8.2 Medications for Alcohol and Tobacco Use Disorders

8.2 Medications for Alcohol and Tobacco Use Disorders

[!IMPORTANT] Targeting Neurochemical Adaptations in AUD and TUD: Chronic consumption of alcohol and nicotine induces profound neuroadaptive changes across multiple central neurotransmitter circuits. Pharmacotherapies for Alcohol Use Disorder (AUD) and Tobacco Use Disorder (TUD) target these neuroadaptations: restoring homeostatic balance between excitatory glutamate (NMDA) and inhibitory gamma-aminobutyric acid (GABA) transmission, blocking endogenous opioid reinforcement, inducing severe aversive physical reactions to ethanol, or competitively modulating nicotinic acetylcholine receptors. Advanced addiction counselors must master the distinct pharmacological mechanisms, organ clearance pathways, and strict contraindications of these life-saving medications.

While pharmacotherapy is widely accepted for opioid use disorder, medications for Alcohol Use Disorder and Tobacco Use Disorder remain significantly underutilized in clinical practice. Master's-level addiction counselors must understand the empirical mechanisms, client selection criteria, and medical contraindications of these medications to provide competent psychoeducation, facilitate collaborative medical referrals, and optimize treatment adherence.

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Pharmacotherapy for Alcohol Use Disorder (AUD)

Chronic heavy alcohol exposure fundamentally disrupts the central nervous system's homeostatic balance by chronically enhancing inhibitory GABAA neurotransmission while suppressing excitatory N-methyl-D-aspartate (NMDA) glutamate receptors. In response, the brain up-regulates NMDA receptors and down-regulates GABAA receptors. When alcohol is abruptly discontinued, the individual experiences severe glutamate-mediated neurotoxicity and autonomic hyperactivity. The three FDA-approved medications for AUD address these pathways through distinct clinical strategies:

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|                 FDA-APPROVED PHARMACOTHERAPIES FOR ALCOHOL USE DISORDER          |
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| 1. ACAMPROSATE (Campral) -> Modulates NMDA/GABA; clears protracted withdrawal   |
| 2. DISULFIRAM (Antabuse) -> Irreversibly blocks ALDH; aversive conditioning     |
| 3. NALTREXONE (ReVia / Vivitrol) -> Blocks mu receptors; extinguishes reward    |
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Acamprosate (Campral): Neurochemical Stabilization & Protracted Withdrawal

Acamprosate (calcium bisacetylhomotaurinate) is a synthetic amino acid derivative chemically resembling GABA:

• Mechanism of Action: Functions as a neuromodulator that dampens hyperactive NMDA glutamate receptor transmission while subtly enhancing GABAA receptor tone. It does not treat acute alcohol withdrawal, but rather stabilizes post-acute neurochemical hyperarousal, mitigating Post-Acute Withdrawal Syndrome (PAWS) symptoms such as chronic insomnia, anxiety, dysphoria, autonomic restlessness, and persistent craving.
• Organ Clearance & Safety Profile: Acamprosate is excreted completely unchanged by the kidneys through glomerular filtration. It undergoes zero hepatic metabolism and is completely non-hepatotoxic. This makes acamprosate the medication of choice for clients with significant hepatic impairment, alcoholic hepatitis, or decompensated liver cirrhosis.
• Contraindications: Absolutely contraindicated in clients with severe renal impairment (creatinine clearance / eGFR < 30 mL/min). Requires dose reduction in moderate renal insufficiency (eGFR 30–50 mL/min).
• Adherence Considerations: Standard adult dosing is 666 mg three times daily (TID) (two 333 mg delayed-release tablets taken three times a day with meals). The requirement to ingest six large pills daily represents a significant adherence hurdle, requiring structured behavioral routines and counselor monitoring.

Disulfiram (Antabuse): Aversive Conditioning via ALDH Inhibition

Disulfiram represents the classical psychological deterrent and aversive conditioning agent in addiction medicine:

• Pharmacodynamics: Irreversibly inhibits hepatic aldehyde dehydrogenase (ALDH), the key enzyme responsible for converting acetaldehyde into harmless acetic acid during alcohol metabolism.
• The Disulfiram-Ethanol Reaction (DER): When an individual taking disulfiram ingests even minute quantities of ethanol, blood levels of toxic acetaldehyde surge 5- to 10-fold within 5 to 15 minutes. This creates an excruciating physical reaction characterized by intense facial flushing, throbbing headache, diaphoresis, dyspnea, violent nausea and vomiting, palpitations, tachycardia, and severe hypotension. In extreme cases, the reaction can progress to cardiac arrhythmias, acute myocardial infarction, cardiovascular collapse, seizures, and death.
• Duration of Effect: Because disulfiram inhibits ALDH irreversibly, new enzyme synthesis is required for recovery; the potential for a DER persists for up to 14 days after discontinuing the medication.
• Clinical Selection & Absolute Contraindications: Disulfiram carries zero effect on alcohol cravings. It functions purely as an external psychological barrier and is effective primarily under directly observed administration (e.g., administered daily by a spouse, clinic nurse, or probation officer). The client must have intact cognitive functioning to comprehend the fatal risks and must achieve verified zero blood alcohol for at least 12 to 24 hours prior to initiation. Disulfiram is strictly contraindicated in coronary artery disease, history of myocardial infarction, congestive heart failure, active psychosis (inhibits dopamine beta-hydroxylase, elevating dopamine and worsening psychosis), severe hepatic failure, and pregnancy.
• Hidden Alcohol Education: Clinicians must rigorously educate clients to avoid everyday products containing concealed ethanol, including over-the-counter cough syrups, mouthwashes, cooking vinegars, fermented sauces, aftershave lotions, and hand sanitizers.

Naltrexone (Oral ReVia & Depot Vivitrol) for Alcohol Dependence

• Mechanism of Action: Chronic alcohol ingestion stimulates the release of endogenous beta-endorphins, which bind to mu-opioid receptors in the VTA, disinhibiting dopaminergic neurons and producing a reinforcing euphoric "high." Naltrexone acts as a competitive mu-opioid receptor antagonist, blocking endorphin binding and disconnecting alcohol consumption from dopaminergic reinforcement.
• Clinical Outcome: Naltrexone significantly reduces alcohol cravings, cuts the frequency of drinking days, and prevents a minor "slip" from escalating into a full-blown relapse or heavy binge drinking episode. Some clinical protocols (e.g., the Sinclair Method) specifically utilize targeted oral naltrexone taken 1 hour prior to drinking to facilitate pharmacological extinction of conditioned reward.
• Formulations: Available as a 50 mg once-daily oral tablet (ReVia) or as a 380 mg once-monthly intramuscular gluteal depot injection (Vivitrol). The monthly depot formulation entirely overcomes daily oral compliance barriers.
• Monitoring & Contraindications: Naltrexone undergoes hepatic metabolism. While safe at standard therapeutic doses, baseline and periodic liver function tests (LFTs) are standard of care, and it is contraindicated in acute hepatitis or liver failure (serum transaminases > 3–5 times the upper limit of normal). Naltrexone is absolutely contraindicated in anyone taking opioid analgesics or undergoing opioid withdrawal.

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Pharmacotherapy for Tobacco Use Disorder (TUD)

Tobacco Use Disorder remains the leading cause of preventable morbidity and mortality worldwide. First-line pharmacotherapies include three distinct classes:

Nicotine Replacement Therapy (NRT)

NRT provides clean, controlled doses of nicotine without the thousands of carcinogenic toxins and carbon monoxide present in combustible tobacco smoke. Available in five FDA-approved forms:

1. Transdermal Patch: Long-acting; provides continuous, steady-state baseline blood nicotine levels over 16 to 24 hours.
2. Nicotine Gum: Short-acting; absorbed transmucosally; requires the "chew-and-park" technique (chew until peppery taste or tingle, then park between cheek and gum).
3. Nicotine Lozenge: Short-acting; dissolves slowly in the buccal mucosa without chewing.
4. Nicotine Nasal Spray: Rapid mucosal absorption; fastest peak blood levels mimicking cigarette kinetics; high potential for sensory irritation (sneezing, watery eyes).
5. Nicotine Oral Inhaler: Delivers nicotine vapor to the buccal mucosa; replicates the behavioral hand-to-mouth ritual.

• Combination NRT Superiority: Clinical practice guidelines strongly recommend combination NRT (pairing a long-acting transdermal patch for baseline stabilization with a short-acting form like gum or lozenge for acute breakthrough cravings) over monotherapy, yielding significantly higher long-term cessation rates.

Varenicline (Chantix): Nicotinic Receptor Partial Agonism

• Mechanism: A high-affinity partial agonist at alpha-4 beta-2 (α4β2) neuronal nicotinic acetylcholine receptors in the brain's reward center:
  • Agonist effect: Sub-maximally stimulates the receptor, evoking moderate dopamine release to alleviate withdrawal symptoms and suppress intense cravings.
  • Antagonist effect: Because of its extremely high binding affinity, it competitively blocks inhaled nicotine from binding. If the client smokes a cigarette, they experience zero reinforcing reward.
• Clinical Administration & Side Effects: Initiated 1 to 2 weeks prior to a client's target quit date and titrated to 1 mg twice daily. Most common adverse effects include nausea (mitigated by taking with food and a full glass of water), insomnia, and abnormal/vivid dreams.
• Neuropsychiatric Safety: While previously carrying a boxed warning, the landmark EAGLES clinical trial demonstrated that varenicline does not significantly increase neuropsychiatric events compared to placebo or NRT, establishing it as the single most effective oral monotherapy for smoking cessation.

Bupropion SR (Zyban / Wellbutrin): Norepinephrine-Dopamine Reuptake Inhibition

• Mechanism: A monocyclic aminoketone functioning as an inhibitor of norepinephrine and dopamine reuptake (NDRI) with non-competitive antagonism at nicotinic acetylcholine receptors. It attenuates nicotine withdrawal symptoms and reduces post-cessation weight gain.
• Dosing: Initiated 1 to 2 weeks prior to the target quit date at 150 mg once daily for 3 days, then titrated to 150 mg twice daily (spaced at least 8 hours apart to prevent seizure risk).
• Absolute Contraindications: Bupropion lowers the cerebral seizure threshold. It is strictly contraindicated in clients with a current or prior diagnosis of anorexia nervosa or bulimia nervosa (due to significantly elevated seizure incidence), active seizure disorders, concurrent administration of MAO inhibitors, or undergoing abrupt discontinuation of alcohol, benzodiazepines, or other sedatives.

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AUD Medications Comparison Matrix

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Tobacco Cessation Pharmacotherapy Matrix

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Clinical Contraindications & Safety Assessment Guide

When evaluating clients for AUD and TUD pharmacotherapy referrals, master's-level counselors must systematically screen for black-letter medical contraindications:

1. Renal vs. Hepatic Cleaving: Check recent metabolic panels. If serum creatinine is significantly elevated or eGFR < 30 mL/min, acamprosate is contraindicated; consider naltrexone. If AST/ALT are markedly elevated or cirrhosis is present, naltrexone and disulfiram are risky or contraindicated; acamprosate is the drug of choice.
2. Cardiovascular & Psychiatric Screening for Disulfiram: Never support disulfiram in clients with angina, prior bypass/stents, heart failure, cognitive deficits, or history of psychosis or active depression.
3. Seizure & Eating Disorder Screening for Bupropion: Inquire specifically about adolescent or adult history of purging, restrictive eating, or unprovoked seizures before supporting bupropion referrals.