Skeletal muscle and the endocannabinoid system
Sugar use, exercise and repair.
Sugar use, exercise and repair. Where the cannabinoid receptors CB1 and CB2 sit in this region, what they do there, and what is actually known about CBD; at three levels for Everyone, Students and Experts, with sources.
Muscles and movementCB1 low · CB2 low (Human Protein Atlas)Last updated:
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Interactive 3D · real anatomy and real data
Where in your body are the cannabinoid receptors?
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Regions
How to read it Choose a region, or tap a glowing point on the map.
- Solid light is the CB1 receptor, a ring is CB2. Each region has its own color; the color only tells regions apart.
- The strength of the light is the receptor gene level measured in human tissue (Human Protein Atlas). That is why the liver’s point is dim: a healthy liver has few receptors.
- With the layer selector above you can also see other receptors, the enzymes that make and break down endocannabinoids, and the liver enzymes that break down CBD and THC.
- Every piece of information shows its source and the type of evidence (human, animal, cell). You can change the reading level above.
- Drag to rotate. Use the + and − buttons to zoom; on a computer, Ctrl or ⌘ with the scroll wheel, on a phone, two fingers.
Skeletal muscle: RNA level of the receptor gene in human tissue (tissue consensus data). RNA for both receptors is at a low level. Human Protein AtlasHuman tissue
| Receptor | Gene | RNA (nTPM) | Level |
|---|---|---|---|
| CB1 | CNR1 | 1.8 | low |
| CB2 | CNR2 | 1.5 | low |
What does it do there?
Across muscle as a whole, RNA for CB1 and CB2 is measured as low. Skeletal muscle carries parts of the endocannabinoid system: in human muscle samples, RNA was found for CB1, CB2, TRPV1 and FAAH, the enzyme that breaks down anandamide. In biopsies taken from the muscle on the front and outer side of the thigh (vastus lateralis), there was more CB1 in older men than in young men; CB1 was concentrated more in type I fibers, which have a high capacity to make energy using oxygen, and CB2 in type II fibers. By contrast, in one cell study CB1 was found to be high in mouse brain but could not be detected in mouse muscle or muscle cells. In samples taken from the tissue fluid of the human shoulder muscle, anandamide and related fat molecules could be measured; in women with chronic neck and shoulder pain, two of them were higher. Human Protein AtlasHuman tissueCavuoto 2007aHuman tissueAnimalDalle and Koppo 2021Human tissueLanger 2022Cell / labAnimalGhafouri 2011Human tissue
According to laboratory findings, the endocannabinoid system may play a role in muscle's response to insulin. In human muscle cells, anandamide weakened insulin's signal inside the cell; drugs that block CB1 prevented this and also prevented substances secreted by fat cells from reducing sugar uptake by the muscle cell. In obese mice, blocking CB1 for one week increased sugar uptake in tissue removed from muscle. In mouse muscle, much of the CB1 was found in the mitochondria, the part of the cell that produces energy. Eckardt 2009Cell / labCavuoto 2007bCell / labLiu 2005AnimalMendizabal-Zubiaga 2016Animal
Exercise raises endocannabinoids in the blood: in a controlled study, 45 minutes of moderate-intensity running raised blood anandamide and 2-AG compared with walking. According to a meta-analysis combining human and mouse studies, these two substances rise after a single bout of exercise, while the effect of regular exercise is inconsistent; the authors think part of the rise may come from skeletal muscle. CB1 in muscle also changes with exercise: in young men, a single bout of resistance exercise reduced CB1 in muscle, while in older people a trend toward an increase was seen with 12 weeks of resistance training. In muscle development, 2-AG slowed the maturation of muscle precursor cells through CB1 (mouse cells and human satellite cells); in rats, stimulating CB2 reduced inflammation and scar tissue signals during the repair of crushed muscle. Siebers 2021Human · clinical studyDesai 2022ReviewPekkala 2015Human tissueCell / labDalle and Koppo 2021Human tissueIannotti 2014bCell / labAnimalZhang 2015Animal
Student level: terms and cell types
In HPA tissue data, skeletal muscle shows CNR1 at 1.8 and CNR2 at 1.5 nTPM. RT-PCR showed CB1, CB2, TRPV1 and FAAH in human and rodent skeletal muscle. In vastus lateralis biopsies (western blot), CB1 was 25% higher in older men (aged 65 and over) than in young men (20–27), and CB2 did not differ; in older men's muscle, CB1 was markedly more abundant in type I fibers than in type II, and CB2 was more abundant in type II fibers. In C2C12 cells and mouse skeletal muscle, CB1 was not detected by western blot, while it was high in the cortex and hippocampus. In trapezius muscle microdialysate, AEA, PEA, SEA and 2-AG could be measured in a single chromatographic analysis; of the N-acylethanolamines, PEA and SEA were clearly detected and were significantly higher in women with chronic neck–shoulder myalgia than in healthy women. Human Protein AtlasHuman tissueCavuoto 2007aHuman tissueAnimalDalle and Koppo 2021Human tissueLanger 2022Cell / labAnimalGhafouri 2011Human tissue
In human skeletal muscle cells (SkM), CB1 protein increased throughout differentiation. Adipocyte-conditioned medium reduced insulin-stimulated Akt(Ser473) phosphorylation by 60%, and anandamide by up to 40%; rimonabant or AM251 cut the effect of the conditioned medium by about half and fully prevented that of anandamide; rimonabant fully blocked the reduction of insulin-stimulated glucose uptake by the conditioned medium. Anandamide activated ERK1/2 and p38 MAPK and increased IRS-1 (Ser307) phosphorylation. In primary myotubes from lean and obese individuals, the CB1 antagonist AM251 increased AMPKα1 mRNA and reduced PDK4; anandamide blocked the AMPKα1 effect of AM251; according to the authors, endocannabinoids regulate oxidative pathways in muscle, most markedly in the myotubes of obese individuals. In Lep(ob)/Lep(ob) mice, 7 days of SR141716 increased glucose uptake by 68% and basal oxygen consumption by 37% in isolated soleus. In mouse gastrocnemius and rectus abdominis, immunoelectron microscopy showed CB1 on 26% and 22% of mitochondrial profiles; about 60% and 55% of CB1 particles were in mitochondria; the signal disappeared in mice lacking CB1. Eckardt 2009Cell / labCavuoto 2007bCell / labLiu 2005AnimalMendizabal-Zubiaga 2016Animal
In a randomized, double-blind, placebo-controlled experiment (63 people), 45 minutes of moderate-intensity treadmill running raised plasma AEA and 2-AG compared with walking; the opioid antagonist naltrexone did not prevent this rise or running-related euphoria. In a systematic review and meta-analysis (33 articles, 57 samples; 10 articles in the meta-analysis), AEA rose after acute exercise in 74.4% of samples that measured AEA, and 2-AG was inconsistent across samples; the meta-analysis, however, showed a consistent rise in AEA and 2-AG; the effect of chronic exercise was inconsistent. In young men (18), a single bout of resistance exercise reduced CB1 expression in vastus lateralis biopsies, and this drop was associated with increased phosphorylation of mTOR signaling proteins; in human myotubes, AM251 increased protein synthesis in an ERK1/2-dependent way. In older people, 12 weeks of resistance training increased CB1 by 11% (p = 0.055) and CB2 by 37% (p = 0.066); the CB2 increase was associated with changes in FOXO3a, Pax7 and MyoD. In C2C12 cells, 2-AG and the CB1 agonist ACEA inhibited myotube formation, and CB1 antagonists stimulated differentiation; 2-AG also inhibited differentiation of primary human satellite cells; the proposed mechanism is CB1-dependent inhibition of the Kv7.4 channel. Muscle bundles of mouse embryos lacking CB1 had more fibers. In rat muscle contusion, the CB2 agonist Gp1a reduced neutrophil and macrophage infiltration, MCP-1, TNF-α, IL-1β, IL-6 and profibrotic cytokines and increased IL-10; the antagonist AM630 did the opposite. Siebers 2021Human · clinical studyDesai 2022ReviewPekkala 2015Human tissueCell / labDalle and Koppo 2021Human tissueIannotti 2014bCell / labAnimalZhang 2015Animal
Expert level: method notes and numbers
Skeletal muscle: RNA level of the receptor gene in human tissue (tissue consensus data). RNA for both receptors is at a low level. Human Protein AtlasHuman tissue
Method note
Location. Cavuoto 2007a: RT-PCR (mRNA) only; no protein or cell type; source of samples not in the abstract. Dalle and Koppo 2021: in experiment 1, 18 young and 14 older men (without sarcopenia), western blot; CB1 +25% (Cohen d = 0.73; p = 0.045; p = 0.04 in the abstract); by fiber type, CB1 +288% in type I, CB2 +268% in type II; half of the older men were taking statins. In experiment 2, 19 older people (7 women), 12 weeks of resistance training, no control group; increases at the border of significance. Langer 2022: C2C12 myotubes, mouse skeletal muscle, cortex and hippocampus; western blot. Ghafouri 2011: 11 women with chronic neck–shoulder pain and 11 healthy women, 4 hours of microdialysis in the trapezius muscle, nLC-MS/MS. Cavuoto 2007aHuman tissueAnimalDalle and Koppo 2021Human tissueLanger 2022Cell / labAnimalGhafouri 2011Human tissue
Sugar and energy. Eckardt 2009: human skeletal muscle cell culture; number of cell donors not in the abstract. Cavuoto 2007b: primary myotubes from 3 people per group, 24 hours of AEA and AM251 (0.2 and 5 µM). Liu 2005: female Lep(ob)/Lep(ob) mice (8–10 weeks old), SR141716 once daily for 7 days. Mendizabal-Zubiaga 2016: mouse; functional measurements only in heart mitochondria (THC 100–200 nM reduced coupled respiration by 12–15%, no difference in mice lacking CB1); respiration was not measured in skeletal muscle mitochondria; in mice lacking CB1, expression of Eno3, Pkm2 and Pdha1 increased. The PubMed record has no MeSH terms. Eckardt 2009Cell / labCavuoto 2007bCell / labLiu 2005AnimalMendizabal-Zubiaga 2016Animal
Exercise, growth, repair. Siebers 2021: 63 people; running and walking, naltrexone or placebo. Desai 2022: MEDLINE search up to December 31, 2020; high heterogeneity in effect size (exercise intensity, fitness, timing of measurement and fasting state are possible causes); human and mouse studies together. Pekkala 2015: single group, biopsies before and after; no control group. Iannotti 2014b: C2C12 mouse myoblasts, in vivo in mouse muscle, primary human satellite cells, Kv7.4 current in CHO cells. Zhang 2015: Sprague-Dawley rat, contusion model. Siebers 2021Human · clinical studyDesai 2022ReviewPekkala 2015Human tissueCell / labIannotti 2014bCell / labAnimalZhang 2015Animal
In this model, skeletal muscle is shown by the front muscle group of the thigh (quadriceps femoris: rectus femoris and the three vastus muscles, in both legs); it stands for all skeletal muscles. Two of the human biopsy studies here took their samples from the vastus lateralis in this group.
What is known about CBD?
Controlled studies measuring the effect of CBD on muscle recovery in healthy, exercising volunteers are few, and their results are not consistent. In a study in trained volunteers that tested a single dose of CBD right after heavy resistance training, small differences between groups were found at hour 72 in squat strength and in blood values that indicate muscle damage; the authors wrote that more data are needed. In another study in untrained men after exercise that strained the arm muscles, no differences were found in muscle soreness, arm circumference or strength. According to a systematic review of seven studies, data on a beneficial effect on strength and recovery are limited. Isenmann 2021Human · clinical studyCochrane-Snyman 2021Human · clinical studyBezuglov 2024ReviewSchouten 2022Review
In the laboratory, CBD increased the maturation of cells in a mouse muscle cell line and in human muscle precursor cells and their formation of muscle structures called myotubes; the effect worked largely through the TRPV1 (mouse cells) and TRPA1 (human cells) channels. In another cell study, CBD did not change growth and inflammation signals in mouse muscle cells. These are laboratory findings. Iannotti 2019Cell / labAnimalLanger 2022Cell / labAnimalSchouten 2022Review
No effect found Insufficient evidence
In the guide: Diabetes and CBD
Research has not shown that CBD helps with this. If you are considering CBD, you can talk with your doctor or pharmacist, including about the medicines you take.
No effect found Moderate evidence
In the guide: Chronic Pain and CBD
Research has not found that CBD helps with this condition. If you are considering CBD, you can talk with your doctor or pharmacist, including about the medicines you take.
Which receptor and enzyme genes are read in this region?
Values in this region for the genes in the map's layer selector: besides CB1 and CB2, the other targets of cannabinoids, the enzymes that make and break down endocannabinoids, and the liver enzymes that break down CBD and THC.
| Gene | What does it do? | Here | Tissue where it is read the most |
|---|---|---|---|
| Receptors | |||
| CB1 CNR1 | Cannabinoid receptor | 1.8 | cerebral cortex (18.6) |
| CB2 CNR2 | Cannabinoid receptor | 1.5 | spleen (8.4) |
| TRPV1 | Heat and chili pepper sensor · ion channel | 6.0 | liver (21.8) |
| GPR55 | Long an "orphan" receptor · in the cell membrane | 0.0 | testis (4.4) |
| PPARγ PPARG | Gene switch · in the cell nucleus | 5.0 | adipose tissue (153.2) |
| 5-HT1A HTR1A | Serotonin receptor · in the cell membrane | 0.0 | hippocampal formation (6.1) |
| TRPV2 | Relative of TRPV1 · ion channel | 3.8 | lung (29.5) |
| Endocannabinoid enzymes | |||
| NAPE-PLD NAPEPLD | Makes anandamide | 2.2 | kidney (13.9) |
| FAAH | Breaks down anandamide | 9.5 | testis (46.0) |
| DAGLα DAGLA | Makes 2-AG | 2.8 | cerebral cortex (12.3) |
| DAGLβ DAGLB | Makes 2-AG | 13.0 | adrenal gland (15.2) |
| MGL MGLL | Breaks down 2-AG | 59.2 | adipose tissue (161.3) |
| ABHD6 | Breaks down 2-AG | 4.8 | liver (60.7) |
| ABHD12 | Breaks down 2-AG | 13.7 | epididymis (125.2) |
| Enzymes that break down CBD and THC | |||
| CYP3A4 | Breaks down CBD and THC | 1.5 | liver (3,367.1) |
| CYP2C19 | Breaks down CBD | 0.0 | liver (178.0) |
| CYP2C9 | Breaks down THC | 0.0 | liver (1,607.6) |
RNA level shows how much the gene is read in this tissue; it does not directly show the amount of protein or how active an enzyme is. Human Protein Atlas (layers)Human tissue
Identifiers and citation
- Skeletal muscle
- Muscle, Skeletal · MeSH D018482 · UBERON 0014892 · Wikidata Q1048687
- Receptors
- CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)
How to cite: cbd.school editorial team. Skeletal muscle and the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/kas/
The body model is derived from BodyParts3D (DBCLS, CC BY 4.0) and Z-Anatomy (CC BY-SA 4.0); receptor levels from Human Protein Atlas v25 (CC BY 4.0). The map, text and downloaded images are CC BY-SA 4.0. An independent expert review has not been done yet. All licenses
Other pages of the map
Overview: what the endocannabinoid system is, the feedback brake at the synapse, CBD's targets, lesson mode, data and licenses.
Sources
Show 20 references
- Human Protein Atlas v25: tissue RNA consensus data (rna_tissue_consensus.tsv, HPA and GTEx, nTPM) and brain region data (rna_brain_region_hpa.tsv, nTPM), CNR1 (ENSG00000118432) and CNR2 (ENSG00000188822); v25.proteinatlas.org, file date November 6, 2025, downloaded October 24, 2026. Uhlén M et al. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419. License CC BY 4.0. PMID 25613900 · doi:10.1126/science.1260419 Human tissue
- Cavuoto P, McAinch AJ, Hatzinikolas G et al. The expression of receptors for endocannabinoids in human and rodent skeletal muscle. Biochem Biophys Res Commun. 2007;364(1):105-10. PMID 17935697 · doi:10.1016/j.bbrc.2007.09.099 Human tissueAnimal
- Dalle S, Koppo K. Cannabinoid receptor 1 expression is higher in muscle of old vs. young males, and increases upon resistance exercise in older adults. Sci Rep. 2021;11(1):18349. PMID 34526596 · doi:10.1038/s41598-021-97859-3 Human tissue
- Langer HT, Avey A, Baar K. Cannabidiol Does Not Impact Acute Anabolic or Inflammatory Signaling in Skeletal Muscle In Vitro. Cannabis Cannabinoid Res. 2022;7(5):628-636. PMID 34762497 · doi:10.1089/can.2021.0132 Cell / labAnimal
- Ghafouri N, Ghafouri B, Larsson B et al. High levels of N-palmitoylethanolamide and N-stearoylethanolamide in microdialysate samples from myalgic trapezius muscle in women. PLoS One. 2011;6(11):e27257. PMID 22125609 · doi:10.1371/journal.pone.0027257 Human tissue
- Eckardt K, Sell H, Taube A et al. Cannabinoid type 1 receptors in human skeletal muscle cells participate in the negative crosstalk between fat and muscle. Diabetologia. 2009;52(4):664-74. PMID 19089403 · doi:10.1007/s00125-008-1240-4 Cell / lab
- Cavuoto P, McAinch AJ, Hatzinikolas G, Cameron-Smith D, Wittert GA. Effects of cannabinoid receptors on skeletal muscle oxidative pathways. Mol Cell Endocrinol. 2007;267(1-2):63-9. PMID 17270342 · doi:10.1016/j.mce.2006.12.038 Cell / lab
- Liu YL, Connoley IP, Wilson CA, Stock MJ. Effects of the cannabinoid CB1 receptor antagonist SR141716 on oxygen consumption and soleus muscle glucose uptake in Lep(ob)/Lep(ob) mice. Int J Obes (Lond). 2005;29(2):183-7. PMID 15558076 · doi:10.1038/sj.ijo.0802847 Animal
- Mendizabal-Zubiaga J, Melser S, Bénard G et al. Cannabinoid CB1 Receptors Are Localized in Striated Muscle Mitochondria and Regulate Mitochondrial Respiration. Front Physiol. 2016;7:476. PMID 27826249 · doi:10.3389/fphys.2016.00476 Animal
- Siebers M, Biedermann SV, Bindila L, Lutz B, Fuss J. Exercise-induced euphoria and anxiolysis do not depend on endogenous opioids in humans. Psychoneuroendocrinology. 2021;126:105173. PMID 33582575 · doi:10.1016/j.psyneuen.2021.105173 Human · clinical study
- Desai S, Borg B, Cuttler C et al. A Systematic Review and Meta-Analysis on the Effects of Exercise on the Endocannabinoid System. Cannabis Cannabinoid Res. 2022;7(4):388-408. PMID 34870469 · doi:10.1089/can.2021.0113 Review
- Pekkala S, Wiklund P, Hulmi JJ et al. Cannabinoid receptor 1 and acute resistance exercise--In vivo and in vitro studies in human skeletal muscle. Peptides. 2015;67:55-63. PMID 25796352 · doi:10.1016/j.peptides.2015.03.007 Human tissueCell / lab
- Iannotti FA, Silvestri C, Mazzarella E et al. The endocannabinoid 2-AG controls skeletal muscle cell differentiation via CB1 receptor-dependent inhibition of Kv7 channels. Proc Natl Acad Sci U S A. 2014;111(24):E2472-81. PMID 24927567 · doi:10.1073/pnas.1406728111 Cell / labAnimal
- Zhang M, Jiang SK, Tian ZL et al. CB2R orchestrates fibrogenesis through regulation of inflammatory response during the repair of skeletal muscle contusion. Int J Clin Exp Pathol. 2015;8(4):3491-502. PMID 26097533 Animal
- Isenmann E, Veit S, Starke L, Flenker U, Diel P. Effects of Cannabidiol Supplementation on Skeletal Muscle Regeneration after Intensive Resistance Training. Nutrients. 2021;13(9):3028. PMID 34578906 · doi:10.3390/nu13093028 Human · clinical study
- Cochrane-Snyman KC, Cruz C, Morales J, Coles M. The Effects of Cannabidiol Oil on Noninvasive Measures of Muscle Damage in Men. Med Sci Sports Exerc. 2021;53(7):1460-1472. PMID 33481484 · doi:10.1249/MSS.0000000000002606 Human · clinical study
- Bezuglov E, Achkasov E, Rudiakova E et al. The Effect of Cannabidiol on Performance and Post-Load Recovery among Healthy and Physically Active Individuals: A Systematic Review. Nutrients. 2024;16(17):2840. PMID 39275158 · doi:10.3390/nu16172840 Review
- Schouten M, Dalle S, Koppo K. Molecular Mechanisms Through Which Cannabidiol May Affect Skeletal Muscle Metabolism, Inflammation, Tissue Regeneration, and Anabolism: A Narrative Review. Cannabis Cannabinoid Res. 2022;7(6):745-757. PMID 36454174 · doi:10.1089/can.2022.0220 Review
- Iannotti FA, Pagano E, Moriello AS et al. Effects of non-euphoric plant cannabinoids on muscle quality and performance of dystrophic mdx mice. Br J Pharmacol. 2019;176(10):1568-1584. PMID 30074247 · doi:10.1111/bph.14460 Cell / labAnimal
- Human Protein Atlas v25: tissue RNA consensus data (rna_tissue_consensus.tsv, HPA and GTEx, nTPM), the 17 genes in the map's layer selector: CNR1, CNR2, TRPV1, GPR55, PPARG, HTR1A, TRPV2, NAPEPLD, FAAH, DAGLA, DAGLB, MGLL, ABHD6, ABHD12, CYP3A4, CYP2C19, CYP2C9; v25.proteinatlas.org/download/tsv/rna_tissue_consensus.tsv.zip, downloaded October 24, 2026. Uhlén M et al. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419. License CC BY 4.0. PMID 25613900 · doi:10.1126/science.1260419 Human tissue