Cannabinoids represent a promising class of compounds for developing novel therapeutic agents. Since the isolation and identification of the major psychoactive component Δ(9)-THC in Cannabis sativa in the 1960s, numerous analogues of the classical plant cannabinoids have been synthesized and tested for their biological activity. These compounds primarily target the cannabinoid receptors 1 (CB1)...

Two cannabinoid receptors have been identified to date; one is located predominantly in the central nervous system (CB1), whereas the other is located exclusively in the periphery (CB2). The purposes of this study were to explore further the binding requirements of the CB2 receptor and to search for compounds displaying distinct affinities for either cannabinoid receptor. The binding affinities...

BACKGROUND Systemic administration of cannabinoid agonists is known to reduce pain induced by bladder inflammation and to modulate cystometric parameters in vivo. We have previously reported that intravesical administration of a cannabinoid agonist reduces the electrical activity of bladder afferents under normal conditions. However, the effects of local activation of bladder cannabinoid recept...

Prevalence of non-alcoholic steatohepatitis (NASH) rises steadily in Western countries with the obesity epidemic. NASH is associated with activation of liver fibrogenesis and predisposes to cirrhosis and associated morbi-mortality. The cannabinoid system is increasingly emerging as a crucial mediator of acute and chronic liver injury. Recent experimental and clinical data indicate that peripher...

Previous studies have shown that inhibiting protein synthesis shortly after reactivation impairs the subsequent expression of a previously consolidated fear memory. This has suggested that reactivation returns a memory to a labile state and that protein synthesis is required for the subsequent restabilization of memory. While the molecular mechanisms underlying the restabilization of reactivate...

Marijuana is the most popular illegal drug worldwide. Recent trends indicate that this may soon change; not due to decreased marijuana use, but to an amendment in marijuana's illegal status. The cannabinoid type 1 (CB1) receptor mediates marijuana's psychoactive and reinforcing properties. CB1 receptors are also part of the brain endocannabinoid (eCB) system and support numerous forms of learni...

Recent studies have suggested that cell migratory responses are often mediated by G(i) protein-coupled receptors. Because it is known that CB1 cannabinoid receptors are coupled to pertussis toxin-sensitive G proteins, we proposed that CB1 may mediate cell migration. To test this hypothesis, modified Boyden chamber assays were used to investigate cell migration mediated by CB1 cannabinoid recept...

The effects of CB1 antagonist/inverse agonists on the acquisition and consolidation of conditioned fear remain uncertain. Recent studies suggest that the CB1 antagonist/inverse agonist AM251 affects acquisition or consolidation of both contextual and discretely cued fear memories. AM251 is frequently referred to as a CB1 antagonist; however in vitro signal transduction assays indicate that this...

Cannabinoid compounds have been shown to produce antinociception and antihyperalgesia by acting upon cannabinoid receptors located in both the CNS and the periphery. A potential mechanism by which cannabinoids could inhibit nociception in the periphery is the activation of cannabinoid receptors located on one or more classes of primary nociceptive neurons. To address this hypothesis, we evaluat...

Objective(s) The objective of this study was to evaluate the effect of cannabinoid on cortical spreading depression (CSD) in rat brain. Cannabis has been used for centuries for both symptomatic and prophylactic treatment of different types of headaches including migraine. CSD is believed to be a putative neuronal mechanism underlying migraine aura and subsequent pain. Materials and Methods T...