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

Haider
June 28, 2019

Hello David,

I have a girlfriend who suffers from cfs i think because she dont produce enough acetylcholine because her vagus nerve doesn’t work properly. I think this is also her main cause of her anxiety, tiredness,brain fog and depression in period. Maybe i am wrong but do you have any reccomendations? From my side of view u know what u are talking about.

    David Tomen
    June 29, 2019

    Haider, there are plenty of things that contribute to Chronic Fatigue Syndrome. The easiest way to determine if it’s a problem with acetylcholine is for her to try Alpha GPC or CDP-Choline. And see if that relieves any of her symptoms.

      Haider
      June 29, 2019

      Hello David,

      Thankyou for your fast reply and advice. I will try it out for her. Right now she take aswghanda and GABA also. Is this oke?

        David Tomen
        June 29, 2019

        Both ashwagandha and GABA are fine as long as they work for her. Ashwagandha helps boost existing acetylcholine. And GABA is the calming neurotransmitter.

Robert
May 18, 2019

Dear David,
For some reason whenever I stack with choline supplements I develop a form of urticaria rash, specifically s tiny red bumbs on my arms and torso which itches like the devil. I’ve tried alpha gpc, cdp, and DMAE in various amounts and combinations and always get the same side effect. The nootropic effect from these supplements is quite satisfactory, but the rash is intolerable so I’ve completely eliminated all forms of choline. I use piracetam daily, 3 to 4 grams, along with ginkgo. Have you heard of any other reports of this side effect from choline, and finally, do you have any recommendations?
Thanks,
Rob

    David Tomen
    May 20, 2019

    Robert, cholinergic urticaria is usually caused by exercise in people prone to this kind of skin issue. I’ve never heard of it being caused by choline supplements. And it never came up in my research either.

Viktor
May 2, 2019

Hi! Is it a good idea to stack citioline (250mg) and NALT (500mg) in the morning? I have previously only used NALT, and now when I started to stack it with citicoline the effect seems to be worse. However, I sleep better now when I take citicoline.

    David Tomen
    May 2, 2019

    Viktor, I personally use Citicoline and NALT in the morning and it works well for me. But it depends on what your system requires for acetylcholine and dopamine. Because each directly boosts those neurotransmitters. If you are already high in acetylcholine then dosing with Citicoline will produce side effects like sleepiness.

Rick
April 30, 2019

Hi, once or twice a week I use Alpha-GPC, Choline, Galantamine and sometimes Nicotine to help induce lucid dreams. One of the concerns is that extra levels of ACh and repeated use of ACh supplements may cause desensitization of ACh receptors and tolerance. A popular recommendation is to use Piracetam after supplementation to aid in ACh synthesis and counter act desensitization and tolerance.

Is Piracetam the best nootropic to use for this purpose? Is there another one that works better for this and/or has extra benefits in relation to the health of the cholinergic system?

    David Tomen
    May 1, 2019

    Rick, I really wish people wouldn’t put this kind of garbage misinformation out there. Natural supplements used in recommended dosages will not “desensitize” receptors. But if you want to ‘drain’ your brain of acetylcholine then Piracetam without Alpha GPC or CDP-Choline will certainly do it.

Moe
January 27, 2019

I’ve been taking Phenylpiractam for a couple months now. At the beginning, it was good and it was helping me stomach issues. Nowadays it is giving me more side effects such as brain fog and stomach issues than it is helping me. I suspect it’s because my choline levels have been depleted by the phenyl and I need to take a break off it until I get a choline supplement such as citicholine. Can racetams deplete choline levels since it uses choline as a source?

    David Tomen
    January 28, 2019

    Moe, most of the racetams including Phenylpiracetam affect acetylcholine in your brain. And must be stacked with a choline supplement like Alpha GPC or CDP-Choline. Otherwise you’ll experience side effects like brain fog and headaches.

Ann
October 11, 2018

Hi David!

Excuse my English, isn’t my first language. I think i have and excess of Ach in my brain or maybe i’m sensitivity to it. I can’t take fish oil or liver, it causes brain fog, anxiety, confusion… The same happens with GPC Choline, is take one capsule and feel so bad. Maybe it would be a good idea eat less food rich in this compound? Is any way to balance this neurotransmitter?

Thanks so much for your time,
Ann

    David Tomen
    October 11, 2018

    Ann, try Forskolin or one of the racetams like Piracetam.

charles comaianni
April 23, 2018

Hey David,

What do you think would be the best way to add another reacetam to by stack? Also, how much would i take of erach if i wanted to do say, aniracetam and piracetam or, noopept and piracetam

    David Tomen
    April 23, 2018

    Charles, choose one that you want to try then check the dosage instructions in the review for that nootropic here on Nootropics Expert. I would only do one at a time so you can see how it works. And not get confused by mixing two or more.

    Amounts are different for each. But they all have in common the need for a choline supplement like CDP-Choline or Alpha GPC. A healthy fat like unrefined coconut oil for absorption. And various B-Vitamins and minerals to help the synthesis of neurotransmitters like dopamine, acetylcholine, and serotonin.

      charles comaianni
      April 23, 2018

      after trying ones i may want to mix, individually, would there be some type of method of mixing them? Or would i take the optimal amount i experienced for myself and just take them together?

        David Tomen
        April 24, 2018

        Charles, I make my own capsules because I buy powder. And rather than trying to calculate a formula and mix everything in one capsule, I just make separate sets of capsules for each. Then take them at the same time. I do my best to not complicate things.

        charles comaianni
        April 26, 2018

        Sorry David, Let me rephrase the question.

        Say I’ve already taken piracetam, aniracetam, and oxiracetam seperately. I then would want to mix piracetam with aniracetam. or oxiracetam with aniracetam. Would there be any ideal ratio mg wise when taking these together since they work synergistically?

        Thanks,

        Charles

        David Tomen
        April 26, 2018

        Charles, I’ve never tried it and am not aware of a steadfast rule on ratios. You are in experimental territory here. Each of these racetams affect AMPA receptors. And have an effect on acetylcholine too. Check the low end of the dosage instructions for each. When combining two of them you may want to try cutting the lowest recommended dose for each by 50%. See how it feels. If you get a headache you’ll know you need to increase your acetylcholine precursor. Either Alpha GPC or CDP-Choline.

Cebanu Iulian
April 19, 2018

I have ADHD, but respond baddly to any supplements that increase ACh. What nootropics should i try? I tried creatine, DMAE and ALCAR. The last two made me feel dumb and creatine might have had some subtle benefit after a few months. I’m thinking on trying NALT, L-Theanine and Zinc next.

    Cebanu Iulian
    April 19, 2018

    Could you please write an article about nootropics that don’t increase ACh?

    David Tomen
    April 19, 2018

    Cebanu, first it’s good that you’ve identified your sensitivity to acetylcholine. You should be OK with NALT, L-Theanine and Zinc. But if you’re going to supplement with zinc, please add 1 – 2 mg of copper because zinc on its own will suppress copper in your system.

    Can you be more specific on what you are trying to fix? And are you using any prescription ADHD meds?

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