The oral administration of trans-caryophyllene attenuates acute and chronic pain in mice

Paula-Freire, Lyvia Izaura Gomes; Andersen, Mônica Levy; Gama, Vanessa Scalco; Molska, Graziella Rigueira; Carlini, E. A.

doi:10.1016/j.phymed.2013.08.006

Cited by 87 publications

(46 citation statements)

References 44 publications

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“…To date, it is unknown which non‐CB 2 receptor mechanisms are responsible for BCP‐induced reductions in nicotine or food self‐administration. Among potential non‐CB 2 receptor targets are fatty acid amide hydrolase (FAAH; Chicca et al, ), the major eCB degrading enzyme (Chicca et al, ), μ opioid receptors(Katsuyama et al, ; Paula‐Freire, Andersen, Gama, Molska, & Carlini, ), and peroxisome proliferator‐activated receptors ( PPAR) ‐γ or ‐α; Justinova et al, ; Youssef et al, ), all of which have been implemented in nicotine‐related behaviours (Justinova et al, ; Krause et al, ; Merritt et al, ) and food consumption (Fu et al, ; King et al, ). Thus, our findings of attenuating effects of BCP on nicotine and food self‐administration in CB2‐KO mice might be partly explained by BCP‐induced inhibition of FAAH or stimulation of PPAR/μ opioid receptors.…”

Section: Discussionmentioning

confidence: 99%

β‐Caryophyllene, a dietary terpenoid, inhibits nicotine taking and nicotine seeking in rodents

Galaj

et al. 2020

British J Pharmacology

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Background and Purpose: β-Caryophyllene (BCP) is a plant-derived terpenoid used as a food additive for many decades. Recent studies indicate that BCP is a cannabinoid CB 2 receptor agonist with medical benefits for a number of human diseases.However, little is known about its therapeutic potential for drug abuse and addiction. Experiment Approach:We used pharmacological, transgenic, and optogenetic approaches to systematically evaluate the effects of BCP on nicotine-taking and nicotine-seeking behaviour in animal models of drug self-administration, electrical, and optical brain-stimulation reward.Key Results: Systemic administration of BCP dose-dependently inhibited nicotine self-administration and motivation for nicotine seeking in rats and mice. The reduction in nicotine self-administration was blocked by AM630, a selective CB 2 receptor antagonist, but not by AM251, a selective CB 1 receptor antagonist, suggesting involvement of a CB 2 receptor mechanism. Genetic deletion of CB 2 receptors in mice blocked the reduction in nicotine self-administration produced only by low doses, but not by high doses, of BCP, suggesting involvement of both CB 2 and non-CB 2 receptor mechanisms. Furthermore, in the intracranial self-stimulation paradigm, BCP attenuated electrical brain-stimulation reward and nicotine-enhanced brainstimulation reward in rats. Lastly, BCP also attenuated brain-stimulation reward maintained by optogenetic stimulation of dopaminergic neurons in the ventral tegmental area in DAT-cre mice, suggesting the involvement of a dopamine-dependent mechanism in BCP's action. Conclusions and Implications:The present findings suggest that BCP has significant anti-nicotine effects via both CB 2 and non-CB 2 receptor mechanisms and, therefore, deserves further study as a potential new pharmacotherapy for cigarette smoking cessation.

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Section: Discussionmentioning

confidence: 99%

β‐Caryophyllene, a dietary terpenoid, inhibits nicotine taking and nicotine seeking in rodents

Galaj

et al. 2020

British J Pharmacology

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“…Interestingly, BCP can diminish an acute and chronic pain not only through cannabinoid, but additionally through opioid system. This was observed in mice after oral administration of BCP, in which licking and jumping latency in the hot plate test was increased, whereas pain feeling in the formalin test was attenuated [53]. In contrast to BCP, BCPO does not attract much attention as a pain modulator, although it may possess some antinociceptive properties since Chavan et al [54] have documented centrally and peripherally mediated analgesia by BCPO isolated from Annona squamosa bark extract, in response to pain stimuli in mice.…”

Section: Bcp(o)asanalgesicagentsmentioning

confidence: 99%

“…In addition, Paula‐Freire et al. reported a decreased level of IL‐1 β in the injured sciatic nerve after BCP treatment, in a model of chronic pain. Another possible mechanism of BCP pain modulation may be related to peripheral CB 2 simulation and β ‐endorphin release from keratinocytes, which was noted after local and intraplantar injections of BCP in response to capsaicin‐induced nociception.…”

Section: Bcp(o) As Analgesic Agentsmentioning

confidence: 99%

β‐caryophyllene and β‐caryophyllene oxide—natural compounds of anticancer and analgesic properties

et al. 2016

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Natural bicyclic sesquiterpenes, β‐caryophyllene (BCP) and β‐caryophyllene oxide (BCPO), are present in a large number of plants worldwide. Both BCP and BCPO (BCP(O)) possess significant anticancer activities, affecting growth and proliferation of numerous cancer cells. Nevertheless, their antineoplastic effects have hardly been investigated in vivo. In addition, both compounds potentiate the classical drug efficacy by augmenting their concentrations inside the cells. The mechanisms underlying the anticancer activities of these sesquiterpenes are poorly described. BCP is a phytocannabinoid with strong affinity to cannabinoid receptor type 2 (CB 2), but not cannabinoid receptor type 1 (CB 1). In opposite, BCP oxidation derivative, BCPO, does not exhibit CB 1/2 binding, thus the mechanism of its action is not related to endocannabinoid system (ECS) machinery. It is known that BCPO alters several key pathways for cancer development, such as mitogen‐activated protein kinase (MAPK), PI3K/AKT/mTOR/S6K1 and STAT3 pathways. In addition, treatment with this compound reduces the expression of procancer genes/proteins, while increases the levels of those with proapoptotic properties. The selective activation of CB 2 may be considered a novel strategy in pain treatment, devoid of psychoactive side effects associated with CB 1 stimulation. Thus, BCP as selective CB 2 activator may be taken into account as potential natural analgesic drug. Moreover, due to the fact that chronic pain is often an element of cancer disease, the double activity of BCP, anticancer and analgesic, as well as its beneficial influence on the efficacy of classical chemotherapeutics, is particularly valuable in oncology. This review is focused on anticancer and analgesic activities of BCP and BCPO, the mechanisms of their actions, and potential therapeutic utility.

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“…It is sesquiterpene found in many EOs especially cloves (28). Trans-Caryophyllene is known for its anti-inflammatory and pain killer effects (29). S. aromaticum activity against FLC resistant Candida species was also suitable (MIC = 700 µ/mL).…”

Section: Discussionmentioning

confidence: 99%

Fungicidal versus Fungistatic activity of five Iranian essences against fluconazole resistant Candida species

Nikaein¹,

Sharifzadeh²,

Khosravi³

2018

J Herbmed Pharmacol

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The oral administration of trans-caryophyllene attenuates acute and chronic pain in mice

Cited by 87 publications

References 44 publications

β‐Caryophyllene, a dietary terpenoid, inhibits nicotine taking and nicotine seeking in rodents

β‐Caryophyllene, a dietary terpenoid, inhibits nicotine taking and nicotine seeking in rodents

β‐caryophyllene and β‐caryophyllene oxide—natural compounds of anticancer and analgesic properties

Fungicidal versus Fungistatic activity of five Iranian essences against fluconazole resistant Candida species

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