DRD2

DRD2 encodes the D2 dopamine receptor. Variants of DRD2 may play a role in feelings of fatigue, PTSD, food choices and eating behavior, as well as cognitive ability and mood by altering dopamine signaling in some parts of the brain [R, R].

Lifestyle, diet, and supplement modifications may counteract the effects of these variants by increasing either the number or sensitivity of D2 receptors.

DRD2 plays a role in [R, R]:

• Movement
• Reward and reinforcement 
• Learning and memory

DRD2 variants have been linked to [R, R]:

• Movement disorders
• Substance abuse 
• Addiction
• Schizophrenia
• Bipolar disorder
• PTSD

Some types of drugs for schizophrenia function by blocking DRD2 [R].

Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.

The DRD2 gene encodes a dopamine receptor. Dopamine, which is important for signalling pleasure and reward, can also reduce the sensation of pain and reduce anxiety and fear [R, R, R].

Because dopamine is highly involved in many processes that are critical for proper cognitive function, SNPs in the DRD2 gene can significantly impact cognitive ability and mental health [R, R, R, R].

Dopamine and its receptors also play a part in controlling the sleep-wake cycle. Mainly, dopamine can help keep you awake and alert [R].

Low levels of DRD2 activation reduce wakefulness and increase Slow Wave (deep) and REM sleep. Low DRD2 furthermore causes rats to become slow and lethargic; the more DRD2 receptors the rats expressed, the more likely they were to spontaneously move around their enclosures [R].

Furthermore, compounds that block both D1 and D2 receptors reduce wakefulness and increase deep sleep [R].

Thus, it’s unsurprising that at least one variant in the DRD2 gene has been associated with feeling tired in the daytime [R, R].

The major factor connecting the DRD2 gene and PTSD is DRD2 receptor density: that is, how many receptors of this type are present on any given dopamine neuron [R].

Dopamine receptor density interacts with COMT, an enzyme that breaks down dopamine, to produce overall susceptibility to PTSD. For people with high COMT, low DRD2 density is potentially harmful; for people with low COMT, high DRD2 density is potentially harmful [R].

Higher COMT is more common than low COMT, so for most people, low DRD2 density is more likely to be detrimental. However, you should check your COMT gene to be sure how DRD2 will affect you.

Unlike other major types of dopamine receptors, D2 receptors are inhibitory. This means that having more of these receptors generally results in lower overall dopamine activity in the brain, and vice-versa [R, R, R].

However, the situation is not always that straightforward: D2 receptor activity also enables dopamine-dependent reward pathways that make certain experiences pleasurable. DRD2 variants can impair the function of D2 receptors and correlate with addictive or reward-dependent behaviors [R, R].

D2 Receptor Function & Eating Behavior

Dietary habits depend heavily on the "anticipatory" and "rewarding" effects of food. Hence, it is no surprise that dopamine plays a key role in food intake and eating behavior via D2 receptors [R].

Along with substance abuse and other addictive behaviors, impairments in D2 receptor signaling can contribute to different eating disorders and influence food preferences [R, R, R, R, R].

Some scientists argue that addiction to tasty, energy-dense food may trigger some of the same mechanisms involved in drug addiction (albeit to a lesser extent). These highly "rewarding" foods may cause the brain to release large amounts of dopamine, which could "over-stimulate" the brain's reward pathways. Eventually, this strong, long-term dopamine stimulation could result in the reduction ("down-regulation") of the total number of D2 receptors in the brain [R, R].

When it comes to the genetic influences of D2 receptor function, most research has focused on one SNP: rs1800497.

Studies often also mention other SNPs — such as rs2283265, rs1076560, rs6275, rs6277, rs6279, and rs2514218 — but these variants are often all inherited together with the variant you carry for rs1800497, so they usually don’t represent truly "independent" genetic factors [R, R, R, R].

According to five clinical trials with over 1,300 participants, the 'A' (also known as the "A1") allele correlates with a higher preference for [R, R, R, R, R]:

• Carbohydrates (especially sugar)
• Fast food
• High-fat, fried foods

Interestingly, these effects also seem to be independent of age, gender, and ethnicity.

One study of 26 volunteers used brain imaging to measure how the brain responded to tasty food, depending on the rs1800497 variant each participant carried. When given a delicious milkshake, all participants rated its tastiness similarly — but those carrying the 'A' allele showed a blunted (weaker) response in the reward system [R].

Among 394 Malaysian adults, those with the 'A' allele were more prone to uncontrolled eating [R]. Similarly, in a trial of 279 Dutch adolescents, this variant correlated with emotional eating in response to high psychological control from parents [R].

In two smaller studies, rs1800497-A correlated with high food reinforcement, which means people with this allele were willing to work harder to obtain food they liked. Consequently, they ultimately consumed significantly more calories than people with other alleles [R, R].

This same genetic variant has been associated with other dopamine-related issues, such as eating disorders, substance abuse, and impulsive behavior [R, R, R, R]. 

Food for Thought: Research of dopamine-dependent reward mechanisms has led some scientists to ask a fundamental question: Is modern society turning us into "mindless pleasure junkies"? In support of this idea, these authors have pointed to the fact that people may becoming more and more addicted to short-term dopamine-boosting experiences, while neglecting "longer-term" concerns such as overall prosperity, health, and well-being [R].

Because dopamine is highly involved in many processes that are critical for proper cognitive function, SNPs in the DRD2 gene can have a very significant impact on overall cognitive ability [R, R, R, R, R].

For example, SNPs in this gene have been associated with many diverse aspects of cognitive function, including:

• Learning and memory [R, R, R]
• Working memory [R, R, R, R]
• Cognitive flexibility [R, R, R]
• Attention and executive function [R, R]
• Problem-solving ability and overall intelligence (IQ) [R, R]
• Creativity [R, R, R, R, R, R]
• Motivation and sensitivity to reward [R, R, R]
• Emotional intelligence (especially in women) [R]

As you can see from the list above, the variants you carry in the DRD2 can be important for many different aspects of your cognitive ability! In this post, we’ll dive more deeply into this key gene, and look at what your genetic variants can tell you about how well your brain’s dopamine system works.

The DRD2 Gene in Chronic Pain

Dopamine, which is important for signalling pleasure and reward, can also reduce the sensation of pain [R, R].

Low DRD2 sensitivity may be common in patients with chronic pain [R].

Variants that reduce DRD2 activity or function may fail to blunt unpleasant sensations, leading to increased pain [R, R, R].

The relationship between dopamine receptors and pain is highly complex, and simply increasing or decreasing DRD2 may or may not reduce pain [R, R, R].

The DRD2 and ANKK1 genes are very close together and often studied together; the variants discussed below may technically belong to one gene or the other but typically affect both.

DRD2 variants have been linked to many different types of pain disorders, including [R, R]:

• Back, neck, shoulder, and chest pain
• Pain from trapped or pinched nerves
• Pain from nerve inflammation (neuralgia)
• Fibromyalgia
• Increased use of opioid painkillers & risk of opioid addiction [R]

Variants that decrease the function or activity of DRD2 may also be linked to a poorer response to triptan medications for migraines [R].

If you have less or less active D2 receptors, it means you want to increase DRD2 receptors or increase DRD2 activation such as precursors for dopamine.

Natural Fixes: 

• Light (R),
• Calorie restriction/Fasting (R),
• Exercise (R), 
• Mucuna (by increasing dopamine), 
• Forskolin (R),
• Curcumin (R),
• CDP-choline (R),
• Blueberry (R),
• Spirulina (R)

Stay away from: 

• Low protein, high carb diets (R)
• Opioids decrease the DRD2 receptor
• Psychostimulants decrease the DRD2 receptor
• High fat or high sugar diet decrease the DRD2 receptor
• Cocaine, which will decrease dopamine D2 receptors (R)
• Alcohol If your homocysteine is higher (say over 9), you should lower it with supplements like methyl folate or methyl B12, because homocysteine can reduce the receptor function (R).
• You might not want to take supplements like Yohimbine because it blocks the D2 receptor (R). You want to be very careful about taking anti-psychotics because this gene is associated with increased weight gain.