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Cannabidiol

Psychiatric Use
There has been some low-quality evidence supporting the anxiolytic effects of acute administration of oral CBD has been found. Research on the use of CBD in treatment of symptoms in schizophrenia has found moderate-quality evidence supporting chronic administration.

Anxiety Disorders
There have been several studies to support the anxiolytic properties of CBD. The evidence shows that these properties are mediated by CBD action on the postsynaptic 5-HT1A receptor and CB1 receptor. These receptors are known to modulate fear and anxiety related behaviours. Another potential mechanism associated with the anxiolytic properties of CBD involves the modification of blood flow in the limbic and paralimbic areas in the brain.

Schizophrenia
The research on the use of cannabidiol as a mono-therapy or additional therapy to antipsychotic medication showed potential for improving symptoms in patients with schizophrenia. The most promising effects were seen in the early stages of illness. The link between CBD treatment and anandamide, an important biomarker in assessing patients with schizophrenia, should be an area of focus for future studies.

Patients with schizophrenia show elevated levels of anandamide as well as differences in cannabinoid receptors expression in several brain regions. Studies suggest a potential link between the CB2 receptors of the endocannabinoid system and an increased risk for schizophrenia, as seen in genetic and animal models.

The main psychoactive component in cannabis, tetrahydrocannabinol (THC), is known to have the potential to induce acute psychotic effects. Cannabis related psychosis risk may be decreased with the use of CBD due to its antagonistic effect in regions of the brain associated with cannabis related schizophrenia. Small scale studies in the use of CBD to treat patients with psychotic symptoms has shown the potential for CBD as an effective and safe antipsychotic treatment, although larger clinical trials will need to be developed in order for CBD to reach clinical practice.

Substance Use Disorder
CBD has been studied for its use in patients with substance use disorder. The agonist activity on the 5-HT1A receptors has been attributed to its anti-craving properties, while the regulation of the glutamatergic signalling through modulation of serotoninergic and endocannabinoid systems impacts addictive behaviour. The effect of CBD on the 5-HT1A receptors potentially can regulate the drug reward system, anxiety symptoms and improve stress management.

The endocannabinoid system may be involved in drug-seeking behaviour, reward, withdrawal and relapse. Animal studies involving the CB1 receptors show that addiction behaviours are absent or diminished in CB1 receptor knockout mice. Since CBD acts as an antagonist to the CB1 receptor, there is potential for its use in substance use disorder.

Anti-Inflammatory
CBD has been seen to have both pro-inflammatory and anti-inflammatory properties. Studies have shown CBD can act similarly to dexamethasone in regulating the inflammatory response in LPS-induced cytokines in lung cells and NFκB activity in monocytes. The anti-inflammatory properties of CBD act as an antagonist with steroids, showing therapeutic benefits in reducing existing inflammation.

Safety
The data regarding the safety with the use of CBD in patients to treat psychiatric disorders has been insufficient, although many studies reported no adverse events with the acute administration and mild to moderate adverse effects with chronic administration. The safety profile of CBD has been compared to other cannabinoids such as THC. There is evidence that CBD is well tolerated in animals and humans at high doses (up to 1500 mg/day). The adverse events that commonly appear at high doses of THC are not seen in high CBD doses. This includes change in heart rate, blood pressure or body temperature, does not induce catalepsy and does not alter psychomotor or psychological functions like THC. The safety profile reflects the lack of direct agonist properties at cannabinoid receptors.

Pharmacodynamics
Cannabidiol has low affinity for the cannabinoid CB1 and CB2 receptors, although it can act as an antagonist of CB1/CB2 agonists despite this low affinity. Cannabidiol may be an antagonist of GPR55, a G protein-coupled receptor and putative cannabinoid receptor that is expressed in the caudate nucleus and putamen in the brain. It also may act as an inverse agonist of GPR3, GPR6, and GPR12. CBD has been shown to act as a serotonin 5-HT1A receptor partial agonist. It is an allosteric modulator of the μ- and δ-opioid receptors as well. The pharmacological effects of CBD may involve PPARγ agonism, inhibition of voltage-gated cation channels, and intracellular calcium release. Cannabidiol is a non‐competitive negative allosteric modulator of CB1 receptors.

Cannabidiol has targets outside of the endocannabinoid system. The potential physiological effects as a result of CBD acting outside cannabinoid system are being studied. Activation of adenosine receptors, A1A and A2A and strychnine-sensitive α1 and α1β glycine receptors and the inhibition of the equilibrative nucleoside transporter potentially mediate the anti-inflammatory immunosuppressive effects of CBD.