Cannabis sativa has been used for centuries in treating pain. However, the analgesic role of many of its constituents including the terpenes is unknown. This research examined the contributions of terpenes (volatile oil) and cannabinoids in cannabis-med...

Despite the success of antiretroviral therapy in suppressing viral load, nearly half of the 37 million people infected with HIV experience cognitive and motor impairments, collectively classified as HIV-associated neurocognitive disorders (HAND). In the CNS, HIV-infected microglia release neurotoxic agents that act indirectly to elicit excitotoxic synaptic injury. HIV trans-activator of transcription (Tat) protein is one such neurotoxin that is thought to play a major role in the neuropathogenesis of HAND. The endocannabinoid (eCB) system provides on-demand neuroprotection against excitotoxicity, and exogenous cannabinoids attenuate neurotoxicity in animal models of HAND. Whether this neuroprotective system is altered in the presence of HIV is unknown. Here, we examined the effects of Tat on the eCB system in rat primary hippocampal cultures. Using whole-cell patch-clamp electrophysiology, we measured changes in retrograde eCB signaling following exposure to Tat. Treatment with Tat significantly reduced th...

Recent experimental evidence suggests oppositely directed actions of cannabinoids, promoting either cell survival in models of stroke, parkinson’s disease and multiple sclerosis, or cell death in models of malignant glioma. However the mechanisms through which these compounds control the cell survival/death decision remain to be established. To identify potential mediators of cannabinoid effects, we employed cDNA microarrays to assess changes in gene expression levels following exposure to two different CB1 receptor agonists in mice. A total of 11,000 cDNA clones were selected from a mouse brain cDNA library, amplified by PCR, and arrayed at high density to investigate differential gene expression profiles following acute (12-h) exposure to either Δ9-tetrahydrocannabinol (Δ9-THC) (10 mg/kg i.p.) or WIN 55,212-2 (1 mg/kg i.p.). cDNA microarrays for each treatment were performed in triplicate. Results revealed a total of 75 genes altered by Δ9-THC and 36 genes altered by WIN 55,212-2; of these, 12 were alter...

Dexanabinol is a derivative of the cannabinoid tetrahydrocannabinol (THC). Dexanabinol shares the neuroprotective properties of THC but lacks its psychotropic effects. Several studies have shown anti-inflammatory effects of dexanabinol including inhibition of tumor necrosis factor (TNF)-α expression. The expression of TNF-α and various other mediators of inflammation is regulated by transcription factor NF-κB. NF-κB, an essential transcription factor for many genes, is involved in the pathophysiology of brain damage and is a major regulator of neural cell death. To investigate the effect of dexanabinol on NF-κB activation we have transiently transfected U373 MG cells with a reporter fusion gene under transcriptional control of NF-κB. Stimulation of NF-κB activity by TNFα detected by luciferse assay was inhibited by dexanabinol in a concentration-dependent manner. Activation of NF-κB is known to be due to the degradation of the inhibitor IκBα. Dexanabinol inhibited the TNF-α-induced degradation of IκBα as s...

Cannabis has been used for centuries as an anti-epileptic therapeutic, and non-psychoactive components of cannabis have reduced seizure activity in both pre-clinical animal models and recent clinical trials (Devinsky et al. 2015). However, the exact mec...

The present study extends the link between food intake and cannabinoid substances, specifically two cannabinoid antagonists AM 630 and AM 281. Previous studies from our lab have focused on the stimulatory effects of delta9-tetrahydrocannabinol (THC) in Lewis rats (SFN abstract 847.18, 1998 and SFN abstract 749.17, 1999), which are responsive to appetite-stimulating effects of THC alone and when combined with lateral hypothalamic stimulation (Trojinar & Wise, 1991). The current research examined the potential of cannabinoid antatonists to affect food intake induced by food deprivation. Following establishment of baseline deprivation-induced chow intake (deprivation was 12 h overnight) male Lewis rats (N=20) were divided into two groups of 10, each of which received intracerebroventricular (i.c.v ) injections of either AM 630 or AM 281 at doses of 0 (veh = 4% DMSO) 2.5, 5, 10 and 20 ug (all in 10 ul volumes) following overnight food deprivation. Food intake was measured at 0.5, 1, 2, 4 & 6h following injecti...

Cannabinoid receptor 1 (CB1R) has strong effects on neurogenesis and axon pathfinding in the prenatal brain. Endocannabinoids that activate CB1R are abundant in the early postnatal brain and in mother’s milk, but few studies have investigated their function in newborns. We examined postnatal CB1R expression in the major striatonigral circuit from striosomes of the striatum to the dopamine-containing neurons of the substantia nigra. CB1R enrichment was first detectable between postnatal days 5 and 7, and this timing coincided with the formation of ‘striosome-dendron bouquets’, the elaborate anatomical structures by which striosomal neurons control dopaminergic cell activity through inhibitory synapses. In Cnr1−/− knockouts lacking CB1R expression, striosome-dendron bouquets were markedly disorganized by postnatal day 11 and at adulthood, suggesting a postnatal pathfinding connectivity function for CB1R in connecting striosomal axons and dopaminergic neurons analogous to CB1R’s prenatal function in other bra...

Cannabis is becoming increasingly prevalent in society, with legalization occurring globally at rapid rates. Cannabis impairs decision making and can lead to addiction, particularly when exposure occurs chronically. This impairment can be quantified usi...

The use of cannabis sativa preparations as recreational drugs can be traced back to the earliest civilizations. However, animal models of cannabinoid addiction allowing the exploration of neural correlates of cannabinoid abuse have been developed only recently. We review these models and the role of the CB1 cannabinoid receptor, the main target of natural cannabinoids, and its interaction with opioid and dopamine transmission in reward circuits. Extensive reviews on the molecular basis of cannabinoid action are available elsewhere ([Piomelli et al., 2000][1];[Schlicker and Kathmann, 2001][2]). [1]: #ref-36 [2]: #ref-43

Pathological tau aggregates occur in Alzheimer’s disease (AD) and other neurodegenerative tauopathies. It is not clearly understood why tauopathies vary greatly in the neuroanatomical and histopathological patterns of tau aggregation, which may contribu...