Nootropics and Genetics: Smart Drugs and Your Genes

Nootropics are supplements used to boost cognition and memory. In other words – smart drugs.

This article covers published research studies on several popular nootropics. I’ll explain the research on how the substance works and the genes connected to the mechanism of action.

Let me be upfront…
Research directly connecting genetic variants to whether a smart drug will work for you is slim. Instead, I’m connecting some dots and giving you the background information to start your research and experimenting.

Please talk with your doctor or pharmacist if you have any questions about a supplement – especially if you are currently on prescription medication.

Noopept (cognitive function, memory)

Noopept is a dipeptide that the Russians discovered in the 1960s. The Russian government had a program to develop cognitive-enhancing drugs, and noopept now has decades of research on it with both human and animal studies.

Noopept may enhance memory and cognitive function in a couple of ways:

  • Noopept can increase HIF-1 activity. HIF-1 (hypoxia factor 1) is important in low oxygen states.[ref] In turn, HIF-1 activates other genes that help cells respond to lower oxygen levels. In the brain, this increases energy metabolism in the mitochondria and activates proteins responsible for controlling GABA receptors.[ref]
  • Noopept also enhances BDNF (brain-derived neurotropic fact) and NGF (nerve growth factor) expression.[ref][ref] Both BDNF and NGF are important in cognitive function and brain plasticity.
  • The noopept metabolite, cyclopropyl glycine, binds to AMPA receptors in the brain.[ref] AMPA receptors are glutamate receptors essential to brain plasticity and neuronal transmission.[ref]

Research on Noopept and the brain

Recently, research has focused on using neuropeptides such as noopept for Alzheimer’s disease. Phase III and other clinical trials have been done in Russia. Unfortunately for me, much of the research is published in Russian. A recent cell study showed that noopept enhances neuronal cell viability by reducing the excessive production of ROS in Alzheimer’s brain cells. This protects against amyloid-beta toxicity.[ref]

Cell studies show that noopept may protect cell viability in an Alzheimer’s model.[ref]

Animal studies on noopept show that it can eliminate the symptoms of learned helplessness.[ref]

A clinical trial in Russia investigated using Noopept for cognitive dysfunction in concussion patients. Oddly, the other arm of the trial used piracetam instead of a placebo. Both noopept and piracetam (a similar drug) showed similar efficacy. Of interest here is that there were fewer linked side effects with noopept than piracetam.[ref]

Another clinical trial in Russia found mild improvements from noopept in stroke patients. The trial (with a placebo control) used a 20 mg daily dose for two months.[ref]

Safety is essential when looking into nootropics. Let’s take a look at what research shows on noopept safety.

  • Animal studies also show that Noopept does not seem to increase cell proliferation. It is important because HIF-1A is increased in cancer cells.[ref]
  • Additionally, animal studies show that noopept is not genotoxic (does not cause DNA damage).[ref]

Noopept: Genotype Report

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BDNF gene: BDNF is important in resiliency to adverse events, brain plasticity, memory, and overall brain health. Long-term (28-days) of noopept increased the expression of BDNF.[ref]

Check your genetic data for rs6265 Val66Met (23andMe v4, v5; AncestryDNA):

  • T/T: decreased BDNF[ref] referred to in studies as Met/Met[ref][ref][ref][ref],
  • C/T: somewhat decreased BDNF, referred to as Val/Met
  • C/C: typical BDNF, referred to as Val/Val

Members: Your genotype for rs6265 is .

Check your genetic data for rs56164415 C270T (23andMe v4; AncestryDNA):

  • A/A: less BDNF in regions of the brain[ref][ref][ref]
  • A/G: less BDNF in specific regions of the brain
  • G/G: typical BDNF

Members: Your genotype for rs56164415 is .

AMPA receptor: Noopept acts on the AMPA receptor, which comprises four protein subunits. GRIA1 – 4 genes encode the subunits of AMPA receptors. Interestingly, GRIA1 and GRIA4 genetic variants are linked to migraine susceptibility.

Check your genetic data for rs548294 (23andMe v4; AncestryDNA):

  • C/C: typical
  • C/T: increased risk of migraines, possibly due to decreased AMPA receptor function
  • T/T: increased risk of migraines, possibly due to decreased AMPA receptor function[ref]

Members: Your genotype for rs548294 is .

HIF1a gene: Noopept increases HIF-1. Two well-studied HIF1A genetic variants generally increase the amount of HIF-1a available in cells. These variants are linked to an increased relative risk of certain cancers. On the plus side, the variants may give advantages in athletic training and decrease the risk of certain inflammatory conditions.

Check your genetic data for rs11549465 Pro582Ser (23andMe v4, v5; AncestryDNA):

  • C/C: typical HIF-1a levels
  • C/T: increased HIF-1a; overall higher risk of several types of cancer; decreased risk of diabetes; greater gains following endurance training; more likely to be an elite athlete; less likely to have a hamstring injury[ref]; decreased risk of knee osteoarthritis
  • T/T: increased HIF-1a; overall higher risk of several types of cancer[ref][ref]; decreased risk of diabetes[ref]; greater gains following endurance training[ref]; more likely to be an elite athlete[ref]; decreased risk of knee osteoarthritis[ref]

Members: Your genotype for rs11549465 is .

Check your genetic data for rs11549467 Ala588Thr (23andMe v4, v5; AncestryDNA):

  • G/G: typical HIF-1a levels
  • A/G: increased HIF-1a;
  • A/A: increased HIF-1a;[ref][ref][ref]

Members: Your genotype for rs11549467 is .

Bacopa monnieri (memory supplement)

Bacopa monnieri, also known as Brahmi, is a native plant found in the wetlands of Australia and India. It has been used in traditional Ayurvedic medicine for over 1400 years as a way to sharpen intellect and help with memory.[ref]

How does bacopa work?

  • The active compounds in Bacopa include bacosides, which can cross the blood-brain barrier easily.[ref]
  • Studies show that Bacopa monnieri has antioxidant properties that may be neuroprotective against oxidative stress in the brain.[ref]
  • Animal studies show that it restores acetylcholine levels in aged brains to that of young animals. Additionally, Bacopa monnieri modulates neurotransmitter levels.[ref]
  • Cell studies show that Bacopa monnieri inhibits the release of proinflammatory cytokines – reducing TNF-alpha and IL-6 in brain cells.[ref]
  • Animal studies also show that the improvements in learning and memory with Bacopa monnieri accompany an increase in amygdala function via dendritic growth.[ref]

Research Studies on Bacopa monnieri

  • A randomized controlled trial of adults aged 40-65 showed that after three months of Bacopa supplements, the study participants increased memory of new information.[ref]
  • A randomized trial in medical students found that 150 mg Bacopa monnieri twice daily for six weeks improved cognitive function.[ref]
  • Studies of Bacopa supplements for children and teens show that it helps to improve memory. Study participants also showed improvements in attention and a reduction in hyperactivity. [ref]
  • A meta-analysis of nine studies concluded that Bacopa monnieri improves cognition and speed of attention.[ref]
Caution with drug interactions: In studies, Bacopa monnieri inhibits several of the major enzymes (CYP2C19, CYP2C9, CYP3A4) used to metabolize pharmaceutical drugs.[ref] If you are on prescription medication, please check with your doctor and/or pharmacist for drug interactions with Bacopa monnieri.

Bacopa: Genotype Report

NPTN gene: A study examining which genes were upregulated in brain cells with Bacopa found that it increases neuroplastin (NPTN gene). Interestingly, this is the same gene that has been identified as impacting the thickness of the brain’s cortex.

Check your genetic data for rs7171755 (23andMe v4; AncestryDNA):

  • A/A: thinner cortex in the left hemisphere of the brain, lower expression of NPTN in the brain[ref]
  • A/G: thinner cortex in the left hemisphere of the brain, lower expression of NPTN in the brain
  • G/G: typical

Members: Your genotype for rs7171755 is .

Neuroinflammation genes: TNF-alpha and IL-6 genetic variants are linked to mood disorders due to heightened inflammation. Bacopa has been shown to reduce TNF-alpha and IL-6.[ref]

There are several genetic variants linked to naturally more active TNF-alpha. Learn more about TNF-alfa and inflammation here.

Check your genetic data for rs1800629 -308A/G (23andMe v4, v5; AncestryDNA):

  • A/A: Higher TNF-alpha levels[ref][ref][ref][ref][ref]
  • A/G: somewhat higher TNF-alpha levels
  • G/G: typical

Members: Your genotype for rs1800629 is .

Check your genetic data for rs361525 (23andMe v4, v5; AncestryDNA):

  • A/A: higher TNF-alpha levels[ref][ref][ref][ref][ref][ref]
  • A/G: somewhat higher TNF-alpha levels
  • G/G: typical

Members: Your genotype for rs361525 is .

The rest of this article is for Genetic Lifehacks members only. It includes information and Genotype reports on methylene blue and St. John’s wort. Consider joining today to see the rest of this article.

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.

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