A common OPRM1 variant alters the mu-opioid receptor and has been studied in relation to opioid dose requirements and naltrexone response, but CPIC found the evidence too weak and inconsistent to support any clinical dosing recommendation.
The mu-opioid receptor is the primary target through which opioid medications and the body's own natural opioid-like chemicals (endorphins) produce pain relief, reward, and other effects. This receptor is built from instructions in a gene called OPRM1. A common variant in this gene, identified by the marker rs1799971 and often referred to as A118G, changes one amino acid in the receptor protein (from asparagine to aspartate, written as p.Asn40Asp).
Researchers have studied this variant for decades because it sits in a plausible, biologically interesting location: it removes a chemical attachment site on the receptor protein, and laboratory studies have found that the altered receptor is produced at lower levels in cells and tissue samples from carriers. That biological plausibility has made this one of the most-studied single variants in all of pharmacogenomics — but "well-studied" and "clinically actionable" are not the same thing, and it is important to be clear about which applies here.
Despite the volume of research, the effects found have been small and inconsistent. The professional body that reviews pharmacogenomic evidence and issues prescribing guidelines, the Clinical Pharmacogenetics Implementation Consortium (CPIC), examined the evidence for OPRM1 and opioid therapy and concluded that no dosing recommendation can be made: the effect on opioid dose requirements that has been observed is small and not consistent enough to guide individual treatment decisions. Similarly, more rigorous prospective studies of naltrexone response have generally failed to reproduce the promising results seen in early retrospective work.
This information is not guidance about pain medication or addiction treatment. It does not tell you what dose of any opioid medication you would need, whether a medication would work for you, or anything about addiction risk. Decisions about pain management and treatment for substance use disorders should always be made with a licensed prescriber based on the full clinical picture — genetic information like this plays no established role in that decision today.
Gene and variant: OPRM1 (mu-1 opioid receptor), variant rs1799971, c.118A>G, p.Asn40Asp (commonly referenced as A118G). The gene is highly polymorphic (more than 200 known variant alleles), but rs1799971 is by far the most extensively studied. The variant eliminates an N-glycosylation site on the receptor protein and is associated with reduced receptor expression in vitro and in vivo, although the precise mechanism underlying reduced expression remains unclear (Zhang et al., 2005, J Biol Chem).
CPIC guideline status (Crews et al., 2021, Clinical Pharmacology & Therapeutics; PMID 33387367): The 2021 CPIC guideline for CYP2D6, OPRM1, and COMT genotypes and opioid therapy explicitly states: "There are no therapeutic recommendations for dosing opioids based on either OPRM1 or COMT genotype (no recommendation, CPIC level C)." The guideline further notes there is evidence for a small increase in postoperative morphine dose requirements (approximately 10%) in some clinical studies among patients carrying at least one copy of the rs1799971 G allele, but characterizes this effect as "so modest as to not be clinically actionable." The guideline also states there is insufficient evidence to conclude an altered analgesic response to other opioids in relation to this variant, and that no standardized genotype-to-phenotype grouping system has been proposed for OPRM1 (unlike the well-defined metabolizer categories that exist for CYP2D6). CPIC level C denotes that current evidence is judged insufficient to support a clinical practice recommendation.
Naltrexone/alcohol use disorder evidence: A systematic review and meta-analysis (Hartwell et al., 2020, Addiction; PMID 31961981) of the moderating effect of rs1799971 on naltrexone treatment response in alcohol use disorder found that while several retrospective analyses reported greater treatment benefit in Asp40 (G-allele) carriers, subsequent prospective trials designed to test this hypothesis directly, including trials that oversampled the variant allele, have produced inconsistent results; a 2020 meta-analysis of seven such trials concluded that it "remains unclear" whether this variant predicts naltrexone response. This pattern — promising retrospective signal, inconsistent prospective replication — is characteristic of an association that has not reached a level of evidence sufficient for clinical use.
Allele frequency: Aggregate population minor (G) allele frequency estimates range from approximately 0.10 to 0.22 across major reference databases (gnomAD, 1000 Genomes, TOPMed, ExAC), reflecting substantial variability by database and ancestry composition; multiple population-genetics studies report the G allele as more common in East Asian-ancestry populations than in European- or African-ancestry populations, though precise population-specific figures vary by study and are not given here at a false level of precision.
Framing for clinical use: No dosing, prescribing, or treatment-selection recommendation should be inferred from this variant. This is a research-associated variant without a CPIC-grade actionable recommendation; it should not be used to guide decisions about opioid analgesic therapy, dosing, or treatment for opioid or alcohol use disorder.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Opioid Receptor Sensitivity (OPRM1) comes down to these specific, well-studied positions — not a diagnosis.
Research-derived gene–drug associations only — not a prescription, dosing guide, or medical advice. Always follow your prescriber's guidance.
| Gene | Drug | What the research shows |
|---|---|---|
| OPRM1 | Opioids (general, including morphine) | CPIC reviewed OPRM1 rs1799971 (A118G) for opioid therapy and issued no dosing recommendation. Some studies show a small (~10%) increase in postoperative morphine dose requirements in G-allele carriers, but CPIC concluded this effect is too modest to be clinically actionable. CPIC level C (insufficient evidence for a recommendation). (Crews KR, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clin Pharmacol Ther. 2021;109(6):1420-1425. PMID 33387367.) |
It changes one building block of the mu-opioid receptor protein, the main target of opioid medications and the body's natural endorphins, and is associated with lower levels of receptor expression in laboratory studies.
No. The CPIC expert panel that reviews pharmacogenomic evidence specifically concluded that no opioid dosing recommendation can be made based on OPRM1 genotype, because the observed effect on dose requirements is small and not clinically actionable.
No. This variant has been studied in relation to naltrexone treatment response for alcohol use disorder, but results have been inconsistent between early retrospective studies and later prospective trials, and it is not used as a risk or diagnostic test for addiction.
Being widely studied is not the same as having a consistent, reproducible effect. CPIC's review found the evidence for OPRM1 mixed and the effect sizes too small to support changing how opioids are prescribed, which is why the guideline states 'no recommendation.'
This tool does not provide medical advice about pain management or medication choices. Any decisions about opioid therapy should be made with a licensed prescriber based on your full clinical situation, not on this variant alone.
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