What is CYP2D6?
CYP2D6 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body .
This enzyme metabolizes:
- Opioids: morphine , hydrocodone , codeine , oxycodone , tramadol .
- Antidepressants: amitriptyline, nortriptyline, venlafaxine, and fluoxetine [8, 5, 9].
- Antipsychotics: haloperidol , risperidone .
- Atomoxetine (used to treat ADHD) .
- Beta-blockers: carvedilol and metoprolol .
- Antimalarials: primaquine and carboxy-primaquine .
- Antiemetics: metoclopramide .
- Antitumor agents: tamoxifen and gefitinib [15, 9].
- Methamphetamine (MDMA) .
- Metabolizes tyramine to dopamine .
- Regenerates serotonin .
- Inactivates neurotoxins [17, 16].
- Metabolizes the antioxidant tyrosol, found in olive oil .
Four metabolizer types are used to describe CYP2D6 activity in individuals:
- ultra-rapid metabolizer
- extensive metabolizer
- intermediate metabolizer
- poor metabolizer 
The activity of your CYP2D6 should be taken into account when administering a number of drugs. For example, a poor metabolizer should not be given codeine since the drug would have no effect. Conversely, an ultra-rapid metabolizer would likely suffer side effects from a normal dose .
Apart from the liver, this enzyme is also found in the brain .
This enzyme influences dopamine and serotonin levels in the brain. That explains why the activity of CYP2D6 has been associated with different personality traits .
Further, those with reduced enzyme activity had a tendency to higher impulsivity (novelty seeking) .
Low enzyme activity is also associated with autoimmune diseases (meta-analysis, 12 studies, 1,472 patients, and 3,328 controls) .
Poor metabolizers have higher conscientiousness/responsibility, orderliness, and the pursuit of achievement through perseverance .
Low CYP2D6 activity may decrease the risk of schizophrenia. A lower frequency of poor metabolizers has been observed in schizophrenia patients (270 subjects) .
High enzyme activity was associated with eating disorders. A higher frequency of CYP2D6 ultra-rapid metabolizers was found in people with bulimia .
Higher CYP2D6 activity was associated with heavier smoking. Poor metabolizers had a lower risk of becoming heavy smokers (1230 subjects) .
Suicide attempters carrying two or more active CYP2D6 genes were more likely to be diagnosed with one or more personality disorders (342 subjects) .
- Normal enzyme function variants (e.g. *1 and *2) [27, 28].
- Reduced function variants (e.g. *9, *10, and *41) [27, 28].
- Nonfunctional variants (e.g. ∗3, ∗4, ∗5, and ∗6) [27, 29].
It gets more complicated, however, because this gene can also be missing, or multiplied. This means that you can have 0, 1, 2, or more than 2 copies of the gene. Therefore, most clinical laboratories also report the copy number .
CYP2D6*5 represents a gene deletion (no gene present). Gene duplications and multiplications are denoted by “xN” (e.g., CYP2D61xN with xN representing the number of gene copies) .
How often do people have more or less of the usual two copies of this gene?
In a set of over 30 000 clinical samples, 12.6% had zero, one, or three or more copies of the CYP2D6 gene .
If you are a poor metabolizer, you are more prone to adverse effects from taking antidepressants (46 studies) .
On the other hand, ultra-rapid metabolizers are more prone to the adverse effects of codeine and tramadol (46 studies) .
People with ultra-rapid metabolism are less frequent in Northern Europe, North America, and Asia (1–5%). They are more common in the Mediterranean (7–12%), Saudi-Arabia (21%), and Ethiopia (29%) .
This variant (A) increases the risk of developing systemic sclerosis (296 and 206 subjects) [31, 32], Alzheimer’s disease (2018 subjects) , and Parkinson’s disease (meta-analysis, 2629 patients, and 3601 controls ) .
It was also associated with autoimmune diseases: systemic lupus erythematosus (SLE) and ankylosing spondylitis (meta-analysis, 12 studies, 1,472 patients, and 3,328 controls) .
The carriers of this variant are more susceptible to pesticide toxicity (59 subjects) .
This variant increases weight gain as a side effect of antipsychotics (81 patients) .
The T/T was associated with lower incidence of lung cancer in a Chinese population (9 studies, 1,516 cases, and 1,950 controls) .
Increasing or Decreasing CYP2D6
These increase CYP2D6:
These decrease CYP2D6:
- Starfruit juice 
- Aloe vera juice 
- Kale 
- St. John’s wort 
- Goldenseal 
- Fennel 
- Garden cress seed extract 
- Curcuma 
- Asafetida 
- Berberine [47, 48]
- Quercetin [49, 50]
- Caffeic acid 
- Gallic acid and ellagic acid [51, 52]
- The leaves of the lotus plant (Nelumbo nucifera) [53, 54]
- Raspberry leaf 
- Licochalcone A, a major compound in traditional Chinese herbal licorice 
- Black pepper fruit and arylamides isolated from black pepper (Piper nigrum) [56, 57]
- Paroxetine [58, 59], melperone , and sarpogrelate 
- Tetrahydrocannabinol, cannabidiol (CBD), and cannabinol (found in marijuana) 
- Chronic kidney disease