Full text in pdf format

In vitro cytogenetic effects of cannabidiol on human lymphocuyte cultures^*

Gilka J. Figaro Gattás^I; Anita Wajntal^II; P.H. Saldanha^II

^IDepartamento de Medicina Legal, Medicina Social e do Trabalho e Deontologia Médica, Faculdade de Medicina, Universidade de São Paulo, Rua Teodoro Sampaio, 115, 05405 São Paulo, SP, Brasil. Send correspondence to G.J.F.G.
^IIUnidade de Aconselhamento Genético, Departamento de Biologia, Instituto de Biociências, Universidade de São Paulo, Caixa Postal 11461, 05499 São Paulo, SP, Brasil

ABSTRACT

The in vitro effect of cannabidiol (CBD) on mitotic index and frequency of cells with numerical and/or structural aberrations was studied in human lymphocyte cultures. In the first phase of the study, CBD was dissolved in absolute ethyl alcohol (0.01 ml/ml medium) at the concentrations of 0.001, 0.01, 0.1, 1.0 and 10.0 m g CBD/ml medium, and in the second phase ethanol was evaporated before the culture medium was added. The clastogenic effect of CBD was stronger when the drug was combined with alcohol. The action of ethanol was predominantly antimitogenic, whereas CBD had a sharper effect on the production of cells with chromosome aberrations. After ethanol evaporation, the proportion of cells with structural chromosome aberrations maintained an approximately linear increasing relationship with the CBD concentration.

Keywords: Cytogenetic; Cannabidiol; Lymphocyte cultures.

REFERENCES

Badr, F.M., Badr, R.S., Asker, R.L. and Hussain, F.H. (1977). Evaluation of the mutagenic effects of ethyl alcohol by different techniques. In: Alcohol Intoxication and Withdrawal, Biological Aspects of Ethanol (Gross, M.M., ed.). Plenum, New York, pp. 25-46.

Bregman, A.A. (1971). Cytogenetic effects of ethanol in human leukocyte cultures. Env. Mut. Soc. Newsl. 4: 35.

Cadotte, M., Allard, S. and Verdy, M. (1973). Lack of effect of ethanol in vitro on human chromosomes. Ann. Genet. 16:55-56.

Carlini, E.A. and Cunha, J.M. (1981). Hypnotic and antiepileptic effects of cannabidiol. J. Clin. Pharmac. 21: 417-427.

Carlini, E.A., Masur, J. and Magalhães, C.C.P.B. (1979). Possível efeito hipnótico do canabidiol no ser humano. Estudo preliminar. Ciênc. Cult. 31: 315-322.

Carlini, E.A., Mechoulam, R. and Lander, N. (1975). Anticonvulsant activity of four oxygenated cannabidiol derivatives. Res. Commun. Chem. Pathol. Pharmac. 12: 1-15.

Cunha, J.M., Carlini, E.A., Pereira, A.E., Ramos, O.L., Pimentel, C., Gagliardi, R., Sanvito, W.L., Lander, N. and Mechoulam, R. (1980). Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 21: 175-185.

Dalton, W.S., Martz, R., Lemberger, L., Rodda, B.E. and Forney, R.B. (1976). Influence of cannabidiol on delta-9-thetrahydrocannabinol effects. Clin. Pharmac. Ther. 19: 300-309.

Henrich, R.T., Nogawa, T. and Morishima, A. (1980). In vitro - induction of segregational errors of chromosomes by natural cannabinoids in normal human lymphocytes. Envir. Mutagen. 2:139-147.

Karler, R., Borys, H.K. and Turkanis, S.A. (1982). Influence of 22-day treatment on the anti-convulsant properties of cannabinoids. Naunyn-Schmiedeberg's Arch. Pharmak. 320: 105-109.

Lester, R. and Van Thiel, D.H. (1977). Gonadal function in chronic alcoholism. Adv. Exp. Med. Biol., 85 (A) : 399-413.

Martin, P.A., Thorburn, M.J. and Bryant, S.A. (1974). In vivo and in vitro studies of the cytogenetic effects of Cannabis sativa in rats and men. Teratology 9:81-85.

Matsuyama, S.S. and Fu, Tsu-Ker (1981). In vivo cytogenetic effects of cannabinoids. J. Clin. Psychopharmac. 1:135-140.

Moorhead, P.S., Nowell, P.C., Melmann, W.J., Battips, D.M. and Hungerford, D.A. (1960). Chromosome preparations of leukocytes cultured from human peripheral blood. Exp. Cell Res. 20: 613-616.

Nahas, G.G., Desoize, B., Armand, J.P., Hsu, J. and Morishima, A. (1976). Natural cannabinóids: Apparent depression of nucleic acids and protein synthesis in cultured human lymphocytes. In: The Pharmacology of Marihuana (Braude, M.C. and Szara, S., eds.). New York, Raven Press, pp. 177-186.

Neu, R.L., Powers, H.O., King, S. and Gardner, L.I. (1970). Δ⁸ and Δ⁹-tetrahydrocannabinol: effects on cultured human leucocytes. J. Clin. Pharmac. 10: 228-230.

Nichols, W.W., Miller, R.C., Heneen, W., Bradt, C., Hollister, L. and Kanter, S. (1974). Cytogenetic studies on human subjects receiving marihuana and Δ⁹- tetrahydrocannabinol. Mu tat. Res. 26: 413-417.

Obe, G. and Ristow, H. (1979). Mutagenic, cancerogenic and teratogenic effects of alcohol. Mutat. Res. 65: 229-259.

Salemink, C.A. (1976). Pyrolysis of cannabinoids. In: Marihuana Chemistry, Biochemistry and Cellular Effects. (Nahas, G.G., ed.). New York, Springer-Verlag, pp. 31-38.

Stenchever, M.A., Parks, K.J. and Stenchever, M.C. (1976). Effects of Δ⁸ -tetrahydrocannabinol, Δ⁹-tetrahydrocannabinol, and crude marihuana on human cells in tissue culture. In: Marihuana Chemistry, Biochemistry, and Cellular Effects. (Nahas, G.G., ed.) New York, Springer-Verlag, pp. 257-263.

Turkanis, S.A., Cely, W., Olsen, D.M. and Karler, R. (1974). Anticonvulsant properties of cannabidiol. Res. Commun. Chem. Pathol. Pharmac. 8: 231-246.

Tuner, C.E., Esohly, M.A. and Boeren, E.G. (1980). Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J. Nat. Prod. 43: 169-234.

Zimmerman, A.M. and Raj, A.Y. (1980). Influence of cannabinoids on somatic cells in vivo. Pharmacology 21: 277-287.

Zwicker, A.P. and Cunha, J.M. (1982). Uso de canabidiol em ansiedade induzida experimentalmente. Ciênc. Cult. (Suppl.) 34: 897.

* Part of a thesis submitted by G.J.F.G. to the Instituto de Biociências, Universidade de São Paulo, in partial fulfillment of the requirements for the Masters degree.