Is 2-Hydroxypropyl-[beta]-cyclodextrin a Suitable Carrier for Central Administration of [Delta]9-Tetrahydrocannabinol? Preclinical Evidence

Preclinical Research [Delta]9-Tetrahydrocannabinol (THC) is a hydrophobic compound that has a potent antinociceptive effect in animals after intrathecal (IT) or intracerebroventricular (ICV) administration. The lack of a suitable solvent precludes its IT administration in humans. 2-Hydroxypropyl-[be...

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Bibliographic Details
Published inDrug development research Vol. 78; no. 8; p. 411
Main Authors Agabio, R, Sanna, F, Lobina, C, Monduzzi, M, Nairi, V, Cugia, F, Mameli, S, Pisanu, G M, Gessa, G L, Melis, M R
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc 01.12.2017
Subjects
Animals
Body temperature
Cyclodextrins
Drugs
Formulations
Hydrophobicity
Latency
Locomotor activity
Pain perception
Rats
Rodents
Tetrahydrocannabinol
Toxicity
β-Cyclodextrin
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Summary:Preclinical Research [Delta]9-Tetrahydrocannabinol (THC) is a hydrophobic compound that has a potent antinociceptive effect in animals after intrathecal (IT) or intracerebroventricular (ICV) administration. The lack of a suitable solvent precludes its IT administration in humans. 2-Hydroxypropyl-[beta]-cyclodextrin (HP[beta]CD) increases the water solubility of hydrophobic drugs and is approved for IT administration in humans. To investigate whether HP[beta]CD might be a suitable carrier for ICV administration of THC in rats, two formulations containing THC complexed with HP[beta]CD (30 and 135 µg of THC per animal) and vehicle were administered to Wistar rats. The antinociceptive effect (using the tail flick test), locomotor activity, and body temperature were evaluated. ICV injection of 135 µg of THC/HP[beta]CD complex increased tail flick latency, reduced locomotor activity, and had a dual effect on body temperature. The 30 µg THC/HP[beta]CD formulation only produced a hyperthermic effect. All animals appeared healthy, with no difference between the groups. These results were similar to those obtained in other preclinical studies in which THC was administered centrally using solvents that are unsuitable for IT administration in humans because of their toxicity. Our findings suggest that HP[beta]CD may be a useful carrier for IT administration of THC in humans. Drug Dev Res 78 : 411-419, 2017. © 2017 Wiley Periodicals, Inc.
ISSN:0272-4391
1098-2299
DOI:10.1002/ddr.21413