ArticleThe Journal of biological chemistry2014
Type 1 cannabinoid receptor ligands display functional selectivity in a cell culture model of striatal medium spiny projection neurons.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases.International journal of molecular sciences · 2020Pooled it
- Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study.Journal of neurodevelopmental disorders · 2025Trial
- A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX).Journal of neurodevelopmental disorders · 2022Trial
- Acute effects of ΔPsychopharmacology · 2022Trial
- Transcriptional and epigenetic regulation of the cannabinoid receptor type-1 (CB1R) in health and disease: an overview.Pharmacological reports : PR · 2026Review
- Interactions of ACEA and WIN 55,212-2 mesylate with temozolomide and cisplatin in neuroblastoma and glioblastoma cell lines: an isobolographic analysis.Pharmacological reports : PR · 2026Article
- Side-Chain Homologs of ΔMolecular neurobiology · 2026Article
- Pharmacological Switching in Minor Phytocannabinoids: A Mechanistic Framework for Compound-Indication Matching and Precision Neurotherapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Envisioning Cannabinoid CB1 Receptor Biased Signaling as a Therapeutic Target for Schizophrenia.The American journal of psychiatry · 2026Review
- Development of a novel risk score reflecting the relative harm potential of synthetic cannabinoids based on prevalence estimates, well-documented intoxication cases and basic pharmacological data.Addiction (Abingdon, England) · 2026Article
- Acute and chronic cannabis vapor exposure produces immediate and delayed impacts on phases of fear learning in a sex specific manner.Psychopharmacology · 2026Article
- CB1 receptor coupling to extracellular regulated kinase via multiple Gαi/o isoforms.Neuroreport · 2025Article
- Structural basis of THC analog activity at the Cannabinoid 1 receptor.Nature communications · 2025Article
- Medicinal Cannabis and the Intestinal Microbiome.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Prenatal cannabis exposure in the clinic and laboratory: What do we know and where do we need to go?Drug and alcohol dependence reports · 2024Review
- Pharmacological Characterization of the Endocannabinoid Sensor GRABCannabis and cannabinoid research · 2024Article
- Article
- Structural basis of ΔResearch square · 2024Article
- The Sobering Sting: Oleoyl Serotonin Is a NovelBiomedicines · 2024Article
- Investigating the Effects of Exogenous and Endogenous 2-Arachidonoylglycerol on Retinal CB1 Cannabinoid Receptors and Reactive Microglia in Naive and Diseased Retina.International journal of molecular sciences · 2023Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Modulation of type 1 cannabinoid receptor (CB1) activity has been touted as a potential means of treating addiction, anxiety, depression, and neurodegeneration. Different agonists of CB1 are known to evoke varied responses in vivo. Functional selectivity is the ligand-specific activation of certain signal transduction pathways at a receptor that can signal through multiple pathways. To understand cannabinoid-specific functional selectivity, different groups have examined the effect of individual cannabinoids on various signaling pathways in heterologous expression systems. In the current study, we compared the functional selectivity of six cannabinoids, including two endocannabinoids (2-arachidonyl glycerol (2-AG) and anandamide (AEA)), two synthetic cannabinoids (WIN55,212-2 and CP55,940), and two phytocannabinoids (cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC)) on arrestin2-, Gα(i/o)-, Gβγ-, Gα(s)-, and Gα(q)-mediated intracellular signaling in the mouse STHdh(Q7/Q7) cell culture model of striatal medium spiny projection neurons that endogenously express CB1. In this system, 2-AG, THC, and CP55,940 were more potent mediators of arrestin2 recruitment than other cannabinoids tested. 2-AG, AEA, and WIN55,212-2, enhanced Gα(i/o) and Gβγ signaling, with 2-AG and AEA treatment leading to increased total CB1 levels. 2-AG, AEA, THC, and WIN55,212-2 also activated Gα(q)-dependent pathways. CP55,940 and CBD both signaled through Gα(s). CP55,940, but not CBD, activated downstream Gα(s) pathways via CB1 targets. THC and CP55,940 promoted CB1 internalization and decreased CB1 protein levels over an 18-h period. These data demonstrate that individual cannabinoids display functional selectivity at CB1 leading to activation of distinct signaling pathways. To effectively match cannabinoids with therapeutic goals, these compounds must be screened for their signaling bias.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.