E. Downer and V. Campbell. * Dept. of Physiology, Trinity College Dublin, Ireland. Δ9-Tetrahydrocannabinol (THC), the principle psychoactive component of marijuana, elicits diverse psychological effects in humans. At a cellular level THC has been shown to have both neurotoxic1 and neuroprotective effects2. The aim of this study was to examine the role of the stress activated protein kinase (SAPK) c-jun N-terminal kinase (JNK) in THC-induced neurotoxicity in cortical neurones. Treatment of cultured cortical neurones with THC (5µM) for 2h resulted in a 49% increase in genomic DNA strand breaks as assessed by TUNEL staining (p<0.01, paired t-test, n=10). Use of a fluorogenic assay has revealed that caspase-3 activity is increased from 13±6 pmol AFC produced/mg/min (mean±SEM) to 24±8 pmol AFC produced/mg/min following treatment of neurones with THC for 2h. Western Blot analysis showed that cell death was preceded by JNK activation (p<0.05, ANOVA, n=6). The specific role of JNK in this system was assessed by do...

We previously assessed rCBF following smoking of marijuana and placebo as subjects repeatedly performed the same cognitive task. The task provided a stable cognitive baseline but did not allow assessment of direct vs task-related effects of marijuana. The present doubly-blinded study used PET with [O-15]water to measure rCBF in 12 volunteers who smoked marijuana or placebo cigarettes on 2 occasions at least a week apart. On each occasion subjects were imaged after smoking a marijuana (~20 mg THC) or placebo cigarette while performing 3 auditory tasks; a baseline RT task (also presented before smoking), and dichotic listening tasks with attend-right and attend-left ear instructions. As in our previous studies, smoking marijuana resulted in intoxication (self report), increased rCBF in orbital frontal cortex, anterior cingulate, temporal pole, insula, and cerebellum, and reduced rCBF in auditory and visual cortices. These changes occurred in all 3 tasks and appear to be direct effects of marijuana on rCBF. T...

The physiological and anatomical underpinnings of the acute cognitive effects of cannbinoids in humans are poorly understood. Here, we investigated acute cerebral effects of THC in 12 healthy human volunteers. Subjects received 10 mg oral Δ-9-THC (Marinol) and were tested with saccadic paradigms during a period of peak subjective intoxication and peak plasma levels of THC two hours after intake. Compared to baseline testing, no change in accuracy of reflexive saccades was found. However, memory-guided saccades showed a significant increase in variable tageting errors (gain variability: 0.24 vs. 0.19, p = 0.02) and a significant increase in erroneous anticipatory saccades during the memory delay (12.0% vs. 4.3%, p = 0.01). Likewise, a significant increase in antisaccade errors was found (13.2% vs 5.8%, p = 0.008). For all types of saccades, changes in latencies were subtle. Saccadic peak velocities were unaffected by THC. We conclude that oral Δ-9-THC mainly acts on prefrontal components of the saccadic sys...

Marijuana is one of the most commonly used illicit recreational drugs and is widely used for medicinal purposes. Cannabidiol (CBD) is the major non-psychoactive ingredient in marijuana, whereas δ9-Tetrahydrocannabinol (δ9-THC) is the main psychoactive i...

The primary psychoactive compound of cannabis, ∆9-tetrahydrocannabinol (THC), causes depression of glutamate signaling and functional changes in the brain as a result of its interaction with cannabinoid receptor type 1 (CB1) receptors. Neuroimaging stud...

Cannabidiol (CBD), a biologically active constituent of the cannabis (hemp) plant, has been approved for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. CBD protects against tonic hindl...

Several pharmacological effects of delta-9-tetrahydrocannabinol (THC) are reduced or blocked by administration of opioid antagonists and rewarding or aversive properties of THC are modified in mice lacking opioid receptors. In this study, rats learned to discriminate a 3 mg/kg i.p. injection of THC from an injection of vehicle under a two-lever choice procedure with food reinforcement. We then investigated whether the subjective effects of THC could be blocked or reduced by administration of opioid antagonists and whether opioid agonists could mimic or potentiate THC’s subjective effects. The opioid antagonist naloxone (1 mg/kg, i.p.) produced a small decrease in the discriminative effects of the training dose of 3 mg/kg THC and significantly shifted the THC dose-response curve to the right. When the opioid agonist morphine (1-10 mg/kg, i.p.) was substituted for THC, it did not produce THC-like discriminative effects. However, a 1 mg/kg dose of morphine potentiated the discriminative effects of THC, shifti...

Cannabis is the most frequently used illicit drug in the world with highest consumption occurring in economically developed countries like the United States, especially among adolescents and young adults. Increased legality of cannabis, and therefore av...

Epilepsy is a chronic neurological disorder due to abnormal activity in neuronal circuits and characterized by repeated seizures. It affects 1% of people worldwide and considerably impacts the quality of life of both patients and caregivers. There are c...