The non-psychoactive phytocannabinoid cannabidiol (CBD) has been shown to have analgesic effects in animal studies but little is known about its mechanism of action. We examined effects of CBD on intrinsic excitability of primary pain-sensing neurons. Studying acutely-dissociated capsaicin-sensitive mouse DRG neurons at 37°C, we found that CBD effectively inhibited repetitive action potential firing, from 15-20 action potentials evoked by 1-s current injections in control to 1-3 action potentials with 2 μM CBD. Reduction of repetitive firing was accompanied by reduction of action potential height, widening of action potentials, reduction of the afterhyperpolarization, and increased propensity to enter depolarization block. Voltage clamp experiments showed that CBD inhibited both TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) sodium currents in a use-dependent manner. CBD showed strong state-dependent inhibition of TTX-R channels, with fast binding to inactivated channels during depolarizations and slow un...

A major challenge for successful treatment of cocaine addiction is to effectively reduce both chronic cocaine intake and long-lasting susceptibility to relapse. Various medications to treat cocaine addiction are currently in use, but with largely unimpr...

Spinal cord injuries (SCI) are commonly associated with motor paralysis, but most people with spinal cord injury also develop involuntary muscle contractions that can severely interfere with function. Spinal cord injuries disrupt messages between the br...

Alcohol dependence is a chronic relapsing disorder of compulsive alcohol seeking and use. Cannabidiol- a major non-psychoactive component of cannabis sativa- has long received attention for its therapeutic potential against a variety of neuropsychiatric...

Marijuana (Cannabis sativa) is widely used and can produce dependence as evidenced by withdrawal symptoms upon discontinuation of use. In order to examine tolerance and dependence to the main psychoactive component in marijuana (Δ9-tetrahydrocannabinol, Δ9-THC), the cannabinoid antagonist SR 141716A has been established as a discriminative stimulus in rhesus monkeys treated with 0.56 mg/kg/day of Δ9-THC. Other dependent measures, including directly observable (e.g. eye closing and head shaking) and physiological measures (e.g. body temperature), were assessed in this study to establish whether tolerance and dependence developed to Δ9-THC in the same monkeys (n = 4) that discriminate SR 141716A compared to another group of monkeys (n = 4) that had not received daily Δ9-THC. Acute Δ9-THC (0.56 mg/kg) increased eye closing and decreased body temperature in all monkeys (-1.0 ± 0.2 oC), and these effects were significantly greater in untreated monkeys compared to Δ9-THC-treated monkeys. SR 141716A (3.2 mg/kg) a...

We have recently confirmed an association between the Tau H1 haplotype and clinically defined Parkinson’s Disease (PD) in the Norwegian population. In this further extended case-control series, we present systematic association and linkage disequilibrium analyses using Single Nucleotide Polymorphisms spanning the Tau gene. Strong disequilibrium in PD cases implicates an intragenic region likely to contain variants attributing to increased risk of PD, Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD).

In adult humans, cannabis use is associated with short-term impairments in memory (Jacobus et al., 2009). However, the enduring effects of cannabis use on mnemonic function are not well understood. Animal models are crucial to understanding the potentia...

Pain involves different brain regions and is critically determined by emotional processing. Among other areas, the rostral anterior cingulate cortex (rACC) is implicated in the processing of affective pain. Drugs that interfere with the endocannabinoid ...

Marijuana is the most widely used illicit drug in the world. Yet when the rewarding properties of the primary psychoactive constituent of the drug, delta-9-tetrahydrocannabinol (THC) have been directly tested in rodent taste and place conditioning parad...

The ventral tegmental area is necessary for reward behavior where dopamine cells are critical for reward motivated behavior and attaching salience to novel rewarding stimuli. These dopamine cells are regulated by neighboring inhibitory GABA cells. Synap...