The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain

Abstract

The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressed cannabinoid receptor 2 (CB₂). It is found in relatively high concentrations in many spices and food plants. A number of studies have shown that CB₂ is critically involved in the modulation of inflammatory and neuropathic pain responses. In this study, we have investigated the analgesic effects of BCP in animal models of inflammatory and neuropathic pain. We demonstrate that orally administered BCP reduced inflammatory (late phase) pain responses in the formalin test in a CB₂ receptor-dependent manner, while it had no effect on acute (early phase) responses. In a neuropathic pain model the chronic oral administration of BCP attenuated thermal hyperalgesia and mechanical allodynia, and reduced spinal neuroinflammation. Importantly, we found no signs of tolerance to the anti-hyperalgesic effects of BCP after prolonged treatment. Oral BCP was more effective than the subcutaneously injected synthetic CB₂ agonist JWH-133. Thus, the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions.

In Vitro and In Vivo Characterization of the New Analgesic Combination Beta‐Caryophyllene and Docosahexaenoic Acid

“…The general modulation of all three pain responses observed in the present study suggested general analgesia, probably due to attenuation of the peripheral inflammation. These results are in agreement with other studies reporting that BCP has analgesic and anti-inflammatory effects in both rats and mice [15, 16]. …”

“…BCP, a common sesquiterpene present in cannabis and in many other plants, is a potent CB2 agonist producing peripheral antinociception [16, 23–25] without the central nervous system effects mediated by CB1 receptors [23, 26]. Therefore, the selective activation of CB2 receptors may produce peripheral pain relief without CNS psychotropic effects.…”

“…BCP has been shown to have multiple functions. In particular, it had strong anti-inflammatory and analgesic effects in rats and mice [14–16] in a model of acute single administration.…”

Natural Products as Promising Pharmacological Tools for the Management of Fibromyalgia Symptoms – A Review

“…In addition, in a neuropathic pain model, β-caryophyllene had an effect on thermal hyperalgesia and mechanical allodynia, reducing spinal neuroinflammation. The oral administration of β-caryophyllene was more effective than the subcutaneously injected synthetic CB2 agonist JWH-133 [84].…”

Short-term efficacy of a fixed association of Palmitoylethanolamide and other phytochemicals as add-on therapy in the management of chronic pain in elderly patients: a real-world retrospective study

“…18,[29][30][31] β-Caryophyllene is a member of sesquiterpene lactone found in large amounts in Piper Nigrum (black pepper) and other plants, 32 with analgesic, antidiabetic, hepatoprotective and neuroprotective properties. 33,34 Whilst myrrh has a Mu opioid effect, β-Caryophyllene is a selective cannabinoid receptor (CB) 2 receptor agonist, thus it does not have the psychotropic effects typical of other cannabinoids that Nausea 4 (8.5%) 3 (6%) 1 (2%) 8 (17%) 7 (15%) 0 (0%) 0 (0%) 7 (15%) 1 (2%) 0 (0%) 0 (0%) 1 (2%) 1 (2%) 0 (0%) 0 (0%) 1 (2%) Vomiting 1 (2%) 0 (0%) 1 (2%) 2 (4%) 1 (2%) 0 (0%) 0 (0%) 1 (2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) Dizziness 9 (19%) 1 (2%) 1 (2%) 1 (2%) 8 (17%) 0 (0%) 0 (0%) 8 (17%) 5 (11%) 0 (0%) 0 (0%) 5 (11%) 4 (8.5%) 0 (0%) 0 (0%) 4 (8.5%) Drowsiness 4 (8.5%) 2 (4%) 1 (2%) 7 (15%) 5 (11%) 1 (2%) 0 (0%) 6 (13%) 3 (6%) 0 (0%) 0 (0%) 3 (6%) 1 (2%) 0 (0%) 0 (0%) 1 (2%) Dry mouth 4 (8.5%) 2 (4%) 1 (2%) 7 (15%) 5 (11%) 0 (0%) 0 (0%) 5 (11%) 1 (2%) 0 (0%) 0 (0%) 1 (2%) 1 (2%) 0 (0%) 0 (0%) 1 (2%) Itch 6 (13%) 0 (0%) 1 (2%) 7 (15%) 4 (8.5%) 1 (2%) 0 (0%) 5 (11%) 3 (6%) 2 (4%) 0 (0%) 5 (11%) 3 (6%) 0 (0%) 0 (0%) 3 (6%) Other 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) AE, adverse event. bind to CB1.…”