Evidence map›Paper›PMID 22718500›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2012

Apparent inverse relationship between cannabinoid agonist efficacy and tolerance/cross-tolerance produced by Δ⁹-tetrahydrocannabinol treatment in rhesus monkeys.

Lenka Hruba, Brett C Ginsburg, Lance R McMahon

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

Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

34 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Mechanisms of cannabinoid tolerance.Biochemical pharmacology · 2023
    Review
  3. Article
  4. Article
  5. Sex, species and age: Effects of rodent demographics on the pharmacology of ∆Progress in neuro-psychopharmacology & biological psychiatry · 2021
    Article
  6. Article
  7. Long-Lasting In Vivo Effects of the Cannabinoid CB1 Antagonist AM6538.The Journal of pharmacology and experimental therapeutics · 2018
    Article
  8. Article
  9. Review
  10. Synthetic Pot: Not Your Grandfather's Marijuana.Trends in pharmacological sciences · 2017
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  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

3 authors at 1 institution in 1 country.

Lenka HrubaDepartment of Pharmacology, the University of Texas Health Science Center, San Antonio, Texas, USA.
Brett C Ginsburg
Lance R McMahon
The University of Texas Health Science Center at San Antonio · US

Funding

Treatment of Cannabinoid Withdrawal in Rhesus MonkeysR01DA019222 · NIDA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI MCMAHON, LANCE R. · 2004 to 2013
$3.6M
NIDA NIH HHS DA19222NIDA NIH HHS R01 DA019222
6 · The paper itself

Abstract

Synthetic cannabinoids (CBs) [naphthalen-1-yl-(1-pentylindol-3-yl) methanone (JWH-018) and naphthalen-1-yl-(1-butylindol-3-yl) methanone (JWH-073)] are marketed, sold, and used as alternatives to cannabis. Synthetic CBs appear to have effects similar to those of Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the drug primarily responsible for the behavioral effects of cannabis. However, synthetic CB products produce atypical effects (e.g., hypertension, seizures, and panic attacks). One potential explanation for atypical effects is CB₁ receptor agonist efficacy, which is reportedly higher for JWH-018 and JWH-073 compared with Δ⁹-THC. The goal of this study was to test a prediction from receptor theory that tolerance/cross-tolerance (i.e., resulting from daily Δ⁹-THC treatment) is greater for a low-efficacy agonist compared with a high-efficacy agonist. Rhesus monkeys discriminated 0.1 mg/kg Δ⁹-THC i.v. from vehicle, and sensitivity to CB(1) agonists was determined before and after 3 and 14 days of Δ⁹-THC treatment (1 mg/kg per day s.c.). (1R,3R,4R)-3-[2-Hydroxy-4-(1,1-dimethylheptyl) phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol (CP-55,940), a prototype high-efficacy CB₁ receptor agonist, JWH-018, and JWH-073 substituted for the discriminative stimulus effects of Δ⁹-THC. Three days of Δ⁹-THC treatment produced less tolerance/cross-tolerance than 14 days of Δ⁹-THC treatment. Three days of Δ⁹-THC did not result in cross-tolerance to CP-55,940, JWH-073, and JWH-018; in contrast, as reported previously, 3 days of Δ⁹-THC treatment decreased sensitivity to Δ⁹-THC 3-fold. Fourteen days of Δ⁹-THC decreased sensitivity to Δ⁹-THC, CP-55,940, JWH-018, and JWH-073 9.2-fold, 3.6-fold, 4.3-fold, and 5.6-fold, respectively. The greater loss of sensitivity to Δ⁹-THC relative to CP-55,940 and JWH-018 suggests that differences in CB₁ receptor agonist efficacy are important in vivo and might underlie differences in the dependence liability and adverse effects of synthetic CBs versus cannabis.

Indexed as

AnimalsCannabinoidsCannabisCyclohexanolsDronabinolDrug ToleranceFemaleIndolesMacaca mulattaMaleNaphthalenesReceptor, Cannabinoid, CB11-pentyl-3-(1-naphthoyl)indole3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanolCannabinoidsCyclohexanolsDronabinolIndolesJWH-073NaphthalenesReceptor, Cannabinoid, CB1

Identifiers

PMID22718500
PMCPMC3422532
OpenAlexW2060481472

What OpenQuestion holds

Textmetadata
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.