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Planta Med 2012; 78(7): 686-691
DOI: 10.1055/s-0031-1298334
Pharmacokinetic Investigations
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Heat Exposure of Cannabis sativa Extracts Affects the Pharmacokinetic and Metabolic Profile in Healthy Male Subjects

Martin Eichler1 [*] , Luca Spinedi1 [*] , Sandra Unfer-Grauwiler1 , Michael Bodmer1 , Christian Surber2 , Markus Luedi3 , Juergen Drewe1
  • 1Departments of Clinical Pharmacology and Gastroenterology & Hepatology, University Hospital Basel, Basel, Switzerland
  • 2Institute for Hospital Pharmacy, University Hospital Basel, Basel, Switzerland
  • 3Cannapharm Ltd., Burgdorf, Switzerland
Further Information

Publication History

received January 2, 2012 revised February 6, 2012

accepted February 10, 2012

Publication Date:
12 March 2012 (online)

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Abstract

The most important psychoactive constituent of Cannabis sativa L. is Δ9-tetrahydrocannabinol (THC). Cannabidiol (CBD), another important constituent, is able to modulate the distinct unwanted psychotropic effect of THC. In natural plant extracts of C. sativa, large amounts of THC and CBD appear in the form of THCA-A (THC-acid-A) and CBDA (cannabidiolic acid), which can be transformed to THC and CBD by heating. Previous reports of medicinal use of cannabis or cannabis preparations with higher CBD/THC ratios and use in its natural, unheated form have demonstrated that pharmacological effects were often accompanied with a lower rate of adverse effects. Therefore, in the present study, the pharmacokinetics and metabolic profiles of two different C. sativa extracts (heated and unheated) with a CBD/THC ratio > 1 were compared to synthetic THC (dronabinol) in a double-blind, randomized, single center, three-period cross-over study involving 9 healthy male volunteers. The pharmacokinetics of the cannabinoids was highly variable. The metabolic pattern was significantly different after administration of the different forms: the heated extract showed a lower median THC plasma AUC24 h than the unheated extract of 2.84 vs. 6.59 pmol h/mL, respectively. The later was slightly higher than that of dronabinol (4.58 pmol h/mL). On the other hand, the median sum of the metabolites (THC, 11-OH-THC, THC-COOH, CBN) plasma AUC24 h was higher for the heated than for the unheated extract. The median CBD plasma AUC24 h was almost 2-fold higher for the unheated than for the heated extract. These results indicate that use of unheated extracts may lead to a beneficial change in metabolic pattern and possibly better tolerability.

Key words

Cannabis sativa L. - Cannabaceae - tetrahydrocannabinol - THC - THC metabolites - CBD - pharmacokinetics

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1 These authors contributed equally to the work.

Prof. Juergen Drewe, MD, MSc

Department of Gastroenterology & Hepatology
University Hospital Basel

Petersgraben 4

4031 Basel

Switzerland

Phone: +41 7 89 23 27 44

Fax: +41 61 2 65 85 81

Email: juergen.drewe@unibas.ch

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