Cannabis constituents for chronic neuropathic pain; reconciling the clinical and animal evidence.

Chronic neuropathic pain is a debilitating pain syndrome caused by damage to the nervous system that is poorly served by current medications. Given these problems, clinical studies have pursued extracts of the plant Cannabis sativa as alternative treatments for this condition. The vast majority of these studies have examined cannabinoids which contain the psychoactive constituent delta-9-tetrahydrocannabinol (THC).

Bidirectional Modulation of Nociception by GlyT2 Neurons in the Ventrolateral Periaqueductal Gray.

The midbrain periaqueductal gray (PAG), particularly its ventrolateral column (vlPAG), is part of a key descending pathway that modulates nociception, fear and anxiety behaviors in both humans and rodents. It has been previously demonstrated that inhibitory GABAergic neurons within the vlPAG have a major role in this nociceptive modulation. However, the PAG contains a diverse range of neuronal subtypes and the contribution of different subtypes of inhibitory neurons to nociceptive control has not been investigated.

The Cannabis Constituent Cannabigerol Does Not Disrupt Fear Memory Processes or Stress-Induced Anxiety in Mice.

Medicinal cannabis has proliferated around the world and there is increasing interest in the therapeutic potential of individual plant-derived cannabinoids (phytocannabinoids). Preclinical evidence suggests the phytocannabinoid cannabigerol (CBG) could be useful in treating brain disorders, including stress and anxiety-related disorders. In this study, we aimed to explore whether CBG disrupts various contextually conditioned fear memory processes and trauma-induced anxiety-related behavior in a mouse model of post-traumatic stress disorder (PTSD).

Cannabidiol disrupts conditioned fear expression and cannabidiolic acid reduces trauma-induced anxiety-related behaviour in mice.

The major phytocannabinoid cannabidiol (CBD) has anxiolytic properties and lacks tetrahydrocannabinol-like psychoactivity. Cannabidiolic acid (CBDA) is the acidic precursor to CBD, and this compound appears more potent than CBD in animal models of emesis, pain and epilepsy. In this short report, we aimed to examine whether CBDA is more potent than CBD in disrupting expression of conditioned fear and generalised anxiety-related behaviour induced by Pavlovian fear conditioning.

Brief optogenetic inhibition of rat lateral or ventrolateral periaqueductal gray augments the acquisition of Pavlovian fear conditioning.

The midbrain periaqueductal gray (PAG) coordinates the expression and topography of defensive behaviors to threat and also plays an important role in Pavlovian fear learning itself. Whereas the role of PAG in the expression of defensive behavior is well understood, the relationship between the activity of PAG neurons and fear learning, the exact timing of PAG contributions to learning during the conditioning trial, and the contributions of different PAG columns to fear learning are poorly understood. We assessed the effects of optogenetic inhibition of lateral (LPAG) and ventrolateral PAG (VLPAG) neurons on fear learning.

Effects of chemogenetic excitation or inhibition of the ventrolateral periaqueductal gray on the acquisition and extinction of Pavlovian fear conditioning.

The midbrain periaqueductal gray (PAG) has been implicated in the generation and transmission of a prediction error signal that instructs amygdala-based fear and extinction learning. However, the PAG also plays a key role in the expression of conditioned fear responses. The evidence for a role of the PAG in fear learning and extinction learning has been obtained almost exclusively using PAG-dependent fear responses.

The organization of defensive behavior elicited by optogenetic excitation of rat lateral or ventrolateral periaqueductal gray.

Rodents display characteristic defense responses to predators that are influenced by predatory imminence. The midbrain periaqueductal gray (PAG) serves an important role controlling these responses. The most influential model states that variations in defensive topography are due to distinct PAG regions: ventrolateral PAG (VLPAG) controls postencounter defense, such as freezing and immobility, whereas lateral PAG (LPAG) controls circa-strike defense, such as escape and flight.

The effects of chronic administration of tranylcypromine and rimonabant on behaviour and protein expression in brain regions of the rat.

Recent findings indicate that CB1 receptor blockade might be relevant to the action of antidepressant drugs as inhibition of endocannabinoid function can increase synaptic availability of neurotransmitters; an effect also seen with chronic antidepressant drug treatment. Chronic treatments with established antidepressants also lead to raised brain BDNF levels. The aim of this study was to compare the effects of rimonabant (an inverse agonist/antagonist of CB1 receptors) with those of the antidepressant tranylcypromine (TCP), on behaviour and expression of BDNF/CREB signalling pathways in rat brain.

Meta-review of the effectiveness of computerised CBT in treating depression.

Background: Several computerised cognitive behaviour therapy (cCBT) packages are now available to treat mild to moderate depression with or without anxiety. These have been usually been reviewed alongside cCBT for a wide range of psychological problems. Here, we single out the results of these reviews for the most common mental disorder, mild to moderate depression.