CARN-AP Set 2 | Advanced Practice Addictions Nursing Exam Prep | 194 Practice Questions Page 1
CARN-AP Advanced Practice Addictions Nursing
Exam Prep
Set 2: 194 Practice Questions
Aligned with the ANCB Certified Addictions Registered Nurse – Advanced Practice (CARN-AP)
Examination Blueprint
Content Coverage: Seven sections mapped to the ANCB CARN-AP examination blueprint — neurobiology & pharmacotherapeutics;
assessment & diagnostic reasoning; complex withdrawal management & toxicology; advanced medication management & prescriptive
authority; evidence-based psychosocial interventions; complex co-occurring disorders & special populations; and advanced practice
leadership, policy, and professional issues.
Question Mix: 82% scenario-based · 18% direct recall · 4-option MCQ (A–D) · ONE correct answer · Cognitive distribution: 20%
recall, 50% application, 30% analysis.
2026/2027 Updates Included: MAT Act (2023) X-waiver elimination · 42 CFR Part 2 (2024 final rule) · CDC 2022 Opioid
Prescribing Guideline · Novel psychoactive substance recognition (nitazenes, synthetic cannabinoids, synthetic cathinones) ·
Pharmacogenomic-guided MAT selection.
INSTRUCTIONS: Select the single best answer for each question. Rationales follow each item and integrate neurobiological
mechanism, pharmacotherapeutic principle, monitoring parameter, safety consideration, and regulatory requirement specific to
advanced practice addictions nursing.
Section 1: Advanced Neurobiology and Pharmacotherapeutics
Neuroadaptation, Receptor Pharmacology, Pharmacogenomics, & Drug Interactions
Aligned with current ANCB CARN-AP Examination Blueprint | For Educational Use
,CARN-AP Set 2 | Advanced Practice Addictions Nursing Exam Prep | 194 Practice Questions Page 2
Q1. A 38-year-old patient with severe opioid use disorder on stable methadone 80 mg/day is started
on voriconazole for an invasive aspergillosis. Within 5 days, the patient presents with sedation,
miotic pupils, and respiratory depression at 8 breaths/min. Which pharmacokinetic mechanism best
explains this interaction?
A. Voriconazole induces CYP3A4, accelerating methadone metabolism and precipitating withdrawal
B. Voriconazole inhibits CYP3A4 and CYP2B6, increasing methadone exposure and risk of
overdose [CORRECT]
C. Voriconazole displaces methadone from alpha-1-acid glycoprotein, transiently raising free fraction
D. Voriconazole induces CYP2D6, generating toxic methadone metabolites that prolong QTc
Correct Answer: B
Rationale: Voriconazole is a potent CYP3A4 and CYP2B6 inhibitor. Methadone is metabolized predominantly by
CYP3A4 (and to a lesser extent CYP2B6), so inhibition raises methadone plasma concentrations, producing classic
mu-agonist toxicity (sedation, miosis, respiratory depression). Option A reverses the effect; CYP3A4 induction (e.g.,
rifampin, carbamazepine) would precipitate withdrawal. Option C describes a theoretical but clinically minor
mechanism for methadone displacement. Option D is incorrect because CYP2D6 is not significantly involved in
methadone metabolism and toxic metabolites do not drive methadone QTc prolongation (the parent drug blocks hERG
channels). The CARN-AP must anticipate this interaction and reduce methadone by 25-50% or select an alternative
antifungal such as isavuconazole or echinocandin when feasible.
Q2. A patient carries the OPRM1 A118G (Asn40Asp) variant in homozygous form. The advanced
practice addictions nurse is counseling the patient about naltrexone for alcohol use disorder. Which
statement is most accurate regarding the pharmacogenomic implications?
A. A118G homozygosity reliably predicts superior naltrexone response, so a higher-than-standard 75
mg/day dose should be initiated
B. A118G homozygosity is associated with blunted endogenous beta-endorphin signaling and may
predict reduced naltrexone efficacy for drinking outcomes, though evidence is mixed [CORRECT]
C. OPRM1 A118G has no bearing on naltrexone therapy and should not influence prescribing decisions
under any circumstances
D. A118G carriers require a 50% dose reduction of naltrexone because of impaired hepatic metabolism via
CYP2D6
Correct Answer: B
Rationale: The OPRM1 A118G (rs1799971) substitution reduces mu-receptor binding affinity for beta-endorphin
and may alter naltrexone binding. Some (predominantly East Asian cohort) studies suggested diminished naltrexone
response in G-allele carriers, but the COMBINE study and subsequent meta-analyses yielded mixed results, so
genotyping is not yet standard of care. Option A overstates the predictive value and recommends unsafe dose
escalation. Option C overstates certainty in the negative direction; the variant is mechanistically relevant even if not
clinically actionable. Option D is incorrect because naltrexone is not a CYP2D6 substrate; it is metabolized primarily
by dihydrolipoamide dehydrogenase to 6-beta-naltrexol, and no dose adjustment is required for OPRM1 carriers.
Aligned with current ANCB CARN-AP Examination Blueprint | For Educational Use
,CARN-AP Set 2 | Advanced Practice Addictions Nursing Exam Prep | 194 Practice Questions Page 3
Q3. A 47-year-old male with alcohol use disorder and a 12-year history of heavy drinking (100+ g
ethanol/day) is being evaluated for acamprosate initiation. The patient asks why the medication
must be dosed three times daily and how it works. Which neurobiologic explanation is most
accurate?
A. Acamprosate is a positive allosteric modulator of GABA-A receptors, requiring scheduled dosing to
maintain sustained chloride influx
B. Acamprosate antagonizes NMDA glutamate receptors (with action at the polyamine site/spares
Mg2+ block) and modulates mGlu5, normalizing the glutamatergic hyperactivity of protracted
withdrawal [CORRECT]
C. Acamprosate acts as a mu-opioid receptor antagonist, blocking ethanol-induced reward via the
mesolimbic pathway
D. Acamprosate irreversibly inhibits aldehyde dehydrogenase, producing aversive reactions if ethanol is
consumed
Correct Answer: B
Rationale: Acamprosate (calcium acetylhomotaurinate) structurally mimics taurine and GABA and antagonizes
NMDA glutamatergic neurotransmission (interacting at the polyamine modulatory site), partially agonizing GABA-A
and dampening the glutamatergic hyperexcitability characteristic of protracted alcohol withdrawal. Its poor oral
bioavailability (~11%) and short half-life (~3-8 hours) necessitate TID dosing (666 mg TID). Option A describes a
benzodiazepine-like mechanism; acamprosate's GABA-A modulation is modest and not its primary action. Option C
describes naltrexone. Option D describes disulfiram, an ALDH inhibitor producing the acetaldehyde-mediated
aversive reaction.
Q4. A CYP2D6 poor metabolizer with opioid use disorder is being considered for buprenorphine
treatment. The CARN-AP correctly understands that:
A. CYP2D6 poor metabolizer status contraindicates buprenorphine because the parent drug cannot be
converted to the active metabolite norbuprenorphine
B. Buprenorphine is primarily metabolized by CYP3A4 to norbuprenorphine (still active at mu
receptors); CYP2D6 status is not clinically significant for buprenorphine dosing [CORRECT]
C. CYP2D6 poor metabolizers require an empiric 50% reduction of buprenorphine induction dose to avoid
respiratory depression
D. CYP2D6 status only matters for naloxone, the combination product component, and therefore requires
dose splitting
Correct Answer: B
Rationale: Buprenorphine is metabolized principally via CYP3A4 N-dealkylation to norbuprenorphine (which retains
mu-agonist activity though with reduced potency and is further glucuronidated). CYP2D6 plays only a minor role;
therefore, CYP2D6 poor metabolizer status does not require dose adjustment. Option A incorrectly assumes a prodrug
mechanism (buprenorphine itself is active). Option C would be appropriate for some CYP3A4 inhibitor combinations
but not for CYP2D6 status. Option D is incorrect because naloxone is included only to deter IV misuse; it is nearly
completely first-pass metabolized and does not depend on CYP2D6.
Aligned with current ANCB CARN-AP Examination Blueprint | For Educational Use
, CARN-AP Set 2 | Advanced Practice Addictions Nursing Exam Prep | 194 Practice Questions Page 4
Q5. A 29-year-old patient reports using fentanyl powder obtained illicitly, then begins
buprenorphine-naloxone induction. Approximately 90 minutes after the first 4 mg/1 mg sublingual
dose, the patient develops worsening withdrawal with COWS rising from 8 to 14. What is the most
appropriate next step according to current buprenorphine induction guidance?
A. Administer naloxone 0.4 mg IM immediately to reverse potential precipitated withdrawal
B. Withhold further buprenorphine, observe, and administer adjunctive alpha-2 agonist
(clonidine/lofexidine) and ondansetron; reassess in 30-60 minutes [CORRECT]
C. Double the next buprenorphine dose to 8 mg to override precipitated withdrawal
D. Discharge the patient with instructions to return after 48 hours of abstinence to retry induction
Correct Answer: B
Rationale: The patient likely experienced precipitated withdrawal from residual fentanyl at mu receptors (fentanyl's
high lipophilicity and long elimination half-life increase this risk). Current ASAM guidance supports continuing
buprenorphine induction judiciously with adjunctive non-opioid symptom management (clonidine or lofexidine for
autonomic symptoms, ondansetron for emesis, sometimes low-dose ketamine in supervised settings) rather than
naloxone reversal, which would worsen withdrawal. Option A would exacerbate withdrawal; naloxone is for opioid
overdose, not precipitated withdrawal from partial agonist administration. Option C may worsen precipitated
withdrawal in some patients, although 'macro-dosing' protocols exist they require expert oversight. Option D ignores
evidence that low-dose initiation or extended micro-dosing with fentanyl-tolerant patients can succeed without
48-hour abstinence. The 'Bernese method' (micro-dosing buprenorphine while continuing full agonist) is an
alternative.
Q6. Long-term cocaine use is associated with downregulation of D2-like dopamine receptors in the
striatum. Which downstream consequence is most directly linked to the dysphoria and craving of
acute cocaine abstinence?
A. Increased phasic dopamine release in the nucleus accumbens producing euphoria
B. Reduced tonic dopamine firing and a 'reward-deficit state' producing anhedonia and craving
[CORRECT]
C. Upregulation of kappa-opioid receptor tone producing aversion suppression
D. Selective loss of serotonin 5-HT2A receptors in the prefrontal cortex
Correct Answer: B
Rationale: Chronic cocaine exposure elevates synaptic dopamine via DAT blockade, leading to homeostatic D2
receptor downregulation. With abstinence, tonic dopamine firing falls below baseline, producing a reward-deficit state
clinically observed as anhedonia, dysphoria, and heightened craving. Option A is the opposite of the abstinence
phenomenon. Option C is partially relevant because dynorphin-kappa opioid systems are actually upregulated by
chronic cocaine (producing dysphoria), but the question asks for the 'most directly linked' downstream consequence
tied to D2 downregulation; the reward-deficit state is the central clinical correlate. Option D is not the primary
mechanism of cocaine abstinence dysphoria.
Aligned with current ANCB CARN-AP Examination Blueprint | For Educational Use
CARN-AP Advanced Practice Addictions Nursing
Exam Prep
Set 2: 194 Practice Questions
Aligned with the ANCB Certified Addictions Registered Nurse – Advanced Practice (CARN-AP)
Examination Blueprint
Content Coverage: Seven sections mapped to the ANCB CARN-AP examination blueprint — neurobiology & pharmacotherapeutics;
assessment & diagnostic reasoning; complex withdrawal management & toxicology; advanced medication management & prescriptive
authority; evidence-based psychosocial interventions; complex co-occurring disorders & special populations; and advanced practice
leadership, policy, and professional issues.
Question Mix: 82% scenario-based · 18% direct recall · 4-option MCQ (A–D) · ONE correct answer · Cognitive distribution: 20%
recall, 50% application, 30% analysis.
2026/2027 Updates Included: MAT Act (2023) X-waiver elimination · 42 CFR Part 2 (2024 final rule) · CDC 2022 Opioid
Prescribing Guideline · Novel psychoactive substance recognition (nitazenes, synthetic cannabinoids, synthetic cathinones) ·
Pharmacogenomic-guided MAT selection.
INSTRUCTIONS: Select the single best answer for each question. Rationales follow each item and integrate neurobiological
mechanism, pharmacotherapeutic principle, monitoring parameter, safety consideration, and regulatory requirement specific to
advanced practice addictions nursing.
Section 1: Advanced Neurobiology and Pharmacotherapeutics
Neuroadaptation, Receptor Pharmacology, Pharmacogenomics, & Drug Interactions
Aligned with current ANCB CARN-AP Examination Blueprint | For Educational Use
,CARN-AP Set 2 | Advanced Practice Addictions Nursing Exam Prep | 194 Practice Questions Page 2
Q1. A 38-year-old patient with severe opioid use disorder on stable methadone 80 mg/day is started
on voriconazole for an invasive aspergillosis. Within 5 days, the patient presents with sedation,
miotic pupils, and respiratory depression at 8 breaths/min. Which pharmacokinetic mechanism best
explains this interaction?
A. Voriconazole induces CYP3A4, accelerating methadone metabolism and precipitating withdrawal
B. Voriconazole inhibits CYP3A4 and CYP2B6, increasing methadone exposure and risk of
overdose [CORRECT]
C. Voriconazole displaces methadone from alpha-1-acid glycoprotein, transiently raising free fraction
D. Voriconazole induces CYP2D6, generating toxic methadone metabolites that prolong QTc
Correct Answer: B
Rationale: Voriconazole is a potent CYP3A4 and CYP2B6 inhibitor. Methadone is metabolized predominantly by
CYP3A4 (and to a lesser extent CYP2B6), so inhibition raises methadone plasma concentrations, producing classic
mu-agonist toxicity (sedation, miosis, respiratory depression). Option A reverses the effect; CYP3A4 induction (e.g.,
rifampin, carbamazepine) would precipitate withdrawal. Option C describes a theoretical but clinically minor
mechanism for methadone displacement. Option D is incorrect because CYP2D6 is not significantly involved in
methadone metabolism and toxic metabolites do not drive methadone QTc prolongation (the parent drug blocks hERG
channels). The CARN-AP must anticipate this interaction and reduce methadone by 25-50% or select an alternative
antifungal such as isavuconazole or echinocandin when feasible.
Q2. A patient carries the OPRM1 A118G (Asn40Asp) variant in homozygous form. The advanced
practice addictions nurse is counseling the patient about naltrexone for alcohol use disorder. Which
statement is most accurate regarding the pharmacogenomic implications?
A. A118G homozygosity reliably predicts superior naltrexone response, so a higher-than-standard 75
mg/day dose should be initiated
B. A118G homozygosity is associated with blunted endogenous beta-endorphin signaling and may
predict reduced naltrexone efficacy for drinking outcomes, though evidence is mixed [CORRECT]
C. OPRM1 A118G has no bearing on naltrexone therapy and should not influence prescribing decisions
under any circumstances
D. A118G carriers require a 50% dose reduction of naltrexone because of impaired hepatic metabolism via
CYP2D6
Correct Answer: B
Rationale: The OPRM1 A118G (rs1799971) substitution reduces mu-receptor binding affinity for beta-endorphin
and may alter naltrexone binding. Some (predominantly East Asian cohort) studies suggested diminished naltrexone
response in G-allele carriers, but the COMBINE study and subsequent meta-analyses yielded mixed results, so
genotyping is not yet standard of care. Option A overstates the predictive value and recommends unsafe dose
escalation. Option C overstates certainty in the negative direction; the variant is mechanistically relevant even if not
clinically actionable. Option D is incorrect because naltrexone is not a CYP2D6 substrate; it is metabolized primarily
by dihydrolipoamide dehydrogenase to 6-beta-naltrexol, and no dose adjustment is required for OPRM1 carriers.
Aligned with current ANCB CARN-AP Examination Blueprint | For Educational Use
,CARN-AP Set 2 | Advanced Practice Addictions Nursing Exam Prep | 194 Practice Questions Page 3
Q3. A 47-year-old male with alcohol use disorder and a 12-year history of heavy drinking (100+ g
ethanol/day) is being evaluated for acamprosate initiation. The patient asks why the medication
must be dosed three times daily and how it works. Which neurobiologic explanation is most
accurate?
A. Acamprosate is a positive allosteric modulator of GABA-A receptors, requiring scheduled dosing to
maintain sustained chloride influx
B. Acamprosate antagonizes NMDA glutamate receptors (with action at the polyamine site/spares
Mg2+ block) and modulates mGlu5, normalizing the glutamatergic hyperactivity of protracted
withdrawal [CORRECT]
C. Acamprosate acts as a mu-opioid receptor antagonist, blocking ethanol-induced reward via the
mesolimbic pathway
D. Acamprosate irreversibly inhibits aldehyde dehydrogenase, producing aversive reactions if ethanol is
consumed
Correct Answer: B
Rationale: Acamprosate (calcium acetylhomotaurinate) structurally mimics taurine and GABA and antagonizes
NMDA glutamatergic neurotransmission (interacting at the polyamine modulatory site), partially agonizing GABA-A
and dampening the glutamatergic hyperexcitability characteristic of protracted alcohol withdrawal. Its poor oral
bioavailability (~11%) and short half-life (~3-8 hours) necessitate TID dosing (666 mg TID). Option A describes a
benzodiazepine-like mechanism; acamprosate's GABA-A modulation is modest and not its primary action. Option C
describes naltrexone. Option D describes disulfiram, an ALDH inhibitor producing the acetaldehyde-mediated
aversive reaction.
Q4. A CYP2D6 poor metabolizer with opioid use disorder is being considered for buprenorphine
treatment. The CARN-AP correctly understands that:
A. CYP2D6 poor metabolizer status contraindicates buprenorphine because the parent drug cannot be
converted to the active metabolite norbuprenorphine
B. Buprenorphine is primarily metabolized by CYP3A4 to norbuprenorphine (still active at mu
receptors); CYP2D6 status is not clinically significant for buprenorphine dosing [CORRECT]
C. CYP2D6 poor metabolizers require an empiric 50% reduction of buprenorphine induction dose to avoid
respiratory depression
D. CYP2D6 status only matters for naloxone, the combination product component, and therefore requires
dose splitting
Correct Answer: B
Rationale: Buprenorphine is metabolized principally via CYP3A4 N-dealkylation to norbuprenorphine (which retains
mu-agonist activity though with reduced potency and is further glucuronidated). CYP2D6 plays only a minor role;
therefore, CYP2D6 poor metabolizer status does not require dose adjustment. Option A incorrectly assumes a prodrug
mechanism (buprenorphine itself is active). Option C would be appropriate for some CYP3A4 inhibitor combinations
but not for CYP2D6 status. Option D is incorrect because naloxone is included only to deter IV misuse; it is nearly
completely first-pass metabolized and does not depend on CYP2D6.
Aligned with current ANCB CARN-AP Examination Blueprint | For Educational Use
, CARN-AP Set 2 | Advanced Practice Addictions Nursing Exam Prep | 194 Practice Questions Page 4
Q5. A 29-year-old patient reports using fentanyl powder obtained illicitly, then begins
buprenorphine-naloxone induction. Approximately 90 minutes after the first 4 mg/1 mg sublingual
dose, the patient develops worsening withdrawal with COWS rising from 8 to 14. What is the most
appropriate next step according to current buprenorphine induction guidance?
A. Administer naloxone 0.4 mg IM immediately to reverse potential precipitated withdrawal
B. Withhold further buprenorphine, observe, and administer adjunctive alpha-2 agonist
(clonidine/lofexidine) and ondansetron; reassess in 30-60 minutes [CORRECT]
C. Double the next buprenorphine dose to 8 mg to override precipitated withdrawal
D. Discharge the patient with instructions to return after 48 hours of abstinence to retry induction
Correct Answer: B
Rationale: The patient likely experienced precipitated withdrawal from residual fentanyl at mu receptors (fentanyl's
high lipophilicity and long elimination half-life increase this risk). Current ASAM guidance supports continuing
buprenorphine induction judiciously with adjunctive non-opioid symptom management (clonidine or lofexidine for
autonomic symptoms, ondansetron for emesis, sometimes low-dose ketamine in supervised settings) rather than
naloxone reversal, which would worsen withdrawal. Option A would exacerbate withdrawal; naloxone is for opioid
overdose, not precipitated withdrawal from partial agonist administration. Option C may worsen precipitated
withdrawal in some patients, although 'macro-dosing' protocols exist they require expert oversight. Option D ignores
evidence that low-dose initiation or extended micro-dosing with fentanyl-tolerant patients can succeed without
48-hour abstinence. The 'Bernese method' (micro-dosing buprenorphine while continuing full agonist) is an
alternative.
Q6. Long-term cocaine use is associated with downregulation of D2-like dopamine receptors in the
striatum. Which downstream consequence is most directly linked to the dysphoria and craving of
acute cocaine abstinence?
A. Increased phasic dopamine release in the nucleus accumbens producing euphoria
B. Reduced tonic dopamine firing and a 'reward-deficit state' producing anhedonia and craving
[CORRECT]
C. Upregulation of kappa-opioid receptor tone producing aversion suppression
D. Selective loss of serotonin 5-HT2A receptors in the prefrontal cortex
Correct Answer: B
Rationale: Chronic cocaine exposure elevates synaptic dopamine via DAT blockade, leading to homeostatic D2
receptor downregulation. With abstinence, tonic dopamine firing falls below baseline, producing a reward-deficit state
clinically observed as anhedonia, dysphoria, and heightened craving. Option A is the opposite of the abstinence
phenomenon. Option C is partially relevant because dynorphin-kappa opioid systems are actually upregulated by
chronic cocaine (producing dysphoria), but the question asks for the 'most directly linked' downstream consequence
tied to D2 downregulation; the reward-deficit state is the central clinical correlate. Option D is not the primary
mechanism of cocaine abstinence dysphoria.
Aligned with current ANCB CARN-AP Examination Blueprint | For Educational Use
