Cannabis is the most abused illegal substance in the United States. Alterations in brain function and motor behavior have been reported in chronic cannabis users, but the results have been variable. The current study aimed to determine whether chronic active cannabis use in humans may alter psychomotor function, brain activation, and hypothalamic-pituitary-axis (HPA) function in men and women. Thirty cannabis users (16 men, 14 women, 18–45 years old) and 30 nondrug user controls (16 men, 14 women, 19–44 years old) were evaluated with neuropsychological tests designed to assess motor behavior and with fMRI using a 3 Tesla scanner during a visually paced finger-sequencing task, cued by a flashing checkerboard (at 2 or 4 Hz). Salivary cortisol was measured to assess HPA function. Male, but not female, cannabis users had significantly slower performance on psychomotor speed tests. As a group, cannabis users had greater activation in BA 6 than controls, while controls had greater activation in the visual area B...

Premature delivery occurs in nearly 12% of pregnancies and is a significant cause of morbidity and mortality for infants. Although administration of synthetic glucocorticoids (sGC) in the setting of imminent preterm delivery has led to decreased rates o...

The formation and refinement of thalamocortical axons (TCAs) is an activity-dependent process ([Katz and Shatz, 1996][1]), but its mechanism and nature of activity are elusive. We studied the role of spike timing-dependent plasticity (STDP) in TCA formation and refinement in mice. At birth (postnatal day 0, P0), TCAs invade the cortical plate, from which layers 4 (L4) and L2/3 differentiate at P3-P4. A portion of TCAs transiently reach toward the pia surface around P2-P4 ([Senft and Woolsey, 1991][2]; [Rebsam et al., 2002][3]) but are eventually confined below the border between L2/3 and L4. We previously showed that L4-L2/3 synapses exhibit STDP with only potentiation (timing-dependent long-term potentiation [t-LTP]) during synapse formation, then switch to a Hebbian form of STDP. Here we show that TCA-cortical plate synapses exhibit robust t-LTP in neonates, whose magnitude decreased gradually after P4-P5. After L2/3 is differentiated, TCA-L2/3 gradually switched to STDP with only depression (t-LTD) afte...

As the most widely used illicit substance, cannabis has been implicated as an environmental risk factor for psychosis. Though the relationship between cannabis use and the risk for psychiatric disorders is evolving, the consistent association between ad...

There are currently no effective treatments for traumatic brain injury (TBI) or posttraumatic Stress Disorder (PTSD). As a result, many combat veterans resort to self-treatment with cannabis. The principal components of cannabis include delta1-tetrahydr...

The CB1 cannabinoid receptor is widely distributed in the Central Nervous System and participates in several central functions. The aim of this study was to investigate whether cannabinoid compounds modulate the activity of locus coeruleus (LC) neurons by using single-unit extra-cellular recordings in anaesthetized rats. The cannabinoid agonists WIN 55,212 (31.2-1000 µg/kg, i.v.), CP 55,940 (62.5-1000 µg/kg, i.v.) and Δ9 THC (0.5-6 mg/kg, i.v.) caused a dose-dependent increase of LC neuron firing rate in vagotomized rats with a maximum effect of 79.2±50.4%, 43.7±23.5% and 29.8±10.4% respectively and an order of potency of WIN 55,212>CP 55,940>Δ9 THC. However, when WIN 55,212 (31-66 pmol) was applied locally into the LC there was not changed in the firing rate. On the other hand, the effect of the agonist WIN 55,212 was abolished by pre-treatment (30 min before the experiment) with the antagonist SR 141716A (2 mg/kg i.p.; this dose did not modify the firing rate of the neurons of the LC) whereas pre-treatme...

Cannabis is the most widely used illicit drug in the U.S., with 7% of the population reporting current use and an estimated 9% of cannabis users displaying signs of abuse or dependence (Lopez-Quintero et al., 2011; SAMHSA, 2013). With the high prevalenc...

Cannabis sativa , or marijuana, a popular recreational drug, alters sensory perception and exerts a range of potential medicinal benefits. The present study demonstrates that the endogenous cannabinoid receptor agonists 2-arachidonoylglycerol (2-AG) and anandamide (AEA) activate a canonical cannabinoid receptor in Caenorhabditis elegans and also modulate monoaminergic signaling at multiple levels. 2-AG or AEA inhibit nociception and feeding through a pathway requiring the cannabinoid-like receptor NPR-19. 2-AG or AEA activate NPR-19 directly and cannabinoid-dependent inhibition can be rescued in npr-19 -null animals by the expression of a human cannabinoid receptor, CB1, highlighting the orthology of the receptors. Cannabinoids also modulate nociception and locomotion through an NPR-19-independent pathway requiring an α2A-adrenergic-like octopamine (OA) receptor, OCTR-1, and a 5-HT1A-like serotonin (5-HT) receptor, SER-4, that involves a complex interaction among cannabinoid, octopaminergic, and serotonerg...

Recruitment of release-ready vesicles at synapses is one of the important factors, which determine dynamic properties of signaling between neurons in the brain. It has been shown that the rate of vesicle recruitment is accelerated by strong synaptic activity. An elevated concentration of calcium ions in the presynaptic terminal ([Ca2+]i) has been proposed to be responsible for this effect. However, the precise relationship between [Ca2+]i and recruitment has not been established yet, and the functional consequences of accelerated recruitment during synaptic activity have not been quantified experimentally. To probe the intracellular Ca2+ dependence of vesicle recruitment and to examine its functional role during trains of action potential (AP)-like stimuli, we monitored [Ca2+]i and synaptic responses simultaneously with paired recordings at the calyx of Held synapse. We found that a distinct, rapidly releasing vesicle pool is replenished with a rate that increases linearly with [Ca2+]i, without any apparen...

As reported previously, a single exposure to the cannabinoid CB1 receptor antagonist/inverse agonist rimonabant (SR141716) resulted in impaired milk suckling and severe growth failure. Children with "non-organic failure-to-thrive" (NOFTT) which appears ...