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Pharmacokinetics and tolerability of oral cannabis preparations in patients with medication overuse headache (MOH)—a pilot study



The recent release of a medical cannabis strain has given a new impulse for the study of cannabis in Italy. The National Health Service advises to consume medical cannabis by vaporizing, in decoction or oil form. This is the first study that explores the pharmacokinetics and tolerability of a single oral dose of cannabis as decoction (200 ml) or in olive oil (1 ml), as a first step to improve the prescriptive recommendations.


This is a single-center, open-label, two-period crossover study designed to assess the pharmacokinetics and tolerability of oral cannabis administered to 13 patients with medication overuse headache (MOH). A liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was conducted for the quantification of THC, CBD, 11-OH-THC, THC-COOH, THC-COOH-glucuronide, THCA-A, and CBDA. Blood pressure, heart rate, and a short list of symptoms by numerical rating scale (NRS) were assessed.


Decoctions of cannabis showed high variability in cannabinoids content, compared to cannabis oil. For both preparations, THCA-A and CBDA were the most widely absorbed cannabinoids, while THC and CBD were less absorbed. The most important differences concern the bioavailability of THC, higher in oil (AUC0–24 7.44, 95% CI 5.19, 9.68) than in decoction (AUC0–24 3.34, 95% CI 2.07, 4.60), and the bioavailability of CBDA. No serious adverse events were reported.


Cannabis decoction and cannabis oil showed different pharmacokinetic properties, as well as distinct consequences on patients. This study was performed in a limited number of patients; future studies should be performed to investigate the clinical efficacy in larger populations.

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We sincerely thank the staff and patients of Medical Toxicology and Headache Centre of Modena, who made possible the realization of the study.

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Correspondence to Lanfranco Pellesi.

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The study was approved by the Ethical Committee of Modena (protocol n. 41/2017) and completed in accordance with the ethical standards of the Helsinki Declaration. Written informed consent was obtained from all patients prior to study participation.

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The authors declare that they have no conflict of interest.

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Pellesi, L., Licata, M., Verri, P. et al. Pharmacokinetics and tolerability of oral cannabis preparations in patients with medication overuse headache (MOH)—a pilot study. Eur J Clin Pharmacol 74, 1427–1436 (2018).

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  • Cannabinoids
  • Oral cannabis
  • Cannabis decoction
  • Cannabis oil
  • Pharmacokinetics
  • Headache