Gene2Rx

Gene2Rx curated guidance

Internally curated set

10 drugs 8 brand products

About Gene2Rx

For a small number of drugs there is a clear, well-supported gene-drug relationship that has not yet been written up as a formal CPIC, FDA, or DPWG guideline. In those cases Gene2Rx curates its own guidance from the primary literature and pharmacogenomic knowledge bases such as PharmGKB.^[1] These entries follow the same structure as the external sources: a phenotype-specific recommendation with the evidence noted, so they read consistently alongside the rest of a report.

What guidance it offers

Gene2Rx-curated guidance is intended to fill gaps, not to replace the established bodies. Where CPIC, the FDA, or the DPWG later publish on the same drug, that source takes precedence. The table below lists the drugs currently covered by Gene2Rx's own curation.

Drugs with Gene2Rx guidance

Gene2Rx reports Gene2Rx pharmacogenetic guidance for 10 drugs, grouped by therapeutic class. Expand any drug to see the Gene2Rx recommendation for each metabolizer group, or open its full pharmacogenetics page.

other substances →

Alcohol ADH1B · ALDH2

Metabolizer group	What it means	Gene2Rx recommendation	Evidence
High Function ADH1B	Homozygous His48 (A/A) genotype produces maximal enzyme activity, causing very rapid ethanol to acetaldehyde conversion, severe flushing, nausea and tachycardia; confers greatest protection against heavy drinking and dependence due to the aversive response.	Avoid or severely limit alcohol to prevent intense adverse reactions and long term harm.	Strong
Increased Function ADH1B	Heterozygous Arg48/His48 (G/A) genotype increases enzyme activity moderately, leading to pronounced flushing, nausea and tachycardia; offers moderate protection against heavy drinking and dependence due to the aversive response.	Limit alcohol to minimize discomfort and protect against long term harm.	Strong
Normal Function ADH1B	Homozygous Arg48 (G/G) genotype yields standard ethanol metabolism and acetaldehyde accumulation, resulting in average flushing and dependence risk.	Follow standard guidelines for alcohol consumption.	—
Normal Function ALDH2	Typical flushing, hangover, addiction risk	Standard advice on safe drinking limits.	—
Decreased Function ALDH2	Moderate flushing, nausea; decreased drinking, increased cancer risk	Limit or avoid alcohol due to accumulation of toxic acetaldehyde and elevated cancer risk.	Strong
Poor Function ALDH2	Severe flushing, nausea; strong aversion to drinking; increased cancer risk	Strongly recommend abstinence from alcohol to prevent severe adverse reactions and long-term carcinogenic effects.	Strong

Caffeine CYP1A2

Metabolizer group	What it means	Gene2Rx recommendation	Evidence
Ultrarapid Metabolizer CYP1A2	Very rapid caffeine clearance; might fail to achieve desired stimulant effect with typical intake.	Caffeine is cleared very quickly, which may reduce its stimulant effect. You may require larger or more frequent servings to achieve your desired level of stimulation. Monitor your intake to avoid excessive consumption.	Moderate
Rapid Metabolizer CYP1A2	Faster than normal clearance; may consume more caffeine to maintain effect.	You clear caffeine faster than average, which may shorten its duration of action. You may need more frequent servings to maintain the desired effect. Space your servings to prevent withdrawal symptoms.	Moderate
Normal Metabolizer CYP1A2	Expected caffeine clearance; typical consumption patterns and effects.	Follow standard moderate intake guidelines (≤400 mg/day).	—
Intermediate Metabolizer CYP1A2	Slower than normal clearance; stronger and longer-lasting stimulant effects.	Standard advice on moderate caffeine intake; consider avoiding late-day caffeine to prevent sleep disturbances.	—
Slow Metabolizer CYP1A2	Markedly slow clearance; increased risk of insomnia, jitteriness, and heart palpitations.	Recommend reduced intake (e.g. ≤100 mg/day) and longer intervals between doses to avoid adverse effects.	Moderate

Ketamine CYP2B6

Metabolizer group	What it means	Gene2Rx recommendation	Evidence
Ultrarapid Metabolizer CYP2B6	Likely increased ketamine clearance compared to average.	Use standard ketamine dosing; monitor for sedation.	—
Rapid Metabolizer CYP2B6	Likely increased ketamine clearance compared to average.	Use standard ketamine dosing; monitor for sedation.	—
Normal Metabolizer CYP2B6	Expected ketamine metabolism and duration of effect	Initiate with standard ketamine doses per clinical practice.	Strong
Intermediate Metabolizer CYP2B6	Moderately reduced N-demethylation leads to increased ketamine concentration and prolonged sedation	Consider reducing ketamine dose and monitor sedation depth and duration closely.	Moderate
Poor Metabolizer CYP2B6	Markedly reduced N-demethylation leads to significantly increased ketamine concentration and prolonged sedation, with heightened risk of prolonged and excessive sedation	Consider starting at a lower dose and extending dosing intervals, and perform intensive monitoring of sedation and vital signs.	Strong

Lsd CYP2D6

Metabolizer group	What it means	Gene2Rx recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Likely increased LSD clearance and experiential responses are within normal limits.	Standard LSD dosing applies; monitor participant-reported experiential responses.	—
Normal Metabolizer CYP2D6	Expected LSD clearance and participant-reported experiential responses align with typical profiles.	Standard LSD dosing applies; monitor participant-reported experiential responses.	Strong
Intermediate Metabolizer CYP2D6	Moderately reduced LSD clearance; slight prolongation of effects with possible increase in intensity.	Standard LSD dosing applies; monitor participant-reported experiential responses.	—
Poor Metabolizer CYP2D6	Reduced CYP2D6-mediated clearance leads to longer LSD half-life and greater overall exposure, increasing risk of intense experiences and anxiety.	Consider starting at a lower dose and increasing gradually to avoid adverse effects.	Strong

MDMA COMT · CYP2D6

Metabolizer group	What it means	Gene2Rx recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	No guidance for your genotype	Use standard MDMA dosing; monitor for adverse effects.	—
Normal Metabolizer CYP2D6	Expected MDMA metabolism and exposure	Use standard MDMA dosing; monitor body temperature and neurological status.	Strong
Intermediate Metabolizer CYP2D6	Moderately reduced MDMA clearance leads to about 2.5-fold higher exposure and increased risk of hyperthermia and neurotoxicity	Consider reducing dose and closely monitor temperature, blood pressure, and neurological status.	Moderate
Poor Metabolizer CYP2D6	Severely reduced MDMA clearance causes 3 to 3.5-fold higher exposure and high risk of hyperthermia and neurotoxicity	Reduce dose or consider avoiding MDMA; perform intensive monitoring of vital signs.	Strong
Normal Function COMT	High COMT activity accelerates dopamine breakdown and has been linked to greater MDMA-induced impairments in attention and memory and increased cardiovascular stimulation	If using MDMA, monitor cognitive function and heart rate; consider reducing dose to mitigate cognitive side effects	Moderate
Intermediate Function COMT	Intermediate COMT activity yields average MDMA pharmacodynamics with expected cognitive and cardiovascular responses	Use standard MDMA dosing; monitor for any unexpected cognitive or cardiovascular effects	Weak
Decreased Function COMT	Low COMT activity slows clearance of dopamine metabolites and increases risk of negative effects such as dizziness, sedation, hyponatremia and tachycardia	Consider reducing dose and closely monitor neurological and cardiovascular status; avoidance may be advisable for those with risk factors	Strong

Nicotine CHRNA5 · COMT · CYP2A6

Metabolizer group	What it means	Gene2Rx recommendation	Evidence
Normal Function CHRNA5	Receptor function and reward signalling are within the typical range; systemic response to nicotine is expected to be standard.	Typical response to nicotine.	—
Increased Risk CHRNA5	Variant may enhance receptor sensitivity to nicotine, producing stronger reward signals and increasing craving intensity. Higher cigarettes-per-day, increased risk of dependence, delayed cessation.	Nicotine may elicit heightened reward and craving. Monitor consumption and consider limiting dose frequency.	Strong
Normal Metabolizer CYP2A6	Nicotine clearance rate is typical, yielding standard plasma concentrations and exposure duration.	Typical response to nicotine.	Strong
Intermediate Metabolizer CYP2A6	Nicotine clearance is moderately reduced, leading to modestly higher plasma concentrations and slightly extended exposure, resulting in moderately lower consumption and dependence.	Nicotine remains in circulation longer but does not substantially change dependence risk.	Moderate
Slow Metabolizer CYP2A6	Nicotine clearance is substantially reduced, resulting in elevated plasma concentrations and prolonged exposure. Reduced withdrawal severity and higher unassisted quit rates.	Consider reducing nicotine dose to prevent excessive accumulation.	Strong
Poor Metabolizer CYP2A6	Nicotine clearance is severely reduced, resulting in elevated concentrations and prolonged exposure. Increased risk of adverse effects such as nausea, headache, dizziness, tachycardia.	Avoid nicotine replacement; non-nicotine approaches may provide more predictable effects.	Strong
Normal Function COMT	COMT activity is typical, leading to standard dopamine turnover in prefrontal cortex and average reward and withdrawal profile.	Expect typical nicotine reward and withdrawal symptoms.	—
Intermediate Function COMT	Moderately reduced COMT activity results in higher dopamine levels after nicotine, enhancing reward and reducing withdrawal severity.	You may experience stronger reward and milder withdrawal; monitor craving intensity.	Moderate
Decreased Function COMT	Low COMT activity causes elevated dopamine after nicotine, increasing reward, craving intensity, and potential dependence risk.	Be aware of stronger reward and higher craving; consider strategies to limit intake.	Strong

THC AKT1 · COMT · CYP2C9 · FAAH

Metabolizer group	What it means	Gene2Rx recommendation	Evidence
Normal Metabolizer CYP2C9	Normal 11-hydroxylation of THC; expected plasma levels and clearance are within typical range.	THC concentrations and duration of effect are expected to be standard. No dose adjustment is required.	Moderate
Intermediate Metabolizer CYP2C9	Slightly reduced 11-hydroxylation leads to modestly higher THC concentrations and a minor prolongation of effect.	Initiate at standard doses but monitor for moderately increased sedation or psychotropic intensity.	Weak
Intermediate Metabolizer CYP2C9	Moderately reduced 11-hydroxylation; increased THC circulating concentration and duration	Consider reducing initial dose and monitor sedation and psychotropic intensity.	Moderate
Poor Metabolizer CYP2C9	Substantial reduction in 11-hydroxylation results in markedly elevated THC exposure and prolonged half-life.	Consider starting at a lower dose and increasing gradually to limit adverse effects.	Moderate
Poor Metabolizer CYP2C9	Minimal 11-hydroxylation causes extreme THC accumulation; peak levels greatly exceed average; highest risk of sedation and cannabis use disorder.	Use extreme caution: begin at no more than 25% of standard dose or consider avoiding THC.	Strong
Normal Function FAAH	Standard hydrolysis of endocannabinoids; baseline cannabinoid receptor activation and THC response are typical.	THC effects are expected to align with population norms.	Moderate
Decreased Function FAAH	Reduced breakdown of endocannabinoids elevates baseline receptor activation and may intensify THC reward and dependence potential.	Consider lower THC doses and monitor for more intense effects or increased craving.	Moderate
Normal Function AKT1	Normal AKT1 signaling supports typical neural response; psychotomimetic risk with THC is average.	Standard THC exposure carries typical risk of transient psychotic-like effects.	Moderate
Decreased Function AKT1	Reduced AKT1 activity may increase dopamine response to THC, raising risk of psychotic-like symptoms and anxiety.	Some research suggests that carriers of this variant may have a moderately higher risk of psychotic-like effects from THC. However these findings are not conclusive. Consider starting at a lower dose and monitoring for psychotic-like effects or avoiding THC altogether.	Strong
Poor Function AKT1	Markedly reduced AKT1 signaling amplifies dopaminergic response to THC, substantially increasing psychosis risk.	Some research suggests that carriers of this variant may have a higher risk of psychotic-like effects from THC, even at low doses. However these findings are not conclusive. Consider starting at a lower dose and monitoring for psychotic-like effects or avoiding THC altogether.	Strong
Normal Function COMT	High COMT activity lowers baseline dopamine; THC-induced dopamine release may produce larger relative increases, increasing cognitive and psychotomimetic vulnerability.	Some research suggests that carriers of this variant may have a higher risk of psychotic-like effects from THC, even at low doses. However these findings are not conclusive. Consider starting at a lower dose and monitoring for psychotic-like effects or avoiding THC altogether.	Moderate
Intermediate Function COMT	Moderate COMT activity yields average dopamine degradation and typical psychotropic response.	Typical response to THC expected based on your genotype.	Weak
Decreased Function COMT	Low COMT activity raises baseline dopamine, which may buffer acute THC-induced dopamine spikes and reduce psychotomimetic effects.	Standard THC dosing applies; monitor for any unexpected reactions.	Weak

weight management →

Retatrutide GIPR · GLP1R

Metabolizer group	What it means	Gene2Rx recommendation	Evidence
Typical Response GLP1R	Baseline GLP1R signal peptide (Pro7/Pro7). Expected weight-loss efficacy and typical nausea/vomiting risk from the GLP1R arm of retatrutide.	Standard dosing and titration are expected to produce an average response.	Moderate
Enhanced Response (heterozygous) GLP1R	One copy of the Leu7 allele (rs10305420 C/T). By extrapolation from semaglutide and tirzepatide, expect modestly greater weight loss compared with Pro7/Pro7, and a modestly elevated risk of nausea and vomiting from the GLP1R arm of retatrutide.	Use standard dosing. Counsel on the likelihood of somewhat greater weight loss and slightly higher GI side-effect risk; consider slower titration if early side effects emerge.	Moderate
Enhanced Response (homozygous) GLP1R	Two copies of the Leu7 allele (rs10305420 T/T). By extrapolation from semaglutide and tirzepatide, expect greater weight loss compared with Pro7/Pro7, with a correspondingly higher risk of nausea and vomiting from the GLP1R arm of retatrutide.	Use standard dosing. Counsel on the likelihood of greater weight loss and higher GI side-effect risk; consider a slower titration schedule to mitigate side effects.	Moderate
Normal Function GIPR	Full-function GIPR (Glu354/Glu354). Typical GI tolerability on retatrutide.	Standard dosing and titration. No specific precautions based on GIPR genotype.	Moderate
Decreased Function GIPR	One copy of the Gln354 partial loss-of-function allele (rs1800437 G/C). The GIPR effect was demonstrated in tirzepatide (~1.8-fold increased odds of moderate-to-severe nausea or vomiting); by mechanism the same risk is expected for retatrutide, which also activates GIPR. The effect does not apply to GLP1R-only agonists such as semaglutide.	Consider a slower dose-escalation schedule for retatrutide. If side effects are intolerable, a GLP1R-only agonist such as semaglutide is unaffected by this variant and may be an alternative.	Moderate
Poor Function GIPR	Two copies of the Gln354 partial loss-of-function allele (rs1800437 C/C). The GIPR effect was demonstrated in tirzepatide (substantially increased risk of moderate-to-severe nausea or vomiting); by mechanism the same risk is expected for retatrutide, which also activates GIPR. The effect does not apply to GLP1R-only agonists such as semaglutide.	Consider slower dose escalation for retatrutide, or consider a GLP1R-only agonist such as semaglutide as an alternative (unaffected by this variant).	Moderate

Semaglutide GLP1R

Metabolizer group	What it means	Gene2Rx recommendation	Evidence
Typical Response GLP1R	Baseline GLP1R signal peptide (Pro7/Pro7). Expected weight-loss efficacy and typical nausea/vomiting risk.	Standard dosing and titration are expected to produce an average response.	Moderate
Enhanced Response (heterozygous) GLP1R	One copy of the Leu7 allele (rs10305420 C/T). Expect approximately 0.76 kg of additional weight loss compared with Pro7/Pro7, and a modestly elevated risk of nausea and vomiting.	Use standard dosing. Counsel on the likelihood of somewhat greater weight loss and slightly higher GI side-effect risk; consider slower titration if early side effects emerge.	Moderate
Enhanced Response (homozygous) GLP1R	Two copies of the Leu7 allele (rs10305420 T/T). Expect approximately 1.5 kg of additional weight loss compared with Pro7/Pro7, with a correspondingly higher risk of nausea and vomiting.	Use standard dosing. Counsel on the likelihood of greater weight loss and higher GI side-effect risk; consider a slower titration schedule to mitigate side effects.	Moderate

Tirzepatide GIPR · GLP1R

Metabolizer group	What it means	Gene2Rx recommendation	Evidence
Typical Response GLP1R	Baseline GLP1R signal peptide (Pro7/Pro7). Expected weight-loss efficacy and typical nausea/vomiting risk from the GLP1R arm of tirzepatide.	Standard dosing and titration are expected to produce an average response.	Moderate
Enhanced Response (heterozygous) GLP1R	One copy of the Leu7 allele (rs10305420 C/T). Expect approximately 0.76 kg of additional weight loss compared with Pro7/Pro7, and a modestly elevated risk of nausea and vomiting.	Use standard dosing. Counsel on the likelihood of somewhat greater weight loss and slightly higher GI side-effect risk; consider slower titration if early side effects emerge.	Moderate
Enhanced Response (homozygous) GLP1R	Two copies of the Leu7 allele (rs10305420 T/T). Expect approximately 1.5 kg of additional weight loss compared with Pro7/Pro7, with a correspondingly higher risk of nausea and vomiting.	Use standard dosing. Counsel on the likelihood of greater weight loss and higher GI side-effect risk; consider a slower titration schedule to mitigate side effects.	Moderate
Normal Function GIPR	Full-function GIPR (Glu354/Glu354). Typical GI tolerability on tirzepatide.	Standard dosing and titration. No specific precautions based on GIPR genotype.	Moderate
Decreased Function GIPR	One copy of the Gln354 partial loss-of-function allele (rs1800437 G/C). Associated with approximately 1.8-fold increased odds of moderate-to-severe nausea or vomiting on tirzepatide. This effect is specific to tirzepatide and does not apply to semaglutide.	Consider a slower dose-escalation schedule for tirzepatide. If side effects are intolerable, semaglutide is unaffected by this variant and may be an alternative.	Moderate
Poor Function GIPR	Two copies of the Gln354 partial loss-of-function allele (rs1800437 C/C). Substantially increased risk of moderate-to-severe nausea or vomiting on tirzepatide. Effect is specific to tirzepatide and does not apply to semaglutide.	Consider slower dose escalation for tirzepatide, or consider semaglutide as an alternative (unaffected by this variant).	Moderate

Brand products with Gene2Rx-guided ingredients

These branded medications contain at least one active ingredient with Gene2Rx pharmacogenetic guidance. Each links to its full breakdown.

Excedrin

acetaminophen, aspirin, caffeine

Fioricet

butalbital, acetaminophen, caffeine

Fiorinal

butalbital, aspirin, caffeine

References

PharmGKB / Stanford University. PharmGKB: The Pharmacogenomics Knowledge Base. pharmgkb.org

See your own Gene2Rx guidance

This page lists the drugs Gene2Rx covers. A Gene2Rx report tells you which metabolizer group you fall into, and what that means for each of these medications.

Get your report All guidance sources

Informational only, not medical advice. The presence of a Gene2Rx pharmacogenetic guideline does not mean every patient needs to change their dose. Never start, stop, or change a medication without talking to your prescribing clinician.