Current and future approaches for clinical research with CBD in anxiety-related disorders

Based on this positive background of preclinical data, anecdote and case reports, and small randomised controlled trials, numerous clinical trials are currently registered (see clinicaltrials.gov) assessing the potential of CBD in anxiety-related disorders. There are three phase 2 trials registered assessing the ability of CBD to reduce general anxiety (NCT02548559, NCT04267679, NCT04286594), one phase 3 clinical trial in generalised anxiety disorder (NCT03549819), one phase 2 trial in social anxiety disorder (NCT04086342), three phase 2 trials in PTSD (NCT03518801, NCT03248167, NCT04197102), one phase 3 trial in bipolar depression (NCT03310593), and one phase 1 trial to assess reducing anxiety in Alzheimer’s Disease (NCT04075435).
Due to the intrinsic issues hindering the effective use of CBD as an oral drug in the solid-state, such as polymorphism, low solubility and bioavailability, and pharmacokinetic variability, some researchers are looking to improve on the physicochemical characteristics of the CBD molecule. Engineering of the crystalline structure of drug molecules by cocrystalization is a well-developed pharmaceutical strategy of enhanced pharmaceutics . Cocrystals are defined as crystalline materials composed of two or more molecules within the same crystal lattice (FDA Guidance for Industry, 2016). A cocrystal composition of CBD has the potential to overcome numerous physicochemical issues, allowing improved stability and bioavailability. Considerations for selection of the appropriate coformer, to form the CBD cocrystal, for a particular application, such as PTSD, include the properties of inert or pharmacologically active coformers. CBD cocrystal coformers such as tetramethylpyrazine (TMP) that have some evidence of activity in anxiety related disorders or PTSD, may be particularly attractive , and have been patented by Artelo Biosciences for development in this area.