A behavioural comparison of acute and chronic Δ9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice

Abstract

Cannabis contains over 70 unique compounds and its abuse is linked to an increased risk of developing schizophrenia. The behavioural profiles of the psychotropic cannabis constituent Delta9-tetrahydrocannabinol (Delta9-THC) and the non-psychotomimetic constituent cannabidiol (CBD) were investigated with a battery of behavioural tests relevant to anxiety and positive, negative and cognitive symptoms of schizophrenia. Male adult C57BL/6JArc mice were given 21 daily intraperitoneal injections of vehicle, Delta9-THC (0.3, 1, 3 or 10 mg/kg) or CBD (1, 5, 10 or 50 mg/kg). Delta9-THC produced the classic cannabinoid CB1 receptor-mediated tetrad of hypolocomotion, analgesia, catalepsy and hypothermia while CBD had modest hyperthermic effects. While sedative at this dose, Delta9-THC (10 mg/kg) produced locomotor-independent anxiogenic effects in the open-field and light-dark tests. Chronic CBD produced moderate anxiolytic-like effects in the open-field test at 50 mg/kg and in the light-dark test at a low dose (1 mg/kg). Acute and chronic Delta9-THC (10 mg/kg) decreased the startle response while CBD had no effect. Prepulse inhibition was increased by acute treatment with Delta9-THC (0.3, 3 and 10 mg/kg) or CBD (1, 5 and 50 mg/kg) and by chronic CBD (1 mg/kg). Chronic CBD (50 mg/kg) attenuated dexamphetamine (5 mg/kg)-induced hyperlocomotion, suggesting an antipsychotic-like action for this cannabinoid. Chronic Delta9-THC decreased locomotor activity before and after dexamphetamine administration suggesting functional antagonism of the locomotor stimulant effect. These data provide the first evidence of anxiolytic- and antipsychotic-like effects of chronic but not acute CBD in C57BL/6JArc mice, extending findings from acute studies in other inbred mouse strains and rats.

Increased Sensorimotor Gating in Recreational and Dependent Cocaine Users Is Modulated by Craving and Attention-Deficit/Hyperactivity Disorder Symptoms

“…In previous studies, cannabis use did not show significant effects on PPI at least passive attention paradigms just as used here (40,75,76). However, controls with positive cannabis urine toxicology showed a slight even though non-significant increase of PPI, which is in line with several animal studies observing that acute administration of cannabinoid-1 receptor agonists increase PPI (77,78). However, controls and cocaine users with negative cannabis urine samples still significantly differed, indicating that our result can not be explained by cannabis co-use (Figure 2).…”

Cannabidiol as a Potential Treatment for Anxiety Disorders

“…Campos et al [66] showed that in rat, CBD treatment for 21 days attenuated inhibitory avoidance acquisition [83]. Long et al [69] showed that, in mouse, CBD produced moderate anxiolytic effects in some paradigms, with no effects in others.…”

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

“…For example, CBD was shown to prevent cocaine-induced hepatotoxicity [52], reverse binge ethanol-induced neurotoxicity [53], and even mitigate the cardiac effects of THC [54,55]. In addition, CBD administration is known to attenuate amphetamine-induced hyperlocomotion [56].…”