Mydriasis Induced by Δ¹-Tetrahydrocannabinol in Rats

Abstract

The biological activity of cannabinoids has been the focus of considerable experimentation by scientists as well as by the lay man. Among its discovered actions, the observation of a decrease in intraocular pressure (IOP) has created interest in its potential therapeutic use in glaucoma. The mechanism underlying the fall of IOP has been studied but the complete picture is still unclear. A prevailing view is that the cannabinoids interact with the sympathetic system. The effects of tetrahydrocannabinol (THC) on the ocular sympathetic system have been studied by investigating the pupillary reaction in rats.

Male Charles-River albino rats, weighing 350–400 g were used. Pupillary diameter was measured using a Zeiss binocular operating microscope equipped with a graded ruler.

Intravenous injections of THC caused dose-dependent mydriasis which reached a maximum of three times the base measurement at a dose of 10 mg/kg. This effect reached its maximum within 1 min and lasted for 30–45 min. Sympathectomy significantly inhibited the response to THC. Intracerebroventricular (ICV) administration of THC also caused mydriasis. The ED₅₀ of this route of administration was 150 μg/kg compared to 5 mg/kg following intravenous administration. This central effect was similarly inhibited by previous sympathectomy.

These data demonstrate that in rats THC produced dose-dependent mydriasis, which is probably of central origin, since ICV injections produced similar results with administration of less than 3% of the systemic dose. The mydriatic response was almost totally inhibited by cervical sympathectomy, thus indicating that the sympathetic system is a major efferent pathway for this effect. The ocular hypotensive action of THC was also shown to be inhibited by sympathectomy. It is therefore possible that the effects on pupillary size and on IOP are controlled by a common mechanism.