Preclinical and Clinical Evidence Supporting Use of Cannabidiol in Psychiatry
Gioacchino Calapai, Carmen Mannucci, Ioanna Chinou, Luigi Cardia, Fabrizio Calapai, Emanuela Elisa Sorbara, Bernardo Firenzuoli, Valdo Ricca, Gian Franco Gensini and Fabio Firenzuoli
Hindawi – Evidence-Based Complementary and Alternative Medicine, 2019, Article ID 2509129, 11 pages
Background : Cannabidiol (CBD) is a major chemical compound present in Cannabis sativa. CBD is a nonpsychotomimetic substance, and it is considered one of the most promising candidates for the treatment of psychiatric disorders. Objective. &e aim of this review is to illustrate the state of art about scientific research and the evidence of effectiveness of CBD in psychiatric patients.
Methods : this review collects the main scientific findings on the potential role of CBD in the psychiatric field, and results of clinical trials carried out on psychiatric patients are commented. A research was conducted in the PUBMED, SCOPUS, and ScienceDirect databases using combinations of the words cannabidiol, psychiatry, and neuropsychiatric.
Results : Preclinical and clinical studies on potential role of CBD in psychiatry were collected and further discussed. We found four clinical studies describing the effects of CBD in psychiatric patients: two studies about schizophrenic patients and the other two studies carried out on CBD effects in patients affected by generalized social anxiety disorder (SAD).
Conclusion : Results from these studies are promising and suggest that CBD may have a role in the development of new therapeutic strategies in mental diseases, and they justify an in-depth commitment in this field. However, clinical evidence we show for CBD in psychiatric patients is instead still poor and limited to schizophrenia and anxiety, and it needs to be implemented with further studies carried out on
The plant Cannabis contains a complex of secondary metabolites, the so-called cannabinoids. Cannabinoids consist of more than 60 compounds of which delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most known. CBD is a resorcinol-based compound capable to mitigate the psychotomimetic effects produced by THC at high dosages . CBD has no psychotomimetic effects and possesses a distinct pharmacological profile not comparable to THC that is the principal psychoactive cannabinoid-type compound in the plant of Cannabis. Despite the pharmacological characteristics, THC and CBD have the same chemical formula even if the atoms are differently displayed  (Figure 1). CBD was isolated for the first time in 1940, and its structure was described by Mechoulam et al. in 1963, while the definitive molecular configuration was established twenty-seven years later . While THC acts as a partial agonist at the G protein-coupled CB1 (CB1r) and CB2 (CB2r) cannabinoid receptors, current evidence suggests that CBD does not directly interact with the endocannabinoid system (ECS) . CBD has not an evident intrinsic activity over these receptors and has low-affinity for CB1r and CB2r binding . Effects of CBD on intracellular signaling are widely independent of CB1 receptors  and the in vivo effects of CBD, including its anti-inflammatory properties, appear to be CB1-independent . Anyway, the relative mechanism of action appears to be complex, and it has been not definitively studied .
Apart from effects involving CB1r and CB2r [9, 10], CBD modulates other cellular systems, such as the transient receptor potential subfamily V member 1 (TRPV1) cation channels , the orphan G-protein coupled receptor 55 also known as GPR55 and operating as a counterpart to the standard CB1R/CB2R signaling pathway , fatty acid amide hydrolase (FAAH) , peroxisome proliferator-activated receptor gamma (PPARc) , serotonin 1A (5-ht1a) [15, 16], and μ- and δ-opioid  receptors. CBD modulates calcium flux through the control on intracellular calcium stores  and is a competitive inhibitor of adenosine uptake [19, 20]. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD’s relatively poor bioavailability . &e volume of distribution of CBD following intravenous administration is 32 l/kg. CBD reaches many organs and tissues, including the eye and the central nervous system (CNS). After hepatic hydroxylation to 7- hydroxy cannabidiol (7-OH-CBD), subsequent faecal and, to a lesser extent, urinary excretion of metabolites occurs .
CBD possesses anti-inflammatory and antioxidant properties and has been considered as a potentially new pharmacological approach for neuroprotection . Early findings showing that CBD attenuated psychotomimetic and anxiogenic effects induced by high doses of THC in humans led to believe that this cannabinoid could possess antipsychotic and anxiolytic properties . Likewise, it is remarkable that CBD is not a psychotomimetic agent since it does not produce effects related to abuse and dependence as THC does  but it can be effective at the CNS level, crossing the blood-brain barrier, and clinical findings suggest that CBD could represent a useful strategy for the treatment of neurological diseases such as epilepsy , neurodegenerative diseases such as Alzheimer’s disease (AD) , Huntington’s disease (HD) , and Parkinson’s disease (PD) , and neonatal brain ischemia .
Several studies suggest that deficiencies of ECS can contribute to the development of psychiatric diseases , particularly mood disorders , schizophrenia , depression , and anxiety . CBD is considered a safe substance and as one of the most promising candidates for the treatment of psychiatric disorders.
The aim of this review is to illustrate the state of art about scientific research and the evidence of effectiveness of CBD in psychiatric disorders.