INHIBITORY EFFECTS OF DELTA-9-TETRAHYDROCANNABINOL AND OTHER PSYCHOTROPIC DRUGS ON CULTURED LYMPHOCYTES

Summary Delta-9-tetrahydrocannabinol (THC) depresses in vitro phytohemagglutinin (PHA) induced lymphocyte transformation as measured by 3 H-thymidine and 3 H-uridine uptake. Cells are harvested after 3 days of culture when there is maximum thymidine uptake and when there is still enough glucose in the medium to meet energy requirements. Care is exerted to disperse the THC-ethanol solution uniformly in the culture, and tritiated THC is used to verify the drug's presence in the medium. Ethanol, in concentrations used in these experiments, does not alter thymidine uptake. The respective concentration of protein (serum) and cells in the culture medium does influence the extent of THC inhibition. With 20% serum in the medium, a concentration of 1.6 × 10 -4 M THC is required to inhibit by 50% the thymidine uptake (IC 50) occurring in a parallel control culture; with 5% serum in the medium the IC 50 is 3.5 × 10 -5 M. Other commonly used lipophilic psychotropic drugs such as diazepam, imipramine, diphenylhydantoin, chlordiazepoxide exert a similar inhibition on thymidine uptake of cultured lymphocytes; haloperidol (IC 50 = 1 × 10 -5 M) has a higher cytotoxicity than THC; phenobarbital and meprobamate are less toxic (IC 50 = 10 -3 M).