Schizophrenia-related psychosis is associated with disturbances in mesolimbic dopamine (DA) transmission, characterized by hyperdopaminergic activity in the mesolimbic pathway. Currently, the only clinically effective treatment for schizophrenia involves the use of antipsychotic medications that block DA receptor transmission. However, these medications produce serious side effects leading to poor compliance and treatment outcomes. Emerging evidence points to the involvement of a specific phytochemical component of marijuana called cannabidiol (CBD), which possesses promising therapeutic properties for the treatment of schizophrenia-related psychoses. However, the neuronal and molecular mechanisms through which CBD may exert these effects are entirely unknown. We used amphetamine (AMPH)-induced sensitization and sensorimotor gating in rats, two preclinical procedures relevant to schizophrenia-related psychopathology, combined with in vivo single-unit neuronal electrophysiology recordings in the ventral teg...

Background: The active principal of cannabis known as 9 α -Tetrahydrocannabinol (THC) binds to cannabinoid (CB) receptors, which are classified into CB1 and CB2 subtypes. These belong to the G-protein coupled receptor family. Cannabis has a prominent an...

Abuse of Δ-9-tetrahydrocannabinol (THC), the major psychoactive ingredient of marijuana, induces persistent cognitive deficits (especially of memory and attention) reminiscent of prefrontal cortical dysfunction in humans. Dopamine and acetylcholine are critical transmitters in the memory and attentional processes of the prefrontal cortex. Preliminary findings from our lab suggest that repeated administration of THC to rats reduces frontal cortical dopamine turnover. Given that these alterations of cortical dopamine may be related to the cognitive deficits induced by chronic THC exposure, we extended the findings on dopamine turnover. Furthermore, we utilized in vivo microdialysis to assess the consequences of chronic exposure to cannabinoid agonists on basal and evoked acetylcholine release in the rat prefrontal cortex. Chronic exposure to THC or WIN 55,212-2 (10 mg/kg, twice daily for 7 or 14 days) caused a selective and persistent reduction in medial prefrontal cortical dopamine turnover and basal extrac...

The cannabinoid (CB) system is a key neurochemical mediator of anxiety and fear learning in both animals and humans. The anxiolytic effects of Δ9-tetrahydrocannabinol (THC), the primary psychoactive ingredient in cannabis, are believed to be mediated through direct and selective agonism of CB1 receptors localized within the basolateral amygdala, a critical brain region for threat perception. However, little is known about the effects of THC on amygdala reactivity in humans. We used functional magnetic resonance imaging and a well validated task to probe amygdala responses to threat signals in 16 healthy, recreational cannabis users after a double-blind crossover administration of THC or placebo. We found that THC significantly reduced amygdala reactivity to social signals of threat but did not affect activity in primary visual and motor cortex. The current findings fit well with the notion that THC and other cannabinoids may have an anxiolytic role in central mechanisms of fear behaviors and provide a rati...

The cannabinoids R-(+)-methanandamide (mAEA) and (-)-Δ9-tetrahydrocannabinol (THC) have been suggested to exert direct effects on nociceptive primary afferents by activating cannabinoid (CB1) receptors at low and vanilloid (TRPV1) receptors at higher concentrations. We studied pretreatment (5 min) effects of both compounds on capsaicin, noxious heat and potassium responses of isolated hindpaw skin of rats and transgenic mice measuring stimulated iCGRP release (EIA). Both compounds 0.1 µM showed significant desensitizations to capsaicin and heat by 42% and 32%, respectively, which were absent in CB1-/- and unchanged in TRPV1-/- mice. Concentrations >1 µM exhibited concentration-dependent intrinsic effects (mAEA>THC) which culminated at 100 µM in marked cross-desensitization to capsaicin and heat, absent in TRPV1-/- (using THC) and unchanged in CB1-/- (using both compounds). At 1 µM THC showed a small inhibitory and mAEA no effect, suggesting a balance between CB1 and TRPV1 actions. At 10 µM both compounds c...

Acute and repeated administration of delta9-tetrahydrocannabinol (THC), the principal psychoactive constituent of Cannabis sativa, is associated with the modulation of motor and emotional behaviours. These effects frequently correlate with altered neuro...

Δ9-tetrahydrocannabinol (THC), the principle psychoactive ingredient of cannabis, and related plant-derived and synthetic compounds produce a variety of biological effects. Among these are their therapeutically valuable anti-tumoral actions, especially ...

Many neurodegenerative diseases are associated with chronic inflammation and invasive therapies such as neuronal transplantation are often hampered by immune mediated inflammatory processes. Both nicotine and Δ9-tetrahydrocannabinol (THC) are well known...

In a national survey on drug use, about 7.4% of persons aged 12-17 years reported using marijuana in the past month. Additionally, use is on the rise despite knowledge that chronic adolescent marijuana exposure leads to a host of neurobiological and beh...

Recent evidence suggests that CB1 knockout mice display impaired extinction of Pavlovian fear conditioning. We explored the potential of low doses of the two principle components of marijuana, the psychoactive cannabinoid, delta-9-tetrahydrocannabinol (THC), and the non-psychoactive cannabinoid, cannibidiol (CBD), to modulate the extinction of amphetamine- and cocaine-induced place preference learning. Both cannabinoids potentiated extinction of place conditioning without producing conditioning on their own. At the doses employed neither drug modified the establishment or the expression of amphetamine-induced place preference learning. Our results support previous reports that the endogenous cannabinoid system plays a role in the modulation of extinction.