Prodrugs can overcome the limitations of existing drugs, enabling a proprietary and highly differentiated product.  Prodrugs are medications or compounds that, after administration, are converted within the body into a pharmacologically active drug, which may already have a long history of clinical investigation and use.  When the reference drug already has independent verification of its safety and efficacy, the prodrug may be approved far more efficiently, while simultaneously being more marketable, due to its ability to eliminate unwanted side effects or undesirable commercial aspects.  As of 2015, there had been approximately 15 prodrugs that have been classified as blockbusters, which is defined as having achieved annual sales that exceeded $1 billion.

Cannabosides for Targeted Delivery

Reducing Psychoactive THC in Brain to Magnify Pain Relief and Anti-inflammatory Effects

Vitality has developed a new class of cannabinoid prodrugs (cannabosides), which enable selective delivery of THC and cannabidiol (CBD) to the gastrointestinal tract. Site-specific delivery could enable potent local therapeutic effects while reducing or avoiding the systemic delivery of THC to the brain. Currently, the psychoactivity of THC limits the dose of cannabinoids that can be used for treatment of pain and inflammation.

Studies have shown that the cannabinoid system is a potent mediator of pain relief and inflammation, as studies have shown that cannabinoid drugs can in some cases be far more potent than opiates for pain relief, and far more potent than aspirin or corticosteroids for providing anti-inflammatory effects.  For example, cannabinoid drugs have been shown to be nearly 10 times as potent as morphine for neuropathic pain relief.   Studies have also shown they can be 20 times as potent as aspirin, and twice as potent as corticosteroids for treating inflammation.

But currently, the “elephant in the room” remains, which is that the desired potent effects cannot be achieved when high doses of THC enter the bloodstream and brain. Patients are forced to limit their doses, so targeted administration is critical. Our solution goes to the heart of this issue and offers an alternative means to increase the beneficial dosage, right at the site of disease – where it matters most, and relegates the psychoactive nature of the drug to a manageable side effect.Intestinal delivery

Our compounds take advantage of a targeted-release mechanism where microbial enzymes present in the intestines will enable a very site-specific localized release of compounds including THC, CBD, and many of the other known cannabinoids. Because of this, we could provide targeted relief of inflammatory bowel diseases (IBD) such as Crohn’s disease or ulcerative colitis, simply by enabling larger doses of cannabinoids to be delivered.

Glycoside Prodrugs

Glycoside prodrugs, upon oral delivery, can target the intestinal tract, enabling targeted delivery of cannabinoids to this area for treatment of various gastrointestinal disorders, such as inflammatory bowel disease or narcotic bowel syndrome, a severe form of opiate-induced abdominal pain.  Targeted, or site-specific delivery of cannabinoids could enable potent local therapeutic effects while reducing or avoiding the systemic delivery of THC to the brain. Currently, the psychoactivity of THC limits the dose of cannabinoids that can be used for treatment of pain and inflammation. In addition, independently conducted studies have shown that glycosylated compounds can selectively target the brain and increase bioavailability.

More water-soluble glycoside prodrugs can dramatically improve the taste and tolerability of oral formulations.  This can help ensure patients comply with physicians’ instructions, and that they do not develop lesions or sores in their mouth due to chronic use of oils or sprays that include high concentrations of harsh organic solvents like ethanol.

More stable glycoside prodrugs are able to pass through the acidic stomach environment unharmed.  Less degradation of cannabosides may lead to improved therapeutic effects as well as safer and more reliable dosing. Sustained and delayed systemic release prodrugs could also provide long-lasting and overnight relief within a convenient oral drug formulation.

Glycoside Prodrugs Image