Development of a Process for GMP Production of Natural THC and CBD

Development Process for Production of Natural THC and CBD AbstractTetrahydrocannabinolTHCand cannabidiolCBDare two major constituents of the cannabis plant that have pharmacological properties with potential therapeutic value in several disease conditionsWhileTHC has already been in use clinically for two indicationsnausea and vomiting in cancer patients receiving chemotherapy and appetite stimulation for AIDS patientsin an oral soft gelatin capsule formulationCBD is awaiting to be developedThere is a great need for supply of these two cannabinoids for product development and there is a market for GMP quality materialThis proposal is directed toward the development of a process for large scale isolation of these two cannabinoids from crude cannabis extracts that is both economic and capable of producing GMP quality productsThis will be accomplished through our discovery thatunlike the free cannabinoidsthe protected amino acid esters of the cannabinoids are much easier to purifyseparateon normal phase silica column chromatography and the derivatives are stable enough to be stored until neededMild base hydrolysis of the esters generates the free cannabinoids in pure form when neededThe specific aims of this proposal areProcure cannabis extracts with high THC contentTHCfor THC production and high CBDCBDfor CBD production and to optimize the process of vacuum distillation of the cannabisextracts sto enhance the cannabinoid concentration in the distillatePrepare different t boc protected amino acid esters of the distillate for chromatographic separationevaluate the separation of the different cannabinoid derivatives from the different esters using TLCchromatographynormal phaseand select the best system and the best derivative for further evaluationon column chromatographyEvaluate the efficiency of separation of the different components of the derivatized extractdistillateonsmall scaleless than gramquantities and evaluate the recovery of THC from the purified ester throughbase hydrolysis and analysis of the recovered THCOptimize the processwhich derivative and which chromatographic systemfor each target cannabinoide gTHCCBDDuring this phase I the emphasis will be on THC but data will be collected for CBD forfurther studies during phase IIScale up the process for isolation of gram quantities of the target cannabinoidsDuring Phase Iapplicationemphasis will be on the separation of THC and CBDOther cannabinoidse gTHCV andCBGwill be targeted in Phase IIIt is anticipated thatat the conclusion of this phase I efforta process will be in place ready to be validated in phase II to produce GMP qualityTHC and CBD Project Narrative This phase I application is designed to develop an efficient and scalable process for the isolation oftetrahydrocannabinolTHC or THCand cannabidiolCBDfrom cannabis extract sDuring this effort the process will be brought to the point where GMP validation and production of GMP materials could be accomplished during phase IImaking GMP supply of THC and CBD available from ElSohly LaboratoriesThe ultimate goal is to make GMP supply of THC and CBD available for product development and commercialization