Effects of cannabidiol in animal models predictive of antipsychotic activity

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.

Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice

“…This is in keeping with similar indications observed in rats in which cannabidiol reversed apomorphine-induced stereotypy (Zuardi et al, 1991) and in a female schizophrenic patient in whom cannabidiol markedly reduced psychotic symptoms (Zuardi et al, 1995). The dose range of cannabidiol (1, 5, and 15 mg/kg) used in the present study is lower than doses previously determined to reverse the effects of psychoactive drugs in rats (Zuardi et al, 1991;Moreira and Guimaraes, 2005); however, it has previously been shown to be active in extinguishing conditioned place preference learning induced by amphetamine and cocaine (Parker et al, 2004). The lack of effect of either capsazepine or cannabidiol per se on PPI and startle response suggests that these drugs do not directly interfere with normal sensorimotor gating in the mouse.…”

“…Cannabidiol was reported to reverse some dopaminergic effects associated with apomorphine, such as stereotypy, prolactin secretion, and palpebral ptosis, while producing none of the catalepsy associated with 'typical' antipsychotics such as haloperidol (Zuardi et al, 1991). This group later showed that cannabidiol increased Fos protein expression in the nucleus accumbens, but not in the striatum, indicating that cannabidiol produces neuronal activation in mesolimbic areas but not in motor control areas, and thus reinforcing the potential of cannabidiol to produce few unwanted motor effects (Guimaraes et al, 2004).…”

The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis

“…CBD and D-9-THC may have pharmacokinetic and pharmacodynamic interactions. Thus, CBD may offset some D-9-THC effects by its anxiolytic effects (Guimaraes et al, 1994;Zuardi et al, 1982), antipsychotic-like effects (Zuardi et al, 1995;Zuardi et al, 1991) and may block the conversion of D-9-THC to the more psychoactive 11-hydroxy-THC (Bornheim et al, 1995). However, the CBD content of cannabis varies greatly and some samples of cannabis have been reported to be devoid of CBD (Pitts et al, 1992).…”

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

“…CBD effects were compared with those of haloperidol [91]. Both drugs reduced apomorphine-induced stereotyped behaviour in a dose-related manner.…”

“…It is unclear how this effect would relate to the antipsychotic properties of CBD because usual antipsychotic drugs act by antagonizing dopamine-2 receptors [123]. Moreover, studies with animal models that involve dopaminergic stimulation suggest that the antipsychotic-like doses of CBD (60-120 mg kg 21 ) are higher than those needed to induce anxiolytic-like effects [7,91,92] and reverse behavioural deficits induced by the NMDA receptor antagonist MK-801 [93,94,99]. These findings indicate that the mechanisms of CBD effects on glutamateor dopamine-based models could be at least partially distinct.…”