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

D9-Tetrahydrocannabinol (THC) is a hydrophobic compound that has a potent antinoci-ceptive effect in animals after intrathecal (IT) or intracerebroventricular (ICV) administration. The lack of asuitable solvent precludes its IT administration in humans. 2-Hydroxypropyl-b-cyclodextrin (HPbCD)increases the water solubility of hydrophobic drugs and is approved for IT administration in humans. Toinvestigate whether HPbCD might be a suitable carrier for ICV administration of THC in rats, two formula-tions containing THC complexed with HPbCD (30 and 135 l g of THC per animal) and vehicle wereadministered to Wistar rats. The antinociceptive effect (using the tail flick test), locomotor activity, andbody temperature were evaluated. ICV injection of 135 lg of THC/HPbCD complex increased tail flicklatency, reduced locomotor activity, and had a dual effect on body temperature. The 30 lg THC/HPbCDformulation only produced a hyperthermic effect. All animals appeared healthy, with no differencebetween the groups. These results were similar to those obtained in other preclinical studies in which THCwas administered centrally using solvents that are unsuitable for IT administration in humans because oftheir toxicity. Our findings suggest that HPbCD may be a useful carrier for IT administration of THC inhumans