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DEEP DIVES WITH RESEARCH

Fatal drug overdoses have become the leading cause of accidental death in the United States, driven largely by prescription opioids. There is an urgent need to develop novel pharmacotherapies to reduce or eliminate the need for opioids. The cannabinoid system offers promise in these areas.

The aims of this project are to (1) advance Planetarie’s proprietary CBDa water-extraction technology to increase scale and efficiency for consistent water-extraction of acidic cannabinoids, (2) test the hypothesis that CBDa has stronger anti-inflammatory effects than CBD using a cell culture model of toll-like receptor-mediated innate inflammatory responses, and (3) test the hypothesis that CBDa has stronger anti-nociceptive effects than CBD using a gold standard animal model of nociceptive pain. We propose to advance this extraction
technology by researching methods to increase scale and efficiency while maintaining a consistently stable and superior acidic cannabinoid product.

For Aim 1, Planetarie is researching engineered methods to scale this production to create larger batches and meet growing demand. Having larger capacity and batches will mitigate the current risk of variability between batches that are required for a consistent pharmacological grade product to mass market. Key milestones include increased throughput of the water extraction process from 1kg/day to 5kg/day of stable CBDa and increased consistency in products produced by the water extraction process.

For Aim 2, we will model a body’s burden of inflammatory mediators, including the generation of proinflammatory cytokines and chemokines, activation of nitric oxide synthetase and release of nitric oxide, and inhibition of cyclooxygenase-2 by inducing prooxidant and proinflammatory signaling by activating TLR4
receptors on macrophages using bacterial lipopolysaccharide. Using such an approach, the terpene beta-caryophyllene inhibits the LPS-induced production of NO by macrophages. Key milestones include a 10X lower dose of CBDa than CBD will fully attenuate the proinflammatory effects of LPS. We will broaden the
scope of this study to assess whether it is effective against the inflammatory response induced by polyinosinic:polycytidylic acid.

For Aim 3, we will conduct further research to fully establish that CBD is effective at treating thermal pain and/or can be used to enhance the therapeutic effects of opioid-like oxycodone without also enhancing other oxycodone-elicited effects (e.g., hypothermia and locomotor stimulation) and compare these effects of CBD to CBDa.

Key milestones include that CBDa will produce a significantly greater anti-nociceptive response than CBD, that it will be considerably more potent than CBD and that CBDa will produce a significantly greater enhancement of the anti-nociceptive effects of oxycodone than CBD, suggesting that CBDa may have a
greater potential opioid-sparing effect than CBD.