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Introduction: Cannabis extracts are being increasingly used to mitigate chronic pain. Current guidelines for their prescription rely on ?9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content as well as the ratio of these major cannabinoids present in the blend. Here we assessed whether these descriptors were representative of product effectiveness to produce a desired outcome such as analgesia. Methods: In this study, we used a rat model of diabetic neuropathy and assessed the reduction in mechanical allodynia following intrathecal injection of pure THC, pure CBD, a 1:1 mix of these compounds and a "balanced" chemotype II cannabis extract. Engagement of endocannabinoid targets by different treatments was investigated using CB1 (AM251) and CB2 (AM630) receptor antagonists as well as a TRPV1 channel blocker (capsazepine). Results: Antinociceptive responses induced by an equivalent amount of THC administered in its pure form, as a THC:CBD mix or as a "balanced" extract were distinct. Furthermore, the 1:1 THC:CBD mix and the balanced extract had not only different response profiles but their relative engagement of CB1, CB2 receptors and TRPV1 channels was distinct. Discussion: These findings indicate that antinociceptive responses and targets engaged by blended cannabinoids are composition-specific, and cannot be simply inferred from THC and CBD contents. This information may have implications in relation to the way medicinal cannabis products are prescribed. [ABSTRACT FROM AUTHOR]

Introduction: Cannabis extracts are being increasingly used to mitigate chronic pain. Current guidelines for their prescription rely on Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content as well as the ratio of these major cannabinoids present in the blend. Here we assessed whether these descriptors were representative of product effectiveness to produce a desired outcome such as analgesia.Methods: In this study, we used a rat model of diabetic neuropathy and assessed the reduction in mechanical allodynia following intrathecal injection of pure THC, pure CBD, a 1:1 mix of these compounds and a “balanced” chemotype II cannabis extract. Engagement of endocannabinoid targets by different treatments was investigated using CB1 (AM251) and CB2 (AM630) receptor antagonists as well as a TRPV1 channel blocker (capsazepine).Results: Antinociceptive responses induced by an equivalent amount of THC administered in its pure form, as a THC:CBD mix or as a “balanced” extract were distinct. Furthermore, the 1:1 THC:CBD mix and the balanced extract had not only different response profiles but their relative engagement of CB1, CB2 receptors and TRPV1 channels was distinct.Discussion: These findings indicate that antinociceptive responses and targets engaged by blended cannabinoids are composition-specific, and cannot be simply inferred from THC and CBD contents. This information may have implications in relation to the way medicinal cannabis products are prescribed.

Earlier studies have demonstrated that essential fatty acid-derived specialized pro-resolving mediators (SPMs) promote the resolution of inflammation and pain. However, the potential analgesic actions of SPMs in chemotherapy-induced peripheral neuropathy (CIPN) are not known. Recent results also showed sex dimorphism in immune cell signaling in neuropathic pain. Here, we evaluated the analgesic actions of D-series resolvins (RvD1, RvD2, RvD3, RvD4, and RvD5) on a CIPN in male and female mice. Paclitaxel (PTX, 2 mg/kg), given on days 0, 2, 4, and 6, produced robust mechanical allodynia in both sexes at 2 weeks. Intrathecal injection of RvD1 and RvD2 (100 ng, i.t.) at 2 weeks reversed PTX-induced mechanical allodynia in both sexes, whereas RvD3 and RvD4 (100 ng, i.t.) had no apparent effects on either sex. Interestingly, RvD5 (100 ng, i.t.) only reduced mechanical allodynia in male mice but not in female mice. Notably, PTX-induced mechanical allodynia was fully developed in Trpv1 or Trpa1 knockout mice, showing no sex differences. Also, intrathecal RvD5 reduced mechanical allodynia in male mice lacking Trpv1 or Trpa1, whereas female mice with Trpv1 or Trpa1 deficiency had no response to RvD5. Finally, RvD5-induced male-specific analgesia was also confirmed in an inflammatory pain condition. Formalin-induced second phase pain (licking and flinching) was reduced by intrathecal RvD5 in male but not female mice. These findings identified RvD5 as the first SPM that shows sex dimorphism in pain regulation. Moreover, these results suggest that specific resolvins may be used to treat CIPN, a rising health concern in cancer survivors.

Earlier studies have demonstrated that essential fatty acid-derived specialized pro-resolving mediators (SPMs) promote the resolution of inflammation and pain. However, the potential analgesic actions of SPMs in chemotherapy-induced peripheral neuropathy (CIPN) are not known. Recent results also showed sex dimorphism in immune cell signaling in neuropathic pain. Here, we evaluated the analgesic actions of D-series resolvins (RvD1, RvD2, RvD3, RvD4, and RvD5) on a CIPN in male and female mice. Paclitaxel (PTX, 2 mg/kg), given on days 0, 2, 4, and 6, produced robust mechanical allodynia in both sexes at 2 weeks. Intrathecal injection of RvD1 and RvD2 (100 ng, i.t.) at 2 weeks reversed PTX-induced mechanical allodynia in both sexes, whereas RvD3 and RvD4 (100 ng, i.t.) had no apparent effects on either sex. Interestingly, RvD5 (100 ng, i.t.) only reduced mechanical allodynia in male mice but not in female mice. Notably, PTX-induced mechanical allodynia was fully developed in Trpv1 or Trpa1 knockout mice, showing no sex differences. Also, intrathecal RvD5 reduced mechanical allodynia in male mice lacking Trpv1 or Trpa1 , whereas female mice with Trpv1 or Trpa1 deficiency had no response to RvD5. Finally, RvD5-induced male-specific analgesia was also confirmed in an inflammatory pain condition. Formalin-induced second phase pain (licking and flinching) was reduced by intrathecal RvD5 in male but not female mice. These findings identified RvD5 as the first SPM that shows sex dimorphism in pain regulation. Moreover, these results suggest that specific resolvins may be used to treat CIPN, a rising health concern in cancer survivors. [ABSTRACT FROM AUTHOR]

Introduction: Cannabis extracts are being increasingly used to mitigate chronic pain. Current guidelines for their prescription rely on Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) content as well as the ratio of these major cannabinoids present in the blend. Here we assessed whether these descriptors were representative of product effectiveness to produce a desired outcome such as analgesia. Methods: In this study, we used a rat model of diabetic neuropathy and assessed the reduction in mechanical allodynia following intrathecal injection of pure THC, pure CBD, a 1:1 mix of these compounds and a "balanced" chemotype II cannabis extract. Engagement of endocannabinoid targets by different treatments was investigated using CB1 (AM251) and CB2 (AM630) receptor antagonists as well as a TRPV1 channel blocker (capsazepine). Results: Antinociceptive responses induced by an equivalent amount of THC administered in its pure form, as a THC:CBD mix or as a "balanced" extract were distinct. Furthermore, the 1:1 THC:CBD mix and the balanced extract had not only different response profiles but their relative engagement of CB1, CB2 receptors and TRPV1 channels was distinct. Discussion: These findings indicate that antinociceptive responses and targets engaged by blended cannabinoids are composition-specific, and cannot be simply inferred from THC and CBD contents. This information may have implications in relation to the way medicinal cannabis products are prescribed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2023 Benredjem and Pineyro.)