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Marihuana-derived material: distribution and effects after systemic administration.

K Green, K Cheeks, K A Bowman

    Current Eye Research
    |May 1, 1984
    PubMed
    Summary
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    Water-soluble marihuana-derived material (MDM) effectively lowers intraocular pressure (IOP) by reducing aqueous humor inflow. However, its effects diminish with repeated use and rapid metabolism in vivo.

    Area of Science:

    • Ophthalmology
    • Pharmacology
    • Neuroscience

    Background:

    • Glaucoma treatment remains a significant challenge, necessitating novel therapeutic agents.
    • Understanding the mechanism of action for existing treatments is crucial for optimizing efficacy and safety.
    • Marihuana-derived material (MDM) has shown potential in lowering intraocular pressure (IOP).

    Purpose of the Study:

    • To elucidate the precise mode of action of water-soluble marihuana-derived material (MDM) in lowering intraocular pressure (IOP).
    • To investigate the systemic and local effects of MDM on ocular physiology and systemic parameters.
    • To assess the duration of action and potential for tolerance development with repeated MDM administration.

    Main Methods:

    • Systemic administration of varying doses of MDM to rabbits to measure IOP, blood pressure, body temperature, and blood gas levels.

    Related Experiment Videos

  • In vitro incubation of MDM with ocular fluids (aqueous and vitreous humor) followed by IOP assessment.
  • Intravitreal injection of ocular fluids from MDM-treated animals into recipient rabbits.
  • Systemic administration of MDM to donor rabbits followed by transfer of blood or serum to recipient rabbits.

    • Main Results:

    • MDM significantly lowered IOP at systemic doses >5 µg/rabbit by reducing aqueous humor inflow.
    • High-dose MDM induced transient systemic changes, including acidosis, while low doses had no systemic effects.
    • Repeated MDM injections led to a diminished IOP-lowering effect, suggesting tolerance.
    • In vitro, MDM reduced IOP after 6-hour incubation, but this effect decreased after 24 hours.
    • Aqueous humor from MDM-treated rabbits retained some IOP-lowering capacity upon reinjection, unlike vitreous humor.
    • Systemic MDM administration in donor rabbits only transiently affected recipient IOP, indicating rapid in vivo binding or metabolism.

    Conclusions:

    • MDM lowers IOP primarily by decreasing aqueous humor inflow.
    • Systemic administration of MDM can induce transient physiological changes, particularly at higher doses.
    • Tolerance to MDM's IOP-lowering effect develops with repeated administration.
    • MDM appears to be rapidly metabolized or bound in vivo, limiting its sustained systemic effect.