Abstract Epilepsy is one of the most common neurological conditions worldwide. Cannabinoids, particularly cannabidiol (CBD) and tetrahydrocannabinol (THC), have demonstrated therapeutic potential in the treatment of epilepsy due to their interaction with the endocannabinoids system. Despite these developments, the use of medical cannabis is still complicated because of legal obstacles, the different psychoactive effects of different cannabinoid receptors, and concerns about long-term safety, especially in populations with young children. The development of new regulations will be essential to increasing access to patients' cannabis medications. Cannabis has the potential to change the therapeutic landscape for neurological illnesses like seizures, provided that science and regulation continue...

Abstract Background Phytocannabinoids inhibit the aggregation and neurotoxicity of the neurotoxic Alzheimer's disease protein β amyloid (Aβ). We characterised the capacity of five proprietary medical cannabis extracts, heated and non-heated, with varying ratios of cannabidiol and Δ9-tetrahydrocannabinol and their parent carboxylated compounds to protect against lipid peroxidation and Aβ-evoked neurotoxicity in PC12 cells. Methods Neuroprotection against lipid peroxidation and Aβ1–42-induced cytotoxicity was assessed using the thiazolyl blue tetrazolium bromide (MTT) assay. Transmission electron microscopy was used to visualise phytocannabinoid effects on Aβ1–42 aggregation and fluorescence microscopy. Results Tetrahydrocannabinol (THC)/tetrahydrocannabinolic acid (THCA)-predominant cannabis extracts demonstrated the most significant overall neuroprotection against Aβ1–42-induced loss of PC12 cell...

Abstract Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds-cannabinoids, terpenes, and flavonoids. While major cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential. This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis's bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis's sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and...

Abstract Phytocannabinoids protect neurons against stressful conditions, possibly via the heme oxygenase (HO) system. In cultures of primary mesencephalic neurons and neuroblastoma cells, we determined the capability of cannabidiol (CBD) and tetrahydrocannabinol (THC) to counteract effects elicited by complex I-inhibitor rotenone by analyzing neuron viability, morphology, gene expression of IL6, CHOP, XBP1, HO-1 (stress response), and HO-2, and in vitro HO activity. Incubation with rotenone led to a moderate stress response but massive degeneration of dopaminergic neurons (DN) in primary mesencephalic cultures. Both phytocannabinoids inhibited in-vitro HO activity, with CBD being more potent. Inhibition of the enzyme reaction was not restricted to neuronal cells...

Abstract Delta-9-Tetrahydrocannabinol and other phytocannabinoids have been previously demonstrated to possess neuroprotective effects in murine mesencephalic cell culture models of Parkinson’s disease, in which increased levels of superoxide radicals led to the loss of dopaminergic neurons. In these models, delta-9-tetrahydrocannabinol did not scavenge these radicals but displayed antioxidative capacity by increasing glutathione levels. Based on these findings, in the present study, we investigated whether the neuroprotective effect of delta-9-tetrahydrocannabinol can also be detected in FeSO4- and H2O2-stressed cells. Mesencephalic cultures were concomitantly treated with FeSO4 (350 μM) or H2O2 (150 μM) and delta-9-tetrahydrocannabinol (0.01, 0.1, 1, 10 μM) on the 12th days in vitro for 48 h. On the 14th DIV, dopaminergic neurons...

Abstract Δ9-Tetrahydrocannabinol (THC), the main bioactive compound found in the plant Cannabis sativa, exerts its effects by activating cannabinoid receptors present in many neural cells. Cannabinoid receptors are also physiologically engaged by endogenous cannabinoid compounds, the so-called endocannabinoids. Specifically, the endocannabinoid 2-arachidonoylglycerol has been highlighted as an important modulator of oligodendrocyte (OL) development at embryonic stages and in animal models of demyelination. However, the potential impact of THC exposure on OL lineage progression during the critical periods of postnatal myelination has never been explored. Here, we show that acute THC administration at early postnatal ages in mice enhanced OL development and CNS myelination in...

Abstract Background and purpose Research on demyelinating disorders aims to find novel molecules that are able to induce oligodendrocyte precursor cell differentiation to promote central nervous system remyelination and functional recovery. Δ9-Tetrahydrocannabinol (THC), the most prominent active constituent of the hemp plant Cannabis sativa, confers neuroprotection in animal models of demyelination. However, the possible effect of THC on myelin repair has never been studied. Experimental approach By using oligodendroglia-specific reporter mouse lines in combination with two models of toxin-induced demyelination, we analysed the effect of THC on the processes of oligodendrocyte regeneration and functional remyelination. Key results We show that THC administration enhanced oligodendrocyte...

Abstract (1) Background: Over the past 10 years, a number of scientific studies have demonstrated the therapeutic potential of cannabinoid compounds present in the Cannabis Sativa and Indica plants. However, their role in mechanisms leading to neurodegeneration following cerebral ischemia is yet unclear. (2) Methods: We investigated the effects of Cannabis extracts (Bedrocan, FM2) or selected cannabinoids (Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol) in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD), an in vitro model of forebrain global ischemia. Cell death in the CA1 subregion of slices was quantified by propidium iodide fluorescence, and morphological analysis and tissue organization were examined by...

Please use this link to access this publication. Abstract Neonatal rat sciatic nerve crush mimics obstetric axonotmesis, leading to extensive loss of motor and sensory neurons. The present study aimed to investigate the neuroprotective potential of cannabidiol (CBD) and the role of cannabinoid receptors after sciatic nerve crush in neonatal rats. For that, two-day-old Wistar rats were used, organized into the following experimental groups: sciatic nerve crush plus CBD treatment (CBD), crush plus vehicle treatment (VE), crush + CBD + AM251 treatment (AM251 – CB1 inverse agonist), crush + CBD + AM630 treatment (AM630 – CB2 antagonist). Spinal motoneuron survival was evaluated by Nissl...

Abstract Each year, more than two million babies die or evolve to permanent invalidating sequelae worldwide because of Hypoxic-Ischemic Brain Injury (HIBI). There is no current treatment for that condition except for therapeutic hypothermia, which benefits only a select group of newborns. Preclinical studies offer solid evidence of the neuroprotective effects of Cannabidiol (CBD) when administered after diffuse or focal HI insults to newborn pigs and rodents. Such effects are observable in the short and long term as demonstrated by functional, neuroimaging, histologic and biochemical studies, and are related to the modulation of excitotoxicity, inflammation and oxidative stress—the major components of HIBI pathophysiology. CBD...