Modulation of CB1 cannabinoid receptor alters the electrophysiological properties of cerebellar Purkinje cells in harmaline-induced essential tremor.

Essential tremor (ET) is one of the most common motor disorders with debilitating effects on the affected individuals. The endocannabinoid system is widely involved in cerebellar signaling. Therefore, modulation of cannabinoid-1 receptors (CB1Rs) has emerged as a novel target for motor disorders. In this study, we aimed to assess whether modulation of cannabinoid receptors (CBRs) could alter the electrophysiological properties of Purkinje cells (PCs) in the harmaline-induced ET model. Male Wistar rats were assigned to control, harmaline (30 mg/kg), CBR agonist WIN 55,212-2 (WIN; 1 mg/kg), CB1R antagonists AM251 (1 mg/kg) and rimonabant (10 mg/kg). Spontaneous activity and positive and negative evoked potentials of PCs were evaluated using whole-cell patch clamp recording. Findings demonstrated that harmaline exposure induced alterations in the spontaneous and evoked firing behavior of PCs, as evidenced by a significant decrease in the mean number of spikes and half-width of action potential in spontaneous activity. WIN administration exacerbated the electrophysiological function of PCs, particularly in the spontaneous activity of PCs. However, CB1R antagonists provided protective effects against harmaline-induced electrophysiological changes in the spontaneous activity of PCs. Our findings reinforce the pivotal role of the endocannabinoid system in the underlying electrophysiological mechanisms of cerebellar disorders and suggest that antagonism of CB1R might provide therapeutic utility.

Unraveling the protective effects of curcumin against drugs of abuse.

Curcumin, a natural compound derived from the turmeric plant (Curcuma longa), has garnered significant attention for its diverse neuroprotective properties. Curcumin has been widely recognized for its remarkable anti-inflammatory, antioxidant, and anti-apoptotic effects, which have shown great potential in the treatment of various disorders, encompassing psychiatric and neurodegenerative diseases. In this review, we delve into the protective effects of curcumin against drugs of abuse, including morphine, methamphetamine, cocaine, nicotine, and alcohol, with a particular focus on the underlying mechanisms from a neuroscience perspective. Overall, curcumin demonstrates promising effects against the neurotoxicity induced by abused drugs through a wide range of mechanisms. These include the modulation of inflammatory cytokines, maintenance of ion homeostasis, epigenetic regulation, enhancement of antioxidant capacity, as well as the activation of the cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) signaling pathways. These findings suggest that curcumin emerges as a promising therapeutic agent in combatting the detrimental effects induced by drugs of abuse, and further research is warranted to fully comprehend the molecular pathways and optimize its utilization for the prevention and treatment of substance abuse-related neurotoxicity.

The Therapeutic Potential and Molecular Mechanisms Underlying the Neuroprotective Effects of Sativex® - A Cannabis-derived Spray.

Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants. Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders. The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.

Cannabis during pregnancy: A way to transfer an impairment to later life.

Epidemiological studies examining the influence of cannabis across the lifespan show that exposure to cannabis during gestation or during the perinatal period is associated with later-life mental health issues that manifest during childhood, adolescence, and adulthood. The risk of later-life negative outcomes following early exposure is particularly high in persons who have specific genetic variants, implying that cannabis usage interacts with genetics to heighten mental health risks. Prenatal and perinatal exposure to psychoactive components has been shown in animal research to be associated with long-term effects on neural systems relevant to psychiatric and substance use disorders. The long-term molecular, epigenetic, electrophysiological, and behavioral consequences of prenatal and perinatal exposure to cannabis are discussed in this article. Animal and human studies, as well as in vivo neuroimaging methods, are used to provide insights into the changes induced in the brain by cannabis. Here, based on the literature from both animal models and humans, it can be concluded that prenatal cannabis exposure alters the developmental route of several neuronal regions with correlated functional consequences evidenced as changes in social behavior and executive functions throughout life.