The Therapeutic Effectiveness of Full Spectrum Hemp Oil Using a Chronic Neuropathic Pain Model, Jacob M. Vigil et al., 2020

The Therapeutic E ffectiveness of Full Spectrum Hemp Oil Using a Chronic Neuropathic Pain Model

Jacob M. Vigil, Marena A. Montera, Nathan S. Pentkowski, Jegason P. Diviant, Joaquin Orozco, Anthony L. Ortiz, Lawrence J. Rael  and Karin N. Westlund

Life, 2020, 10, 69, 1-12

doi : 10.3390/life10050069


Abstract :

Background : Few models exist that can control for placebo and expectancy eff ects commonly observed in clinical trials measuring ‘Cannabis’ pharmacodynamics. 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.

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). The suture, wedged along the V2 trigeminal nerve branch, creates a continuous irritation that develops into secondary mechanical hypersensitivity on the snout. 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 L 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).

Results : Mechanical allodynia was alleviated within 1 h (d = 2.50, p < 0.001) with a peak reversal e ect at 4 h (d = 7.21, p < 0.001) and remained significant throughout the 6 h observation window. There was no threshold change on contralateral whisker pad after hemp oil administration, demonstrating the localization of anesthetic response to a ected areas. Conclusion: Future research should focus on how whole plant extracted hemp oil a ects multi-sensory and cognitive-attentional systems that process pain.

Keywords : endocannabinoids; cannabidiol; pain; allodynia; Cannabis; hemp


1. Introduction

The enactment of the Hemp Farming Act, e ectively 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. Only di ering 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 o er potent therapeutics, both individually and synergistically [1–4]. 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 e ectiveness of common and commercially available cannabis-based products for pharmaceutical application.

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. [5,6]. Another frequent and unavoidable limitation of extant human trials measuring Cannabis’ pharmacodynamics is that they cannot control for placebo and expectancy e ects, 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 [7,8].

While animal models can control for expectancy e ects, few paradigms have created a persistent state of chronic pain, with the majority of conventional pain models resulting in a recoverable, and hence qualitatively di erent forms of pain than one that is ‘chronic’ in nature, and hence often and uniquely tethered with comorbid a ective disturbances (e.g., depression) [9,10]. 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 [11]. 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. 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 [12,13].

Studies examining the neuropharmacology of neuropathic pain have implicated opioid (e.g., MOP/DOP) [14–16], serotonin (e.g., 5-HT7) [17,18], dopamine (e.g., D2) [19,20] and glutamate (e.g., GluN2B) [21–23] receptor systems as potential therapeutic targets; however, no studies to date have examined the e ects of whole plant-extracted hemp oil on chronic pain. Therefore, in the present study, we investigated the analgesic e ects of “full-spectrum” whole plant oil extracted from the hemp plant, using ethanol and evaporation-based procedures commonly used in the Cannabis industry, on mechanical neuropathic chronic pain sensitivity in mice. By creating a continuous state of irritation in the infraorbital nerve, the FRICT-ION mouse model of chronic orofacial neuropathic pain can initiate mechanical allodynia in the mouse whisker pad for pharmaceutical investigation. We use a standard von Frey test for mechanical hypersensitivity at 7 weeks post-surgery to measure the eff ects of orally administered hemp oil over a 6 h observation window, in comparison to vehicle only and naïve control mice, to estimate the general ecacy of commonly used hemp-based products for therapeutic application.