Abstract
The effects of cannabidiol (CBD) were compared to those produced by haloperidol in rats submitted to experimental models predictive of antipsychotic activity. Several doses of CBD (15–480 mg/kg) and haloperidol (0.062–1.0 mg/kg) were tested in each model. First, CBD increased the effective doses 50% (or) ED50 of apomorphine for induction of the sniffing and biting stereotyped behaviors. In addition, both CBD and haloperidol reduced the occurrence of stereotyped biting induced by apomorphine (6.4 mg/kg), increased plasma prolactin levels and produced palpebral ptosis, as compared to control solutions. However, CBD did not induce catalepsy even at the highest doses, in contrast to haloperidol. Such a pharmacological profile is compatible with that of an “atypical” antipsychotic agent, though the mechanism of action is uncertain and may not be identical to that of the dopamine antagonists.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Agurell S, Carlsson S, Lindgren JE, Ohlsson A, Gillespie H, Hollister LE, (1981) Interactions of Δ1-tetrahydrocannabinol with cannabinol and cannabidiol following oral administration in man. Assay of cannabinol and cannabidiol by mass fragmentography. Experientia 37:1090–1091
Benedito MA, Leite JR (1981) Açáo de canabinóides em convulsões induzidas pelo ácido 3-mercaptopropiônico. Ciência e cultura 33:727–731
Carter CJ, Pycock CJ (1981) The role of 5-hydroxytryptamine in dopamine-dependent stereotyped behaviour. Neuropharmacology 20:261–265
Casanueva F, Apud J, Locatelli V, Martinez-Campos A, Civati C, Racagni G, Cocchi D, Müller EE (1981) Mechanisms subserving the stimulatory and inhibitory components of γ-aminobutyric acid-ergic control of prolactin secretion in the rat. Endocrinology 109[2]:567–575
Clemens JA, Smalstig EB, Sawyer BD (1974) Antipsychotic drugs stimulate prolactin release. Psychopharmacologia 40:123–127
Colasanti BK, Brown RE, Craig CR (1984) Ocular hypotension, ocular toxicity and neurotoxicity in response to marihuana extract and cannabidiol. Gen Pharmacol 15:479–484
Costall B, Naylor RJ (1975) Detection of the neuroleptic properties of clozapine, sulpiride and thioridazine. Psychopharmacologia 43:69–74
Costall B, Naylor RJ, Nohria V (1981) Use of the intracerebral injection technique to elucidate mechanisms of apomorphyne climbing and its antagonism in the mouse. Psychopharmacology 73:91–94
Dougherty GG, Ellinwood Jr EH (1983) Influence of gamma-butyrolactone on behavior due to dopaminergic drugs Physiol Behav 30:607–612
Fairbairn JW, Pickens JT (1979) The oral activity of Δ1-Tetrahydrocannabinol and its dependence on prostaglandin E2. Br J Pharmacol 67:379–385
Fernandes M, Schabarek A, Coper H, Hill R (1974) Modification of Δ9-THC-actions by cannabinol and cannabidiol in the rat. Psychopharmacologia 38:329–338
Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, De Costa BR, Rice KC (1990) Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA 87:1931–1936
Hollander M, Wolfe DA (1973) Nonparametric statistical methods. John Wiley, New York
Izquierdo I, Orsingher OA, Berardi AC (1973) Effect of cannabidiol and otherCannabis sativa compounds on hippocampal seizure discharges. Psychopharmacologia 28:95–102
Janssen PAJ, Van Bever WFM (1975) Advances in the search for improved neuroleptic drugs. In: Essman WB, Valzelli L (ed) Current developments in psychopharmacology. Spectrum publications, New York, pp 167–184
Janssen PAJ, Niemegeers CJE, Schellekens KHL (1965) It is possible to predict the clinical effects of neuroleptic drugs (major tranquillizer) from animal data? Arzneimittelforschung 15:104–117
Janssen PAJ, Niemegeer CJE, Schellekens KHL, Lanaerts FM (1977) Is it possible to predict the clinical effects of neuroleptic drugs (major tranquillizer) from animal data? Part IV. Arzneimittelforschung 17:841–854
Jenner P, Marsden CD (1983) Neuroleptics. In: Grahame-Smith DG (ed) Preclinical psychopharmacology. Excerpta Medica, Amsterdam, pp 180–247
Jenner P, Clow A, Reavill C, Theodorov A, Marsden LD (1978) A behavioral and biochemical comparison of dopamine receptor blockade produced by haloperidol with that produced by substituted benzamide drugs. Life Sci 23:545–550
Johnson KM (1976) Some structural requirements for inhibition of high affinity synaptosomal serotonin uptake by cannabinoids. Mol Pharmacol 12[3]:345–352
Jones G, Pertwee RG (1972) A metabolic interaction in vivo between cannabidiol and Δ1-tetrahydrocannabinol. Br J Pharmacol 45:375–377
Karniol IG, Carlini EA (1973) Pharmacological interaction between cannabidiol and Δ9-tetrahydrocannabinol. Psychopharmacologia 33:53–70
Krulich L, Hefco E, Illner P, Read CB (1974) The effects of acute stress on the secretion of LH, FSH, prolactin and GH in the normal male rats, with comments on their statistical evaluation. Neuroendocrinology 16:293–331
Martin BR (1986) Cellular effects of cannabinoids. Pharmacol Rev 38[1]:45–74
Meltzer HY, So R, Miller RJ, Fang VS (1979) Comparison of the effects of substituted benzamides and standard neuroleptics on the binding of3H-spiroperidol in the rat pituitary and striatum with in vivo effects on rat prolactin secretion. Life Sci 25:573–584
Monti JM (1977) Hypnotic like effects of cannabidiol in the rat. Psychopharmacology 55:263–265
Niswender GD, Chen CL, Migdley Jr AR, Meites J, Ellis S (1969) Radioimmunoassay for rat prolactin. Proc Soc Exp Biol Med 130:793
Nye JS, Seltzman HH, Pitt CG, Snyder SH (1985) High-affinity cannabinoid binding sites in brain membranes labeled with3H-5'-Trimethylammonium Δ8-tetrahydrocannabinol. J Pharmacol Exp Ther 234:784–791
Pickens JT (1981) Sedative activity of cannabis in relation to its Δ1-trans-tetrahydrocannabinol and cannabidiol content. Br J Pharmacol 72:649–656
Puech AJ, Simon P, Boissier JR (1976) Antagonism by sulpiride of three apomorphine-induced effects in rodents. Eur J Pharmacol 36:439–441
Revuelta AV, Cheney DL, Wood PL, Costa E (1979) Gabaergic mediation in the inhibition of hippocampal acetylcholine turnover rate elicited by Δ9-tetrahydrocannabinol. Neuropharmacology 18:525–530
Robertson A, MacDonald C (1986) The effects of some atypical neuroleptics on apomorphine induced behavior as a measure of their relative potencies in blocking presynaptic versus postsynaptic dopamine receptors. Pharmacol Biochem Behav 24:1639–1643
Rottanburg D, Robins AH, Ben-Aire O, Teggin A, Elk R (1982) Cannabis-associeted psychosis with hypomanic feature. Lancet II:1364–1366
Scatton B, Bartholini G (1982) Gamma-aminobutyric acid (Gaba) receptor stimulation. IV Effect of progabid (S2 76002) and other gabaergic agents on acetylcholine turnover in rat brain areas. J Pharmacol Exp Ther 220:689–695
Siegel S (1956) Nonparametric statistics for the behavioral sciences. Mac Graw-Hill and Kogakusha, Japan
Weil CS (1952) Tables for convenient calculation of median-effective dose (LD50 or ED50) and instructions in their use. Biometrics 8:249–263
Weiner RI, Ganong WF (1978) Role of brain monoamines and histamine in regulation of anterior pituitary secretion. Physiol Rev 58:905–976
Zivkovic B, Scatton B, Dedek J, Worms P, Lloyd KG, Bartholine G (1980) Involvement of different types of dopamine receptors in the neuroleptic actions. Prog Neuropsychopharmacol (Suppl):369–370
Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG (1982) Action of cannabidiol on the anxiety and other effects produced by Δ9-THC in normal subjects. Psychopharmacology 76:245–250
Zuardi AW, Teixeira NA, Karniol IC (1984) Pharmacological interaction of the effects of Δ9-trans-tetrahydrocannabinol and cannabidiol on serum corticosterone levels in rats. Arch Int Pharmacodyn 269:12–19
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zuardi, A.W., Antunes Rodrigues, J. & Cunha, J.M. Effects of cannabidiol in animal models predictive of antipsychotic activity. Psychopharmacology 104, 260–264 (1991). https://doi.org/10.1007/BF02244189
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02244189