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Licensed Unlicensed Requires Authentication Published by De Gruyter September 19, 2018

Cannabinoids determination in bronchoalveolar lavages of cannabis smokers with lung disease

  • Maria Concetta Rotolo , Manuela Pellegrini , Paola Martucci , Raffaela Giacobbe , Angela De Palma , Roberta Pacifici , Simona Pichini , Francesco Paolo Busardò EMAIL logo and Mario Bisconti



Cannabis smoke affects the lungs similarly to tobacco smoke, causing symptoms such as increased cough, sputum, hyperinflation and chronic bronchitis. Chronic use can also cause serious lung diseases and airway obstruction. We developed and validated a method for the identification and quantification of cannabinol (CBN), cannabidiol (CBD), Δ-9-tetrahydrocannabinol (THC) and its metabolites 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THC-COOH) in bronchoalveolar lavages (BALs) from hospitalized former or current tobacco smoking patients with lung disease and a long history of cannabis consumption and limited current tobacco use.


For the extraction of cannabinoids from BALs, a 1 mL sample was added with 300 µL of 0.1 N NaOH and 3 mL of hexane/ethyl acetate (9:1). The solvent was then evaporated to dryness. Trimethylsilyl derivatives were prepared and then analyzed by gas chromatography/mass spectrometry.


The method was linear for the analytes under investigation with coefficients of determination of at least 0.99. Absolute analytical recovery was always better than 80%, imprecision and inaccuracy was always under 15%. Six cases out of 15 were positive for THC, CBN and CBD. In two BALs samples, the presence of 11-OH-THC was also measured while THC-COOH was not detected. In the six positive cases, the last cannabis smoking occurred in the previous 2–14 days.


This is the first time that cannabinoids have been detected in BALs, demonstrating the presence of a drug with its metabolites in a target organ of consumers who present with a lung disease. This occurrence let us hypothesize a role of cannabinoids in the development of the disease and prompted an investigation on possible associations between cannabis smoking and clinical outcomes in patients with lung disease and eventually evaluate a cytotoxic effect of cannabinoids themselves.

Corresponding author: Prof. Francesco Paolo Busardò, MD, MSc, DipFMS, PhD, Associate Professor of Forensic Toxicology and Legal Medicine, Department of Legal Medicine, Università Politecnica delle Marche, Ancona, Italy


The authors thank Michele Sciotti, Simonetta di Carlo and Antonella Bacosi for technical assistance.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


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Received: 2018-04-23
Accepted: 2018-08-26
Published Online: 2018-09-19
Published in Print: 2019-03-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

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