The plant cannabinoid Δ9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice

Daniele Bolognini, Barbara Costa, S. Maione, Francesca Comelli, Pietro Marini, Vincenzo Di Marzo, Daniela Parolaro, Ruth Alexandra Ross, Lisa Anne Gauson, Maria Grazia Cascio, Roger Guy Pertwee

Research output: Contribution to journalArticle

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Abstract

BACKGROUND AND PURPOSE: The phytocannabinoid, Delta(9)-tetrahydrocannabivarin (THCV), can block cannabinoid CB(1) receptors. This investigation explored its ability to activate CB(2) receptors, there being evidence that combined CB(2) activation/CB(1) blockade would ameliorate certain disorders.

EXPERIMENTAL APPROACH: We tested the ability of THCV to activate CB(2) receptors by determining whether: (i) it inhibited forskolin-stimulated cyclic AMP production by Chinese hamster ovary (CHO) cells transfected with human CB(2) (hCB(2)) receptors; (ii) it stimulated [(35)S]GTPgammaS binding to hCB(2) CHO cell and mouse spleen membranes; (iii) it attenuated signs of inflammation/hyperalgesia induced in mouse hind paws by intraplantar injection of carrageenan or formalin; and (iv) any such anti-inflammatory or anti-hyperalgesic effects were blocked by a CB(1) or CB(2) receptor antagonist.

KEY RESULTS: THCV inhibited cyclic AMP production by hCB(2) CHO cells (EC(50)= 38 nM), but not by hCB(1) or untransfected CHO cells or by hCB(2) CHO cells pre-incubated with pertussis toxin (100 ng.mL(-1)) and stimulated [(35)S]GTPgammaS binding to hCB(2) CHO and mouse spleen membranes. THCV (0.3 or 1 mg.kg(-1) i.p.) decreased carrageenan-induced oedema in a manner that seemed to be CB(2) receptor-mediated and suppressed carrageenan-induced hyperalgesia. THCV (i.p.) also decreased pain behaviour in phase 2 of the formalin test at 1 mg.kg(-1), and in both phases of this test at 5 mg.kg(-1); these effects of THCV appeared to be CB(1) and CB(2) receptor mediated.

CONCLUSIONS AND IMPLICATIONS: THCV can activate CB(2) receptors in vitro and decrease signs of inflammation and inflammatory pain in mice partly via CB(1) and/or CB(2) receptor activation.

Original languageEnglish
Pages (from-to)677-687
Number of pages11
JournalBritish Journal of Pharmacology
Volume160
Issue number3
Early online date22 Mar 2010
DOIs
Publication statusPublished - Jun 2010

Keywords

  • Animals
  • CHO Cells
  • Cell Line, Transformed
  • Cricetinae
  • Cricetulus
  • Cyclic AMP
  • Dose-Response Relationship, Drug
  • Edema
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Humans
  • Inflammation
  • Male
  • Membranes
  • Mice
  • Mice, Inbred C57BL
  • Pain
  • Pain Measurement
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Spleen
  • Tetrahydrocannabinol

Cite this

The plant cannabinoid Δ9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice. / Bolognini, Daniele; Costa, Barbara; Maione, S.; Comelli, Francesca; Marini, Pietro; Di Marzo, Vincenzo; Parolaro, Daniela; Ross, Ruth Alexandra; Gauson, Lisa Anne; Cascio, Maria Grazia; Pertwee, Roger Guy.

In: British Journal of Pharmacology, Vol. 160, No. 3, 06.2010, p. 677-687.

Research output: Contribution to journalArticle

Bolognini, D, Costa, B, Maione, S, Comelli, F, Marini, P, Di Marzo, V, Parolaro, D, Ross, RA, Gauson, LA, Cascio, MG & Pertwee, RG 2010, 'The plant cannabinoid Δ9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice' British Journal of Pharmacology, vol. 160, no. 3, pp. 677-687. https://doi.org/10.1111/j.1476-5381.2010.00756.x
Bolognini, Daniele ; Costa, Barbara ; Maione, S. ; Comelli, Francesca ; Marini, Pietro ; Di Marzo, Vincenzo ; Parolaro, Daniela ; Ross, Ruth Alexandra ; Gauson, Lisa Anne ; Cascio, Maria Grazia ; Pertwee, Roger Guy. / The plant cannabinoid Δ9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice. In: British Journal of Pharmacology. 2010 ; Vol. 160, No. 3. pp. 677-687.
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T1 - The plant cannabinoid Δ9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice

AU - Bolognini, Daniele

AU - Costa, Barbara

AU - Maione, S.

AU - Comelli, Francesca

AU - Marini, Pietro

AU - Di Marzo, Vincenzo

AU - Parolaro, Daniela

AU - Ross, Ruth Alexandra

AU - Gauson, Lisa Anne

AU - Cascio, Maria Grazia

AU - Pertwee, Roger Guy

PY - 2010/6

Y1 - 2010/6

N2 - BACKGROUND AND PURPOSE: The phytocannabinoid, Delta(9)-tetrahydrocannabivarin (THCV), can block cannabinoid CB(1) receptors. This investigation explored its ability to activate CB(2) receptors, there being evidence that combined CB(2) activation/CB(1) blockade would ameliorate certain disorders. EXPERIMENTAL APPROACH: We tested the ability of THCV to activate CB(2) receptors by determining whether: (i) it inhibited forskolin-stimulated cyclic AMP production by Chinese hamster ovary (CHO) cells transfected with human CB(2) (hCB(2)) receptors; (ii) it stimulated [(35)S]GTPgammaS binding to hCB(2) CHO cell and mouse spleen membranes; (iii) it attenuated signs of inflammation/hyperalgesia induced in mouse hind paws by intraplantar injection of carrageenan or formalin; and (iv) any such anti-inflammatory or anti-hyperalgesic effects were blocked by a CB(1) or CB(2) receptor antagonist. KEY RESULTS: THCV inhibited cyclic AMP production by hCB(2) CHO cells (EC(50)= 38 nM), but not by hCB(1) or untransfected CHO cells or by hCB(2) CHO cells pre-incubated with pertussis toxin (100 ng.mL(-1)) and stimulated [(35)S]GTPgammaS binding to hCB(2) CHO and mouse spleen membranes. THCV (0.3 or 1 mg.kg(-1) i.p.) decreased carrageenan-induced oedema in a manner that seemed to be CB(2) receptor-mediated and suppressed carrageenan-induced hyperalgesia. THCV (i.p.) also decreased pain behaviour in phase 2 of the formalin test at 1 mg.kg(-1), and in both phases of this test at 5 mg.kg(-1); these effects of THCV appeared to be CB(1) and CB(2) receptor mediated. CONCLUSIONS AND IMPLICATIONS: THCV can activate CB(2) receptors in vitro and decrease signs of inflammation and inflammatory pain in mice partly via CB(1) and/or CB(2) receptor activation.

AB - BACKGROUND AND PURPOSE: The phytocannabinoid, Delta(9)-tetrahydrocannabivarin (THCV), can block cannabinoid CB(1) receptors. This investigation explored its ability to activate CB(2) receptors, there being evidence that combined CB(2) activation/CB(1) blockade would ameliorate certain disorders. EXPERIMENTAL APPROACH: We tested the ability of THCV to activate CB(2) receptors by determining whether: (i) it inhibited forskolin-stimulated cyclic AMP production by Chinese hamster ovary (CHO) cells transfected with human CB(2) (hCB(2)) receptors; (ii) it stimulated [(35)S]GTPgammaS binding to hCB(2) CHO cell and mouse spleen membranes; (iii) it attenuated signs of inflammation/hyperalgesia induced in mouse hind paws by intraplantar injection of carrageenan or formalin; and (iv) any such anti-inflammatory or anti-hyperalgesic effects were blocked by a CB(1) or CB(2) receptor antagonist. KEY RESULTS: THCV inhibited cyclic AMP production by hCB(2) CHO cells (EC(50)= 38 nM), but not by hCB(1) or untransfected CHO cells or by hCB(2) CHO cells pre-incubated with pertussis toxin (100 ng.mL(-1)) and stimulated [(35)S]GTPgammaS binding to hCB(2) CHO and mouse spleen membranes. THCV (0.3 or 1 mg.kg(-1) i.p.) decreased carrageenan-induced oedema in a manner that seemed to be CB(2) receptor-mediated and suppressed carrageenan-induced hyperalgesia. THCV (i.p.) also decreased pain behaviour in phase 2 of the formalin test at 1 mg.kg(-1), and in both phases of this test at 5 mg.kg(-1); these effects of THCV appeared to be CB(1) and CB(2) receptor mediated. CONCLUSIONS AND IMPLICATIONS: THCV can activate CB(2) receptors in vitro and decrease signs of inflammation and inflammatory pain in mice partly via CB(1) and/or CB(2) receptor activation.

KW - Animals

KW - CHO Cells

KW - Cell Line, Transformed

KW - Cricetinae

KW - Cricetulus

KW - Cyclic AMP

KW - Dose-Response Relationship, Drug

KW - Edema

KW - Guanosine 5'-O-(3-Thiotriphosphate)

KW - Humans

KW - Inflammation

KW - Male

KW - Membranes

KW - Mice

KW - Mice, Inbred C57BL

KW - Pain

KW - Pain Measurement

KW - Receptor, Cannabinoid, CB1

KW - Receptor, Cannabinoid, CB2

KW - Spleen

KW - Tetrahydrocannabinol

U2 - 10.1111/j.1476-5381.2010.00756.x

DO - 10.1111/j.1476-5381.2010.00756.x

M3 - Article

VL - 160

SP - 677

EP - 687

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 3

ER -