CASAC Pharmacology and Co-Occurring Disorders 2 — Questions and Answers

Question 1: Which medication is an opioid antagonist used as part of medication-assisted treatment (MAT) for opioid use disorder and requires complete detoxification before initiation?

Methadone
Buprenorphine
Naltrexone (Correct answer)
Clonidine

Correct answer: Naltrexone

Naltrexone is an opioid antagonist that blocks opioid receptors, and patients must be fully detoxified before starting it to avoid precipitated withdrawal.

Naltrexone (available as oral Revia or injectable Vivitrol) is a full opioid antagonist that blocks mu-opioid receptors, preventing any opioid from producing euphoria. Unlike methadone (a full agonist) or buprenorphine (a partial agonist), naltrexone has no opioid activity and no abuse potential. The critical clinical consideration is that naltrexone will precipitate severe withdrawal if administered to a patient with opioids still in their system. Patients must be opioid-free for a minimum of 7-10 days before initiation. The extended-release injectable formulation (Vivitrol) addresses the adherence challenge of daily oral dosing by providing 28 days of continuous blockade. Naltrexone is also FDA-approved for alcohol use disorder. Clonidine is an alpha-2 agonist used to manage withdrawal symptoms but is not an MAT medication.

Question 2: A client with co-occurring alcohol use disorder and major depressive disorder asks their counselor whether their depression will improve if they stop drinking. What is the most clinically accurate response?

Depression always resolves completely once alcohol use stops
Alcohol can cause depressive symptoms that may improve with abstinence, but an independent depressive disorder may require separate treatment — a period of abstinence helps clarify the diagnosis (Correct answer)
Depression and alcohol use are completely unrelated conditions
Antidepressant medication is never effective for people with alcohol use disorders

Correct answer: Alcohol can cause depressive symptoms that may improve with abstinence, but an independent depressive disorder may require separate treatment — a period of abstinence helps clarify the diagnosis

Substance-induced depressive symptoms often improve with abstinence, but independent depressive disorder requires separate treatment. A period of sobriety (typically 2-4 weeks) helps differentiate between the two.

The relationship between alcohol use disorder and depression is complex and bidirectional. Alcohol is a CNS depressant that can directly cause depressive symptoms through neurochemical disruption — particularly of serotonin, norepinephrine, and GABA systems. These substance-induced depressive symptoms typically improve significantly within 2-4 weeks of abstinence. However, independent major depressive disorder (which may have preceded or developed alongside the alcohol use) will persist after abstinence and requires separate treatment, potentially including psychotherapy and/or antidepressant medication. The DSM-5 distinguishes between substance-induced depressive disorder and independent major depressive disorder, and a period of monitored abstinence is the standard approach for differential diagnosis. Integrated treatment addressing both conditions simultaneously is the evidence-based standard of care.

Question 3: Which of the following substances acts primarily on the dopamine system by blocking reuptake, producing intense but short-lived euphoria and carrying a high risk of cardiovascular complications?

Cannabis
Cocaine (Correct answer)
Psilocybin
Benzodiazepines

Correct answer: Cocaine

Cocaine blocks the reuptake of dopamine (and also serotonin and norepinephrine), producing intense euphoria and significant cardiovascular risks including heart attack and stroke.

Cocaine exerts its primary reinforcing effects by blocking dopamine reuptake transporters (DAT) in the mesolimbic reward pathway, particularly the nucleus accumbens. This causes a rapid accumulation of dopamine in the synapse, producing intense euphoria. Cocaine also blocks serotonin and norepinephrine reuptake, contributing to its stimulant and mood-altering effects. The cardiovascular complications arise from sympathetic nervous system activation: cocaine causes vasoconstriction, tachycardia, hypertension, and can trigger coronary artery spasm, myocardial infarction, stroke, and aortic dissection even in young, otherwise healthy individuals. The short duration of action (30-90 minutes for powder, 5-10 minutes for crack) contributes to binge patterns of use. There is currently no FDA-approved medication for cocaine use disorder, making behavioral interventions (contingency management, CBT) the primary evidence-based treatments.

Question 4: What is the primary mechanism of action of disulfiram (Antabuse) in the treatment of alcohol use disorder?

It reduces alcohol cravings by modulating glutamate receptors
It blocks the enzyme aldehyde dehydrogenase, causing an aversive reaction when alcohol is consumed (Correct answer)
It substitutes for alcohol at GABA receptors
It blocks alcohol absorption in the stomach

Correct answer: It blocks the enzyme aldehyde dehydrogenase, causing an aversive reaction when alcohol is consumed

Disulfiram inhibits aldehyde dehydrogenase, causing accumulation of acetaldehyde when alcohol is consumed, which produces highly unpleasant symptoms including nausea, flushing, and tachycardia.

Disulfiram (Antabuse) works through aversive conditioning rather than craving reduction. It irreversibly inhibits the enzyme aldehyde dehydrogenase, which normally converts acetaldehyde (the first metabolite of alcohol) into harmless acetate. When a person taking disulfiram drinks alcohol, acetaldehyde accumulates rapidly, causing the disulfiram-ethanol reaction: facial flushing, nausea, vomiting, headache, tachycardia, hypotension, and chest pain. This reaction can be severe and potentially dangerous. Disulfiram is most effective for highly motivated patients who take it as part of a comprehensive treatment program, often under observed dosing. It does not reduce cravings or treat withdrawal. Patients must be warned about hidden alcohol sources (mouthwash, cooking wine, vinegar) and the reaction can occur up to two weeks after the last dose. Acamprosate modulates glutamate, not disulfiram.

Question 5: A client diagnosed with schizophrenia and methamphetamine use disorder reports hearing voices that command them to use drugs. This presentation is best understood as:

A normal part of methamphetamine use that does not require intervention
An example of how co-occurring psychotic symptoms can directly undermine substance abuse recovery and require integrated psychiatric and addiction treatment (Correct answer)
Evidence that the client is malingering
A side effect of antipsychotic medication

Correct answer: An example of how co-occurring psychotic symptoms can directly undermine substance abuse recovery and require integrated psychiatric and addiction treatment

Command auditory hallucinations directing substance use demonstrate the complex interaction between psychiatric symptoms and addiction, requiring integrated treatment of both conditions.

This case illustrates the critical intersection of co-occurring disorders where psychiatric symptoms directly undermine addiction recovery. Command hallucinations directing a person to use substances create an extremely challenging clinical situation: the psychotic symptoms are not merely co-existing with the substance use disorder — they are actively perpetuating it. This presentation requires an integrated treatment approach where both the schizophrenia and the methamphetamine use disorder are treated simultaneously by a coordinated team. Antipsychotic medication management is essential to reduce hallucinations, while substance abuse counseling addresses the addiction. Methamphetamine use can also exacerbate psychotic symptoms independently, creating a feedback loop. The dual-diagnosis capable counselor should collaborate with the prescribing psychiatrist, understand the interaction between symptoms, and adjust counseling strategies to account for the client's psychiatric presentation.

Question 6: Which of the following is a key difference between buprenorphine and methadone in the treatment of opioid use disorder?

Buprenorphine is more likely to cause fatal overdose than methadone
Buprenorphine is a partial opioid agonist with a ceiling effect on respiratory depression, while methadone is a full agonist without such a ceiling (Correct answer)
Methadone can be prescribed by any physician, while buprenorphine requires a special clinic
Both medications work identically on opioid receptors

Correct answer: Buprenorphine is a partial opioid agonist with a ceiling effect on respiratory depression, while methadone is a full agonist without such a ceiling

Buprenorphine's partial agonist properties create a ceiling effect on respiratory depression, making it safer in overdose compared to methadone, which is a full agonist.

Buprenorphine and methadone are both FDA-approved for opioid use disorder but differ significantly in pharmacology and clinical application. Buprenorphine is a partial mu-opioid agonist, meaning it activates opioid receptors but with a ceiling effect — beyond a certain dose, increasing the amount does not increase receptor activation. This ceiling effect provides a significant safety advantage, as respiratory depression (the primary cause of opioid overdose death) plateaus at higher doses. Methadone is a full mu-opioid agonist without a ceiling effect, meaning dose-dependent respiratory depression can be fatal. However, methadone may be more effective for patients with higher levels of physical dependence. Historically, methadone required dispensing through federally regulated opioid treatment programs (OTPs), while buprenorphine could be prescribed in office-based settings (though regulations have evolved). Both medications significantly reduce illicit opioid use, overdose deaths, and criminal activity when combined with counseling.

CASAC Pharmacology and Co-Occurring Disorders 2

Which medication is an opioid antagonist used as part of medication-assisted treatment (MAT) for opioid use disorder and requires complete detoxification before initiation?