Can trazodone (an antidepressant medication) cause a false positive result on a drug test for tetrahydrocannabinol (THC)?

Trazodone and False Positive Drug Tests

Trazodone does NOT cause false positive results for THC (marijuana) on drug tests, but it can cause false positive results for amphetamines and MDMA (ecstasy) through its metabolite meta-chlorophenylpiperazine (m-CPP). 1, 2

Specific False Positive Patterns

Amphetamine Screens

• Trazodone's metabolite m-CPP cross-reacts with the Amphetamines II immunoassay (Roche Diagnostics), producing false positive amphetamine results 1
• This occurs frequently enough that at one institution, at least 8 trazodone-associated false positive amphetamine results occurred during a single 26-day period 1
• There is a strong correlation (r = 0.990) between m-CPP concentration in urine and the degree of immunoreactivity on amphetamine screening tests 1
• Patients taking therapeutic doses of trazodone can produce sufficient urinary m-CPP concentrations to trigger false positive results 1

MDMA/Ecstasy Screens

• Trazodone and m-CPP both cross-react significantly with the EMIT II Ecstasy immunoassay 2
• Patients taking trazodone may receive false positive results on urine EMIT tests for MDMA 2

THC/Marijuana Screens

• No evidence exists linking trazodone to false positive THC results - the available literature does not identify trazodone as causing false positive marijuana/cannabinoid screens 3, 4, 5, 6

Critical Clinical Action Steps

When You See a Positive Amphetamine or MDMA Result

• Immediately obtain the patient's complete medication history, specifically asking about trazodone use 4, 5
• Order confirmatory testing using gas chromatography-mass spectrometry (GC-MS) before making any clinical decisions - this will definitively distinguish between true amphetamine/MDMA use and trazodone-related false positives 4, 5
• Never make consequential decisions (dismissal from treatment, legal actions, custody issues) based solely on immunoassay screening results 5, 6

Understanding the Testing Limitation

• Standard immunoassay drug screens are designed as screening tests only and have known limitations in specificity due to cross-reactivity 4, 5
• These preliminary screening tests should never be considered definitive 4
• Confirmatory testing adds cost but is essential when results will affect patient management 6

Common Pitfalls to Avoid

• Assuming all positive drug screens represent illicit drug use - many prescribed medications cause false positives, and trazodone is a common culprit for amphetamine screens 4, 1
• Failing to discuss unexpected results with laboratory personnel or toxicologists before taking action 5, 6
• Not establishing which specific drugs are included in your local testing panel - different laboratories use different immunoassays with varying cross-reactivity patterns 6
• Overlooking that m-CPP itself is emerging as a recreational drug, which adds forensic complexity to interpretation 2

Documentation When False Positive Occurs

• If confirmatory GC-MS testing is negative (as expected with trazodone causing the false positive), clearly document that the initial screening was a false positive and reassure the patient and family 5
• Maintain open dialogue with patients about all possible explanations for positive results 5