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For the team, CannaGo is differentiating itself by improving the delivery driver experience. A fter watching other food and cannabis delivery services navigate the market , they realized the importance of ethically paying drivers and building a quality fleet of drivers across the city.

“It’s forced us to be empathetic to other people…and also to see talent where other people might not,” Nwadike said.

Now, Mom & Pop shops are across the country — particularly in Atlanta — have emerged to serve clients looking for quality products. This is particularly important for the close to 15,000 patients in Georgia’s medical marijuana list who may lack access to a quality CBD store.

CannaGo and the Changing CBD Market

The key, Gaffney says, is transparency.

The new last-mile, next-day delivery service and marketplace brings non-medicated skin care products, cosmetics, essential oils, and other CBD smoking products safely and directly to your door.

The Entrepreneurial Journey

While CBD has been tied up in larger legal debates, it has gained widespread acceptance and was ultimately legalized in Georgia in May 2019 with the passage of The Georgia Hemp Farming Act (HB 213).

Matthew Gaffney, N. Victor Nwadike, and Kevin Tolliver were all Morehouse students when they first met at an internship info session on campus.

An oral capsule developed by Lexaria Bioscience Corp called “TurboCBD” claims to result in increased circulating CBD levels compared to control CBD, and contains American ginseng, ginkgo biloba, and organic hemp oil, produced using DehydraTECH™ delivery technology [69].

Complexation of CBD with cyclodextrins (CD) has also been investigated as a potential method to increase the water solubility and subsequently improve the bioavailability of sublingually delivered CBD. Mannila and colleagues demonstrated precipitation complexation of CBD and β-CD at a 1:2 ratio could increase the water solubility of CBD and increase the dissolution rate [88]. The authors noted sublingual delivery of the CBD/β-CD complex produced superior bioavailability compared to oral dosage forms of CBD in rabbits. However, in this study, CBD delivered in an ethanol solution sublingually was comparable to sublingual delivery of the CBD/β-CD complex. Two formulations of CBD and CDs are currently in development by Medexus pharmaceuticals and Vireo health LLC. These companies propose complexes of CBD and CDs will increase the aqueous solubility and subsequently improve bioavailability. However no clinical studies have been performed using these exact formulations to date.

A number of alternative delivery methods by-passing the digestive tract and first pass metabolism are currently under investigation including transdermal and nasal routes, and eye drops, which have been reviewed elsewhere [29].

Drug–drug interactions (DDIs) with CBD are a high risk as it is metabolised by, and a competitive inhibitor of, CYP450 enzymes (specifically CYP3A4 and CYP2C19) [39,42]. A case report of a 32-year-old woman with refractory epilepsy receiving tacrolimus (5 mg/day) and CBD (2000–2900 mg/day) reported that after two weeks of co-administration there was a threefold increase in dose-normalised tacrolimus concentrations [43]. A case report of a 37-year-old male similarly suggested CBD can increase warfarin concentrations [44]. More robust evidence of DDIs comes from a meta-analysis assessing four randomised, double-blind, placebo-controlled trials in Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) (n = 396 LGS, 318 DS) [45]. Authors noted incidences of serious AEs were 8% higher in CBD groups relative to placebo, and in patients taking clobazam alongside CBD, AEs were 14% more common than CBD alone. Blood plasma levels of the pharmacological active metabolite of clobazam, N-desmethylclobazam, were three times higher when administered alongside CBD. Likewise, increases in the CBD metabolite, 7-OH-CBD, are also seen when these drugs are co-administered [46]. Valprorate, another common anti-epileptic drug, is strongly associated with increased liver transaminases levels with CBD use. An FDA report describing clinical data for Epidiolex ® in the treatment of LGS or Dravet syndrome highlighted alanine aminotransferase (ALT) levels were three times the normal limit in 13% of Epidiolex ® treated patients. This AE was also true for patients taking clobazam, but was more common in valproate treated patients. Another study investigating the potential for DDIs with cannabis-based medications using the FDA drug interaction database identified three of the main cytochrome enzymes (CYP3A4, CYP2C9 and CYP2C19) responsible for 20–70% of total cytochrome p450 activity were inhibited by CBD [47]. Furthermore, following oxidative reactions at phase 1 metabolism, CBD is then subject to phase II glucuronidation reactions by the enzymes UGT1A9 UGT2B7 and UGT1A7. Competitive binding for these enzymes between drugs also presents another point at which drug metabolite levels could be altered [47]. These observations indicate the potential for DDIs with CBD in a variety of conditions are likely, and needs to be investigated using large patient studies.

3.3. Improved Single Crystal Structures

Methods to increase oral CBD bioavailability have included self-emulsifying drug delivery systems (SEDDS). These involve mixtures of oils, surfactants, and solvents that produce nano or micro sized droplets when they come into contact with an aqueous solution such as in the gut [51]. The small nature of the droplets increases the surface area available for drugs to be dissolved and absorbed. For example, soft gelatin capsules containing CBD developed by Satipharm, based on an advanced self-nanoemulsifying technology, have demonstrated greater bioavailability (about 31–34% higher compared to a reference oromucosal spray), solubility, and faster time to peak plasma concentrations in humans [52,53,54]. However, inter-individual variations were still high. This formulation has been proven safe and effective in a paediatric population with treatment-resistant epilepsy [1]. Another group recently reported a 4.4-fold increase in Cmax, enhanced bioavailability, and shorter Tmax with a SEDDS-CBD formulation based on VESIsorb ® technology compared to a control CBD oil [51]. VESIsorb ® is a novel lipid-based delivery system which self-assembles on contact with an aqueous phase into a colloidal delivery system, which solubilises the drug and improves diffusion and absorption and thus bioavailability [55]. In rats, another approach of a nano-emulsion (NE) formulation has been tested. CBD-NE oil drops increased absorption and bioavailability (21% higher) compared to a control CBD oil [56]. However, there may be practical (stability, complex formulations, safety of excipients, scalability) and economic (cost of formulation, patentability) issues with this method of increasing oral CBD bioavailability.

Some researchers claim to have improved the single crystal form of CBD. For example, one patent listed describes a crystalline CBD of a novel form, including (R,R)-(−)-crystalline cannabidiol [80]. This crystalline form was shown to possess a melting point of 37–50 °C, compared with a melting point of 66–67 °C for CBD. Intramolecular crystal lattice binding between ions within a crystal affects its melting point and reductions in lattice energies may increase aqueous solubility [8]. PureForm CBD™ is described as a molecularly identical, non-hemp-based CBD that has been developed using their Inter-Molecular Stacking Technology to improve solubility and stability [81]. There is no further publicly available information on these products.

A sublingual formulation by Diverse Biotech Inc., and an oral liquid by Emerald Health Pharmaceuticals containing a pure synthetic CBD are both in early clinical phases (see Table 1 ).

3.5. Other Delivery Systems and Formulation in Development

Solid-state oral delivery allows for 100% of the drug to reach the GI tract and has the potential to improve PK characterisation [76,77]. CBD delivered via this route would also further avoid local side effects associated with use of Sativex oromucosal spray (1:1 CBD:THC) or GI discomfort or pain associated with the vehicle itself in oral liquid formulations [78]. Current investigated solid-dose oral formulations of CBD include a 200 mg CBD tablet by Columbia Care called BeneCeed™, which will be used in a UK clinical trial. Elsewhere, a patent by GW pharmaceuticals lists a solid-state CBD as a potential clinical consideration in the treatment of inflammatory bowel disease [79]. Whilst dosing in this fashion ensures a consistent dose, formulations of this nature do not necessarily address problems associated with poor bioavailability.

Artelo Biosciences have developed a cocrystal with CBD that was designed to take advantage of cocrystal properties and help alleviate some of the problems with CBD delivery. This cocrystal uses the co-former tetramethylpyrazine (TMP; also called ligustrazine), a plant-derived compound from the Ligusticum species that is widely used in Chinese medicine. TMP may offer increased efficacy and bioavailability, by acting synergistically and changing the physiochemical properties that are associated with ineffective absorption. ART12.11 (CBD:TMP cocrystal) is currently in the nonclinical phase of pharmaceutical development targeted towards post-traumatic stress disorder (PTSD), inflammatory bowel disease (IBD), stroke and rare diseases, and has been recently granted a composition of matter patent in the US.