Marihuana-derived material: distribution and effects after systemic administration

Abstract

Studies have been made in an attempt to elucidate the mode of action of water-soluble marihuana-derived material (MDM). MDM lowers intraocular pressure (IOP) at systemic dose levels greater than 5 μg/rabbit by reducing aqueous humor inflow. Blood pressure, body temperature, and PO₂. remain constant despite the wide variation in IOP caused by high dose levels of MDM, viz. an initial hypertensive phase followed by a hypotensive phase. Blood PCO₂ and pH, however, both decrease with 1 mg MDM/rabbit indicating an acidosis which may partially explain some of the fall in IOP caused by MDM at this high dose level. Low doses of MDM (50 μg/animal), however, induce no such changes in systemic chemistry, illustrating the absence of an MDM effect which can explain the greater than 50% fall in IOP. Repeated injections of MDM on a weekly basis indicate a sequentially reduced effect on IOP. MDM, when incubated in vitro for 6 hours with saline, aqueous or vitreous, always induced a fall in IOP; incubation in these media for 24 hours, however, reduced the capacity to induce an IOP decrease. When aqueous or vitreous was removed from animals which had received intravitreal injections of MDM 24 hours previously (thus, at a time when the IOP in these animals was low) and was reinjected intra-vitreally into fresh recipient rabbits, the IOP fell in the recipients with aqueous, but not vitreous. Only when high doses of MDM (≥ 2 mg) were given systemically to a donor rabbit was any evidence obtained of a fall in IOP in recipient rabbits at short times after the donor injection (< 10 min); at greater times after the donor injections whole blood or serum from donor rabbits failed to elicit a fall in IOP in recipient animals. These data indicate that, in vivo, MDM is bound or metabolized rapidly in rabbits when MDM is given systemically.