The legalization and increased use of cannabis has enhanced research interest related to the potential interactions of cannabis use and other psychological conditions. Adults and adolescents often report using cannabis as a way of coping with stress and...

Lesion to the immature peripheral nervous system, such as the transection of a peripheral nerve, results in extensive degeneration of motoneurons and dorsal root ganglia (DRG) sensory neurons, mostly by apoptotic events. We have previously shown that ca...

Nowadays major depression presents a high prevalence in the world population, and it is predicted to increase in the following years. One of the main problems in major depression treatment is that current pharmacological drugs are highly ineffective and...

CB1 cannabinoid receptors are G-protein-coupled receptors that primarily activate Gi/Go. CB1 receptors are abundant in the CNS, where they mediate the effects of psychoactive cannabinoids such as Δ9-tetrahydrocannabinol (THC) and endocannabinoid lipid messengers. Our previous studies have shown that chronic THC administration in mice produces widespread desensitization and downregulation of CB1 receptors in the CNS, with hippocampus exhibiting profound CB1 receptor adaptation. The present study examined the mechanism of CB1 receptor downregulation in brain. THC was administered by subcutaneous injection twice daily using an escalating dosage paradigm in which the dose was ramped from 10 to 160 mg/kg over 15 days. Results showed that CB1 receptor-mediated G-protein activation was reduced by approximately 50% in THC-treated mice compared to control, as determined by agonist-stimulated [35S]GTPγS binding in hippocampal or striatal membranes. CB1 receptor binding sites measured with the antagonist [3H]SR141716...

Cannabis use during critical developmental periods in adolescence can cause long-lasting cognitive impairments and schizophrenia-like symptoms that extend into adulthood. Previous research has demonstrated that chronic delta-9-tetrahydrocannabinol (THC)...

Medical marijuana is most frequently reported to be used for pain relief, however there is a paucity of preclinical studies evaluating the effects of cannabis components in chronic pain models. Anecdotal observations show patients with spinal cord injur...

Previous work in both animal models and humans has demonstrated that exposure to either alcohol or THC, the primary psychoactive component of cannabis, can lead to adverse consequences including deficits in learning, behavioral flexibility, and attentio...

Cannabis has shown therapeutic potential in neuropsychiatric pathologies associated with mood and anxiety. The two main phytochemicals in cannabis, cannabidiol (CBD) and delta9-tetrahydrocannabinol (THC), produce distinct effects on a variety of molecul...

Working memory is an executive function that orchestrates the use of limited amounts of information, referred to as working memory capacity, in cognitive functions. Cannabis exposure impairs working memory in humans; however, it is unclear if Cannabis facilitates or impairs rodent working memory and working memory capacity. The conflicting literature in rodent models may be at least partly due to the use of drug exposure paradigms that do not closely mirror patterns of human Cannabis use. Here, we used an incidental memory capacity paradigm where a novelty preference is assessed after a short delay in spontaneous recognition-based tests. Either object or odor-based stimuli were used in test variations with sets of identical (IST) and different (DST) stimuli (3 or 6) for low- and high-memory loads, respectively. Additionally, we developed a human-machine hybrid behavioral quantification approach which supplements stopwatch-based scoring with supervised machine learning-based classification. After validating...

The nonpsychoactive phytocannabinoid cannabidiol (CBD) has been shown to have analgesic effects in animal studies but little is known about its mechanism of action. We examined the 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 a 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 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 unbin...