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CYP2D6 is one of the most important enzymes associated with detoxification. 25% of clinical drug clearance is carried out by this enzyme, which includes antitumor drugs and antipsychotic drugs. This enzyme is also responsible for the metabolism of serotonin and dopamine and it also constitutes 40% of hepatic human phase I metabolism.

As humans, we are exposed to a lot of toxins, from the natural plant-based toxins to man-made toxins, to the pollutants discharged by chemical factories to chemicals present in skin creams among others. Our body, however, has the ability to remove certain toxic waste from it. The CYP2D6 enzymes coded by the CYP2D6 genes play an important role in liver detox.

Evolutionary and molecular aspects of CYP2D6

CYP2D6 belongs to the cytochrome P450 family of genes which originated from a prokaryotic ancestral gene. The CYP family of genes were instrumental in protecting the prokaryotes form oxygen toxicity. These genes constantly expanded and about 1.5 billion years ago, they expanded to include genes that were endogenous compound metabolising. The last expansion of the CYP genes occurred about 400 million years ago.

The CYP family of genes are found to be one of the most  rapidly evolving genes, an imperative characteristic required to protect cells and to avoid injuries when the cells are exposed to toxins.

The CYP2D6 gene is present in chromosome 22q13.1 and contains more than 100 allelic variants. With the advent of farming and modern day practices, humans have restricted the type of food consumed. This has lead to a loss of selection pressure which is required to keep genes active. Therefore, humans have only one functional gene, while other organisms like rat or mouse have multiple.

CYP2D6 metabolizer status:

Evolution of human CYP2D locus has resulted in the following types of alleles

The metabolic activity of CYP2D6 depends on the highest functioning allele

CYP2D6 metabolizer statusAllelesGeographic distribution
Ultrarapid Metabolizers (UMs)2 fully functional alleles16% of Ethiopians, 3–5% of Caucasians, 2% of Swedish Caucasians. UMs are present in Oceania and North Africa.
Extensive Metabolizers (EM)One fully functional and one reduced function allele70–80% of Caucasians
Intermediate Metabolizers (IM)2 reduced function alleles or one reduced function and one non functional allele10–17% of Caucasians. IMs are mainly in Asia
Poor Metabolizers (PM) 2 non functional alleles19% of African Americans, 5–10% of Caucasians,1% Chinese population and 0.6% of South Indian population.
PMs are found mainly in Europe


Genetic Variants of CYP2D6 – How is it important?


“Identifying the CYP2D6 variant carried can help in finding out which medications will work for you or which toxins you are hypersensitive to.”

The detox genes we carry work at different efficiencies and finding out about those helps us in understanding the metabolism and dosage of various drugs. A lack of CYP2D6 enzyme is associated with lowered drug effectiveness among drugs that require activation by CYP2D6

Use your 23andme raw data or your Ancestry DNA raw data to check for rs1135840 (CYP2D6 s486t )

This is one of the important and well known SNP of CYP2D6- CYP2D6 s486t

GenotypePhenotype
CCTwo non functioning alleles
CTOne non functioning allele
TTNormal

Use your 23andme raw data or your Ancestry DNA raw data to check for rs1065852

GenotypePhenotype
AATwo non functioning alleles
AGOne non functioning allele
GGNormal

Use your 23andme raw data or your Ancestry DNA raw data to check for rs5080367

GenotypePhenotype
GGTwo non functioning alleles
TGOne non functioning allele
TTNormal

Apart from these SNPs that are reported in the 23andme reports, there are other important CYP2D6 polymorphisms which contribute to determining CYP2D6 activity. Authority sites like Pharm GKB list out the significant polymorphisms, all of which are included in the Xcode Life science’s PGX report. Upload your 23andme raw data or your ancestry DNA raw data into Xcode Life science’s dashboard to get your comprehensive report.

For the entire list of CYP2D6 inducers and CYP2D6 inhibitors, check out CYP2D6 in wikipedia.

As the liver is the major source of the CYP2D6 enzymes, ensuring a healthy liver is important.

What is the need for a liver detox?

Every individual should focus on liver detox, especially with the amount of processed foods that are consumed and the amount of synthetic chemicals that enter our water and food supply through industrial, agricultural and other activities. While people may look good on the outside, their internal organs may be stressed due to non clearance of toxins.


The liver is responsible for many essential functions like

  1. It plays a role in protein, fat and carbohydrate metabolism
  2. Produces bile which is essential for breaking down fats
  3. Associated with storage of fat soluble vitamins
  4. Production of cholesterol: According to Harvard health reports, the liver produces 1000 mg of cholesterol which is required for the production of vitamin D, bile and hormones
  5. Protein synthesis: According to a study by Brown University, the liver is responsible for the synthesis of certain proteins that are required for the clotting of blood and for transporting nutrients.
  6. The liver plays a role in maintaining blood sugar
  7. Detoxification: The liver contains numerous enzymes that play a role in detoxification. A healthy liver can transform a potentially harmful substance into harmless products to be excreted.

The detoxification potential of a liver is very important and makes it important to focus on liver detox to keep it healthy.

How to detox liver naturally- 6 tips for detoxification

  1. Vegetable juice: Vegetables are a good source of nutrients and fibre which help in detoxifying the liver. Since it is difficult to consume a lot of salad, juicing vegetables like cabbage, brussels sprouts, beetroot, beans, carrots and cucumber may be the next best thing to do. Adding a dash of lime or mint could improve flavour.
  2. Bust the visceral fat: A study published in nature showed that the presence of excess of visceral fat leads to a protein called TRIP-Br2 initiating an inflammatory response. Regular exercise will help in reducing visceral fat.
  3. Intermittent fasting: Intermittent fasting will help in lowering fat content and is also found to increase stem cells which are needed to regenerate organ tissue.
  4. Avoid processed foods: Processed foods are high in saturated fat, sugar and salt, all of which get the liver to work harder. This can affect liver health over time. Therefore, the first step would be to avoid such foods.
  5. Increase intake of Vitamin C : Vitamin C plays an important role in reducing inflammatory markers. Detox water, which is nothing but lime water, consumed regularly could up your levels.
  6. Broccoli sprout extract: A study by researchers from The University of Tokyo showed that consumption of broccoli sprout extract protected the liver from xenobiotic substances by upregulating certain detox genes and by glutathione synthesis.

Genetic testing for medication effectiveness- CYP2D6

There is an intricate drug-gene interaction which makes genetic testing for medication effectiveness imperative.

DNA testing for drug effectiveness can be used for the following

Pharmacogenomics is a growing industry with many physicians utilising DNA testing for drug effectiveness. The significance of this method of testing was understood by the former President of the United States, Mr. Barack Obama, who felt that pharmacogenomics could make US healthier. He had wanted to dedicate $215 million towards precision medicine in his budget, signalling the growing interest in the field.

CYP2D6 gene polymorphisms are included in the Xcode PGX reports and should be interpreted only by a medical practitioner to identify the right drug and the right dose for each individual.  

References:

  1. https://www.nature.com/articles/ncomms11378
  2. https://www.ncbi.nlm.nih.gov/pubmed/29727683

Do you suffer from sniffles or a runny nose? Does drinking red wine make your face flush? Do you get sudden and unexplained headaches? These are some histamine intolerance symptoms which often feel like they appeared without any apparent trigger.

Histamine is a biogenic amine which is derived when the amino acid histidine is decarboxylated. This bioamine is stored in the mast cells and in the basophils and is produced by the body during allergic reactions. It is also known to be a neurotransmitter as well as a vasodilator. Though the condition is termed histamine intolerance, the body can ‘tolerate’ a certain amount of histamine. It’s only when there is histamine overload that people with reduced activity of the DAO enzyme start exhibiting histamine intolerance symptoms.

The body metabolizes histamine via the following two known degradation pathways

Apart from the histamine produced by the body, ingested histamine is also degraded by one of the two pathways.

How much of histamine could lead to histamine intolerance?

Histamine Intolerance symptoms:

Histamine intolerance symptoms include nasal congestion, irregular menstrual cycles, nausea, fatigue, vomiting, hives or headaches.

Histamine Intolerance test: A blood test to determine the level of DAO enzyme activity is not very definitive as the level of DAO enzyme in the blood is not reflective of its activity levels in the body. In a study conducted on 384 children with chronic abdominal pain, the level of serum DAO enzyme tested did not correlate with the levels of serum or urine histamine. When the children were put on a low histamine diet, 50% showed reduction in symptoms. According to ‘German guideline for the management of adverse reactions to ingested histamine’ (2017), measuring DAO enzyme activity in the serum was inconclusive in the detection of histamine intolerance.

Genetic testing for determining DAO enzyme activity can be used for informative purpose but there are other factors which could contribute to the development of histamine intolerance.

Genetics of Histamine Intolerance

When there is a reduction in the activity of the DAO enzyme, it is shown to be associated with an increased risk of histamine intolerance. DAO enzyme is synthesized from the AOC1 gene. 23andme raw data includes the following polymorphisms

Use your 23andme raw data or your Ancestry DNA raw data to check for AOC1- rs10156191

GenotypePhenotype
CCNormal
CTLikely lower DAO enzyme activity
TTLikely lower DAO enzyme activity

Use your 23andme raw data or your Ancestry DNA raw data to check for- AOC1- rs1049742

GenotypePhenotype
CCNormal
CTLikely lower DAO enzyme activity
TTLikely lower DAO enzyme activity

Use your 23andme raw data or your Ancestry DNA raw data to check for-AOC1- rs1049793

GenotypePhenotype
CCNormal
CGLikely lower DAO enzyme activity
GGLikely lower DAO enzyme activity

Use your 23andme raw data or your Ancestry DNA raw data to check for-AOC1- rs2052129

GenotypePhenotype
GGNormal
GTLikely lower DAO enzyme activity
TTLikely lower DAO enzyme activity

Use your 23andme raw data or your Ancestry DNA raw data to check for-AOC1- rs2268999

GenotypePhenotype
AANormal
ATLikely lower DAO enzyme activity
TTLikely lower DAO enzyme activity

MTHFR and histamine intolerance

The methylation cycle is also associated with the breakdown of histamine and other monoamine neurotransmitters. Finding out about the MTHFR mutations carried will help in identifying the extent of histamine clearance via the methylation pathway. To do this, 23andme raw data or Ancestry DNA raw data may be uploaded onto sites like Genetic genie which list out the various MTHFR mutations. However, although Genetic genie provides a list of SNPs, Xcode Life, provides recommendations and likely enzyme activity levels based on the 2 prominent MTHFR SNPs- C677T, A1298C.

Histamine Intolerance treatment

The most effective treatment for histamine intolerance is to opt for a low histamine diet. Many research studies have found that elimination diet, or a low histamine diet, can help in identifying if an individual has histamine intolerance.

High histamine foods

Here is a list of high histamine foods

Intoxication due to histamine may occur due to consumption of spoiled tuna or mackerel, which are high histamine foods, and should, therefore, be avoided.

Low histamine foods

The bane of opting for low histamine foods is that it could increase the risk for malnutrition. Care should be taken to include sufficient nutrition to ensure good health.

A low histamine diet is primarily to identify the presence of histamine intolerance and it should be carried out by eliminating certain high histamine foods and then slowly adding them, checking for the return of symptoms. It should ideally be carried out under the supervision of a medical practitioner. The extent of histamine intolerance varies from one individual to another.

An ideal way of designing your own low histamine diet is to opt for one or two vegetarian meals. Meat should be consumed when it is prepared the same day, though the skin of poultry has high histamine levels, irrespective of when it is prepared. Portion control could also play an important role, a bit of lime present in a dish like hummus may not harm while a glass of lime juice could.

DAO supplement

One of the major factors for histamine intolerance is the reduced DAO enzyme activity. There are many DAO supplements that are available to boost the activity of this enzyme, thereby reducing the extent of histamine intolerance.

A word of caution on DAO supplement production, many of these have porcine sources and contain rice and corn, and so should be avoided by individuals with any allergies to these. Alternatively, pea shoots are high in DAO and can be consumed by vegetarians or people looking for alternate DAO supplement.

Histamine intolerance can affect your quality of life and finding out about the level of DAO enzyme activity based on genetic variations may help in altering the diet to reduce symptoms. Xcode Life reports include information on SNPs associated with histamine intolerance and can be purchased here.

References:

  1. https://www.ncbi.nlm.nih.gov/pubmed/17490952
  2. https://pubchem.ncbi.nlm.nih.gov/compound/histamine
  3. https://link.springer.com/content/pdf/10.1007%2Fs40629-017-0011-5.pdf
  4. https://www.researchgate.net/publication/256331686_Histamine_intolerance_in_children_with_chronic_abdominal_pain

It is hard to believe that caffeine, a stimulant that holds popularity in battling fatigue and improving creativity, can do any harm.

1. Caffeine Sensitivity

Caffeine sensitivity is a term that describes the efficiency of the human body to process caffeine and to metabolize it.

We have all heard of co-workers who drink 6 cups of coffee, the recreational drink for nearly 60% of Americans, every day, and friends who guzzle a cup an hour before bedtime.

Yet there are some of us who feel jittery, anxious, or even restless after a single cup.

So, is caffeine a scourge, a tonic, or a mix of both?

Is coffee good for you?

For starters, coffee has a few benefits.

A large research study showed that Americans get more antioxidants from coffee than from any other dietary source.

Other studies have shown that there are several nutrients in a cup of brewed coffee, like Magnesium, Niacin, and Potassium, depending on the soil nutrients and the type of processing.

2. How caffeine works

Adenosine is an organic compound that inhibits arousal and promotes sleepiness upon binding to its receptor.

Caffeine has a structure similar to adenosine and works as an adenosine receptor antagonist.

It competes with adenosine to bind to the adenosine receptor.

This process promotes wakefulness.

Though this can affect the quality of sleep among certain people, it could help in situations like driving at night or averting jet lag, where mental alertness is critical.

Analyze Your Genetic Variants For Caffeine Sensitivity

According to the U.S. Food and Drug Administration (FDA), 300 milligrams of caffeine are consumed every day by the average American. The Mayo Clinic states that drinking up to 400 milligrams per day is safe, which is approximately 4 cups.

A good cup of coffee is the most popular caffeine delivery mechanism that comes with a few health benefits like being a good source of antioxidants, warding off liver disease, and protecting against Parkinson’s.

The health risks and benefits have been understood, over the years, however, caffeine and metabolism, or the way in which our body processes the chemical, varies on several key factors.

3. Caffeine content in popular beverages

BeverageCaffeine content (mg)
Coffee8 oz cup – 95 mg
Espresso1 oz shot – 63 mg
Green tea8 oz cup – 28 mg
Black tea8 oz cup – 26 mg
Energy drinks8 oz cup – 91 mg
Sodas (Cola)16 oz cans – 49 mg
Coffee liqueur1.5 oz shot – 14 mg
Dark chocolate1 oz square 24 mg

4. Caffeine Metabolism: What CYP1A2 gene says

Caffeine, an alkaloid, is also known as  1,3,7-trimetilksantin.

It is acidic in its pure crystalline form and is found in over 60 plant species.

The enzyme CYP1A2 is responsible for the metabolism of caffeine in the liver.

Due to potentially ineffective CYP1A2 enzyme activity, some people can experience issues like caffeine jitters after 2-3 cups of coffee per day.

Such slower metabolizers of caffeine may experience problems with blood pressure, headaches, etc.

Learn More

<strong>Coffee and <em>CYP1A2</em>: 3 ways high caffeine intake can affect you!</strong>

5. More about the CYP1A2 gene

The CYP1A2 gene regulates the synthesis of the enzyme, and small variations in this gene have an association with the efficiency of caffeine metabolism.

Some people have a genetic predisposition to produce very little of CYP1A2 enzyme while others may produce a large amount.

Approximately 10% of the population is found to be rapid caffeine metabolizers, which rates them high on caffeine sensitivity.

Analyze Your Genetic Variants For Caffeine Sensitivity

Approximately 10% of the population are found to be rapid caffeine metabolizers, which rates them high on caffeine sensitivity.

6. Slow metabolizer variant

The polymorphism associated with caffeine metabolism is rs762551.

Studies have shown that individuals with AC or CC genotypes are slow metabolizers of caffeine.

These individuals have a high caffeine sensitivity.

They tend to have a slightly increased risk for heart attack upon consumption of more than 2 cups of coffee every day.

7. Rapid metabolizer variant

Individuals who have the A.A. genotype in the specific polymorphism of the CYP1A2 gene may be fast metabolizers.

These individuals have a low caffeine sensitivity.

study conducted on 553 individuals found that people with this genotype had a 70% reduction in the risk of a heart attack on increased caffeine consumption.

8. How many cups of coffee should you consume? Genetic testing for Caffeine metabolism

The polymorphism in the CYP1A2 gene is well studied and is useful to determine the caffeine metabolism status.

This, in turn, can shine some light on the tendency to consume caffeine. 

9. 23andMe caffeine results

The 23andMe reports provide caffeine metabolizer status.

There are other well known 23andMe third-party tools, like Xcode Life, that can provide a better understanding.

Upload your 23andMe raw data to find out your caffeine metabolism status.

GenotypePhenotype
CC[Slow Metabolizers] Likely higher risk of heart attack when more than 4 cups of coffee are consumed
AC[Slow Metabolizers] Likely higher risk of heart attack when more than 4 cups of coffee are consumed
AA[Fast Metabolizers] Likely lower risk of heart attack on increased consumption of coffee

23andMe DNA raw data is the genetic information obtained after a genetic test, and it is usually provided as a text file.

This information can be downloaded after utilizing the 23andMe login provided to all 23andMe customers.

10. Using your Ancestry DNA raw data to identify your caffeine metabolizer status

There is a wealth of information provided by ancestry DNA that can be used to identify a number of health and nutrition-based traits.

Use your ancestry DNA login to download your Ancestry DNA raw data.

You can then upload your Ancestry DNA raw data onto our site to identify the caffeine metabolizer status.

11. 23andme vs. AncestryDNA vs. Xcode Life

23andme vs. AncestryDNA vs. Xcode Life pertaining to caffeine metabolizer status

23andmeAncestry DNAXcode Life
Provides ancestry and health reports Provides only ancestry reportsProvides Ancestry and health reports
Caffeine metabolism status provided in 23andme reportsCaffeine metabolism status not provided in Ancestry DNA reportsCaffeine metabolism status provided in Xcode reports
Caffeine Consumption status NOT provided in 23andme reportsCaffeine Consumption status NOT provided in Ancestry DNA reportsCaffeine Consumption status provided in Xcode reports

12. Your genetic predisposition to consume caffeine

People of certain genetic types tend to have a genetic predisposition to drink more cups of coffee.

Identification of this tendency will help in moderating coffee consumption, taking into account the caffeine metabolism status of the individual.

Genetic tests can help identify such parameters.

After all, it would be good to know if you are prone to guzzling down a little too much, especially when your caffeine sensitivity scale is tipped at the wrong end.

Updated on 10 June, 2020

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Do you have your 23andMe DNA data?

Learn about your MTHFR gene status for free!


WATCH: How to interpret your MTHFR report

What is MTHFR?

The methylenetetrahydrofolate reductase (MTHFR) gene carries instructions for the production of an enzyme with the same name.  

This important enzyme is associated with the processing of amino acids, which are the building blocks for protein molecules.

In the MTHFR pathway, the enzyme converts  5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate.

This is one of the steps in the process that converts the ‘ harmful’ amino acid homocysteine to the ‘useful’ amino acid, methionine.

MTHFR gene mutations

All of us have the MTHFR gene. But the type of MTHFR gene differs from person to person.

To explain this better, let’s take the example of blood groups. All of us have red blood. But you may have O+ve blood type, while the other person may be A-ve – and these different blood groups have different health implications. 

Like how O+ve and A+ve are the most common blood types, the MTHFR gene also has 2 common variants (type): C677T and A1298C, the former being more common than the latter.

About 40% of the American population have the C677T type, which has been associated with up to 80% reduction in the enzyme’s efficiency

This reduction has been found to lead to increased levels of homocysteine, which in turn increases the risk of venous thrombosis and heart disease. 

Once you learn about the type of MTHFR gene you carry, its effects can be ameliorated by simple fixes such as dietary changes and folic acid supplements.

How common are the MTHFR mutations?

MTHFR mutation prevalence in the U.S,

MTHFR C677T mutation is the most common and is found at a higher frequency in certain ethnic populations.

MTHFR C677T: Homozygous vs. Heterozygous

MTHFR mutations are typically referred to as heterozygous or homozygous. Heterozygous means only one copy of the variant allele, which here is T. So the person’s MTHFR gene type will be CT.

Homozygous means two copies of the variant allele – TT

MTHFR mutation prevalence in North America, Australia, and Europe

What Does A Positive MTHFR Mean?

A positive MTHFR test result indicates that you have any of the above-mention change in one or both copies of your MTHFR gene.

While only one copy of the change is less likely to cause any health issues, two copies can significantly increase your risk for conditions associated with higher homocysteine levels.

How to find MTHFR on 23andMe?

23andMe provides your genomic information in the form of raw data that can be easily accessed and then uploaded onto sites like Xcode Life to find out the specific variant carried.

23andMe MTHFR results for rs1801133 (MTHFR C677T)

AA2 copies of the variant allele, reduction in MTHFR enzyme activity by nearly 80%
AG1 copy of the variant allele, reduction in MTHFR enzyme activity by 40%
GGBoth normal alleles, no reduction in enzyme activity due to this polymorphism

23andMe MTHFR results for rs1801131 (A1298C)

GG2 copies of the variant allele, reduction in MTHFR enzyme activity
GT1 copy of the variant allele, reduction in MTHFR enzyme activity
TTBoth normal alleles, no reduction in enzyme activity due to this polymorphism

Apart from 23andMe, raw data from companies like AncestryDNA.com, FTDNA.com, and other similar genetic testing service providers may be uploaded to find out more about your MTHFR gene mutations.

What is the difference between 23andMe MTHFR test and AncestryDNA MTHFR test?

ContentsMTHFR status from 23andme raw dataMTHFR status from Ancestry DNA raw data
Raw data23andme raw data can be downloadedAncestry DNA raw data can be downloaded
MTHFR C677T and A1298C23andme MTHFR test includes these two SNPsAncestryDNA MTHFR test includes these two SNPs
MTHFR test cost23andme test cost is $99Ancestry DNA test cost is $99 (with a 10% discount on offer currently)
MTHFR test report23andme report does not include information on MTHFR gene. Information is present as raw data which needs interpretation.Ancestry report does not include information on MTHFR gene. Information is present as raw data which needs interpretation.
MTHFR gene report from Alternate providersA variance report generated using 23andme raw data V5 chip has less number of SNPs compared to ancestry DNA.A variance report generated using Ancestry DNA raw data has more number of SNPs compared to 23andme V5 chip.

Health implications of MTHFR mutations

Here are a few studies which show an association with various health conditions among people with the different types of the MTHFR gene.

According to the NIH, there are over 40 mutations in the MTHFR gene that are associated with poor enzyme activity and the associated increase in homocysteine levels in the body.

Certain genetic testing companies check for only the two major MTHFR gene mutations, while there are many others, like us, who give you a detailed report based on the 23andme MTHFR variants present in the 23andme raw data.

The Xcode Life MTHFR report covers several of these genetic variations covered in the NIH publication above.

More About MTHFR Gene Mutations

References

  1. http://circ.ahajournals.org/content/132/1/e6
  2. https://www.ncbi.nlm.nih.gov/pubmed/26629412
  3. https://www.ncbi.nlm.nih.gov/pubmed/25808073

23andme cannabis information provides insights into dependency and side effects that this drug could possibly bring about. According to the National Survey on Drug Use and Health, 22.2 million people used it in a month in the U.S. This makes it the most popularly used contraband drug in the world, and the most widely used among the younger population. Certain estimates state that 1% of the European population use cannabis every day.

cannabis

Why is using 23andme data for identifying the response to Cannabis important?

Cannabis is now being introduced in a few states for medicinal purpose. To better manage the problems associated with cannabis use, the 23andme cannabis data can be used for

Finding out the risk of addiction will help in putting together effective management strategies that will restrict use, solely for medicinal purpose.

What are some of negative aspects of cannabis use?

The regular use of cannabis can lead to

  1. Increased risk of accidents, aggressive behaviour and suicidal attempts
  2. Affects the quality of work carried out by the individual.

Understanding the heredity pattern of 23andme cannabis dependence


There have always been speculation that cannabis and other narcotic drug use runs in the family. There have been moderate parent-child and sibling association with cannabis dependence.

A study by Merikangas et al.showed that there was increased risk for cannabis use disorders among children and siblings.  A meta analysis of twin studies conducted showed that genetic influence on cannabis use was

The same study showed that the genetic influence on problematic cannabis use was

CB1 and CB2 receptors – cannabis binding receptors

The cannabinoid receptor 1 is a G protein-coupled receptor  and is known to modulate the effects of cannabis. A high concentration of this receptor is expressed on axons and terminals of neurons and glial elements, via the  central nervous system. These receptors are also found in thyroid, liver, pituitary and fat cells, apart from the spinal cord.


One of the important roles of the CB1 receptor is to modulate the release of neurotransmitters which are known to maintain homeostasis by preventing excessive neuronal activity in the central nervous system. The body produces certain cannabinoids, known as endocannabinoids, that bind to these receptors to keep the excitatory neurotransmitters under control. Certain studies have also shown that these receptors are associated with the regulation of food intake, and thereby, in obesity.

The other cannabinoid receptor, CB2, has been associated with a number of disease conditions including atherosclerosis, neurodegenerative disease, neuropathy and cancer. This receptor is found in certain neurons and, largely, in immune cells. Specifically, these receptors are present on T and B cells of the immune system, as well as in the peripheral nervous system, gastrointestinal system and in the central nervous system.

Use your 23andme cannabis data to find your cannabis response

In a study conducted by Hopfer et al, among people of different ethnicities Caucasian, Hispanic and African-American, people with the G allele for rs806380 were found to have a protective effect.

Upload your 23andme raw data or your Ancestry DNA raw data to find the variant of rs806380  that you carry.

GenotypePhenotype
AA[Advantage] More likely to have decreased risk of cannabis dependence
CTMore likely to have moderately decreased risk of cannabis dependence
TTNormal

Ancestry raw data can be used to identify variants in multiple genes that have been shown to be associated with initiation of cannabis use or symptoms of dependence. Of significance are rs806368 (CRB1), rs1406977 (CNR1), rs1049353 (CNR1) rs2501432 (CRB2), rs324420 (FAAH) and more.

Can 23andme cannabis data be used to identify craving and withdrawal symptoms?

Research studies have shown that the genetic variants carried by an individual can be used to determine the following

  1. Craving
  2. Withdrawal symptoms
  3. Sensitivity to the effects of cannabis

Craving for cannabis: The mesocorticolimbic dopamine transmission, modulated by CB1 binding, has been associated with feelings of cannabis craving.  Craving and absence of control over drug use can lead to severe addiction.

Withdrawal symptoms: There is a decrease in mesocorticolimbic dopamine transmission, which is mediated by lowered CB1 binding

Cannabis sensitivity:  Sensitivity to cannabis is associated with genetic variants carried, with positive reactions during early teens associated with greater risk of dependence later.

In a study conducted by researchers from Mind Research Network, Yale, showed that people with the C allele of FAAH C385A had greater craving for cannabis on abstinence, more severe withdrawal symptoms and increased positive association and fewer negative association on cannabis use.

How will finding out 23andme cannabis variant help?

Our body produces its own version of cannabis: Endocannabinoids like anandamide are synthesized by the body which can be used to produce the positive feeling and reduce cravings among people at high risk.

  1. Eat chocolates: Chocolates have been found to suppress the effect of FAAH, thereby, increasing the production of anadaminde.
  2. Reduce stress: Excessive stress can lead to increased secretion of glucocorticoid and resulting in reduced endocannabinoid secretion.
  3. Increase exercise: Exercise increases the sensitivity of the CB1 receptor, thereby increasing production of anandamide

DNA raw data can be used to identify cannabis dependence, craving, withdrawal symptoms and sensitivity which will help in moderating intake based on effect. Information on cannabis response is provided as part of Xcode’s substance dependence report.

References:

  1. https://www.drugabuse.gov/publications/research-reports/marijuana/what-scope-marijuana-use-in-united-states
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858354/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289952/
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2703788/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2863054/
  6. https://www.ncbi.nlm.nih.gov/pubmed/?term=Interindividual+variation+in+the+pharmacokinetics+of+Delta9-tetrahydrocannabinol+as++related+to+genetic+polymorphisms+in+CYP2C9
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