Muscular System – Cannabis and Cannabinoid Research

Muscular System and ECS-Based Interactions

Endocannabinoid Signaling Across the Muscular System

All components of the endocannabinoid system (ECS) are present throughout the muscular system, where they play roles in muscle development, repair, and regulation of inflammation and pain. Key ECS components identified in muscle tissues include:

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  Cannabinoid receptors:

  
  
  
  
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    CB1 receptors are expressed in skeletal muscle fibers, where they modulate glucose uptake, energy metabolism, and neuromuscular signaling. They are also present in motor neurons that innervate muscle tissue. (J. Mendizabal-Zubiaga et al., 2016; Z. Singlár et al., 2022; H. Kalkan et al., 2023)

    
    
  
  
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    CB2 receptors are found primarily in immune cells (e.g. macrophages) within and around muscle tissue, especially during inflammation, injury, or disease states such as Duchenne Muscular Dystrophy. Their activation appears to support anti-inflammatory and regenerative responses. (M. Argenziano et al., 2023)

    
    
  
  
  
  


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  Endocannabinoids:

  
  
  
  
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    Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are  detected in muscle tissues and play a diverse role in muscular properties and function. (M. Schönke et al., 2020)

    
    
  
  
  
  


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  ECS-related enzymes:

  
  
  
  
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    FAAH (fatty acid amide hydrolase) and MAGL (monoacylglycerol lipase), which degrade AEA and 2-AG respectively, are also expressed in muscle tissues, helping to regulate the duration and intensity of ECS signaling. (M. Schönke et al., 2020)

    
    
  
  
  
  


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  Extended ECS (eCBome) modulators:

  
  
  
  
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    Molecules such as palmitoylethanolamide (PEA) (Z. Huschtscha et al., 2024), oleoylethanolamide (OEA), and their corresponding receptors (e.g., PPAR-α) are active in skeletal muscle and may be harnessed to support muscle repair, metabolic regulation, and inflammation control. (H. Bahari et al., 2025)

    
    
  
  
  
  

Overall, the ECS appears to contribute to muscle homeostasis, regeneration, energy balance, and neuro-muscular communication, especially in the context of exercise, injury, and neuromuscular diseases.

How ECS Imbalance Impacts Muscle Health

Suboptimal ECS signaling may contribute to both the development and progression of muscular system pathologies. Dysregulation of the ECS—whether due to insufficient endocannabinoid production, receptor imbalance, or enzyme overactivity—can impact muscle function in several ways:

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  Impaired muscle regeneration: Reduced CB1 or CB2 signaling may hinder the activation and differentiation of cells critical for muscle repair following injury or stress.

  
  


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  Increased inflammation: Without adequate CB2-mediated modulation, inflammatory responses in muscle tissue may become chronic or excessive, contributing to muscle degeneration and diseases such as muscular dystrophy or myositis.

  
  


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  Metabolic dysfunction: Altered CB1 signaling in skeletal muscle can disrupt glucose uptake, fat metabolism, and insulin sensitivity, increasing vulnerability to metabolic myopathies and muscle fatigue.

  
  


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  Neuromuscular imbalance: ECS dysfunction may affect the regulation of motor neuron activity, potentially exacerbating spasticity, myotonia, or neurodegenerative conditions affecting muscle control.

  
  

In short, a well-functioning ECS is essential for maintaining muscle homeostasis, repair capacity, and resilience, and its disruption may increase the risk of both acute and chronic muscular disorders.

Harnessing Cannabinoid-Based Therapeutics and the eCBome: Emerging Therapies for Muscle Repair, Recovery, and Resilience

A growing body of scientific evidence suggests that cannabinoid-based therapeutics and modulators of the endocannabinoidome (eCBome) may support muscular system function, performance, and recovery. (J. Burr et al., 2021) More specifically:

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  Reducing inflammation and muscle damage: Cannabinoids such as CBD (M. Schouten et al., 2022) and THC (A. Pinzone et al., 2023) have demonstrated anti-inflammatory and antioxidant effects in preclinical models of muscle injury and muscular dystrophy, potentially limiting tissue damage, improving recovery and performance. Consider this surveys confirming real-live recovery effects after excercise with both the use of CBD and THC. (A. Pinzone et al., 2023)

  
  


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  Enhancing muscle regeneration: Studies show that modulation of CB1 (antagonism) can stimulate satellite cell differentiation and increase myofiber regeneration—a critical process in recovery from trauma or degenerative disease such as in Duchenne muscular dystrophy. (F. Iannotti et al., 2018)

  
  


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  Modulating neuromuscular signaling: CBD has been shown in silico to favorably interact with Nav1.4 sodium channels, suggesting potential benefits for myotonic disorders by stabilizing aberrant electrical activity in muscle fibers.

  
  


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  Relieving symptoms of spasticity and rigidity: Clinical and anecdotal reports document the use of cannabis-based medicines (e.g., THC:CBD formulations) for managing spasticity, pain, and cramping in neuromuscular conditions like ALS, multiple sclerosis, and Isaacs Syndrome.

  
  


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  Preventing chronic dysfunction: Modulators such as PEA, omega-3 fatty acids, and exercise-induced endocannabinoids (e.g., AEA and 2-AG) may help maintain muscle tone, mitochondrial function, and metabolic balance, potentially reducing the risk of age-related sarcopenia and metabolic myopathies.

  
  

Overall, this growing body of evidence points toward a therapeutic role for ECS-targeted interventions—both for prevention and treatment of muscular system pathologies—though more clinical trials are needed to establish efficacy and best-use practices.

ECS Biomarkers, Exercise, and Safety in Muscle Medicine

Emerging studies suggest that ECS biomarkers may correlate with disease progression and treatment response in neuromuscular conditions. Potential biomarkers include:

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  CB1 and Muscular Dystrophy: The ECS influences the progression of degenerative muscle diseases by regulating muscle differentiation, regeneration, and repair—positioning the CB1 receptor as a potential target for adjuvant therapy in muscular dystrophies. (F. Iannotti et al., 2018).

  
  


• CB2 and ALS: Modulating CB2 receptors and other components of the endocannabinoid system to slow the progression of amyotrophic lateral sclerosis (ALS). (C. Rodriguez-Cueto et al., 2021)


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  Endocannabinoid levels: Physical exercise, such as running, significantly elevates endocannabinoid levels (AEA and 2-AG), reinforcing the ECS’s role in regulating muscle-related functions like energy metabolism, recovery, and inflammation. These findings support the therapeutic relevance of exercise-induced ECS activation in maintaining muscular health and managing neuromuscular conditions. (T. Weiermair et al., 2024)

  
  


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  eCBome modulators: Shifts in levels of PEA may indicate inflammation and metabolic stress in muscle tissue with potential relevance to conditions affecting the muscular system. (A. Mallard et al., 2020)

  
  

Research Gap: No standardized clinical assays currently exist for ECS biomarker profiling in muscle disease. Future longitudinal studies are needed to validate predictive utility.

Drug Interactions and Safety in Neuromuscular Disorders

Patients with neuromuscular diseases often take polypharmacy regimens (e.g., antispasmodics, steroids, or immunosuppressants). Cannabinoid-based therapies may interact in ways that warrant caution. For more information see "Drug Interaction for THC and CBD" at the bottom of each Conditions Dashboard.