What you carry at this position in your DNA and what research says about it.
Opioid and Pain Response: 10/10 evidence, 112 publications.
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Sample genotype (not yours): A/A
Typical Pain Response and Standard Opioid Sensitivity
This genotype is associated with a standard response to opioid medications and typical baseline pain sensitivity. However, there is a slightly higher statistical risk of developing opioid use issues compared to G allele carriers.
What this genotype means: Standard sensitivity to opioid medications; Typical risk of opioid-induced nausea and vomiting; Slightly higher statistical risk of opioid use disorder.
Sample genotype (not yours): A/G
Altered Opioid Sensitivity and Fewer Side Effects
Carrying one copy of the G variant may reduce your sensitivity to certain opioid painkillers, meaning opioid painkillers may be less effective for you. Carriers also tend to report fewer opioid-related side effects.
What this genotype means: May respond less strongly to opioids for pain relief; Reduced likelihood of opioid-induced nausea; Enhanced clinical response to naltrexone therapy.
Sample genotype (not yours): G/G
Reduced Opioid Efficacy and Lower Side Effect Risk
Carrying two copies of the G variant is linked to a significantly reduced response to opioid painkillers. This genotype is also associated with less opioid-induced nausea.
What this genotype means: Likely to respond less strongly to opioid painkillers; Significantly lower risk of post-operative nausea; Highly favorable response to naltrexone for alcohol cravings.
Gene function and biological role
Gene Function: The OPRM1 gene encodes the mu-opioid receptor, which serves as the primary binding site for both endogenous endorphins and external opioid medications [1]. This receptor is highly concentrated in brain regions that regulate pain perception, reward pathways, and emotional processing [2]. When activated, it dampens pain signals and triggers the release of dopamine, reinforcing pleasurable behaviors [2]. Genetic variations in this gene can alter how efficiently the receptor transmits signals, directly influencing an individual's natural pain tolerance and susceptibility to addictive substances [1] [3].
Variant Impact: The rs1799971 variant, historically known as A118G or Asn40Asp, is a missense mutation in exon 1 of the OPRM1 gene. This genetic change replaces the typical amino acid asparagine with aspartate at position 40 of the receptor protein. This structural alteration reduces the receptor's overall expression and alters its binding affinity for beta-endorphins [1]. Consequently, individuals carrying the variant G allele often experience altered signaling in response to both natural endorphins and opioid medications [1] [4]. This single nucleotide change is widely studied for its impact on clinical pain management and substance dependence [4] [3].
Key Insight: Carriers of the G allele typically show a significantly reduced response to opioid painkillers such as morphine, and are at the same time less likely to experience common opioid side effects such as post-operative nausea and vomiting.
Location: OPRM1. Chromosome 6 · 6q25.2 · 154.0 Mb
Estimated prevalence by population
Global 76.5%; European 76.4%; African 94.2%; East Asian 37.1%; South Asian 38.5%; Americas 65.6%; Ashkenazi 67.9%; Finnish 64.2%; Middle Eastern 73.5%; Amish 72.7%.
Estimated AA genotype frequency.
Global 21.0%; European 22.0%; African 5.7%; East Asian 47.6%; South Asian 47.1%; Americas 30.8%; Ashkenazi 29.0%; Finnish 31.9%; Middle Eastern 24.5%; Amish 25.1%.
Estimated AG genotype frequency.
Global 2.5%; European 1.6%; African 0.1%; East Asian 15.3%; South Asian 14.4%; Americas 3.6%; Ashkenazi 3.1%; Finnish 4.0%; Middle Eastern 2.0%; Amish 2.2%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Pharmacogenomics
Pain Medication Response
Opioid Painkiller Dose. Evidence: 6/10. Source: PMID 25102313. Typical Response.
Opioid Side Effects. Evidence: 6/10. Source: PMID 31077873. Typical Risk.
Neurology & Mental Health
Addiction & Reward
Alcohol Dependence Drug Response. Evidence: 4/10. Source: PMID 31961981. Typical Response.
Opioid Use Disorder. Evidence: 10/10. Source: PMID 32492095. Slightly Higher Risk.
Showing effects for A/G genotype
Opioid Painkiller Dose. Evidence: 6/10. Source: PMID 25102313. Higher Tolerance.
Opioid Side Effects. Evidence: 6/10. Source: PMID 31077873. Lower Nausea Risk.
Alcohol Dependence Drug Response. Evidence: 4/10. Source: PMID 31961981. 2x Better Response.
Opioid Use Disorder. Evidence: 10/10. Source: PMID 32492095. Typical Risk.
Showing effects for G/G genotype
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Carrying two copies of the common A allele means your mu-opioid receptors are expressed at typical levels in the brain. Response to standard opioid medications such as morphine or oxycodone is typical for this genotype [1]. However, you also face a standard risk of common opioid-induced side effects, such as nausea, itching, and constipation [2]. Large-scale genomic studies indicate that the A allele slightly increases the relative risk of developing opioid use disorder compared to those carrying the G allele [3]. If struggling with alcohol dependence, individuals with this genotype tend to show a more modest clinical response to the treatment drug naltrexone [4].
Standard sensitivity to opioid medications; Typical risk of opioid-induced nausea and vomiting; Slightly higher statistical risk of opioid use disorder.
Sample genotype: AG (Heterozygous)
Having one copy of the G allele alters the physical structure of your mu-opioid receptors, reducing their overall abundance in the nervous system [1]. Clinical studies show that post-surgery patients with this genotype often respond less strongly to opioids like morphine or fentanyl for acute pain [2]. Despite needing more medication, carriers of the G allele consistently report lower rates of bothersome side effects, such as post-operative nausea and vomiting [3]. This variant has also been studied as a possible predictor of how well naltrexone works in alcohol dependence, but a meta-analysis of seven randomised placebo-controlled trials found a nominally significant effect on only one of five drinking outcomes, which did not survive correction for multiple comparisons, and concluded that it remains unclear whether this position predicts treatment response [4].
May respond less strongly to opioids for pain relief; Reduced likelihood of opioid-induced nausea; Enhanced clinical response to naltrexone therapy.
Sample genotype: GG (Homozygous)
Individuals with two copies of the G allele experience the most pronounced changes in mu-opioid receptor function [1]. Multiple clinical trials and meta-analyses confirm that this genotype is associated with a reduced response to post-operative pain medications, which may feel less effective [2]. Interestingly, this receptor reduction also makes you less susceptible to common opioid side effects, particularly nausea and vomiting [3]. Furthermore, this genotype is associated with a lower statistical risk of developing opioid use disorder [4]. This position has also been studied as a predictor of how well naltrexone works in alcohol dependence; a meta-analysis of seven randomised placebo-controlled trials concluded that it remains unclear whether it predicts treatment response [5].
Likely to respond less strongly to opioid painkillers; Significantly lower risk of post-operative nausea; Highly favorable response to naltrexone for alcohol cravings.
Variants with shared genetic architecture
rs540825 · OPRM1 Gene · Chr 6 · Antidepressant and Pain Response
rs1799972 · OPRM1 Gene · Chr 6 · Substance Dependence Risk
rs2075572 · OPRM1 Gene · Chr 6 · Pain and Opioid Response
Opioid receptor and peptide gene polymorphisms: potential implications for addictions.
Genetic contribution to PONV risk.
Content updated September 2026.
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