Protext Pharma, Inc. recently added ownership of Cannabis Biosciences Inc. to its portfolio as a wholly-owned subsidiary. Cannabis Biosciences was incorporated in 2013 to develop non- psychoactive medicines from live cannabis plant and will focus on developing cannabis extracts under legal government licenses and permits which the Company is currently pursuing.
Using Plandaí’s proprietary processing and extraction technology, the company intends to commence investigations in conjunction with independent researchers to develop and validate a full-profile cannabis extract, one that contains both CBD and the precursor acid form of THC (THC-A and THC-B) found in live cannabis plant. The hypothesis is that the resultant extract will have similar, superior bioavailability of other Phytofare® extracts with the added benefit of being non-psychoactive.
Live cannabis leaf is inherently non-psychoactive. It is the process of drying and heating the leaf that metabolizes these acid forms into THC, a chemical that triggers the euphoria sought after by recreational users. In developing pharmaceutical applications, the commonly used super critical extraction method also uses extreme temperatures that causes THC to retain these properties. Our process, which uses live leaf and low temperatures to extract the phyto-chemicals, should leave the acid forms of THC intact, resulting in a non-psychoactive extract with full medicinal potential.
Where most pharma companies have chosen to focus on the non-psychoactive CBD chemical, we believe that this strategy limits the potential medical benefits. Our full profile, non-psychoactive extract is intended to give researches all of the benefits of cannabis with none of the unwanted side effects.
The plant Cannabis sativa produces over 421 chemical compounds including 80 terpeno-phenol compounds (phytocannabinoids) that have not been detected in any other plant. Currently commercial attention has been focused on producing extracts of ∆⁹- tetrahydrocannabinol (∆⁹- THC) which is the most psychotropic component and rapidly metabolizes in the body to a number of oxygenated products; but specifically binds to the G-protein- coupled CB1and CB2 neuron receptors.
The major problem in the current world of medical marijuana is the inability of the industry to deliver botanical cannabinoid agents with therapeutic action in a validated dosage and without psychotropic side effects.
As the industry of medical marijuana has rapidly grown in the United States and many other parts of the world over the past few years so have the scientific challenges and responsibilities. Numerous, largely unregulated, botanical cannabis products sold through licensed dispensaries have entered the market. Medicinal applications range from formulated foods, liquids, capsules, vapour pens and inhalers, or simply smoking the dried flower. The claims are disparate, unsupported by clinical trials, and fail to take into account varying dosage levels or differences in chemical values of the different strains.
This new industry has not addressed or overcome multiple challenges associated with the development of a safe wellness product. These products, targeted for disease prevention rather than recreational use, still rely mainly on psychoactive oral administration as the only viable route. The undesirable consequences are disturbing and heavily stigmatized in most societies.
For cannabinoids to become an approved FDA botanical drug, the questions of psychoactivity, metabolization, excretion, target tissue uptake, and residence time must be clinically addressed.
The endocannabinoid system (ECS) is a group of endogenous cannabinoid receptors located in the brain and throughout the central and peripheral nervous systems. The ECS system is responsible in controlling a variety of physiological processes including appetite, pain-sensation, mood and memory. Evidence suggests that endocannabinoids may function as both neuromodulators and immunomodulators in the immune system where they seem to serve an autoprotective role to ameliorate muscle spasms, inflammation, and other symptoms of multiple sclerosis and skeletal muscle spasms.
The endocannabinoid system is a main target for pharmacotherapy though it presents numerous treatment challenges. We know that the cannabinoid receptors are activated by endogenous ligands and that the mechanisms of the endocannabinoid biosynthesis and inactivation constitute the endocannabinoid release in the central and peripheral nervous system, pain perception, and cardiovascular, gastrointestinal and liver functions.
The Company’s strategy is to both improve the efficacy and manipulate the endocannabinoid system through delivering a complex of highly bioavailable non- psychoactive cannabinoids and polyphenols. It is suggested this may include targeting of the cannabinoid receptors located outside the blood brain barrier and modulating the endocannabinoid system. We further propose eliminating of the psychotropic side effects of ∆⁹- tetrahydrocannabinol by retaining it in its natural form: ∆⁹- tetrahydrocannabinol acid (∆⁹-THCA), cannabidiolic acid (CBDA) and ∆⁹ tetrahydrocannabivarin (∆⁹-THCV). Research shows that these compounds exert multiple actions through mechanisms related to the modulation of the endocannabinoid system. Together with cannabidiol (CBD), which exerts several safe positive pharmacological effects in inflammation, diabetes and cancer, ∆⁹-THCV has demonstrated the pharmacological profile of a CB1 antagonist with obesity.
The hypothesis follows the scientific evidence showing that different diseases (neurodegenerative, neurotrauma, cancer) share common factors with inflammation, oxidative stress and excitotoxicity.
We propose that the known wide distribution of the endocannabinoid system, and particularly the link between the endocannabinoid system, the immune system, the oxidative stress reactions (antioxidant properties of cannabinoids), excitotoxicity (modulation of excitatory glutamatergic transmissions), neuroinflammation, neurodegeneration, the MAPK signaling pathway and the PI3K–Akt pathway, all support a palliative action from Phytofare ® cannabinoid complex including for the treatment and prevention of Parkinson, Alzheimer, epilepsy, Multiple Sclerosis, traumatic brain injury and cancer. It is argued that the main target for the mechanisms of action is the CB2R, being CB1R also involved but mainly in the cognitive and motor effects.
Cannabis Biosciences will utilize Plandai’s processing and extraction protocols using leaf and flower of the live cannabis plant which is expected to yield a non- psychoactive complex of the entire plant phytonutrients, including phytocannabinoids, cannabinoid acids and polyphenols. The resultant extract will be entrapped in the liposome system, thereby conferring high bioavailability, efficacy and protection through the stomach and liver to the plasma.
Phytofare® phytocannabinoids are expected to travel through the blood-brain barrier where cannabinoids have been shown to protect the brain in a variety of conditions (Rom et al., 2013). Pharmaceutical drugs have demonstrated restricted ability to cross the blood brain barrier and thereby have shown to have little to no benefit in treating neuron disorders (Avraham et al., 2013).
It is postulated that the Phytofare ® phytocannabinoid complex will exhibit no psychoactive activity because the conditions for the formation of THC from THCA and THCB acids will not be introduced, and it is already proven that the acids in their natural state are not psychoactive.
In conclusion, it is expected that the high bioavailability characteristics, the presence of the phytocannabinoids precursors (acids) with polyphenols and terpenes, together with the known action of cannabinoids in the immune system, will translate to an efficient physiological action for the treatment of neurodegenerative diseases and cancers.
The objective of this project is to produce an FDA approved botanical drug/dietary supplement containing Phytofare ® non-psychoactive phytocannabinoids entrapped in liposome with high bioavailability and efficacy for the treatment and prevention of neurodegenerative diseases and cancer. The project will incorporate the following elements:
The growing of stable and specific cannabis specie is critical to ensuring pharmacologic consistency and repeatability of the final extract. The chemical profile of cannabis can vary not only strain-to- strain, but also from fluctuations in growing temperature, light, nutrients, and airflow. The project will require the cannabis plant to be grown in a controlled environment cultivation system.
Cannabis Biosciences intends to build on the successful farming model put in place by the parent company, Plandaí Biotechnology, in South Africa. This project developed the standards in farming husbandry and methodologies with green tea that have established a platform that should allow a Phytofare® extract from cannabis plants to be successfully grown in a specific and controlled environment.
The second phase of the project will involve the creation of a Phytofare ® phytocannabinoid complex from live cannabis flower and leaf; with the processing system located at an approved research facility. Our protocols for producing the extract are specific to the cannabis plant and are free of solvents or chemicals.
During the various processing stages of cavitation and sonoluminescence, the complex of phytonutrients and phytocannabinoids are converted into highly- bioavailable amorphous crystals, expressed in a unique cis- and trans-isomer forensic molecular footprint. The resulting Phytofare® complex is then entrapped in liposome for further protection of molecules and then delivered in capsules for oral consumption. Detailed analysis and chemical profiling will support the final product.
Following the initial profiling, the project will evaluate the antioxidant activities of the complex by means of in vitro and in vivo (murine) studies. This phase includes evaluating anti-inflammatory and antioxidant activities; toxicity and mutagenicity; bioavailability and absence of psychoactivity.
The blood-brain barrier (BBB) is formed by highly specialized endothelial cells that line brain capillaries and transduce signals from the vascular system and from the brain. The medical challenges of delivering an effective therapy to the brain is formidable as the blood–brain barrier (BBB) is a dynamic barrier protecting the brain against invading organisms and unwanted substances.
It is also the most important barrier impeding drug transport into the brain via the blood circulation. Despite the rapid development in our understanding of the molecular structure of components of the BBB, our knowledge in receptor expression at the BBB, advances in medical technology, and breakthroughs in nanotechnology- based approaches, many of the brain or central nervous system associated diseases remain under-treated by effective therapies.
A feature of the BBB is its low and selective permeability to molecules which can be attributed to its unique biological characteristics and undergo significant changes when the brain is developing a neurological disorder, in inflammatory conditions or under attack by pathogens.
Phytocannabinoids have been researched to effectively pass through the BBB and have been shown to have both anti-inflammatory activities and neuron free radical scavenging. Specific in vitro and mouse modelling studies are required to confirm that Phytofare® phytocannabinoids are transported into the brain via the blood circulation and provide both anti-inflammatory activities as well as perform oxygen free radical scavenging and support the endocannabinoid system. This could also include new botanical strategies for treating diseases like Alzheimer's and Parkinson's.