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The CB₂ Receptor in Immune Regulation and Disease: Genetic Architecture, Epigenetic Control, and Emerging Therapeutic Strategies

2025· preprint· en· W4412147782 on OpenAlexfundno aff
Hilal Kalkan, Nicolas Flamand

Bibliographic record

VenuePreprints.org · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsnot available
FundersNatural Sciences and Engineering Research Council of CanadaInstitut universitaire de cardiologie et de pneumologie de Québec, Université Laval
KeywordsEpigeneticsImmune systemDiseaseGenetic architectureEpigenesisBiologyComputational biologyMedicineGeneticsDNA methylationGenePhenotypeGene expressionInternal medicine

Abstract

fetched live from OpenAlex

The cannabinoid receptor type 2 (CB₂) is gaining recognition as a critical regulator of immune equilibrium, neuroinflammation, and tissue repair processes. Unlike its counterpart, the CB₁ receptor, which produces psychoactive effects when activated, the CB₂ receptor presents itself as a more appealing and safer target for therapeutic interventions. This review investigates the genetic and epigenetic regulation of CB₂ receptor and examines how its signaling affects both immune and nervous system cells. We emphasize its influence on microglial activity, the modulation of immune responses, and its regulation by non-coding RNAs and chromatin remodeling. Through these pathways, CB₂ receptor plays a significant role in various disease processes, with increasing evidence connecting it to depression, chronic pain, schizophrenia, inflammatory conditions such as asthma and colitis, and even cancer immunotherapy. We also explore how CB₂ receptor interacts with components of the endocannabinoid system, including Transient Receptor Potential (TRP) channels, prostanoids, and Peroxisome proliferator-activated receptors (PPARs). Lastly, we analyze how innovative therapies targeting CB₂ receptor, such as selective agonists, positive allosteric modulators (PAMs), and biased ligands, could pave the way for more precise and effective treatments for neurological, inflammatory, and immune-related disorders.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.027
GPT teacher head0.311
Teacher spread0.284 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designTheoretical or conceptual
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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