Effect of Hashish on the Cardiovascular System

Smoking hashish or administration of Δ⁹-THC to various mammals decreased the arterial blood pressure via:

1. Central mechanisms located in the brain stem.

2. Release of peripheral PGs that dilate blood vessels.

3. Direct peripheral vasodilatation.

The central component of the induced hypotension was clearly demonstrated by the failure of Δ⁹-THC to induce hypotension in spinal pitted animals. Furthermore, tolerance to the hypertensive effect was observed.

Following smoking of hashish or administration of Δ⁹-THC to humans an increase in heart rate was observed. The induced increase may be >25% of the basal heart rate and is probably due to inhibition of the vigil nuclei via the inhibitory of the bar receptors on the nucleus tract us solitaries in the brain stem i.e. reflex tachycardia. However, administration of hashish or Δ⁹THC to various animals (rats, dogs) induced bradycardia that seemed to be mediated centrally since it was not observed in pitted animals or in those animals with transaction of the spinal cord at C1-C2level. However, a direct effect on the heart cannot be ruled out since addition of Δ⁹-THC to the isolated rat heart decreased the heart rate.

Effect on Hormones

1. Effect on gonadotrophins:

Chronic smoking of hashish induced significant decrease in LH level without affecting FSH level. The effect is probably due to the ability of hashish to stimulate release of encephalin that act on the hypothalamus to depress release of LH-RF. Furthermore, both THC and cannabidiol reduced the sensitivity of the pituitary gland to the stimulant effect of LH-RF. Similarly, THC inhibited the binding of human chorionic gonadotrophin to the ovarian granulose cells and the testes. These changes resulted in decreased synthesis of testosterone and impotence in males and to disturbances in ovulation and menstrual cycles and sub-fertility in females.

2. Effect on Oestrogen and Progesterone:

Addition of Δ⁹-THC to ovarian granulosa cells in vitro or addition of cannabinol, cannabigerol or cannabichromene inhibited FSH-induced release of oestrogen. In addition Δ⁹-THC decreased the level of hydroxyl steroid dehydrogenate in the ovaries. Similarly, Δ⁹-THC inhibited progesterone release and decreased serum progesterone level during the luteal phase.

3. Effect on Corticosteroids:

Administration of Δ⁹-THC to rats but not mice or rabbits elevated plasma level of corticosterone. The release seemed to be due to stimulation of ACTH release from the hypothalamus.

4. Effects on other Hormones:

Chronic administration of Δ⁹-THC to various mammals or smoking of hashish decreased plasma level of GH and prolactin. However, smoking of a single cigarette of hashish did not affect plasma prolactin level. Similarly, exposure of mammals to hashish smoke or administration of Δ⁹-THC decrease plasma level of both thyroxin and triiodothyronine.

Studies on humans and animals revealed that smoking of hashish, systemic or topical application of Δ⁹-THC induced significant decreases in intraocular pressure especially in patients suffering from glaucoma. There was also slight mydriasis, conjunctival reddening, corneal irritation, photophobia, cycloplegia and lachrimation.

The decrease in intraocular pressure is probably due to:

1. Δ⁹-THC-induced increase of aqueous humor outflow resulting from vasodilatation of the efferent blood vessels of the anterior urea. Inhibition of ocular PGs synthesis.

2. Reduction of aqueous humor formation due to activation of B-adrenoceptors in the eye.

Besides the above changes in the eye hashish smoking induces alteration in visual perception since colors seem to be more vivid than usual.