As it is the case worldwide, marijuana (cannabis) use in the United States and Canada is highly prevalent and societal views of its use are changing rapidly, as are the policies that govern the legality of its recreational and medical use. With the rece...

Marijuana (MJ) is one of the most commonly used drugs among adolescents with an estimated 1.6 million adolescents between the ages of 12 to 17 reporting past month MJ use. Chronic MJ use has been associated with altered neurodevelopmental and behavioral...

Cyclin-dependent-kinase-like 5 (CDKL5) mutation and loss of function result in a range of autistic-like behaviors, neurodevelopmental deficits, and often refractory seizures. Recent clinical studies with cannabidiol have shown efficacy in suppressing se...

Cannabidiol (CBD) is reported to have therapeutic potential for psychiatric conditions that affect learning and memory, including anxiety and post-traumatic stress disorders. Pre-clinical contextual fear-learning and memory experiments in rodents have c...

Cannabis produces complex psychotropic effects across various brain circuits. Previous research in our laboratory has demonstrated that the two major phytocannabinoids in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) produce highly ...

The non-psychoactive phytocannabinoid cannabidiol (CBD) has been shown to have analgesic effects in animal studies but little is known about its mechanism of action. We examined effects of CBD on intrinsic excitability of primary pain-sensing neurons. Studying acutely-dissociated capsaicin-sensitive mouse DRG neurons at 37°C, we found that CBD effectively inhibited repetitive action potential firing, from 15-20 action potentials evoked by 1-s current injections in control to 1-3 action potentials with 2 μM CBD. Reduction of repetitive firing was accompanied by reduction of action potential height, widening of action potentials, reduction of the afterhyperpolarization, and increased propensity to enter depolarization block. Voltage clamp experiments showed that CBD inhibited both TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) sodium currents in a use-dependent manner. CBD showed strong state-dependent inhibition of TTX-R channels, with fast binding to inactivated channels during depolarizations and slow un...

Spinal cord injuries (SCI) are commonly associated with motor paralysis, but most people with spinal cord injury also develop involuntary muscle contractions that can severely interfere with function. Spinal cord injuries disrupt messages between the br...

Alcohol dependence is a chronic relapsing disorder of compulsive alcohol seeking and use. Cannabidiol- a major non-psychoactive component of cannabis sativa- has long received attention for its therapeutic potential against a variety of neuropsychiatric...

A major challenge for successful treatment of cocaine addiction is to effectively reduce both chronic cocaine intake and long-lasting susceptibility to relapse. Various medications to treat cocaine addiction are currently in use, but with largely unimpr...

Chronic exposure to Δ9-tetrahydrocannabinol (THC) induces tolerance to cannabinoid-induced locomotor effects, which are mediated by cannabinoid receptors (CB1Rs) located in motor control regions, including the cerebellum. There is substantial evidence of cerebellar CB1R molecular adaptation and modifications in receptor signaling after prolonged cannabinoid exposure. However, very little is known about the effects of chronic cannabinoid administration on cerebellar synaptic plasticity, which may contribute to the development of cannabinoid behavioral tolerance. In the cerebellar cortex, activation of CB1R inhibits excitatory synaptic transmission at parallel fiber (PF)–Purkinje cell (PC) synapses by decreasing neurotransmitter release. Our study aimed to investigate the neurophysiological adaptive responses occurring at cerebellar PF-PC cell synapses after repeated THC exposure. In THC-tolerant mice, an increase of the basal release probability was found at PF-PC synapses, in parallel with a facilitation ...