The transcriptional regulation of the cannabinoid receptor 1 (CB1R) by promoter/enhancer elements and transcription factors is an area of cannabinoid research that has historically been understudied. To map the promoter region of the human CNR1 gene (the gene encoding CB1R), a 997-base-pair fragment from the sequence upstream of the CNR1 gene was cloned into a secreted luciferase reporter vector, and a series of deletion fragments were constructed. The transcriptional activity of these constructs was tested in human cell lines from three tissues: neuronal tissue (SHSY5Y), kidney tissue (HEK293T), and colonic epithelium (HCT116). Through this mapping, we have identified two key regulatory regions within the promoter. Increased levels of cAMP suppressed reporter expression from the full-length promoter fragment in all three cell lines, and in silico modeling predicts potential cAMP response elements (CRE) within one of the key regulatory sequences. Additionally, the minimal promoter region for CNR1 also appears to be in the second regulatory region identified, and in silico modeling predicts BRE and INR elements within this sequence. These findings begin to unravel the mechanisms by which CNR1 is transcriptionally regulated.

Fractures are common musculoskeletal injuries associated with severe pain, and effective analgesia is essential for fracture management. Current therapies such as NSAIDs and opioids have significant limitations, driving interest in alternative analgesics, an avenue where cannabinoids hold great promise. While cannabinoids are increasingly promoted for various indications, robust scientific evidence supporting their use remains limited. We previously demonstrated that cannabidiol (CBD) and cannabigerol (CBG), two non-psychoactive cannabinoids, alleviate fracture pain and promote bone repair. Cannabichromene (CBC), another non-psychoactive cannabinoid, has shown analgesic effects in different disease models, but its impact on fracture pain and healing is unknown. Using a murine tibial fracture model, we investigated CBC's effects on pain and bone healing. CBC significantly reduced fracture pain, improving mechanical and cold allodynia, thermal hyperalgesia, and gait function. However, bone healing was impaired, with delayed soft-callus resorption, increased bone cell apoptosis, elevated osteoclast activity, and reduced bone formation and mineralization. In vitro, CBC promoted osteoclastogenesis, supporting its resorptive effect. These findings contrast with the reported benefits of CBD and CBG on fracture repair, highlighting that not all cannabinoids are suitable for fracture management. Individual compounds must be carefully evaluated to balance analgesia with bone healing. Caution is warranted when using medical cannabis or cannabinoid oils with variable compositions, as their effects on healing are unpredictable. The divergent effects of CBD and CBG versus CBC may also guide future structure-activity relationship studies for designing synthetic cannabinoids to promote fracture healing.

Background: The rising popularity of medicinal and recreational use of Cannabis sativa L. has prompted a parallel increase in the number of studies administering the plant and extracts of its constituent compounds to animal models. Typical routes of administration of Cannabis to animals differ from traditional use by humans, reducing the translatability of the results of these studies. Summary: While inhalation and ingestion are the most common routes of cannabinoid delivery in humans, injections (intraperitoneal or subcutaneous) are most common in animal models due to the inherent ease of dosing. Human pharmacokinetic studies utilizing the intravenous parenteral route of administration of cannabinoids (specifically Δ9-tetrahydrocannabinol) induce severe side effects, and hence its use is uncommon in humans. Key Messages: To assess the use of cannabinoids as an alternative therapeutic option, it is important to test patient-compliant formulations and routes of administration. Further, since bioavailability of cannabinoids varies greatly with the route of administration, mimicking human cannabinoid drug delivery in animal models becomes crucial. This review provides insights into cannabinoid pharmacokinetics across different delivery routes in rodent models and the translatability to humans.

Background:Our objective was to provide an overview of the currently available scientific and clinical data supporting the use of Cannabis and Cannabis-derived products for the treatment of chronic pain disorders. We also provide information for researchers, clinicians, and patients to be better informed and understand the approach behind the recommendation of Cannabis as a potential adjuvant in the treatment/control of chronic pain. Cannabis and its bioactive compounds have sparked interest in the field of pain treatment in spite of its controversial history and status as a controlled substance in many countries. With the increase in chronic pain, physicians and patients have started to look at alternative ways to treat pain aside from traditional treatments. One alternative is the use of cannabis to reduce/treat chronic pain disorders based on anecdotal accounts and the function of its phytocannabinoids. The two main cannabinoids in cannabis, tetrahydrocannabinol (THC) and cannabidiol, act on CB1 and CB2 receptors (in addition to several additional receptors). It is through these pleiotropic receptor interactions that these compounds elicit their biological function including the reduction of chronic pain. In this narrative review, we included the most recent evidence supporting the use of cannabis in the treatment of chronic pain disorders including chronic neuropathic pain, cancer-induced neuropathic pain, chronic musculoskeletal pain, and chronic headaches and migraines. Summary:Evidence suggests that cannabis and cannabinoids have an analgesic effect that arises from a combination of compounds and various receptor systems. These effects may be maximized with the use of a combination of cannabinoids. At the same time, the combination of cannabinoids helps minimize the undesirable side effects of some cannabinoids such as the psychoactivity of THC. With these findings, further research is necessary to assess the analgesic properties of other cannabinoids like cannabichromene and cannabigerol and their contributions to the reduction of pain. Key Messages:Cannabis and its bioactive compounds show potential in the reduction of chronic pain.

Purpose (the aim of the study): Osteoarthritis (OA) is the leading cause of disability in older adults and involves complex interactions of local and systemic factors. OA is clinically characterized by joint pain and loss of function. Current treatments focus on symptom management and eventually joint replacement surgery at late stages, with no disease modifying agents available. Many patients already use cannabinoid products for pain management, but there is not solid scientific evidence demonstrating their efficacy.

BACKGROUND:Silent inflammatory bowel disease (IBD) is a condition in which individuals with the active disease experience minor to no pain. Voltage-gated Na+ (NaV ) channels expressed in sensory neurons play a major role in pain perception. Previously, we reported that a NaV 1.8 genetic polymorphism (A1073V, rs6795970) was more common in a cohort of silent IBD patients. The expression of this variant (1073V) in rat sympathetic neurons activated at more depolarized potentials when compared to the more common variant (1073A). In this study, we investigated whether expression of either NaV 1.8 variant in rat sensory neurons would exhibit different biophysical characteristics than previously observed in sympathetic neurons. METHODS:Endogenous NaV 1.8 channels were first silenced in DRG neurons and then either 1073A or 1073V human NaV 1.8 cDNA constructs were transfected. NaV 1.8 currents were recorded with the whole-cell patch-clamp technique. KEY RESULTS:The results indicate that 1073A and 1073V NaV 1.8 channels exhibited similar activation values. However, the slope factor (k) for activation determined for this same group of neurons decreased by 5 mV, suggesting an increase in voltage sensitivity. Comparison of inactivation parameters indicated that 1073V channels were shifted to more depolarized potentials than 1073A-expressing neurons, imparting a proexcitatory characteristic. CONCLUSIONS AND INFERENCES:These findings differ from previous observations in other expression models and underscore the challenges with heterologous expression systems. Therefore, the use of human sensory neurons derived from induced pluripotent stem cells may help address these inconsistencies and better determine the effect of the polymorphism present in IBD patients.

There is a growing interest in the use of medicinal plants to treat a variety of diseases, and one of the most commonly used medicinal plants globally is Cannabis sativa. The two most abundant cannabinoids (Δ9-tetrahydrocannabinol and cannabidiol) have been governmentally approved to treat selected medical conditions; however, the plant produces over 100 cannabinoids, including cannabichromene (CBC). Although the cannabinoids share a common precursor molecule, cannabigerol, they are structurally and pharmacologically unique. These differences may engender differing therapeutic potentials. In this review, we will examine what is currently known about CBC with regards to pharmacodynamics, pharmacokinetics, and receptor profile. We will also discuss the therapeutic areas that have been examined for this cannabinoid, notably antinociceptive, antibacterial, and anti-seizure activities. Finally, we will discuss areas where new research is needed and potential novel medicinal applications for CBC. SIGNIFICANCE STATEMENT Cannabichromene (CBC) has been suggested to have disparate therapeutic benefits such as anti-inflammatory, anticonvulsant, antibacterial, and antinociceptive effects. Most of the focus on the medical benefits of cannabinoids has been focused on Δ9-tetrahydrocannabinol and cannabidiol. The preliminary studies on CBC indicate that this phytocannabinoid may have unique therapeutic potential that warrants further investigation. Following easier access to hemp, CBC products are commercially available over-the-counter and are being widely utilized with little or no evidence of their safety or efficacy.

INTRODUCTION: Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970, A1073V; 1073val/val) related to Nav1.8, a voltage-gated sodium channel preferentially expressed on nociceptors. It was unclear whether this relationship existed for both Crohn's disease (CD) and ulcerative colitis (UC). This study evaluated a larger, carefully phenotyped IBD cohort to investigate this question. METHODS: Allelic and genotypic frequencies of rs6795970 were compared among study cohorts characterized by concomitant assessment of intestinal inflammatory status and abdominal pain experience. Visceral sensory perception was performed in healthy individuals using rectal balloon distension. RESULTS: We analyzed 416 patients with IBD (261CD:155UC) and 142 healthy controls. In the IBD cohort, 84 individuals (43CD:41UC) were determined to have hypoalgesic disease. The allelic frequency of rs6795970 was significantly higher in patients with hypoalgesic IBD when compared with other patients with IBD and healthy controls. Patients with hypoalgesic IBD were also more likely to be homozygous for this polymorphism when compared with other patients with IBD and healthy controls. Hypoalgesic CD (30% vs 12%, P = 0.004) and hypoalgesic UC (32% vs 15%, P = 0.036) were each significantly more likely to be associated with homozygosity for the rs6795970 polymorphism. In a cohort of healthy individuals (n = 50), rs6795970 homozygotes (n = 11) also demonstrated reduced abdominal discomfort to rectal balloon distension. DISCUSSION: These findings indicate that Nav1.8 plays a key role in human visceral pain perception, and could serve as a novel diagnostic target in the management of hypoalgesic CD and UC, and potential therapeutic target for conditions associated with chronic abdominal pain.

Pain is a major issue in healthcare throughout the world. It remains one of the major clinical issues of our time because it is a common sequela of numerous conditions, has a tremendous impact on individual quality of life, and is one of the top drivers of cost in medicine, due to its influence on healthcare expenditures and lost productivity in those affected by it. Patients and healthcare providers remain desperate to find new, safer and more effective analgesics. Growing evidence indicates that the voltage-gated sodium channel Nav1.8 plays a critical role in transmission of pain-related signals throughout the body. For that reason, this channel appears to have strong potential to help develop novel, more selective, safer, and efficacious analgesics. However, many questions related to the physiology, function, and clinical utility of Nav1.8 remain to be answered. In this article, we discuss the latest studies evaluating the role of Nav1.8 in pain, with a particular focus on visceral pain, as well as the steps taken thus far to evaluate its potential as an analgesic target. We also review the limitations of currently available studies related to this topic, and describe the next scientific steps that have already been undertaken, or that will need to be pursued, to fully unlock the capabilities of this potential therapeutic target.

Background:In this review, we summarize current scientific knowledge on psychoactive cannabinoids synthesized from cannabidiol (CBD) and sold in the semi-legal market established in response to the passage of the US Agriculture Improvement Act of 2018, commonly known as the 2018 Farm Bill. The discussion focuses on recent developments that suggest this unregulated market may be fertile ground for a potential health crisis.Summary:Current research into CBD-derived cannabinoids is mainly limited to Δ8-tetrahydrocannabinol (Δ8-THC) products, with some recent publications beginning to explore O-acetyl-THC, a term describing the acetate ester of Δ8-THC or Δ9-THC, and its potential pulmonary toxicity. We advance the discussion on the CBD-derived cannabinoid market, shedding light on the introduction and associated dangers of novel cannabinoids, likely produced via fully synthetic routes using sidechain variants of CBD, with purportedly greater agonist activity at the human cannabinoid receptor 1 (as a source of euphorigenic activity) than Δ9-THC. We discuss the expanded incorporation of the acetate ester motif into other THC analogues. We also discuss the lack of regulatory oversight for the production of CBD-derived cannabinoids and the unlabeled presence of under-researched cannabinoids formed as reaction side products in the CBD-derived cannabinoid products being sold. Accordingly, we suggest approaches to monitoring the CBD-derived cannabinoid market and investigating the pharmacology of the cannabinoids being consumed. Finally, important epidemiological findings are discussed and future directions for research are suggested to call investigators to this critically understudied field.Key Messages:The CBD-derived cannabinoid market is growing internationally, and the market has diversified to include potent synthetic cannabinoids. The products sold on this unregulated market are under-researched despite growing availability and consumer interest. Ernest investigation of the pharmacology of these novel cannabinoids and the contents of CBD-derived cannabinoid products is critical for monitoring this potential source of another vaping-related epidemic.

BackgroundThe recent exponential increase in legalized medical and recreational cannabis, development of medical cannabis programs, and production of unregulated over-the-counter products (e.g., cannabidiol (CBD) oil, and delta-8-tetrahydrocannabinol (delta-8-THC)), has the potential to create unintended health consequences. The major cannabinoids (delta-9-tetrahydrocannabinol and cannabidiol) are metabolized by the same cytochrome P450 (CYP) enzymes that metabolize most prescription medications and xenobiotics (CYP3A4, CYP2C9, CYP2C19). As a result, we predict that there will be instances of drug-drug interactions and the potential for adverse outcomes, especially for prescription medications with a narrow therapeutic index.MethodsWe conducted a systematic review of all years to 2023 to identify real world reports of documented cannabinoid interactions with prescription medications. We limited our search to a set list of medications with predicted narrow therapeutic indices that may produce unintended adverse drug reactions (ADRs). Our team screened 4,600 reports and selected 151 full-text articles to assess for inclusion and exclusion criteria.ResultsOur investigation revealed 31 reports for which cannabinoids altered pharmacokinetics and/or produced adverse events. These reports involved 16 different Narrow Therapeutic Index (NTI) medications, under six drug classes, 889 individual subjects and 603 cannabis/cannabinoid users. Interactions between cannabis/cannabinoids and warfarin, valproate, tacrolimus, and sirolimus were the most widely reported and may pose the greatest risk to patients. Common ADRs included bleeding risk, altered mental status, difficulty inducing anesthesia, and gastrointestinal distress. Additionally, we identified 18 instances (58%) in which clinicians uncovered an unexpected serum level of the prescribed drug. The quality of pharmacokinetic evidence for each report was assessed using an internally developed ten-point scale.ConclusionDrug-drug interactions with cannabinoids are likely amongst prescription medications that use common CYP450 systems. Our findings highlight the need for healthcare providers and patients/care-givers to openly communicate about cannabis/cannabinoid use to prevent unintended adverse events. To that end, we have developed a free online tool (www.CANN-DIR.psu.edu) to help identify potential cannabinoid drug-drug interactions with prescription medications.

Antidepressant medications (AMs) are frequently used in inflammatory bowel disease (IBD). Many AMs enhance serotonin (5-HT) availability, but this phenomenon may actually worsen IBD. We hypothesized that use of 5-HT-enhancing AMs would be associated with poor clinical outcomes in these disorders. We performed a retrospective cohort study using the Merative Health Marketscan® commercial claims database between 1/1/05 and 12/31/14. Participants (18–63 years) were either controls or had ≥ 2 ICD-9 diagnoses for IBD with ≥ 1 year of continuous insurance enrollment before index diagnosis and 2 years after. We identified new AM prescriptions using the medication possession ratio. Primary outcomes were corticosteroid use (IBD-only), IBD-related complication (IBD-only), IBD-related surgery (IBD-only), hospitalization, and emergency department (ED) visit(s) within 2 years of diagnosis or starting AM. We calculated adjusted hazard ratios (aHRs) in IBD AM users (for each outcome). We also performed subgroup analyses considering IBD and AM subtype. In the IBD cohort (n = 29,393, 41.4% female; 42.2%CD), 5.2% used AMs. In IBD, AM use was independently associated with corticosteroid use, ED visits, and hospitalizations, but not IBD-related complications. AM use was associated with a decreased risk of surgery. In the control cohort (n = 29,393, 41.4% female), AM use was also independently associated with ED visits and hospitalizations, and there was an increased likelihood of these two outcomes compared to the IBD cohort. In conclusion, while AM use was independently associated with an increased risk of ED visits and hospitalization in IBD, these risks were statistically more common in a matched control cohort. Additionally, AM use was associated with reduced risk of surgery in IBD, demonstrating a potential protective role in this setting.

A variety of techniques have been developed to extract hemp phytochemicals for research and consumption. Some of the most common processes in the industry include supercritical CO2 extraction, hydrodistillation, and solvent-based (ethanol) extractions. Each of these processes has the potential to differentially extract various phytochemicals, which would impact their efficacy, tolerability, and safety. However, despite these differences, there has been no direct comparison of the methods and the resulting phytochemical composition. This work aimed to compare cannabinoid and terpene profiles using the three primary commercial procedures, using hemp inflorescence from a CBD/CBG dominant Cannabis sativa L. cultivar. Extracts were then evaluated for their terpene and cannabinoid content using GC-MS and LC-MS/MS, respectively. Hydrodistilled extracts contained the most variety and abundance of terpenes with β-caryophyllene to be the most concentrated terpene (25–42 mg/g). Supercritical CO2 extracts displayed a minimal variety of terpenes, but the most variety and abundance of cannabinoids with CBD ranging from 12.8–20.6 mg/g. Ethanol extracts contained the most acidic cannabinoids with 3.2–4.1 mg/g of CBDA along with minor terpene levels. The resulting extracts demonstrated substantially different chemical profiles and highlight how the process used to extract hemp can play a large role in product composition and potential biological effects.

IntroductionAlcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate continued alcohol use. Alcohol increases neuroimmune activity in the brain. Our recent evidence indicates that alcohol directly modulates neuroimmune function in the central amygdala (CeA), a key brain region regulating anxiety and alcohol intake, to alter neurotransmitter signaling. We hypothesized that cannabinoids, such as cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), which are thought to reduce neuroinflammation and anxiety, may have potential utility to alleviate alcohol withdrawal-induced stress-sensitivity and anxiety-like behaviors via modulation of CeA neuroimmune function.MethodsWe tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor.ResultsWe found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100β and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects..DiscussionThese results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA.

Cannabigerol (CBG), derived from the cannabis plant, acts as an acute analgesic in a model of cisplatin-induced peripheral neuropathy (CIPN) in mice. There are no curative, long-lasting treatments for CIPN available to humans. We investigated the ability of chronic CBG to alleviate mechanical hypersensitivity due to CIPN in mice by measuring responses to 7 and 14 days of daily CBG. We found that CBG treatment (i.p.) for 7 and 14 consecutive days significantly reduced mechanical hypersensitivity in male and female mice with CIPN and reduced pain sensitivity up to 60–70% of baseline levels (p < 0.001 for all), 24 h after the last injection. Additionally, we found that daily treatment with CBG did not evoke tolerance and did not incur significant weight change or adverse events. The efficacy of CBG was independent of the estrous cycle phase. Therefore, chronic CBG administration can provide at least 24 h of antinociceptive effect in mice. These findings support the study of CBG as a long-lasting neuropathic pain therapy, which acts without tolerance in both males and females.

Cannabigerol (CBG), the precursor of the major cannabinoid compounds synthesized from Cannabis sativa L., has emerged as a novel potential therapeutic target due to its lack of psychoactive effects and efficacy at reducing pain and inflammation in animal models. Despite this, little is known about the safety of CBG, including its impact on cardiovascular function. Our laboratory recently showed that acute CBG administration lowers blood pressure, by over 20 mmHg, in phenotypically normal male mice via an α2-adrenoreceptor mechanism, which could suggest the need for caution in using this compound in healthy individuals. In this study, we tested the hypothesis that CBG can also lower blood pressure in mice when administered chronically. To test this hypothesis, four male C57BL/6J mice were implanted with radiotelemetry probes at 8-10 weeks of age and allowed to recover for 10 days. This approach allows for continuous measurement of blood pressure, heart rate, and locomotor activity in conscious animals. Baseline blood pressure and heart rate were recorded for 24-hours prior to drug treatment. Mice were then administered CBG at a dose previously found to acutely lower blood pressure (10 mg/kg, intraperitoneal) for 14 days, with vital signs recorded for 24-hours at the end of treatment. We found that chronic CBG reduced 24-hour systolic blood pressure by ~5 mmHg (129±3 mmHg baseline vs. 124±2 mmHg post-CBG; p=0.040 via paired t-test), with similar trends for diastolic and mean blood pressure. This depressor effect was accompanied by a significant decrease in heart rate (581±15 bpm baseline vs. 502±19 bpm post-CBG; p=0.003), with no effect on locomotor activity. These overall findings suggest that chronic CBG may produce a small, but significant, decrease in blood pressure in phenotypically normal male mice. The magnitude of chronic CBG depressor effects was smaller than previously observed for acute administration. This could reflect multiple mechanisms including a2-adrenoreceptor desensitization or baroreflex buffering, but this remains to be tested. Regardless, these findings may provide caution for potential hypotensive effects of CBG under normotensive conditions. Funding sources: PA Options for Wellness and Penn State Medical Marijuana Academic Clinical Research Center This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

BACKGROUND:Cannabis use is common in inflammatory bowel disease (IBD). Recent studies demonstrated that use of cannabis may relieve symptoms; however, it is still unclear how safe cannabis and its derivatives are for IBD patients. We performed this study to evaluate the impact of cannabis use on several key clinical outcomes in IBD. METHODS:We performed a retrospective study using the TriNetX Diamond Network. Cannabis use and noncannabis use subcohorts were identified for 3 patient groups: (1) IBD, (2) Crohn's disease (CD), and (3) ulcerative colitis (UC). Baseline differences between subcohorts for each group were controlled by propensity score matching. In each group, we compared relative incidence of emergency department (ED) visits, hospitalization, corticosteroid use, opioid use, IBD-related surgery, and death between cannabis users and noncannabis users. RESULTS:Inflammatory bowel disease cannabis users demonstrated an increased risk for corticosteroid use (risk ratios [R],1.095; 95% CI, 1.021-1.174; P = .011), ED visits (RR, 2.143; 95% CI, 2.034-2.257; P < .001), hospitalizations (RR, 1.925; 95% CI, 1.783-2.079; P < .001) and opioid use (RR, 1.35; 95% CI, 1.14-1.6); P < .001), but not an increased risk of IBD-related surgery or death. The CD and UC groups exhibited similar outcomes, except only CD demonstrated an increased risk for corticosteroid and opioid use. CONCLUSIONS:Cannabis use in IBD patients is associated with several poor clinical outcomes, including increased risk of corticosteroid and opioid use, ED visits and hospitalization, though not IBD-related surgery or death. It is not clear what drives these risks or whether they are directly related to IBD-associated disease activity or other factors. Further prospective studies are warranted to more carefully investigate these relationships.

Cannabis sativa contains minor cannabinoids that have potential therapeutic value in pain management. However, detailed experimental evidence for the antinociceptive effects of many of these minor cannabinoids remains lacking. Here, we employed artificial intelligence (AI) to perform compound–protein interaction estimates with cannabichromene (CBC) and receptors involved in nociceptive signaling. Based on our findings, we investigated the antinociceptive properties of CBC in naïve or neuropathic C57BL/6 male and female mice using von Frey (mechanical allodynia), tail-flick (noxious radiant heat), formalin (acute and persistent inflammatory pain), and acetone (cold thermal) tests. For von Frey assessments, CBC dose (0–20 mg/kg, i.p.) and time (0–6 h) responses were measured in male and female neuropathic mice. For tail-flick, formalin, and acetone assays, CBC (20 mg/kg, i.p.) was administered to naïve male and female mice 1 h prior to testing. The results show that CBC (10 and 20 mg/kg, i.p.) significantly reduced mechanical allodynia in neuropathic male and female mice 1–2 h after treatment. Additionally, CBC treatment caused significant reductions in nociceptive behaviors in the tail-flick assay and in both phase 1 and phase 2 of the formalin test. Finally, we found a significant interaction in neuropathic male mice in the acetone test. In conclusion, our results suggest that CBC targets receptors involved in nociceptive signaling and imparts antinociceptive properties that may benefit males and females afflicted with diverse forms of acute or chronic/persistent pain.