![]() Studies examining the neuropharmacology of neuropathic pain have implicated opioid (e.g., MOP/DOP), serotonin (e.g., 5-HT 7), dopamine (e.g., D 2) and glutamate (e.g., GluN2B) receptor systems as potential therapeutic targets however, no studies to date have examined the effects of whole plant-extracted hemp oil on chronic pain. The extended 3–10 week timeframe for study allowed by the FRICT-ION model is reportedly equivalent to 5–8 years of chronic pain in clinical patients. Mechanical hypersensitivity reliably develops on the snout persisting through >100 days, likely due to consistent inflammatory response caused in part by movement of the nerve during chewing. One well-established and reliable chronic pain model, the Foramen Rotundum Inflammatory Constriction Trigeminal Infraorbital Nerve injury (FRICT-ION) model involves an insertion of 3 mm of chromic gut suture (4-0) along the maxillary branch as it passes into the foramen rotundum through a tiny scalpel incision in the buccal/cheek crease. ![]() While animal models can control for expectancy effects, few paradigms have created a persistent state of chronic pain, with the majority of conventional pain models resulting in a recoverable, and hence qualitatively different forms of pain than one that is ‘chronic’ in nature, and hence often and uniquely tethered with comorbid affective disturbances (e.g., depression). Another frequent and unavoidable limitation of extant human trials measuring Cannabis’ pharmacodynamics is that they cannot control for placebo and expectancy effects, or visceral, perceptual, and/or cognitive reactions to enrollment in a cannabis-themed experiment, with several studies observing Cannabis-related experiences reported by both active agent and placebo group participants. ![]() This is because the federal government has largely limited clinical investigations to plant-inspired isolates, concocted formulants, or synthetic analogues not representative of the whole, natural Cannabis plant-based products most widely used by millions of people in the U.S. Despite widespread Cannabis usage in the U.S., with estimated annual revenues now in the tens of billions of dollars, current patients and providers still have little scientific evidence on the likely effectiveness of common and commercially available cannabis-based products for pharmaceutical application. Only differing from their federally illegal counterparts, arbitrarily defined as Cannabis plants containing over 0.3% tetrahydrocannabinol (THC) potency levels, the legal variety of the Cannabis plant-conventionally referred to as ‘hemp’-still contains hundreds of additional phytochemicals, including cannabinoids (e.g., cannabidiols, CBDs), terpenes, terpenoids, and flavonoids that may offer potent therapeutics, both individually and synergistically. The enactment of the Hemp Farming Act, effectively beginning in 2019, was a monumental milestone in the history of Cannabis prohibition in the United States (U.S.), because it enabled the legal consumption, commercial production, and market trade of any type of product made from certain variants of the Cannabis plant. Conclusion: Future research should focus on how whole plant extracted hemp oil affects multi-sensory and cognitive-attentional systems that process pain. There was no threshold change on contralateral whisker pad after hemp oil administration, demonstrating the localization of anesthetic response to affected areas. Results: Mechanical allodynia was alleviated within 1 h (d = 2.50, p < 0.001) with a peak reversal effect at 4 h (d = 7.21, p < 0.001) and remained significant throughout the 6 h observation window. Von Frey filament stimuli on the mouse whisker pad was used to assess the mechanical pain threshold from 0–6 h following dosing among animals (n = 6) exposed to 5 μL of whole plant extracted hemp oil combined with a peanut butter vehicle (0.138 mg/kg), the vehicle alone (n = 3) 7 weeks post-surgery, or a naïve control condition (n = 3). The suture, wedged along the V2 trigeminal nerve branch, creates a continuous irritation that develops into secondary mechanical hypersensitivity on the snout. ![]() Methods: Male BALBc mice were submitted to the FRICT-ION chronic neuropathic pain model with oral insertion through an incision in the buccal/cheek crease of 3 mm of chromic gut suture (4-0). ![]() We used the Foramen Rotundum Inflammatory Constriction Trigeminal Infraorbital Nerve injury (FRICT-ION) model to measure the effect of “full-spectrum” whole plant extracted hemp oil on chronic neuropathic pain sensitivity in mice. Background: Few models exist that can control for placebo and expectancy effects commonly observed in clinical trials measuring ‘ Cannabis’ pharmacodynamics. ![]()
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