Cannabidiol CBD: A Promising Cannabis Derived Extract for New Drug Development

Specific Aims

The primary goal of this research proposal is to provide exploratory cannabis-based formulations for clinical therapeutics as well as for drug discovery and an adult user market governed on the basis of subjectivity, such as taste and aroma, so as to concomitantly develop appropriate modifications for process for manufacturing pharmaceutical grade CBD and related cannabis plant derived bioactive terpenes and flavonoids. These processes will follow current Good Manufacturing Practices (cGMP) of the USFDA to enable their use in standardized clinical trials in future. Our commercial goal is to develop a panel of standardized, enriched cannabis derived bioactive extracts proven to have clinical utility and formulated for drug delivery. We hypothesize that these components, focusing first on CBD, can be cost-effectively manufactured from high CBD content cannabis sativa (hemp) plants and by utilizing supercritical fluid technology, and that such a process could also produce other bioactive cannabinoid mixtures for future research and therapeutic use.

Specific Aim 1: To deliver useful suggestions for the selection of the optimal and most suitable method of extraction of cannabinoids in biomedical and cannabis derived samples for therapeutic or adult recreational use. Cannabis products have recently regained much attention due to the high pharmacological potential of their cannabinoid content. Widely used sample preparation strategies for the extraction of cannabinoids are required for the specific application to either plant materials or biological matrices. Several analytical techniques, and, in particular, chromatographic methods, such as TLC, GC and HPLC, are being widely used. The most preferred extraction method is to use Super Critical Extraction (SCE), and the possibility of including preprocessing steps enables adaptation of the industrial chemistries that require thorough analyses so as to provide optimal complex mixtures capable of scale-up production and FDA compliance.

We propose to manufacture pharmaceutical-grade CBD (>98.5% and < 0.3% Δ9-THC) and a standardized CW fraction (30% CBD and < 0.3% Δ9-THC) both following cGMP guidelines by utilizing supercritical fluids and near-critical fluids with or without polar co-solvents such as alcohols (Superfluids). These fluids are gases, such as carbon dioxide, which when compressed, exhibit enhanced thermodynamic properties that can be "finetuned" for rapid and selective extraction of bioactive molecules. We will obtain enough quantities of high CBD content cannabis sativa from growers California and/or NIDA to conduct the proposed research.

Our Phase I Specific Aims are as follows:
(1) Establish optimum conditions for the selective Superfluids fractionation of cannabis sativa to isolate CBD with absolute purities >30% and < 0.3% Δ9-THC
(2) Define Superfluids chromatographic purification conditions for the further purification of CBD with absolute purities >80% and < 0.3% 9-THC
(3) Establish downstream chromatographic conditions for the final purification of CBD with absolute purities of CBD >98.5% and< 0.3% Δ9-THC

Our Phase II Specific Aims are as follows:
(4) Design cGMP processes for Superfluids CXP and segmentation chromatography of cannabis sativa to produce standardized CW and pharmaceutical-grade CBD
(5) Modify extant Superfluids CXP Unit, construct segmentation chromatography systems and upgrade facility to manufacture standardized CW and pharmaceutical-grade CBD following cGMP
(6) Manufacture a minimum of 3 back-to-back large-scale batches of CW and CBD following cGMP guidelines and document in batch records and product release
(7) Document manufacturing process in a CMC (chemistry, manufacturing and controls) for IND applications to the FDA, and establish a Drug Master File (DMF) with the FDA. In Phase III, we will manufacture pharmaceutical-grade CBD for clinical evaluation by the NIH and other pharmaceutical companies. In order to avoid intra-state trafficking issues with the Federal government, we will sell small scale CXP manufacturing units, process conditions and supporting documentation for manufacturing standardized CW products to other state with Medical Marijuana dispensing laws. The legitimate use of marijuana for several medical indications has far outpaced the medical and clinical evaluation of marijuana and specific cannabinoids for different medical uses.

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