What are the interactions between Strattera (atomoxetine) and marijuana?

Interactions Between Strattera (Atomoxetine) and Marijuana

There are no well-documented direct pharmacokinetic or pharmacodynamic interactions between Strattera (atomoxetine) and marijuana, but caution is warranted due to potential additive cardiovascular and central nervous system effects, as well as theoretical concerns about CYP2D6 metabolism.

Pharmacokinetic Considerations

Metabolic Pathways

• Atomoxetine is primarily metabolized by CYP2D6, with aromatic ring-hydroxylation being the main metabolic pathway 1
• Cannabis and cannabinoids inhibit several cytochrome P450 enzymes, specifically CYP3A4 and CYP2C19, but CYP2D6 inhibition by cannabis is not well-established 2
• The lack of direct evidence for cannabis-mediated CYP2D6 inhibition suggests that significant pharmacokinetic interactions are unlikely, though this remains theoretically possible 1

Variable Cannabis Composition

• Cannabis products have highly variable THC and CBD content, making any potential drug interactions unpredictable 2
• CBD at higher doses (>300 mg/day) presents risks for hepatotoxicity with dose-related, reversible transaminase elevations 2

Potential Clinical Consequences

Cardiovascular Effects

• Atomoxetine causes statistically significant increases in both heart rate and blood pressure in pediatric patients 3
• Cannabis can cause tachycardia and orthostatic hypotension, particularly with more serious adverse effects 2
• The combination may produce additive cardiovascular effects, including increased heart rate and blood pressure instability 4, 3

Central Nervous System Effects

• Cannabis commonly causes dizziness, confusion, somnolence, and dry mouth 4
• Atomoxetine adverse effects include dizziness, somnolence, and headache 3
• These overlapping side effect profiles may result in enhanced sedation, confusion, and impaired cognitive function when used together 4, 3

Psychiatric Considerations

• Cannabis may exacerbate psychiatric disorders in vulnerable individuals and is associated with increased risk for developing depressive disorders 2
• Atomoxetine carries a black-box warning for suicidal ideation, with significantly higher incidence than placebo 3
• Patients with ADHD and comorbid psychiatric conditions should exercise particular caution when combining these substances 2, 3

Clinical Management Recommendations

Monitoring Strategy

• Monitor cardiovascular parameters closely: measure heart rate and blood pressure regularly when both substances are used 3
• Assess for enhanced CNS depression: watch for excessive sedation, dizziness, confusion, or impaired coordination 4, 2
• Screen for psychiatric symptoms: monitor for mood changes, anxiety, paranoia, or suicidal ideation 2, 3

Dosing Considerations

• If cannabis use is ongoing, start atomoxetine at the lower end of the dosing range (40 mg daily) and titrate slowly every 7-14 days 5
• Advise patients to start cannabis products at the lowest possible dose and increase slowly with sufficient time between doses to gauge effects 2
• Avoid high-fat meals when taking oral cannabis products, as this significantly increases cannabinoid absorption and may exacerbate interactions 2

Patient Counseling

• Strongly advise against driving when feeling the effects of either substance, as cannabis users are more than twice as likely to be involved in motor vehicle crashes 2
• Recommend avoiding cannabis use during atomoxetine initiation and titration to better assess medication response and tolerability 3, 6
• Inform patients that cannabis withdrawal symptoms are common (96% report at least one symptom) if they attempt to discontinue use 6

Special Population Considerations

CYP2D6 Poor Metabolizers

• Poor CYP2D6 metabolizers have 10-fold higher atomoxetine plasma concentrations and a half-life of 21.6 hours versus 5.2 hours in extensive metabolizers 1
• If cannabis does inhibit CYP2D6 to any degree, poor metabolizers would be at highest risk for enhanced atomoxetine effects and toxicity 1

Adolescents and Young Adults

• Most cannabis-dependent individuals with ADHD are young (mean age 20-27 years in studies) 6
• This population may be at higher risk for impulsive behavior and poor judgment regarding substance combinations 6

Hepatic Considerations

• Patients with hepatic insufficiency show increased atomoxetine exposure 3
• CBD can cause hepatotoxicity, particularly at higher doses, requiring consideration of liver function monitoring 2

Common Pitfalls to Avoid

• Do not assume cannabis is benign simply because it may be legal in your jurisdiction; it carries significant cardiovascular and psychiatric risks 4, 2
• Do not overlook the black-box warning for suicidal ideation with atomoxetine, especially when combined with cannabis use that may exacerbate mood disorders 3
• Do not fail to ask about cannabis use, as patients may not volunteer this information; direct questioning is essential 2
• Do not ignore the variable potency of cannabis products; street cannabis and dispensary products can have vastly different THC/CBD ratios 2

Evidence Limitations

• No controlled studies have specifically examined atomoxetine-cannabis interactions 7
• Available evidence on atomoxetine for cannabis dependence treatment is insufficient for definitive conclusions 7
• Most interaction concerns are based on theoretical considerations and overlapping side effect profiles rather than documented clinical interactions 2, 3