Evidence map›Paper›PMID 27257556›Full record

ArticlePeerJ2016

ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice.

Natalia Brzozowska, Kong M Li, Xiao Suo Wang, Jessica Booth, Jordyn Stuart, Iain S McGregor, Jonathon C Arnold

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PeerJ, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Research and Clinical Practice Involving the Use ofPharmaceuticals (Basel, Switzerland) · 2024
    Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Cannabis Pharmacogenomics: A Path to Personalized Medicine.Current issues in molecular biology · 2023
    Review
  13. Review
  14. Article
  15. Article
  16. Clinical Pharmacokinetics of Cannabinoids and Potential Drug-Drug Interactions.Advances in experimental medicine and biology · 2021
    Article
  17. The Essential Medicinal Chemistry of Cannabidiol (CBD).Journal of medicinal chemistry · 2020
    Review
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Natalia BrzozowskaDiscipline of Pharmacology, School of Medical Science, University of Sydney , Sydney, NSW , Australia.
Kong M LiDiscipline of Pharmacology, School of Medical Science, University of Sydney , Sydney, NSW , Australia.
Xiao Suo WangBosch Mass Spectrometry Facility, Bosch Institute, Sydney Medical School, University of Sydney , Sydney, NSW , Australia.
Jessica BoothPsychopharmacology Laboratory, School of Psychology, Faculty of Science, University of Sydney , Sydney, NSW , Australia.
Jordyn StuartThe Lambert Initiative of Cannabinoid Therapeutics, The Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia; Psychopharmacology Laboratory, School of Psychology, Faculty of Science, University of Sydney, Sydney, NSW, Australia.
Iain S McGregorThe Lambert Initiative of Cannabinoid Therapeutics, The Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia; Psychopharmacology Laboratory, School of Psychology, Faculty of Science, University of Sydney, Sydney, NSW, Australia.
Jonathon C ArnoldDiscipline of Pharmacology, School of Medical Science, University of Sydney, Sydney, NSW, Australia; The Lambert Initiative of Cannabinoid Therapeutics, The Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
University of Sydney · AURobert Bosch (Australia) · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cannabidiol (CBD) is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy. ABC transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) mediate pharmacoresistance in these disorders. P-gp and Bcrp are expressed at the blood brain barrier (BBB) and reduce the brain uptake of substrate drugs including various antipsychotics and anticonvulsants. It is therefore important to assess whether CBD is prone to treatment resistance mediated by P-gp and Bcrp. Moreover, it has become common practice in the drug development of CNS agents to screen against ABC transporters to help isolate lead compounds with optimal pharmacokinetic properties. The current study aimed to assess whether P-gp and Bcrp impacts the brain transport of CBD by comparing CBD tissue concentrations in wild-type (WT) mice versus mice devoid of ABC transporter genes. P-gp knockout (Abcb1a/b (-∕-)), Bcrp knockout (Abcg2 (-∕-)), combined P-gp/Bcrp knockout (Abcb1a/b (-∕-) Abcg2 (-∕-)) and WT mice were injected with CBD, before brain and plasma samples were collected at various time-points. CBD results were compared with the positive control risperidone and 9-hydroxy risperidone, antipsychotic drugs that are established ABC transporter substrates. Brain and plasma concentrations of CBD were not greater in P-gp, Bcrp or P-gp/Bcrp knockout mice than WT mice. In comparison, the brain/plasma concentration ratios of risperidone and 9-hydroxy risperidone were profoundly higher in P-gp knockout mice than WT mice. These results suggest that CBD is not a substrate of P-gp or Bcrp and may be free from the complication of reduced brain uptake by these transporters. Such findings provide favorable evidence for the therapeutic development of CBD in the treatment of various CNS disorders.

Indexed as

ABC transportersBrain dispositionBreast cancer resistance proteinCannabidiolP-glycoproteinRisperidoneSubstrate

Identifiers

PMID27257556
PMCPMC4888295
OpenAlexW2401156716

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.