Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 521

The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.

Are cannabidiol and Δ9‐tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review

Open access
McPartland, John M, Duncan, Marnie, Di Marzo, Vincenzo, Pertwee, Roger G·2015·British Journal of Pharmacology
DOI 10.1111/bph.12944
Open this paper in CoChat — free account

Abstract

Based upon evidence that the therapeutic properties ofCannabis preparations are not solely dependent upon the presence of Δ 9‐tetrahydrocannabinol (THC), pharmacological studies have been recently carried out with other plant cannabinoids (phytocannabinoids), particularly cannabidiol (CBD) and Δ 9‐tetrahydrocannabivarin (THCV). Results from some of these studies have fostered the view that CBD and THCV modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first‐generation CB1 receptor inverse agonists, such as rimonabant. Here, we review in vitro and ex vivo mechanistic studies of CBD and THCV, and synthesize data from these studies in a meta‐analysis. Synthesized data regarding mechanisms are then used to interpret results from recent pre‐clinical animal studies and clinical trials. The evidence indicates that CBD and THCV are not rimonabant‐like in their action and thus appear very unlikely to produce unwanted CNS effects. They exhibit markedly disparate pharmacological profiles particularly at CB1 receptors:CBD is a very low‐affinity CB1 ligand that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high‐affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism.THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant. These cannabinoids illustrate how in vitro mechanistic studies do not always predict in vivo pharmacology and underlie the necessity of testing compounds in vivo before drawing any conclusion on their functional activity at a given target.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/bph.12944

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 25 references

Research works printed but not linked: 98

  1. 10.1111/bph.12445 · DOI · Paper page
  2. 10.1111/bph.12451 · DOI · Paper page
  3. 10.1111/bph.12447 · DOI
  4. 10.1111/bph.12450 · DOI
  5. 10.1111/bph.12446 · DOI
  6. 10.1111/bph.12448 · DOI
  7. 10.1074/jbc.271.17.9902 · DOI
  8. 10.1016/j.pbb.2010.03.012 · DOI
  9. 10.1038/npp.2009.184 · DOI · Paper page
  10. 10.1111/j.1476-5381.2010.00756.x · DOI
  11. 10.1016/j.drugalcdep.2009.06.009 · DOI
  12. 10.1002/j.1552-4604.1981.tb02599.x · DOI
  13. 10.1007/s00213-008-1168-x · DOI · Paper page
  14. 10.1016/j.pnpbp.2009.08.017 · DOI · Paper page
  15. CawthorneM StottC WrightS GuyG ZaibiM WargentE(2008).The metabolic effects of tetrahydrocannabivarin (THCV) and cannabidiol (CBD). Proceedings of the 18th Annual Symposium on the Cannabinoids. International Cannabinoid Research Society Burlington VT p. 42.
  16. 10.1177/106002808101501104 · DOI
  17. 10.1038/sj.bjp.0705920 · DOI · Paper page
  18. 10.1111/j.1476-5381.2010.01166.x · DOI · Paper page
  19. 10.1007/s00213-011-2415-0 · DOI · Paper page
  20. Demirakca T, 2011, Diminished gray matter in the hippocampus of cannabis users: possible protective effects of cannabidiol, Drug Alcohol Depend, 114, 242
  21. 10.1038/nrd2553 · DOI · Paper page
  22. 10.1038/nn1210-1446 · DOI
  23. 10.1016/S0166-2236(98)01283-1 · DOI · Paper page
  24. 10.1054/plef.2001.0349 · DOI · Paper page
  25. 10.1038/sj.bjp.0703170 · DOI · Paper page
  26. 10.1177/0269881112460109 · DOI · Paper page
  27. 10.1016/j.neuropharm.2004.08.009 · DOI
  28. 10.1021/ja01062a046 · DOI · Paper page
  29. 10.1111/j.1476-5381.2011.01278.x · DOI · Paper page
  30. 10.1038/228134a0 · DOI
  31. Glass GV, 1981, Meta‐Analysis in Social Research
  32. 10.1007/s00213-010-2036-z · DOI
  33. 10.1016/j.pnpbp.2013.06.005 · DOI
  34. Grinspoon L, 1997, Marihuana, the Forbidden Medicine
  35. 10.1007/3-7643-7358-X_14 · DOI
  36. Hanuš L, 2008, Pharmacological and therapeutic secrets of plant and brain (endo)cannabinoids, Med Res Rev, 29, 213, 10.1002/med.20135 · DOI
  37. 10.1016/j.brainres.2007.09.090 · DOI
  38. 10.1111/j.1528-1167.2010.02523.x · DOI
  39. 10.1007/BF01946311 · DOI
  40. 10.1038/nchembio.118 · DOI · Paper page
  41. 10.1016/0006-2952(89)90628-X · doi:10.1016/0006-2952(89)90628-x
  42. 10.1097/00008877-200509000-00023 · DOI
  43. 10.1016/j.tips.2009.07.006 · DOI · Paper page
  44. IzzoAA ZaibiMS WargentE CapassoR ArbuckleC DuncanMet al. (2013).The effect of Δ9‐tetrahydrocannabivarin on food deprivation‐induced food intake and upper gastrointestinal motility: differences from rimonabant. Proceedings of the 7th Conference on Cannabinoids in Medicine. International Association for Cannabis as Medicine Köln p. 57.
  45. 10.1111/j.1476-5381.2010.00791.x · DOI
  46. Järbe TU, 1977, Delta9‐THC as a discriminative cue in pigeons: effects of delta8‐THC, CBD, and CBN, Arch Int Pharmacodyn Ther, 228, 68
  47. Jeon YJ, 1996, Attenuation of inducible nitric oxide synthase gene expression by delta 9‐tetrahydrocannabinol is mediated through the inhibition of nuclear factor‐ kappa B/Rel activation, Mol Pharmacol, 50, 334, 10.1016/S0026-895X(25)09237-5 · DOI
  48. 10.1016/j.jpainsymman.2009.06.008 · DOI · Paper page
  49. 10.1016/j.seizure.2012.03.001 · DOI
  50. 10.1373/clinchem.2010.152439 · DOI
  51. 10.1074/jbc.M109.069294 · DOI · Paper page
  52. 10.1523/JNEUROSCI.5844-09.2010 · DOI
  53. 10.1016/S0091-3057(00)00201-X · DOI
  54. 10.1371/journal.pmed.1000100 · DOI · Paper page
  55. 10.1124/jpet.106.105247 · DOI · Paper page
  56. Loewe WS, 1941, The action of chemical components of cannabis extracts, J Pharmacol Exp Ther, 72, 27
  57. 10.1017/S1461145709990605 · DOI · Paper page
  58. 10.1111/j.1476-5381.2010.01063.x · DOI
  59. 10.1016/j.pbb.2009.04.010 · DOI
  60. 10.1158/1535-7163.MCT-09-0407 · DOI
  61. 10.1111/j.1471-4159.2010.07101.x · DOI
  62. 10.1146/annurev.pharmtox.47.120505.105159 · DOI · Paper page
  63. McPartland JM, 2004, The Medicinal Use of Cannabis, 71
  64. McPartland JM, 1999, Side effects of pharmaceuticals not elicited by comparable herbal medicines: the case of tetrahydrocannabinol and marijuana, Altern Ther Health Med, 5, 57
  65. 10.1038/sj.bjp.0707399 · DOI · Paper page
  66. 10.1016/S0014-2999(98)00649-9 · DOI · Paper page
  67. 10.1093/genetics/163.1.335 · DOI · Paper page
  68. 10.1097/01.jcp.0000125688.05091.8f · DOI · Paper page
  69. 10.1016/j.pbb.2012.10.008 · DOI
  70. 10.1093/nar/gkt1143 · DOI · Paper page
  71. Pertwee RG, 2004, Cannabinoids, 32
  72. 10.1208/aapsj070364 · DOI
  73. 10.1038/sj.bjp.0707442 · DOI · Paper page
  74. 10.1038/sj.bjp.0707124 · DOI
  75. 10.1124/pr.110.003004 · DOI · Paper page
  76. 10.1016/S0024-3205(98)00238-0 · DOI
  77. 10.1523/JNEUROSCI.0504-08.2008 · DOI · Paper page
  78. Reed GF, 2002, Use of coefficient of variation in assessing variability of quantitative assays, Clin Diagn Lab Immunol, 9, 1235
  79. 10.1021/jm970126f · DOI
  80. 10.1111/j.1476-5381.2008.00107.x · DOI
  81. 10.1111/bph.12322 · DOI
  82. 10.1007/s00406-009-0868-5 · DOI
  83. 10.1016/j.mehy.2005.08.026 · DOI · Paper page
  84. 10.1522/cla.roj.let · doi:10.1522/cla.roj.let
  85. 10.1038/sj.bjp.0705577 · DOI
  86. 10.1016/j.schres.2011.04.017 · DOI
  87. 10.1016/j.neuropharm.2004.04.011 · DOI
  88. 10.1007/s00228-012-1441-0 · DOI
  89. 10.1016/j.drugalcdep.2007.11.017 · DOI
  90. 10.1007/s00213-006-0356-9 · DOI
  91. 10.1191/0269215503cr581oa · DOI · Paper page
  92. 10.1124/jpet.103.051920 · DOI · Paper page
  93. 10.1038/nutd.2013.9 · DOI
  94. 10.1211/0022357022304 · DOI
  95. 10.1078/0944-7113-00060 · DOI · Paper page
  96. 10.1186/1478-811X-8-12 · DOI · Paper page
  97. 10.1038/nchembio.552 · DOI
  98. Zuardi AW, 1981, Characteristics of the stimulus produced by the mixture of cannabidiol with delta 9‐tetrahydrocannabinol, Arch Int Pharmacodyn Ther, 249, 137

Cited by

See all 521

Metadata

Authors
McPartland, J. M., Duncan, M., Di Marzo, V., & Pertwee, R. G.
Venue
British Journal of Pharmacology
Publisher
Wiley
Published
2015-01-08
Volume
172
Issue
3
Pages
737-753
ISSN
  • 0007-1188 (ISSN-L)
  • 1476-5381
DOI
10.1111/bph.12944
OpenAlex
W2101643484
Cited by
521
References
25
FWCI
5.78
Type
journal article
Language
en
Open access
bronze
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Are cannabidiol and Δ9‐tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. https://app.cochat.ai/papers/10.1111/bph.12944
The paper
McPartland, J. M., Duncan, M., Di Marzo, V., & Pertwee, R. G. (2015). Are cannabidiol and Δ9‐tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. British Journal of Pharmacology. https://doi.org/10.1111/bph.12944

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.