Cannabis is the most used psychoactive drugs with an estimates 125-227 million consumers all over the world. The most powerful component of cannabis is the Δ9- Tetrahydrocannabinol (Δ9-THC), which acts as agonist on cannabinoid receptor 1 (CB1R) modulat...

Effective treatment for amyotrophic lateral sclerosis (ALS) remains elusive. Two of the primary hypotheses underlying motor neuron vulnerability are susceptibility to excitotoxicity and oxidative damage. We have found that delta-9-tetrahydrocannabinol (THC) inhibits both excitotoxic and oxidative damage in spinal cord cultures and slows progression and improves survival in the ALS mouse model (hSODG93A transgenic mice) even when administered after onset of disease signs. Mice were treated daily beginning on day 75 (when tremors were first observed) with 20 mg/kg THC or with 40 mg/kg cannabidiol i.p. or with vehicle. Treatment with THC resulted in a 7 day extension of survival. There was a trend toward increased survival in female mice treated with cannabidiol, but this did not reach statistical significance. Male mice showed no improvement with cannabidiol. Female mice lived significantly longer than male mice. We present an improved method for the analysis of disease progression in the ALS mouse model. Th...

Cannabidiol (CBD), the non-psychoactive component of cannabis, has received increased attention as a potential therapy for treatment-resistant epilepsy. Cannabinoids have beneficial effects in multiple animal models of seizure, ischemia, and traumatic b...

Cannabis and its chemical constituent that is responsible for the majority of its psychoactive effects, Tetrahydrocannabinol (THC), is the most commonly used illicit substance in the United States. With state laws and regulations undergoing changes in t...

Chronic adolescent exposure to Δ-9-Tetrahydrocannabinol (THC) is linked to elevated neuropsychiatric risk and induces neuronal, molecular and behavioural abnormalities resembling neuropsychiatric endophenotypes. Previous evidence has revealed that the mesocorticolimbic circuitry, including the prefrontal cortex (PFC) and mesolimbic dopamine (DA) pathway are particularly susceptible to THC-induced pathological alterations, including dysregulation of DAergic activity states, loss of PFC GABAergic inhibitory control and affective and cognitive abnormalities. There are currently limited pharmacological intervention strategies capable of preventing THC-induced neuropathological adaptations. L-theanine is an amino acid analogue of L-glutamate and L-glutamine derived from various plant sources, including green tea leaves. L-theanine has previously been shown to modulate levels of GABA, DA and glutamate in various neural regions and to possess neuroprotective properties. Using a pre-clinical model of adolescent TH...

5-HT3 receptor agonists produce vomiting in the least shrew whereas 5-HT2A agonists induce the head-twitch response (HTR) in this species. Both behaviors were induced by the 5-HT precursor 5-hydroxytryptophan (5-HTP) in the absence and presence of a peripheral decarboxylase inhibitor, carbidopa (10 mg/kg). The aim of this study was to investigate: 1) whether Δ9-THC can prevent the induced behaviors, and 2) if the inhibitory effects are CB1 receptor-mediated. 5-HTP (0, 10, 50 and 100 mg/kg, i.p.) increased the frequencies of vomiting and HTR in shrews in a dose-dependent manner both in the absence and presence of carbidopa. However, in the presence of carbidopa the number of HTRs produced were 2-6.5 fold greater whereas the frequency of observed vomiting tended to be less. Two doses of 5-HTP (50 and 100 mg/kg) were chosen to determine the inhibitory action of Δ9-THC (1, 2.5, 5, 10 and 20 mg/kg) on the induced behaviors in the absence and presence of carbidopa. Lower doses of Δ9-THC were required to signific...

The effect of cannabinoids on calcium transients and the cell viability in astrocyte culture were studied. Both THC and Win 55,212-2 (WIN) induced decrease in the cell viability and raised [Ca2+]i in a dose-dependent manner. Threshold concentration was 1 and 10 μM, respectively. Cannabinoids (10 μM) produced a biphasic response in [Ca2+]i; a rapid change in [Ca2+]i was followed by a slow/delayed irreversible increase in [Ca2+]i. The delayed, irreversible calcium elevation was accompanied with the cell loss at the end of the experiment. Exposure of the cultures to 2.5 μM THC in duration of 24 hours produced a massive disintegration in astrocyte cultures. SR-141716A, a CB1 receptor antagonist blocked both THC stimulatory effects on Ca2+ transients and THC-induced astrotoxicity. PTX pretreatment abrogated THC toxic effect pointing to the role of Gi protein in signaling mechanism. PKC and ERK kinase inhibitors significantly (p<0.001,n=8) protected astrocytes against THC toxicity. Actinomycin D, an inhibitor of...

In previous studies, we found that THC and capsaicin can protect AF5 cells from NMDA-induced cell toxicity, an effect apparently related to antioxidant properties of these compounds (Chen J, et al., in preparation). We have investigated the signaling pathways involved in neuroprotection against NMDA-induced toxicity mediated by THC and capsaicin in AF5 cells. Gene expression profiles were studied using a mouse developmental cDNA microarray. Expression of the 14-3-3 transcript was altered after exposure to NMDA alone, NMDA plus cannabinoids, or capsaicin. The 14-3-3 transcript was decreased by 2.14-fold after exposure to 7.5 mM NMDA as compared to the untreated control condition, while THC increased 14-3-3 expression by 3.08 fold as compared to NMDA alone. Capsaicin also significantly increased the 14-3-3 transcript, but to a smaller degree than THC. WIN55,212 produced no significant change. Changes in 14-3-3 expression measured by Q-PCR were consistent with those obtained using microarrays. The 14-3-3 prot...

Cannabis is the most widely used illicit drug in the US, and cannabis use among young adults continues to rise. Previous studies have shown that chronic systemic administration of delta 9-tetrahydrocannabinol (THC), the main psychoactive component of ca...

The biochemical substrates underlying rewarding effects of Δ9-tetrahydrocannabinol (THC) are poorly understood. We analyzed intracellular signaling pathways mediating immediate early gene expression (c-Fos and Zif 268) after acute administration of THC in striatal neurons. In male CD1 mouse brain, immunohistochemical detection of phosphorylated ERK/MAPK proteins showed a progressive but transient activation of this pathway in the striatum. Activation of ERK occurred in both striatal neurons and the neuropil surrounding these activated neurons, suggesting a pre- and post-synaptic activation of this signaling pathway. A systemic injection of a specific inhibitor of ERK/MAPK (SL 327) prevented THC-induced expression of c-Fos and Zif 268. As previous reports show that THC induces DA release in the striatum, we then analyzed whether DA transmission played a role in these molecular events. We found that injection of a selective antagonist of DA-D1 receptors (SCH 23390), prior to THC administration, prevented ERK...