Effects on the Liver

Exposure of liver cells to hashish smoke or Δ⁹-THC in vivo resulted in:

1. Inhibition of microtonal lipid per-oxidation due to stabilization of the microtonal membranes.

2. Stimulation of glucose metabolism by increasing the activity of the enzymes UDP-G-dehydrogenate and fructose 1, 6-diphosphate aldolase.

3. Stimulation of glycogenolysis.

4. Inhibition of hepatic oxidizing microtonal enzymes (mixed function oxidize system) but stimulation of hepatic hems oxygenize.

Effects on the Kidney

Treatment of various mammals with Δ⁹-THC or hashish extracts induced dieresis due to inhibition of renal Na+, K+-ATPase involved in active sodium re absorption by the renal tubules or via inhibition of ADH release.

Effects on Blood Constituents

Administration of hashish extracts or Δ⁹-THC to various mammals induced various changes in blood constituents. These include:

• Elevation of blood glucose level. The increase may be due to 9-THC ability to antagonize insulin and/or stimulation of adrenaline release from the adrenal medulla.

• Elevation of plasma level of non-esterifies fatty acids i.e. enhancement of lipolysis.

• Elevation of plasma bilirubin level.

• Elevation of plasma cholesterol level.

• Elevation of plasma Ca2+ and decrease in plasma K+ levels.

• Decrease in number and disturbance in plasma membranes of RBC and decrease in hemoglobin content.

• Increase in blood carboxy hemoglobin level. This effect may deteriorate the condition of patients with heart diseases.

• De granulation and release of lissome enzymes from neutrophils together with reduction in phospholipids content and splitting of the nuclear membranes.

• Inhibition of platelet aggregation in small doses but complete aggregation and de granulation of the platelets with higher doses.

• Stimulation of adenosine diphosphate release from RBC with concomitant aggregation of the platelets.

• Disturbances in platelet membrane phospholipids.

• Activation of phospholipase A2 enzyme with enhancement of arachidonic acid release concurrently with inhibition of PG cyclooxygenase and thromboxane synthesis and activation of lipoxygenase enzymes in platelets.

Effects on the Gastrointestinal Tract

Administration of Δ⁹-THC or hashish smoking is consistently observed to decrease gastric acid and pepsin secretion and to suppress the development of stress-induced ulcers. Furthermore, hashish extracts exerted spasmolytic effects on the gastrointestinal tract due to both a direct effect and inhibition of ACh release from the intestine. However, the ability of hashish components to release PGs usually predisposes to diarrhea.

Effects on Microorganisms

In vitro studies revealed the ability of cannabidiol, cannabigerol, cannabidiolic acid and Δ⁹-THC to exert antibacterial activity against gram positive bacteria e.g. Staphylococci and Streptococci. Furthermore, cannabichromene exerted both antifungal and antibacterial activity. In addition, Δ⁹-THC exerted an antiviral activity against herpes simplex virus type 1 and type 2. However, it should be noted that the immuno-suppressant effect of Δ⁹-THC decreased host resistance to herpes simplex type 2 vaginal infection. In addition, the inhibitory concentration required for these effects on microorganisms cannot be attained in vivo by smoking hashish.

Effects on Enzymes

Administration of Δ⁹-THC to animals or addition of the compound to organs in vitro revealed the ability of this substance to inhibit various enzymes e.g. MAO in platelets and brain, Na+, K+-ATPase and Mg-ATPase in brain, PG cyclooxygenase in platelets and Lysophosphatidyl acyltransferase in lymphocytes and brain.