The effect of cannabinoid receptor ligands including 2-arachidonylglycerol, anandamide, methanandamide, Δ9-THC, WIN 55,212-2 and CP 55,940 on the function of homomeric α7 nicotinic ACh receptors expressed in Xenopus oocytes was investigated using the two-electrode voltage-clamp technique. The endogenous cannabinoid receptor ligands 2-arachidonylglycerol, anandamide and methanandamide inhibited currents evoked with ACh (100 μM). The inhibitory effects of all endogenous ligands tested developed gradually, reaching maximum within 20 to 30 min and was fully reversible following 10 to 30 min of washout. The IC50 values for 2-arachidonylglycerol, anandamide and methanandamide were 110, 218 nM and 103 nM, respectively. In contrast, the synthetic cannabinoid receptor agonists CP 55,940 and WIN 55,212-2, and the active ingredient of marijuana, Δ9-THC, inhibited these currents only at much higher concentrations (1 μM to 100 μM). The inhibition of α7-mediated currents by 2-arachidonylglycerol was non-competitive and ...

The endocannabinoid (eCB) system can mediate anxiolysis, and exogenous cannabinoid agonists (e.g. Δ9-tetrahydrocannabinol) are frequently used for their anxiolytic effects. However, the neural circuits whereby cannabinoids exert these effects remain inc...

Alzheimer disease (AD) is a devastating neurodegenerative disorder with no disease-modifying therapies currently available. Since AD pathology is preceded by inflammation and neural dysfunction, control of these early manifestations has the potential to...

Many people report using cannabis as a way to cope with stress. Acute, low doses of THC have been reported to induce stress relieving effects, which may drive continued use for individuals looking to cope with stress. It is unclear whether heavy cannabi...

Delta-9-tetrahydrocannabinol (Δ9-THC) has profound effects on cognitive functions subserved by the prefrontal cortex (PFC), and exposure to THC has been associated with the appearance or exacerbation of the clinical features of schizophrenia. These actions appear to be mediated via the CB1 receptor, the only cannabinoid receptor expressed in the brain. We therefore investigated the immunocytochemical localization of the CB1 receptor in the macaque monkey and human PFC using antibodies that specifically recognize the C-terminus of the CB1 receptor. In monkeys, intense CB1-immunoreactivity (CB1-IR) was observed primarily in axons and boutons. Compared to most other regions, such as the primary visual cortex (PVC), the overall density of CB1-IR axons was much higher in the PFC. The PFC also exhibited a dense band of CB1-IR axons in layer 4, whereas in PVC layer 4 contained the lowest density of CB1-IR axons. The same regional and laminar distributions of CB1-IR were also present in the human cortex. CB1-IR ax...

Cannabinoids can reduce pain responses in rodents when applied locally to the site of a peripheral inflammation or nerve injury. To induce these effects, cannabinoids may interact directly or indirectly with peripheral sensory nerve terminals to modulate nociceptive transmission from injured areas. Receptors mediating the actions of cannabinoids are expressed by Dorsal Root Ganglion (DRG) neurons and cannabinoids can modulate the functions of DRG neurons in vitro. We used FURA-2 ratiometric calcium imaging and vital staining techniques to investigate the effects of different cannabinoid compounds on intracellular calcium levels [Ca2+]i measured in sub-populations of mouse L3-L5 DRG neurons maintained for 24hr in culture. Drugs were applied through a perfusion system at timed intervals during cell imaging. The cannabinoid Δ9 Tetrahydrocannabinol (THC) applied for 70 seconds at 50µM, produced a >10% increase in baseline calcium levels in 550 cells (n=3 mice). THC response kinetics varied: In 66 ± 9% (mean ± ...

A number of studies have shown that long-term abusers of alcohol, cocaine, heroin, and methamphetamine exhibit impairments on the “Gambling Task,” developed by Bechara and colleagues, which tests the ability to balance immediate rewards against future negative consequences (Petry et al. 1998, Mazas et al. 2000, Grant et al. 2000, Bechara et al. 2001). The purpose of the present study was to determine if similar impairments would be seen in chronic cannabis users. To this end, we compared Gambling Task performance of long-term cannabis users (daily marijuana use for at least 5 years, and the presence of urinary cannabinoids), to controls (no more than 50 life-time marijuana uses, and no urinary cannabinoids). Chronic marijuana users chose significantly more cards from the decks that yielded high immediate gains despite higher future losses (net score = -15.1 ± 36, mean±SEM), as compared to controls (36.5 ± 15). In contrast to Gambling Task performance, no significant differences were observed on the perform...

Following legalization of cannabis in some U.S. states, its use among adults over 50 years of age has increased more than twice as fast as any other age group. This population frequently suffers chronic diseases including type-II diabetes, metabolic syn...

Substance abuse occurs at elevated rates in patients with chronic schizophrenia and a role for cannabis has been suggested in the onset of psychosis, but substance use in populations at high risk for developing psychosis is limited. Here, we aim to eluc...

The recent shift in sociopolitical debates and growing liberalization of cannabis use across the globe has raised concern regarding its impact on vulnerable populations, such as pregnant women and adolescents. Epidemiological studies have long demonstrated a relationship between developmental cannabis exposure and later mental health symptoms. This relationship is especially strong in people with particular genetic polymorphisms, suggesting that cannabis use interacts with genotype to increase mental health risk. Seminal animal research directly linked prenatal and adolescent exposure to delta-9-tetrahydrocannabinol, the major psychoactive component of cannabis, with protracted effects on adult neural systems relevant to psychiatric and substance use disorders. In this article, we discuss some recent advances in understanding the long-term molecular, epigenetic, electrophysiological, and behavioral consequences of prenatal, perinatal, and adolescent exposure to cannabis/delta-9-tetrahydrocannabinol. Insigh...