Evaluating the Antinociceptive Efficacy of Cannabidiol Alone or in Combination with Morphine Using the Formalin Test in Male and Female Mice

Sepulveda, Diana E.; Morris, Daniel P.; Raup‐Konsavage, Wesley M.; Sun, Dongxiao; Vrana, Kent E.; Graziane, Nicholas

doi:10.1089/can.2021.0108

Cited by 14 publications

(14 citation statements)

References 84 publications

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“…These results are interesting when considering that many pain treatments affect males and females differently (Bartley & Fillingim, 2013; Calderone, 1990; Chanda & Mogil, 2006; Leresche, 2011; Pieh et al, 2012; Pieretti et al, 2016; Sepulveda et al, 2021). For example, preclinical studies have shown that females require a higher dose of morphine to reach analgesic effects that are equivalent to males (Craft et al, 2008; Dawson‐Basoa & Gintzler, 1993; Doyle et al, 2017; Loyd et al, 2008; Mogil et al, 2000; Sepulveda et al, 2021; Wang et al, 2006). However, similar anti‐nociceptive effects between males and females are not uncommon after phytocannabinoid treatment, as observed with CBD (Britch et al, 2017; Vivanco‐Estela et al, 2021).…”

Section: Discussionmentioning

confidence: 90%

“…In direct comparisons between males and females at each CBG dose using a one-way ANOVA, we observed no sex differences (direct comparisons not shown). These results are interesting when considering that many pain treatments affect males and females differently (Bartley & Fillingim, 2013;Calderone, 1990;Chanda & Mogil, 2006;Leresche, 2011;Pieh et al, 2012;Pieretti et al, 2016;Sepulveda et al, 2021). For example, preclinical studies have shown that females require a higher dose of morphine to reach analgesic effects that are equivalent to males (Craft et al, 2008;Dawson-Basoa & Gintzler, 1993;Doyle et al, 2017;Loyd et al, 2008;Mogil et al, 2000;Sepulveda et al, 2021;Wang et al, 2006).…”

Section: Sex Comparisonsmentioning

confidence: 94%

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Cannabigerol (CBG) attenuates mechanical hypersensitivity elicited by chemotherapy‐induced peripheral neuropathy

Sepulveda

Morris

Raup‐Konsavage

et al. 2022

European Journal of Pain

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Background Cannabigerol (CBG) is a non‐psychoactive phytocannabinoid produced by the plant Cannabis sativa with affinity to various receptors involved in nociception. As a result, CBG is marketed as an over‐the‐counter treatment for many forms of pain. However, there is very little research‐based evidence for the efficacy of CBG as an anti‐nociceptive agent. Methods To begin to fill this knowledge gap, we assessed the anti‐nociceptive effects of CBG in C57BL/6 mice using three different models of pain; cisplatin‐induced peripheral neuropathy, the formalin test, and the tail‐flick assay. Results Using the von Frey test, we found that CBG‐attenuated mechanical hypersensitivity evoked by cisplatin‐induced peripheral neuropathy in both male and female mice. Additionally, we observed that this CBG‐induced reduction in mechanical hypersensitivity was attenuated by the α2‐adrenergic receptor antagonist atipamezole (3 mg/kg, i.p.) and the CB1R antagonist, AM4113 (3 mg/kg, i.p.), and blocked by the CB2R antagonist/inverse agonist, SR144528 (10 mg/kg, i.p.). We found that the TRPV1 antagonist, SB705498 (20 mg/kg, i.p.) was unable to prevent CBG actions. Furthermore, we show that CBG:CBD oil (10 mg/kg, i.p.) was more effective than pure CBG (10 mg/kg) at reducing mechanical hypersensitivity in neuropathic mice. Lastly, we show that pure CBG and CBG:CBD oil were ineffective at reducing nociception in other models of pain, including the formalin and tail flick assays. Conclusions Our findings support the role of CBG in alleviating mechanical hypersensitivity evoked by cisplatin‐induced peripheral neuropathy, but highlight that these effects may be limited to specific types of pain. Significance There are few effective treatments for neuropathic pain and neuropathic pain is projected to increase with the aging population. We demonstrate that CBG (cannabigerol) and CBG:CBD oil attenuate neuropathy‐induced mechanical hypersensitivity mice. Second, we identify receptor targets that mediate CBG‐induced reduction in mechanical hypersensitivity in neuropathic mice. Third, we demonstrate that an acute injection of CBG is anti‐nociceptive specifically for neuropathic pain rather than other forms of pain, including persistent pain and thermal pain.

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Section: Discussionmentioning

confidence: 90%

Section: Sex Comparisonsmentioning

confidence: 94%

Cannabigerol (CBG) attenuates mechanical hypersensitivity elicited by chemotherapy‐induced peripheral neuropathy

Sepulveda

Morris

Raup‐Konsavage

et al. 2022

European Journal of Pain

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“…The meta-analysis and a systematic review of modulators of the endocannabinoid system found verity in CBD treatment outcomes based on the in ammatory and pain model. The studies CBD has signi cantly decreased nociceptive behaviors with mixed results in neuropathic and in ammatory pain models 28,29 . Other pre-clinical and clinical studies have found CBD to be a promising antinociceptive agent for decreasing neuropathic and in ammatory pain 22,[30][31][32][33][34] .…”

Section: Discussionmentioning

confidence: 99%

Study the Effect of Cannabidiol Topical on Antinociceptive and Anti-inflammatory Activities in Animal Model

Bunman

Muengtaweepongsa

Piyayotai

et al. 2022

Preprint

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Introduction: Cannabidiol (CBD) is a non-psychoactive compound of cannabis. Due to the therapeutic potential of CBD, there were given drugs through oral administration to treat pain and anti-inflammatory. The bioavailability of CBD has been reported to be poor when given through oral administration because of the high first-pass effect with cytochrome P450. Transdermal delivery systems of CBD may increase bioavailability and decrease first-pass metabolism with cytochrome P450. This study aimed to evaluate the antinociceptive and anti-inflammatory activities of CBD cream in an animal model. Formalin test and Antinociceptive activity. Materials and Methods: We examined the antinociceptive and anti-inflammatory of CBD cream in an animal model. Formalin and writhing tests were used for the antinociceptive activity, and Acute inflammatory was used carrageenan-induced edema test. Result: In this study, we tested the efficacy of CBD topical for antinociceptive and anti-inflammatory in an animal model. For the formalin test, in the early phase, AUC values in all treatments were significantly decreased when compared with placebo cream (P<0.0001, P<0.0001, P<0.0001, respectively), which were the same results in the late phase. Moreover, mice treated with CBD and CBD+levomenthol group showed less pain than with diclofenac usage. For the acetic induce writhing response test, The results have demonstrated that diclofenac, CBD, and CBD+levomenthol cream showed an ability to reduce writhes compared with a placebo group. Carrageenan-induced edema, The 1% CBD cream could significantly decrease paw volume from 1 to 4 h compared to the placebo group. Overall, 1% CBD cream treatment may have a high efficacy in decreasing paw volume from 1 to 4 h. Conclusion: The study demonstrated that 1% CBD cream has potential effects for analgesia and anti-inflammation. Even though the mechanism of the therapeutic effect of a new formulation of CBD has not been completely understood, the topical of 1%CBD cream may also be a good candidate for treatment for analgesic and anti-inflammatory conditions.

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“…The data demonstrated the efficiency of the cannabinoids in low back pain, headache, cancer, and surgical pain [112,250,255]. Cannabinoids may be a viable strategy to limit opioids since their effects are independent and addictive, considering their independent mechanism of action and less-addictive potential [251,256,257].…”

Section: Pain Perception In the Context Of Cannabinoid Usementioning

confidence: 99%

Considerations for Cannabinoids in Perioperative Care by Anesthesiologists

Laudański

Wain

2022

JCM

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Increased usage of recreational and medically indicated cannabinoid compounds has been an undeniable reality for anesthesiologists in recent years. These compounds’ complicated pharmacology, composition, and biological effects result in challenging issues for anesthesiologists during different phases of perioperative care. Here, we review the existing formulation of cannabinoids and their biological activity to put them into the context of the anesthesia plan execution. Perioperative considerations should include a way to gauge the patient’s intake of cannabinoids, the ability to gain consent properly, and vigilance to the increased risk of pulmonary and airway problems. Intraoperative management in individuals with cannabinoid use is complicated by the effects cannabinoids have on general anesthetics and depth of anesthesia monitoring while simultaneously increasing the potential occurrence of intraoperative hemodynamic instability. Postoperative planning should involve higher vigilance to the risk of postoperative strokes and acute coronary syndromes. However, most of the data are not up to date, rending definite conclusions on the importance of perioperative cannabinoid intake on anesthesia management difficult.

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Evaluating the Antinociceptive Efficacy of Cannabidiol Alone or in Combination with Morphine Using the Formalin Test in Male and Female Mice

Cited by 14 publications

References 84 publications

Cannabigerol (CBG) attenuates mechanical hypersensitivity elicited by chemotherapy‐induced peripheral neuropathy

Cannabigerol (CBG) attenuates mechanical hypersensitivity elicited by chemotherapy‐induced peripheral neuropathy

Study the Effect of Cannabidiol Topical on Antinociceptive and Anti-inflammatory Activities in Animal Model

Considerations for Cannabinoids in Perioperative Care by Anesthesiologists

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