Evidence map›Paper›PMID 27449567›Full record

ArticleNeuropharmacology2016

Evaluation of first generation synthetic cannabinoids on binding at non-cannabinoid receptors and in a battery of in vivo assays in mice.

Jenny L Wiley, Timothy W Lefever, Julie A Marusich, Megan Grabenauer, Katherine N Moore, John W Huffman, Brian F Thomas

Open access · greenAbstract read
In one paragraph

Article in Neuropharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
5.5field-weighted citation impact, top 5% 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

27 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. ΔDrug and alcohol dependence reports · 2023
    Article
  10. Article
  11. Correction to: The Potential Proconvulsant Effects of Cannabis: a Scoping Review.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2023
    Article
  12. Observational
  13. Article
  14. Article
  15. The Spicy Story of Cannabimimetic Indoles.Molecules (Basel, Switzerland) · 2021
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Positive Allosteric Modulation of the 5-HTACS chemical neuroscience · 2020
    Article
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.

Jenny L WileyRTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USA. Electronic address: jwiley@rti.org.
Timothy W LefeverRTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USA.
Julie A MarusichRTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USA.
Megan GrabenauerRTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USA.
Katherine N MooreRTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USA.
John W HuffmanProfessor Emeritus, Clemson University, PO Box 695, Dillsboro, NC 28725-0695, USA.
Brian F ThomasRTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USA.
RTI International · USClemson University · US

Funding

THC RECEPTORSR01DA003672 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI WILEY, JENNY L. · 1985 to 2018
$4.9M
Investigation of Synthetic Cannabinoid Exposures and Pharmacological ConsequencesR01DA040460 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI RANGAN MAITRA, Yanan Zhang · 2016 to 2026
$4.5M
THC RECEPTORSR37DA003672 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI MARTIN, BILLY R · 1997 to 2006
$2.8M
Behavioral Pharmacology of Synthetic CannabinoidsR03DA031988 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI WILEY, JENNY L. · 2011 to 2012
$197k
NIDA NIH HHS R01 DA003672NIDA NIH HHS R01 DA040460NIDA NIH HHS R03 DA031988NIDA NIH HHS R37 DA003672
6 · The paper itself

Abstract

Anecdotal reports suggest that abused synthetic cannabinoids produce cannabis-like "highs," but some of their effects may also differ from traditional cannabinoids such as Δ(9)-tetrahydrocannabinol (THC). This study examined the binding affinities of first-generation indole-derived synthetic cannabinoids at cannabinoid and noncannabinoid receptors and their effects in a functional observational battery (FOB) and drug discrimination in mice. All seven compounds, except JWH-391, had favorable affinity (≤159 nM) for both cannabinoid receptors. In contrast, binding at noncannabinoid receptors was absent or weak. In the FOB, THC and the six active compounds disrupted behaviors in CNS activation and muscle tone/equilibrium domains. Unlike THC, however, synthetic cannabinoids impaired behavior across a wider dose and domain range, producing autonomic effects and signs of CNS excitability and sensorimotor reactivity. In addition, mice acquired JWH-018 discrimination, and THC and JWH-073 produced full substitution whereas the 5-HT2B antagonist mianserin did not substitute in mice trained to discriminate JWH-018 or THC. Urinary metabolite analysis showed that the compounds were extensively metabolized, with metabolites that could contribute to their in vivo effects. Together, these results show that, while first-generation synthetic cannabinoids shared some effects that were similar to those of THC, they also possessed effects that differed from traditional cannabinoids. The high nanomolar (or absent) affinities of these compounds at receptors for most major neurotransmitters suggests that these divergent effects may be related to the greater potencies and/or efficacies at CB1 receptors; however, action(s) at noncannabinoid receptors yet to be assessed or via different signaling pathways cannot be ruled out.

Indexed as

AnimalsCannabinoidsDose-Response Relationship, DrugDronabinolIllicit DrugsIndolesMaleMianserinMiceMice, Inbred C57BLMice, Inbred ICRNaphthalenesProtein BindingReceptor, Cannabinoid, CB1Receptor, Serotonin, 5-HT2B1-pentyl-3-(1-naphthoyl)indoleCannabinoidsDronabinolIllicit DrugsIndolesJWH-073MianserinNaphthalenesReceptor, Cannabinoid, CB1Receptor, Serotonin, 5-HT2BAlkylindolesFunctional observation batteryJWH-018Receptor bindingSynthetic cannabinoids

Identifiers

PMID27449567
PMCPMC5028280
OpenAlexW2491075455

What OpenQuestion holds

Textmetadata
LicenceTDM
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.