inner and outer shell of brain cell membranes. Made up largely of DHA, these cellular membranes regulate entry into the cell, and control neuroreceptor function.[vii] Which facilitates cellular communication between, and within cells.

Phosphatidylcholine (PC) also contributes the choline needed to synthesize acetylcholine. And DHA regulates calcium oscillations, which are involved in neurotransmitter release, mitochondrial function, gene activation, oxidative stress and brain cell development and growth (BDNF).

A DHA supplement is one of the most important nootropics you can add to your stack. Recommended daily dosage is 1,000 mg of DHA per day.

Ginkgo Biloba

Ginkgo biloba (Ginkgo or Maidenhair) is known for regulating neurotransmitters, protecting from brain cell degeneration, boosting cerebral circulation and is a potent antioxidant.[viii]

Research also shows Gingko’s cognitive enhancing capabilities are due to its effect on the cholinergic system in your brain. It modulates pre-synaptic choline uptake and acetylcholine release, upregulates post-synaptic acetylcholine muscarinic receptors, and has an indirect effect on choline function by modulating the serotonin system.[ix]

Ginseng

One study using Cereboost™, a branded form of American ginseng (Panax quinquefolius), which has a high concentration of Rb1 ginsenoside, enhanced the activity of the enzyme choline acetyltransferase (ChAT). ChAT is the enzyme responsible for acetylcholine synthesis.

This ginseng supplement also restored brain microtubule-associated protein 2 (MAP2) as well as acetylcholine concentration.[x] And scientists just discovered that MAP2 is the main “traffic regulator” in neurons in the brain. This neuron traffic signaling system plays a key role in brain diseases like Alzheimer’s.[xi]

Gotu Kola

Gotu Kola (Centella asiatica) is often called “the student herb” in Bali. Because it sharpens the mind. Gotu Kola extract increases dendrite and axon growth in brain cells which helps memory.

Gotu Kola is rich in triterpene saponosides. These triterpenes inhibit  acetylcholinesterase (AChE). The enzyme that breaks down acetylcholine. Meaning more acetylcholine is available in your brain.[xii]

Holy Basil (Tulsi)

Holy Basil (Tulsi) or “The Incomparable One” is the most sacred plant in the Hindu religion. And has been valued for millennia by Ayurveda, Greek, Roman, Siddha and Unani because of its benefits for mind, body and spirit.

Supplementing with Holy Basil increases levels of dopamine, is a monoamine oxidase inhibitor (MAOI), and inhibits acetylcholinesterase (AChE) which boosts acetylcholine.

Recommended dosage of Holy Basil extract is 300 – 2,000 mg per day.

Huperzine-A

Huperzine-A is a natural compound extracted from the Chinese club moss huperzia serrata. Huperzine-A is an acetylcholinesterase (AChE) inhibitor.  Which means it boosts levels of the neurotransmitter acetylcholine in your brain.acetylcholine supplement benefits

Nootropics users report Huperzine-A provides a boost in mental energy. Without the side effects normally associated with a stimulant. Improved cognition and clear thinking are common when using Hup-A. Many report a boost in short-term memory. Recall is better in the long-term.

Researchers at Walter Reed Army Institute of Research in Washington D.C. found Huperzine-A to be twice as effective in protecting soldiers against the lethal effect of the nerve agent soman, as the leading drug in that role called physostigmine.

Huperzine-A’s effects lasted for six hours compared to only 90 minutes for the drug.[xiii] Nerve gas used in chemical warfare attack the acetylcholine system in your body and brain.

Iodine

Iodine is required for the production of thyroid hormones T4 and T3. Thyroid hormone receptors in the brain help regulate the production and use of all important neurotransmitters.

Thyrotrophic-releasing hormone (TRH) increases acetylcholine (ACh) synthesis.[xiv] One study showed that those with hypothyroidism had significantly decreased acetylcholine in the hippocampus. And that administration of T4 normalized ACh levels.[xv] Iodine is required to make T4.

Lemon Balm

Lemon Balm increases the activity of the neurotransmitter acetylcholine (ACh) in your brain. When your brain sends signals, it uses acetylcholine to keep the signals moving. But once used, your brain removes acetylcholine with an enzyme called acetylcholinesterase (AChE).

The rosmarinic acid in Lemon Balm is an AChE inhibitor. By inhibiting AChE, more acetylcholine is available to boost learning and memory. And Lemon Balm also has cholinergic receptor-binding properties. Which boosts the ability of ACh to bind to its receptors.[xvi]

Nicotine

acetylcholine pillsNicotine works primarily by upregulating nicotinic acetylcholine receptors (nAChR) in the brain. Boosting the release of acetylcholine (ACh), dopamine, serotonin, and glutamate. Increasing neural signaling of neurotransmitters and boosting alertness, cognition, memory and mood.

But studies have shown this upregulation of nAChR is dose dependent. And too much nicotine desensitizes these receptors.[xvii] So low doses of nicotine are key in using nicotine as a nootropic for cognitive benefit.

The National Institute of Drug Abuse conducted a meta-analysis of 41 double-blind, placebo-controlled studies conducted between 1994 and 2008. The analysis found significant positive effects of nicotine on fine motor performance, alertness, attention and accuracy, response time, short-term and working memory.[xviii]

Phosphatidylcholine (PC)

Phosphatidylcholine serves as a storage pool for the choline needed as a precursor for acetylcholine (ACh) synthesis. ACh is synthesized from choline derived from the degradation of Phosphatidylcholine.

PC performs a 2nd important function in your brain. The hydrolysis of Phosphatidylcholine (by a process called phospholipase A2-catalyzed hydrolysis) is used to make the free fatty acids AA, oleic, linoleic, linolenic and DHA.

These free fatty acids facilitate synaptic transmission by targeting nicotinic ACh receptors using protein kinase C (PKC). This messenger system is needed for long-term potentiation (LTP). Researchers have determined that these fatty acids are critical for learning and memory.[xix]

Phosphatidylserine (PS)

Phosphatidylserine is a phospholipid component of the membrane encasing every one of your brain cells. In fact, Phosphatidylserine is one of the most effective memory boosters known.

PS is an integral part of the flow of crucial neurotransmitters like dopamine and acetylcholine. And phospholipids contain choline which is a precursor to acetylcholine (ACh). So PS will increase ACh levels in your brain. Affecting cognition, memory and mood. And reducing anxiety.

Rhodiola Rosea

In Russia, Rhodiola Rosea is widely used as a remedy for fatigue, poor concentration, and decreased memory. It’s also believed to make workers more productive.

Rhodiola improves mood by influencing serotonin and norepinephrine levels in your brain. And the ‘feel-good’ opioids like beta-endorphins. It helps repair and grow new brain cells (neurogenesis). Rhodiola activates synthesis and re-synthesis of ATP. And reduces inflammatory C-reactive protein. Protecting your brain cells from oxidative damage.

Researchers at China Pharmaceutical University also found that Rhodiola extract inhibits acetylcholinesterase. Meaning it increases levels of available acetylcholine in your brain.[xx]

SAM-e

Supplementing with SAM-e (S-Adenosyl Methionine) to increase muscarinic acetylcholine receptors in your brain can boost neuroplasticity. And increase learning, memory, mood and even smell and vision.

Muscarinic receptors are part of a large family of G-protein-coupled receptors (GPCRs) which are used as an intracellular secondary messenger system.

G proteins work by binding neurotransmitters, hormones, growth factors, cytokine, odorants and photons at the cell surface to the GPCR, and activating that receptor. Everything you see, hear, smell, or taste goes through this signaling process.

SAM-e also has a critical role as a methyl donor (called methylation) in the production and breakdown all the major neurotransmitters in your brain. Including acetylcholine.

Uridine Monophosphate

Uridine is a precursor to the formation of CDP-Choline which is a precursor to the formation phosphatidylcholine (PC). PC separates into choline and sphingomyelin in your brain. Choline is then available to form acetylcholine (ACh). Optimal ACh levels is crucial for cognitive performance.[xxi]

Vitamin B1 (Thiamine)

Thiamine contributes to the production of the enzyme PDH (pyruvate dehydrogenase) which is essential for making acetylcholine.[xxii]

Sulbutiamine is a synthetic derivative of Vitamin B1. It’s simply two Vitamin B1 molecules bonded together. This chemical bond helps thiamine more easily cross the blood-brain barrier. And is often a better alternative in a nootropic stack than just plain Vitamin B1 (thiamine).

Vitamin B5 (Pantothenic Acid)

Vitamin B5 is a precursor in the biosynthesis of Coenzyme-A (CoA). Adding an acetyl group to CoA makes Acetyl-CoA. Choline + Acetyl-CoA go on to produce acetylcholine.

Vitamin B12 (Cobalamin)

Vitamin B12 is a co-factor in the one-carbon cycle that is required for the synthesis of all major neurotransmitters in your brain including acetylcholine, dopamine, GABA, norepinephrine and serotonin.

Typical recommended dosage for nootropic benefit and optimal brain health is 100 mcg or 1 mg of Vitamin B12 (methylcobalamin) per day. Neurohackers older than 40 and those who have a problem with Vitamin B12 absorption should use 100 – 400 mcg or 1-4 mg of B12 per day. See the extended review of B12 for details.

acetylcholine tablets

Acetylcholine and the Racetams

Most of the nootropics in the racetam-family of compounds influence acetylcholine (ACh) in one way or another. Your chosen racetam could increase the synthesis of ACh. It could boost acetylcholine receptor density. Or increase the use of acetylcholine through the High Affinity Choline Uptake (HACU) process in parts of your brain. And even modulate the flow of acetylcholine.

This means that use of a racetam in your nootropic stack demands the addition of a quality choline supplement like Alpha GPC or CDP-Choline. To give your brain the ability to make the acetylcholine it requires.

If you neglect to use a choline supplement, you’ll not experience the full benefit of that racetam. And likely end up with a racetam-headache.

Please refer to my Advanced Guide to Choline in Nootropic Stacks for more.

Here are the best racetams for influencing acetylcholine in your brain.

Coluracetam

Coluracetam (BCI-540, or MKC-231) is a fat-soluble nootropic in the racetam-class of compounds. And is much more potent than the original racetam, Piracetam.

Coluracetam boosts your brain’s choline conversion to acetylcholine (ACh) through the high affinity choline uptake (HACU) process.

Nefiracetamdrugs that decrease acetylcholine

Nefiracetam is a fat-soluble nootropic developed in Japan for the treatment of cerebrovascular disease. This racetam is structurally similar to Aniracetam. And helps modulate GABA levels in the brain which improves memory formation and recall, and provides anti-anxiety and antidepressant benefits.

Nefiracetam also potentiates presynaptic nicotinic acetylcholine receptors in the hippocampus. Which encourages glutamate release and Long-Term Potentiation (LTP).[xxiii]

Noopept

Noopept is an ampakine nootropic similar in action to the racetam-class of compounds. And considered up to 1000X more potent than Piracetam.

Noopept does not appear in blood samples when taken as a supplement. Instead it elevates concentrations of cycloprolylglycine (CPG) in the brain.

CPG is a dipeptide consisting of proline and glycine which acts as a modulator of acetylcholine transmission, and AMPA receptor function.[xxiv]

Oxiracetam

Oxiracetam is a water-soluble racetam nootropic. And considerably more potent than Piracetam. Oxiracetam enhances choline-acetyltransferase (ChAT) in your brain.[xxv] ChAT is the enzyme needed to stimulate acetylcholine (ACh) synthesis.

Oxiracetam also enhances protein kinase C (PKC) which affects M1 acetylcholine receptors. Oxiracetam even demonstrates the ability to repair these receptors when damaged.[xxvi]

And Oxiracetam seems to prevent an imbalance of acetylcholine activity when NMDA receptors are malfunctioning.[xxvii]

Phenylpiracetam

Phenylpiracetam is a water-soluble nootropic in the racetam-class of compounds. This racetam increases the density of acetylcholine (ACh), NMDA, GABA and dopamine receptors in the brain.[xxviii]

This translates into more receptors for each of these important neurotransmitters to bind with and boosts their effectiveness.

Phenylpiracetam has a positive effect on physical performance by increasing endurance, and reducing physical and mental fatigue. In fact, these effects are so potent that Phenylpiracetam has been banned from professional sports by the World Anti-Doping Agency.

Piracetam

Piracetam was developed by Romanian chemist, and the godfather of nootropics, Dr. Corneliu E. Giurgea in 1964. This is the first racetam ever developed.

Piracetam potentiates the flow of, and increases the effect of acetylcholine (ACh). And boosts the sensitivity and density of ACh receptors in the brain.[xxix]

Pramiracetam

Pramiracetam is a fat-soluble nootropic in the racetam-class of compounds. It has been shown to significantly increase High Affinity Choline Uptake (HACU) in the hippocampus. This action boosts acetylcholine (ACh) use which accounts at least in part for Pramiracetam’s ability to enhance cognition and memory.[xxx]

Pramiracetam also has a profound effect on the synthesis of the acetylcholine (ACh).[xxxi] Positively affecting encoding of new memories, concentration, cognition and neuroplasticity.

Anticholinergic Medications

Not using a choline supplement while taking racetams is only one of the ways to you can deplete your brain of acetylcholine. Racetam-headaches happen because your brain will start to literally consume itself to get the building blocks it needs to make acetylcholine.

But what most neurohackers don’t realize is that we have easy access to plenty of anticholinergic medications that will do a great job of depleting your brain of acetylcholine. Drugs that decrease acetylcholine.

Any prescription or over-the-counter medication that blocks the action of acetylcholine is considered an anticholinergic.

These meds include antidepressants, antibiotics, antihypertensives, antipsychotics, and antispasmodics. If it starts with “anti”, it will very likely lower your acetylcholine levels.

Now, I’m not saying don’t use these medications. Just know how critical it is to replace the acetylcholine lost or suppressed while using it, with one or more of the supplements listed in this post.

Acetylcholine Supplements – The Last Word

So there you have it. The best nootropic supplements to boost acetylcholine. You can’t get acetylcholine from a pill or tablet. You must get it from either food or a supplement.Best nootropics to boost acetylcholine

Optimal levels of acetylcholine are critical for brain optimization and function.

Your diet, medications, some nootropics, and neurological disorders can all contribute to depleted levels of this critical neurotransmitter – acetylcholine.

We have dozens of supplements that can increase the synthesis of acetylcholine (ACh), increase density of ACh receptors, improve how ACh is used, and even amp-up the flow of acetylcholine in your brain.

But the way each of these nootropic supplements work vary from person to person. What works for me may not work as well for you. Experimenting is key to finding the best combination for your unique brain chemistry and genetics.

One final note – if you’re dealing with unusually significant memory loss. Memory loss that feels in your gut like it’s worse than it should be. Don’t take chances on trying every nootropic supplement and hoping for the best. Do yourself and your family a favor. And see a qualified neurologist.

As an Amazon Associate I earn from qualifying purchases. This post may also contain other affiliate links and I will be compensated if you make a purchase after clicking on my links.

[i] White H.L., Scates P.W. “Acetyl-L-carnitine as a precursor of acetylcholine.” Neurochemical Research 1990 Jun;15(6):597-601. (source)

[ii] Ahmed H.H. “Modulatory effects of vitamin E, acetyl-L-carnitine and α-lipoic acid on new potential biomarkers for Alzheimer’s disease in rat model.” Experimental Toxicologic Pathology 2012 Sep;64(6):549-56. (source)

[iii] Choudhary M.I., Yousuf S., Nawaz S.A., Ahmed S., Atta-ur-Rahman. “Cholinesterase inhibiting withanolides from Withania somnifera.” Chemical and Pharmaceutical Bulletin (Tokyo) 2004 Nov;52(11):1358-61. (source)

[iv] Pingali U., Pilli R., Fatima N. “Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants” Pharmacognosy Res. 2014 Jan-Mar; 6(1): 12–18. (source)

[v] Aguiar S., Borowski T. “Neuropharmacological Review of the Nootropic Herb Bacopa monnieri” Rejuvenation Research 2013 Aug; 16(4): 313–326. (source)

[vi] Neale C, Camfield D, Reay J, Stough C, Scholey A.  “Cognitive effects of two nutraceuticals ginseng and bacopa benchmarked against modafinil: a review and comparison of effect sizes.” British Journal of Clinical Pharmacology 2013; 75(3): 728-737. (source)

[vii] Litman B.J., Niu S.L., Polozova A., Mitchell D.C. “The role of docosahexaenoic acid containing phospholipids in modulating G protein-coupled signaling pathways: visual transduction.” Journal of Molecular Neuroscience 2001 Apr-Jun;16(2-3):237-42 (source)

[viii] EGb 761: ginkgo biloba extract, Ginkor. Drugs in R. & D.2003;4(3):188-93. (source)

[ix] Nathan P. “Can the cognitive enhancing effects of ginkgo biloba be explained by its pharmacology?” Medical Hypothesis 2000 Dec;55(6):491-3. (source)

[x] Shin K. et. Al. “Cereboost™, an American ginseng extract, improves cognitive function via up-regulation of choline acetyltransferase expression and neuroprotection.” Regulatory Toxicology and Pharmacology. 2016 Jul;78:53-8 (source)

[xi] Utrecht University. “Crucial ‘traffic regulator’ in neurons discovered by cell biologists: First comprehensive map of transport in mammalian axons.” Science Daily, 19 April 2017 (source)

[xii] Orhan I.E. “Centella asiatica (L.) Urban: From Traditional Medicine to Modern Medicine with Neuroprotective Potential” Evidenced Based Complementary and Alternative Medicine 2012; 2012: 946259. (source)

[xiii] Saxena A., Qian N., Kovach I.M., Kozikowski A.P., Pang Y.P., Vellom D.C., Radić Z., Quinn D., Taylor P., Doctor B.P. “Identification of amino acid residues involved in the binding of Huperzine A to cholinesterases.” Protein Science. 1994 Oct;3(10):1770-8. (source)

[xiv] Annerbo S., Lokk J. “A Clinical Review of the Association of Thyroid Stimulating Hormone and Cognitive Impairment” ISRN Endocrinology. 2013; 2013: 856017. (source)

[xv] Wang N., Cai Y., Wang F., Zeng X., Jia X., Tao F., Zhu D. “Effects of thyroxin and donepezil on hippocampal acetylcholine content and syntaxin-1 and munc-18 expression in adult rats with hypothyroidism.”Experimental and Therapeutic Medicine. 2014 Mar;7(3):529-536. (source)

[xvi] Kennedy D.O., Wake G., Savelev S., Tildesley N.T., Perry E.K., Wesnes K.A., Scholey A.B. “Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties.” Neuropsychopharmacology. 2003 Oct;28(10):1871-81. (source)

[xvii] Gentry C.L., Lukas R.J. “Regulation of nicotinic acetylcholine receptor numbers and function by chronic nicotine exposure.” Current Drug Targets: CNS and Neurological Disorders. 2002 Aug;1(4):359-85. (source)

[xviii] Heishman S.J., Kleykamp B.A., Singleton E.G. “Meta-analysis of the acute effects of nicotine and smoking on human performance.” Psychopharmacology (Berlin). 2010 Jul;210(4):453-69. (source)

[xix] Nagat T., Yaguchi T., Nishizaki T. “DL- and PO-phosphatidylcholines as a promising learning and memory enhancer” Lipids Health Dis. 2011;10:25. (source)

[xx] Wang H. Zhou G., Gao X., Yao W. “Acetylcholinesterase inhibitory-active components of Rhodiola rosea L.” Food Chemistry Volume 105, Issue 1, 2007, Pages 24–27 (source)

[xxi] Wang L., Albrecht M.A., Wurtman R.J. “Dietary supplementation with uridine-5′-monophosphate (UMP), a membrane phosphatide precursor, increases acetylcholine level and release in striatum of aged rat.” Brain Research. 2007 Feb 16;1133(1):42-8. (source)

[xxii] Martin P.R., Singleton C.K., Hiller-Sturmhofel S. “The Role of Thiamine Deficiency in Alcoholic Brain Disease” National Institute on Alcohol Abuse and Alcoholism nih.gov Retrieved May 5, 2016 (source)

[xxiii] Nishizaki T., Matsuoka T., Nomura T., Kondoh T., Watabe S., Shiotani T., Yoshii M. “Presynaptic nicotinic acetylcholine receptors as a functional target of nefiracetam in inducing a long-lasting facilitation of hippocampal neurotransmission.” Alzheimer’s Disease and Associated Disorders. 2000;14 Suppl 1:S82-94. (source)

[xxiv] Gudasheva T.A. et. Al. “The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine.” European Journal of Drug Metabolism and Pharmacokinetics. 1997 Jul-Sep;22(3):245-52. (source)

[xxv] Mochizuki D., Sugiyama S., Shinoda Y. “[Biochemical studies of oxiracetam (CT-848) on cholinergic neurons].” in Japanese Nihon Yakurigaku Zasshi. 1992 Jan;99(1):27-35. (source)

[xxvi] Fordyce D.E., Clark V.J., Paylor R., Wehner J.M. “Enhancement of hippocampally-mediated learning and protein kinase C activity by oxiracetam in learning-impaired DBA/2 mice.” Brain Research. 1995 Feb 20;672(1-2):170-6. (source)

[xxvii] Belfiore P., Ponzio F., Biagetti R., Berettera C., Magnani M., Pozzi O. “Oxiracetam prevents the hippocampal cholinergic hypofunction induced by the NMDA receptor blocker AP7.” Neuroscience Letters. 1992 Aug 31;143(1-2):127-30. (source)

[xxviii] Firstova Y.Y., Abaimov D.A., Kapitsa I.G., Voronina T.A., Kovalev G.I. “The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task” Neurochemical Journal June 2011, Volume 5, Issue 2, pp 115-125 (source)

[xxix] Bering B., Müller W.E. “Interaction of piracetam with several neurotransmitter receptors in the central nervous system. Relative specificity for 3H-glutamate sites.” Arzneimittelforschung. 1985;35(9):1350-2. (source)

[xxx] Pugsley T.A., Shih Y.H. “Some neurochemical properties of pramiracetam (CI-879), a new cognition-enhancing agent” Drug Development Research Volume 3, Issue 5, pages 407–420, 1983 (source)

[xxxi] Brust P. “Reversal of scopolamine-induced alterations of choline transport across the blood-brain barrier by the nootropics piracetam and pramiracetam.” Arzneimittelforschung. 1989 Oct;39(10):1220-2. (source)

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Join The Discussion - 68 comments

Samuel
December 2, 2020

Hi,

Do acetylcholine supplements increase/restore parasympathetic tone?

Regards

    David Tomen
    December 2, 2020

    Samuel, the parasympathetic nervous system relies solely on acetylcholine to function properly. So it’s possible.

Flavio
November 11, 2020

David can i increase the amount of acetylcholine with suplements without create imbalance of another neurotransmitter?,
like the relationship between dopamine and serotonin, which neurotransmitter is depleted when too much acetylcholine is consumed?

    David Tomen
    November 14, 2020

    Flavio, acetylcholine does not directly affect other neurotransmitters like the dopamine/serotonin balance. You can have too much acetylcholine which means you would need to cut back on whatever you are using the boost it.

Belen
October 10, 2020

Hey David,

Thanks so much for this useful information. I have been doing some research on supplements and after seeing so many different supplements, I am left a little confused.

I am 24 years old and I am really just looking to optimize my brain as much as possible, but I don’t suffer from anything specific. A few things I guess I deal with is memory, focus, alertness, and energy.

What would be a good stack to start out with for someone like me?

I appreciate the help!

    David Tomen
    October 11, 2020

    Belen, if you are 24 and reasonably healthy then the best and easiest solution is Mind Lab Pro (https://bit.ly/3lh3w8a). It will help memory, focus, alertness, and energy. And more. It works.

kant
August 22, 2020

Cholinergic Supplements create symptoms like anhedonia and depression in my brain.
Whenever i take these cholinergic system.
My energy level gets reduced and i become couch potato.
Also i loose all motivation of goal-oriented activity.
last month i had taken the stack of Bacopa + Ashwagandha + Citicholine + Fishoil +Huperzine.
ever since i got anhedonia..
is there a way to reverse this condition .

    David Tomen
    August 24, 2020

    Kant, the only thing I know of that “reverses” anhedonia is Ketamine. But since you need a prescription and willing doctor to get your hands on Ketamine, we look into the Ketamine “mechanism of action” in your brain.

    Turns out Ketamine is an NMDA receptor antagonist. So you do a search of Nootropics Expert for “NMDA receptor antagonist”. And this is what turns up: L-Theanine, Huperzine-A, Noopept, Lithium Orotate, Cat’s Claw, and Piracetam.

    I suggest using the Nootropics List here: https://nootropicsexpert.com/nootropics-list/. Scroll through and look up my review on each of these nootropics. And choose a couple to try following dosage recommendations. If I was in your shoes I’d work through that list until anhedonia was gone.

Stephen Pearson
May 25, 2020

Hi David!

What’s your opinion on Cyproheptadine? Is that safe to use? Does it cause any side effect in the long term? Is there any alternative?

    David Tomen
    May 26, 2020

    Stephen, Cyproheptadine is a very potent antihistamine. And like all antihistamines has a negative effect on acetylcholine. The list of side effects is two columns a page long (https://en.wikipedia.org/wiki/Cyproheptadine).

    Not sure what you mean by an ‘alternative’. Do you mean an alternative to antihistamines? What are you trying to accomplish?

      Stephen Pearson
      May 26, 2020

      Yes, antihistamine and antiserotoninergic.

      My goal is to reduce Serotonin, which Cyproheptadine does very well, but I want something which doesn’t mess with Cholinergic system. I want the acetylcholine to be running as smooth as it could be.

        David Tomen
        May 26, 2020

        Stephen, the most effective way I know of to reduce serotonin is to boost dopamine using L-Tyrosine, NALT or Mucuna Pruriens. Excess dopamine suppresses serotonin.

        Stephen Pearson
        May 26, 2020

        Thanks David!

        L Tyrosine sounds a good option to me.

        Is there any Nootropic that you recommend which causes more hunger? Pharmaceutical or herbal.

        David Tomen
        May 28, 2020

        Stephen, not sure that I would consider it a nootropic. But THC is the only one I can think of.

Dylan Burns
February 12, 2020

Hi David,

First off just wanted to say I think it’s awesome that you offer this platform for people looking for an alternative to many of the prescription medications that have long lists of side effects and long- term use damage. I’m fairly new to the nootropics world and have ADD. I’m currently taking 10mg Instant Release Generic Adderall (Ampheta/Dextro Combo) 3 times a day. I’m a full time student and need to be performing at peak performance mentally and physically. I created a custom stack based on a bit of research from your website and a few other sources . I decided to save some money in the long run and make my own pills from the powder form into gelatin capsules except for a few vitamins. Here’s what I came up with :
1)Mind Lab Pro (2 capsules)
2) Sulbutiamine (400mg)
3) Acetyl-L-Carnitine (500mg)
4) L-Theanine (+150mg on top of the 100mg in MindLabPro, total = 250mg)
5) Bacopa Monnieri (+300mg on top of the 150mg included in MindLabPro, total = 450mg)
6) Gotu Kola (400mg)
7) Ashwagandha (500mg)
8) Huperzine-A (200mcg)
9) Maca Root (450mg)
10) Gingko Biloba (150mg)
11) Siberian Ginseng (100mg)
12) Creatine (3g)
13) Coconut oil (5000mg)
14) “Natures Made Multi-complete vitamin – 23 key nutrients (1 Capsule)

Any advice would be greatly appreciated. Thank you !

    David Tomen
    February 14, 2020

    Dylan, you’re missing a couple of things. You’re not directly supporting dopamine or acetylcholine which are critical when using Adderall. You are using several cofactors but no direct precursors to boost those neurotransmitters.

    You need at least 500 mg L-Tyrosine 3-times per day for dopamine and 300 mg Alpha GPC or CDP-Choline 3-times per day for acetylcholine. Morning, noon and around 4 PM. To support Adderall use and to prevent the late afternoon crash.

    I suggest you cycle Huperzine-A also and use it once every 2 or 3 days because it has a 24 hour half life. Or eliminate it altogether because you don’t need it.

    And coconut oil each time you take your stack to support whatever fat-soluble ingredients you have in your stack.

    And finally, I suggest changing that Nature Made multi for a better quality supplement. You want a multi that is using bio-identical nutrients and not synthetics that your body cannot use.

Wim
January 2, 2020

Thanks David, this info is gold , I wish I stumbled on it years ago when I was studying your other supplement info pages.

5 years ago I noticed I had a problem with Caffeine.
4 years of trying stacks out, with first 2 years I could handle all. About 20 pills a day.

I thought my stress came due to high cortisol so used Ashwagandha to combat it successful for some months until that also caused more stressfull feelings inside.
Last year I started to have AF(detected) and by trail & error found that Carnitine & Vinpocetine caused it, leaving then and AF went away.

Stayed with the stack of ALCAR & ALA & DHA + others not on this list.
Nicotine, made me shiver for 30min
VIT B complex (even lower Dosis) , SAMe I took for 1,5y daily could not handle anymore the last months. Even a VIT B pill increased my nervousness a lot.
Low dosis of Iodine did the same , had to leave it to.

Nervousness I combated with Teanine and CBD successful , only had to increase a lot gradually the dosis per day.

I started to have the idea my sympathetic nervous system was the cause.

Now with this page of you I found the link between many supplements I took that all increased the acetylcholine level to a high level with below as result.

At synapses within the sympathetic ganglia, preganglionic sympathetic neurons release acetylcholine, a chemical messenger that binds and activates nicotinic acetylcholine receptors on postganglionic neurons.

For example, when the sympathetic nervous system is activated, the pituitary gland, which anatomically branches off of the hypothalamus in the brain, releases Adrenocorticotropic hormone (ACTH) into the bloodstream, increases cortisol levels, causing various physiological changes including heart rate increase. Simultaneously, the adrenal gland, a neural ganglion located on the kidneys, releases norepinephrine and has a similar effect on the heart.
________
I do not want to stop taking ALCAR & ALA & DHA & VIT B complex as they are good for many other things.

I see 2 solutions:
1. Cycling the supplements and never take them all on the same day. Do you have good info for how best to cycle supplements David ?
2. An other supplement that uses acetylcholin as a building block for something else so the level in the body goes down. Do you know any David ?

Itrn
July 7, 2019

Hello David,

I’ve read that prolonged increases of any certain neurotransmitter in the brain causes the brain to become more desensitized to those neurotransmitters, if it’s only the amount of, say, acetylcholine being increased. Is this true? To what extent, and what should I do about it? Does it mean that one I get off acetylcholine enhancing nootropics, I’ll be less smart than I once was?

    David Tomen
    July 7, 2019

    Too much of anything is not a good idea. Balance is key with neurotransmitters. It’s receptors that may become desensitized but with common sense use of a choline supplement shouldn’t be a problem.

    Most of these nootropics help repair and restore your brain with the resulting benefits to cognition. Once you stop taking them you may regress to where you started from. But not likely all the way back because of the brain repair that you did.

    den
    March 24, 2023

    I think you can use additives that enhance the sensitivity of receptors, Unfortunately, little attention has been paid to this.

      David Tomen
      March 28, 2023

      Using an acetylcholine precursor is much more effective in increasing acetylcholine in your brain. You can increased receptor density all you want but if you do not have enough acetylcholine to attach to those receptors there is not benefit to increasing the receptors.

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