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Study register · detail Fallbericht · Cancer · 2020

Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol

Madden et al. ·Pediatrics Impact 4.3
Clear benefit GRADE Very low 58 citations
Samplen = 1 Pat.
Duration14 days follow-up after…
EndpointMethadone serum level
Blindingn.a.
DesignFallbericht
Cannabinoidcbd
Routeoral
Key finding

After discontinuation of cannabidiol, the methadone serum level decreased from 271 to 125 ng/mL, which correlated with improvement of somnolence and fatigue.

Summary

Single case report of a 13-year-old patient with metastatic cancer and chronic pain; CBD-methadone interaction led to an increased methadone serum level (271 ng/mL, reduction to 125 ng/mL after CBD discontinuation) with sedation/fatigue. Mechanism: CBD inhibits CYP3A4/CYP2C19.

P
Population13-year-old girl with metastatic cancer and chronic pain, n=1
I
InterventionCannabidiol (oral, dose not specified, increasing) in addition to methadone 7,5 mg p.o. 2x daily
O
OutcomeSerum methadone level initially 271 ng/mL, decreased to 125 ng/mL after 14 days of discontinuing CBD; clinical improvement of somnolence and fatigue
Confidence in the evidence
Very low

The lowest GRADE level, the effect estimate remains uncertain.

Downgraded for
Imprecision
Quality profile
Sample size ★★★★★
Blinding —
Effect size Clear benefit
Citations / year ★★★★★
Authors
Madden K, Tanco K, Bruera E
DOI 10.1542/peds.2019-3256↗
Design: Fallbericht
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Abstract
The use of cannabidiol products in pediatric patients is becoming more frequent because of the increased ease of accessibility. This case report illustrates the potential for cannabidiol to interact with stable medication regimens. A 13-year-old girl with metastatic cancer and chronic pain presented with increased sleepiness and fatigue. She had been started on 7.5 mg of methadone by mouth twice daily 4 months earlier. Unbeknownst to her physicians, her parents had commenced her on cannabidiol and subsequently increased the dose leading up to her presentation, thinking it would result in tumor shrinkage. The initial serum methadone level was 271 ng/mL, which decreased to 125 ng/mL 14 days after discontinuing cannabidiol. The reduced serum methadone level coincided with improved sleepiness and fatigue. Cannabidiol inhibits CYP3A4 and CYP2C19, both of which are involved in the metabolism of methadone. Pediatricians should be aware of this potential interaction and inquire if their patients are receiving cannabidiol.
Indication
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Cannabis-based medicines and medical cannabis for adults with cancer pain.
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Umfassende SR über 79 RCTs (n=6.462) zu medizinischem Cannabis; moderate Evidenz für Chemotherapie-induzierte Übelkeit/Erbrechen (CINV), schwache Evidenz für Appetit-Stimulation bei HIV/Krebs-Kachexie; Nabilon/Dronabinol überlegen vs. Placebo (OR=3.82 für CINV-Kontrolle, 95%-KI 1.55–9.42).

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The impediment to action advances action. — Marcus Aurelius