humulene and Edema

Although preclinical studies generally report robust antinociceptive effects of cannabinoids in rodent persistent pain models, randomized controlled trials in chronic pain patients report limited pain relief from cannabis/cannabinoids. Differences between animal and human studies that may contribute to these discrepant findings include route of cannabis/cannabinoid administration, type of cannabis/cannabinoid, and how pain is measured. To address these factors, rats with complete Freund adjuvant (CFA)-induced hind paw inflammation were exposed acutely or repeatedly to vaporized cannabis extract that was either tetrahydrocannabinol (THC) or cannabidiol (CBD)dominant. One measure of evoked pain (mechanical threshold), 2 functional measures of pain (hind paw weight-bearing, and locomotor activity), and hind paw edema were assessed for up to 2 hours after vapor exposure. Acute exposure to vaporized THC-dominant extract (200 or 400 mg/mL) decreased mechanical allodynia and hind paw edema and increased hind paw weight-bearing and locomotor activity, with no sex differences. After repeated exposure to vaporized THC-dominant extract (twice daily for 3 days), only the antiallodynic effect was significant. Acute exposure to vaporized CBD-dominant cannabis extract (200 mg/mL) did not produce any effects in either sex; repeated exposure to this extract (100, 200, or 400 mg/mL) decreased mechanical allodynia in male rats only. Sex differences (or lack thereof) in the effects of vaporized cannabis extracts were not explained by sex differences in plasma levels of THC, CBD, or their major metabolites. These results suggest that although vaporized THC-dominant extract is likely to be modestly effective against inflammatory pain in both male and female rats, tolerance may develop, and the CBD-dominant extract may be effective only in male rats.

Topics: Animals; Cannabidiol; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Chronic Pain; Dronabinol; Edema; Female; Humans; Hyperalgesia; Male; Rats

Bothrops moojeni snake venom (VBm) has toxins that cause pronounced tissue damage and exacerbated inflammatory reaction. Cannabis sativa L. is a plant species that produces an oil (CSO) rich in unsaturated fatty acids. Nano-emulsions have several advantages, such as better stability and higher penetrating power in membranes. Therefore, this study evaluated the effect of a nano-emulsion based on this herbal derivative (NCS) against VBm-induced inflammation in Wistar rats.. The CSO and NCS were submitted to physicochemical characterization. The inflammatory process was induced by the VBm (0.10 mg/kg) as follows: rat paw edema, peritonitis, analysis of leukocyte infiltrate in gastrocnemius muscle of rats and formation of granulomatous tissue.. The results obtained in this study showed anti-inflammatory activity of the CSO which may be due to a high UFA content. The nanosizing, as evidenced by the incorporation of the CSO in the NCS improved the effect and opens the perspective for the obtainment of a nanomedicine in which a kinetic stable phytotherapic can be used at low doses.

Topics: Animals; Anti-Inflammatory Agents; Bothrops; Cannabis; Crotalid Venoms; Edema; Emulsions; Inflammation; Male; Muscle, Skeletal; Nanostructures; Particle Size; Plant Oils; Rats; Rats, Wistar

Cannabis sativa L. is an aromatic annual herb belonging to the family Cannabaceae and it is widely distributed worldwide. Cultivation, selling, and consumption of cannabis and cannabis related products, regardless of its use, was prohibited in Lebanon until April 22, 2020. Nevertheless, cannabis oil has been traditionally used unlawfully for many years in Lebanon to treat diseases such as arthritis, diabetes, cancer and few neurological disorders.. The present study aims to evaluate the phytochemical and anti-inflammatory properties of a cannabis oil preparation that is analogous to the illegally used cannabis oil in Lebanon.. Dried Cannabis flowers were extracted with ethanol without any purification procedures to simulate the extracts sold by underground dealers in Lebanon. GC/MS was performed to identify chemical components of the cannabis oil extract (COE). In vivo anti-inflammatory effect of COE was evaluated by using carageenan- and formalin-induced paw edema rat models. TNF-α production were determined by using LPS-activated rat monocytes. Anti-inflammatory markers were quantified using Western blot.. Chemical analysis of COE revealed that cannabidiol (CBD; 59.1%) and tetrahydrocannabinol (THC; 20.2%) were found to be the most abundant cannabinoids.Various monoterpenes (α-Pinene, Camphene, β-Myrecene and D-Limonene) and sesquiterpenes (β-Caryophyllene, α-Bergamotene, α-Humelene, Humulene epoxide II, and Caryophyllene oxide) were identified in the extract. Results showed that COE markedly suppressed the release of TNF-α in LPS-stimulated rat monocytes. Western blot analysis revealed that COE significantly inhibited LPS-induced COX-2 and i-NOS protein expressions and blocked the phosphorylation of MAPKs, specifically that of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 MAPK. COE displayed a significant inhibition of paw edema in both rat models. Histopathological examination revealed that COE reduced inflammation and edema in chronic paw edema model.. The current findings demonstrate that COE possesses remarkable in vivo and in vitro anti-inflammatory activities which support the traditional use of the Lebanese cannabis oil extract in the treatment of various inflammatory diseases including arthritis.

Topics: Animals; Anti-Inflammatory Agents; Cannabis; Carrageenan; Disease Models, Animal; Edema; Flowers; Formaldehyde; Inflammation; Lebanon; Lipopolysaccharides; Male; MAP Kinase Signaling System; Monocytes; Phytochemicals; Plant Extracts; Primary Cell Culture; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

There are many studies and therapeutic properties attributed to the flowers and leaves of the Cannabis species, but even with few pharmacological studies, Cannabis sativa L. (Cannabaceae) roots presents several therapeutic indications in folk medicine.. This study aimed to evaluate the anti-inflammatory and spasmolytic effects as well as the toxicological profile of the aqueous extract of Cannabis sativa roots (CsAqEx) in mice.. We assessed the anti-inflammatory effect with carrageenan-induced leukocyte migration assay, and carrageenan and histamine-induced paw edema methods; The spasmolytic effect was assessed through in vitro assays with isolated mice trachea. To assess motor coordination and mobility, mice went through the rotarod and open field tests, respectively. For the single-dose toxicity study, we administered CsAqEx at the dose of 1000 mg/kg by gavage. In a repeated dose toxicity study, animals received CsAqEx at doses of 25 mg or 100 mg/kg for 28 days.. The results suggest that the anti-inflammatory effect of CsAqEx is related to the reduction of vascular extravasation and migration of inflammatory cells, without effects on the central nervous system. Moreover, there was no spasmolytic effect on airway smooth muscle and no toxicity was observed on mice.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Behavior, Animal; Cannabis; Carrageenan; Edema; Histamine; Inflammation; Kidney; Liver; Mice; Muscle, Smooth; Open Field Test; Parasympatholytics; Plant Extracts; Plant Roots; Psychomotor Performance; Rotarod Performance Test; Stomach; Trachea

In folklore medicine, the plant Emilia sonchifolia, belonging to the family Asteraceae, is used for treating tumour and inflammation. In our previous studies, we have done a thorough phytochemical investigation of E. sonchifolia with a report on its potent antimetastatic activity. Further, we isolated and characterised its active fraction (AFES) containing the major compound γ-humulene with an evaluation of the antiangiogenic effect of AFES (5 mg/kg b.wt.). In the first part of the present study, AFES in different concentrations was used for the assessment of its possible anti-inflammatory effect employing three in vivo inflammatory models. Further using the most effective concentration of AFES 5 mg/kg b.wt, its effect on proinflammatory cytokine levels was recorded along with a confirmatory gene expression analysis. The results manifested with a reduction in the paw oedema significantly decreased levels of proinflammatory cytokines, C-reactive protein, nitric oxide and also there was an efficient downregulation of cyclooxygenase-2 and inducible nitric oxide. Urotoxicity is one of the major side effects of conventional chemotherapy. So in the second part of the study, we used AFES in combination with the conventional therapeutic agent cyclophosphamide in vivo in mice. The effect of AFES on urotoxicity was assessed from various biochemical parameters, cytokine markers and finally with a histopathology of the bladder. The current study revealed the protective effects of AFES, implicating reduced levels of urea nitrogen, by revamping of glutathione and marker cytokine levels towards positive amelioration. The results obtained altogether proved the safeguarding effect of AFES in murine experimental models.

Topics: Animals; Anti-Inflammatory Agents; Asteraceae; C-Reactive Protein; Cell Line; Cytokines; Edema; Inflammation; Male; Medicine, Traditional; Mice; Mice, Inbred BALB C; Monocyclic Sesquiterpenes; Nitric Oxide; Plant Extracts; Sesquiterpenes

We assessed the prevalence of potential health hazards to intervention staff and cannabis growers in Belgian indoor cannabis plantations. Surface mold swab samples were taken at 16 Belgian indoor plantations contained mostly Penicillium sp. and Aspergillus sp. However, their precise health impact on intervention staff and illicit growers is unclear as no molds spore concentrations were measured. Atmospheric gas monitoring in the studied cannabis plantations did not reveal dangerous toxic substances. Health symptoms were reported by 60% of 221 surveyed police, but could not be linked to specific plantation characteristics. We conclude that Belgian indoor cannabis plantations pose a potential health threat to growers and intervention staff. AS there are currently no clear safety guidelines for seizure and dismantling of Belgian indoor cannabis plantations, we recommend first responders to follow strict safety rules when entering the growth rooms, which include wearing appropriate personal protective equipment.

Topics: Adult; Air Pollution, Indoor; Aspergillus; Belgium; Cannabis; Carbon Dioxide; Dermatitis, Irritant; Dizziness; Drug Trafficking; Dyspnea; Edema; Female; Headache; Humans; Male; Middle Aged; Penicillium; Police; Pruritus; Spores, Fungal

The psychoactive cannabinoids from Cannabis sativa L. and the arachidonic acid-derived endocannabinoids are nonselective natural ligands for cannabinoid receptor type 1 (CB(1)) and CB(2) receptors. Although the CB(1) receptor is responsible for the psychomodulatory effects, activation of the CB(2) receptor is a potential therapeutic strategy for the treatment of inflammation, pain, atherosclerosis, and osteoporosis. Here, we report that the widespread plant volatile (E)-beta-caryophyllene [(E)-BCP] selectively binds to the CB(2) receptor (K(i) = 155 +/- 4 nM) and that it is a functional CB(2) agonist. Intriguingly, (E)-BCP is a common constituent of the essential oils of numerous spice and food plants and a major component in Cannabis. Molecular docking simulations have identified a putative binding site of (E)-BCP in the CB(2) receptor, showing ligand pi-pi stacking interactions with residues F117 and W258. Upon binding to the CB(2) receptor, (E)-BCP inhibits adenylate cylcase, leads to intracellular calcium transients and weakly activates the mitogen-activated kinases Erk1/2 and p38 in primary human monocytes. (E)-BCP (500 nM) inhibits lipopolysaccharide (LPS)-induced proinflammatory cytokine expression in peripheral blood and attenuates LPS-stimulated Erk1/2 and JNK1/2 phosphorylation in monocytes. Furthermore, peroral (E)-BCP at 5 mg/kg strongly reduces the carrageenan-induced inflammatory response in wild-type mice but not in mice lacking CB(2) receptors, providing evidence that this natural product exerts cannabimimetic effects in vivo. These results identify (E)-BCP as a functional nonpsychoactive CB(2) receptor ligand in foodstuff and as a macrocyclic antiinflammatory cannabinoid in Cannabis.

Topics: Administration, Oral; Animals; Binding Sites; Binding, Competitive; Cannabinoids; Cannabis; Carrageenan; Cells, Cultured; Computational Biology; Diet; Edema; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; GTP-Binding Protein alpha Subunits, Gi-Go; Humans; Interleukin-1beta; JNK Mitogen-Activated Protein Kinases; Ligands; Lipopolysaccharides; Mice; Monocytes; Oils, Volatile; Polycyclic Sesquiterpenes; Receptor, Cannabinoid, CB2; Sesquiterpenes; Signal Transduction; Tumor Necrosis Factor-alpha

The anti-inflammatory and anti-allergic effects of the essential oil of Cordia verbenacea (Boraginaceae) and some of its active compounds were evaluated. Systemic treatment with the essential oil of Cordia verbenacea (300-600mg/kg, p.o.) reduced carrageenan-induced rat paw oedema, myeloperoxidase activity and the mouse oedema elicited by carrageenan, bradykinin, substance P, histamine and platelet-activating factor. It also prevented carrageenan-evoked exudation and the neutrophil influx to the rat pleura and the neutrophil migration into carrageenan-stimulated mouse air pouches. Moreover, Cordia verbenacea oil inhibited the oedema caused by Apis mellifera venom or ovalbumin in sensitized rats and ovalbumin-evoked allergic pleurisy. The essential oil significantly decreased TNFalpha, without affecting IL-1beta production, in carrageenan-injected rat paws. Neither the PGE(2) formation after intrapleural injection of carrageenan nor the COX-1 or COX-2 activities in vitro were affected by the essential oil. Of high interest, the paw edema induced by carrageenan in mice was markedly inhibited by both sesquiterpenic compounds obtained from the essential oil: alpha-humulene and trans-caryophyllene (50mg/kg, p.o.). Collectively, the present results showed marked anti-inflammatory effects for the essential oil of Cordia verbenacea and some active compounds, probably by interfering with TNFalpha production. Cordia verbenacea essential oil or its constituents might represent new therapeutic options for the treatment of inflammatory diseases.

Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Carrageenan; Cordia; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Edema; Interleukin-1beta; Mice; Monocyclic Sesquiterpenes; Neutrophils; Oils, Volatile; Peroxidase; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; Polycyclic Sesquiterpenes; Rats; Rats, Wistar; Sesquiterpenes; Tumor Necrosis Factor-alpha

This study evaluated the anti-inflammatory properties of two sesquiterpenes isolated from Cordia verbenacea's essential oil, alpha-humulene and (-)-trans-caryophyllene. Our results revealed that oral treatment with both compounds displayed marked inhibitory effects in different inflammatory experimental models in mice and rats. alpha-humulene and (-)-trans-caryophyllene were effective in reducing platelet activating factor-, bradykinin- and ovoalbumin-induced mouse paw oedema, while only alpha-humulene was able to diminish the oedema formation caused by histamine injection. Also, both compounds had important inhibitory effects on the mouse and rat carrageenan-induced paw oedema. Systemic treatment with alpha-humulene largely prevented both tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) generation in carrageenan-injected rats, whereas (-)-trans-caryophyllene diminished only TNFalpha release. Furthermore, both compounds reduced the production of prostaglandin E(2) (PGE(2)), as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) expression, induced by the intraplantar injection of carrageenan in rats. The anti-inflammatory effects of alpha-humulene and (-)-trans-caryophyllene were comparable to those observed in dexamethasone-treated animals, used as positive control drug. All these findings indicate that alpha-humulene and (-)-trans-caryophyllene, derived from the essential oil of C. verbenacea, might represent important tools for the management and/or treatment of inflammatory diseases.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Brazil; Cordia; Cyclooxygenase 2; Dexamethasone; Dinoprostone; Edema; Interleukin-1beta; Male; Medicine, Traditional; Mice; Monocyclic Sesquiterpenes; Nitric Oxide Synthase Type II; Oils, Volatile; Plant Components, Aerial; Plants, Medicinal; Polycyclic Sesquiterpenes; Rats; Rats, Wistar; Sesquiterpenes; Tumor Necrosis Factor-alpha

Cannabidiol, the major non-psychoactive component of marijuana, has various pharmacological actions of clinical interest. It is reportedly effective as an anti-inflammatory and anti-arthritic in murine collagen-induced arthritis. The present study examined the anti-inflammatory and anti-hyperalgesic effects of cannabidiol, administered orally (5-40 mg/kg) once a day for 3 days after the onset of acute inflammation induced by intraplantar injection of 0.1 ml carrageenan (1% w/v in saline) in the rat. At the end of the treatment prostaglandin E2 (PGE2) was assayed in the plasma, and cyclooxygenase (COX) activity, production of nitric oxide (NO; nitrite/nitrate content), and of other oxygen-derived free radicals (malondialdehyde) in inflamed paw tissues. All these markers were significantly increased following carrageenan. Thermal hyperalgesia, induced by carrageenan and assessed by the plantar test, lasted 7 h. Cannabidiol had a time- and dose-dependent anti-hyperalgesic effect after a single injection. Edema following carrageenan peaked at 3 h and lasted 72 h; a single dose of cannabidiol reduced edema in a dose-dependent fashion and subsequent daily doses caused further time- and dose-related reductions. There were decreases in PGE2 plasma levels, tissue COX activity, production of oxygen-derived free radicals, and NO after three doses of cannabidiol. The effect on NO seemed to depend on a lower expression of the endothelial isoform of NO synthase. In conclusion, oral cannabidiol has a beneficial action on two symptoms of established inflammation: edema and hyperalgesia.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cannabidiol; Cannabis; Carrageenan; Dose-Response Relationship, Drug; Edema; Hyperalgesia; Male; Nitric Oxide; Rats; Rats, Wistar

Cannabis Sativa (marijuana) may cause a variety of respiratory disorders including uvular oedema. This case illustrates that uvular oedema secondary to marijuana inhalation may cause a potentially serious postoperative clinical problem.. A healthy 17-yr-old man who inhaled marijuana prior to general anaesthesia. In the recovery room, after an uneventful general anaesthetic, acute uvular oedema resulted in post operative airway obstruction and admission to hospital. The uvular oedema was treated successfully with dexamethasone.. Recent inhalation of marijuana before general anaesthesia may cause acute uvular oedema and post operative airway obstruction. The uvular oedema can be easily diagnosed and treated.

Topics: Administration, Inhalation; Adolescent; Cannabis; Edema; Humans; Male; Postoperative Complications; Uvula

Topics: Abdomen; Acetates; Adjuvants, Immunologic; Adrenal Glands; Adrenalectomy; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Aspirin; Cannabis; Carrageenan; Dronabinol; Edema; Hydrocortisone; Hypophysectomy; Male; Pituitary Gland; Pressure; Rats; Rats, Inbred Strains; Tail; Yeast, Dried

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Aspirin; Body Temperature; Cannabis; Carrageenan; Dose-Response Relationship, Drug; Dronabinol; Edema; Fever; Hyperesthesia; Male; Phenylbutazone; Phytotherapy; Rats; Time Factors; Yeasts

Topics: Animals; Anti-Inflammatory Agents; Cannabis; Carrageenan; Central Nervous System; Depression, Chemical; Dose-Response Relationship, Drug; Dronabinol; Edema; Hexobarbital; Indomethacin; Male; Motor Activity; Phytotherapy; Postural Balance; Propylene Glycols; Rats; Sleep; Time Factors

Topics: Cannabis; Edema; Heart; History, 19th Century; History, 20th Century; Humans; Indians, North American; Medicine, Traditional; Phytotherapy; United States

Topics: Abnormalities, Drug-Induced; Animals; Cannabis; Central Nervous System; Cricetinae; Edema; Embryo, Mammalian; Female; Fetal Death; Fetus; Gestational Age; Leg; Liver; Plant Extracts; Pregnancy; Rabbits; Resins, Plant