Introduction 

The influence of cannabis on muscle control among multiple sclerosis has been a topic of growing popularity and research in the medical community. Multiple sclerosis (MS) is a complex autoimmune condition affecting the central nervous system (CNS), causing a wide range of symptoms including muscle stiffness, tremor, and loss of coordination. There is still no cure for MS currently, despite supportive and rehabilitative treatments.¹ Due to the effectiveness of the two cannabis chemical compounds, THC and CBD, in alleviating relevant symptoms while improving muscle control among some MND cases.² Understanding how cannabis interacts with the nervous system and affects muscle functioning upon MS is crucial for developing effective treatment strategies. Despite the exploration of potential alternative treatment, it also raises important considerations about cannabis's potential benefits, risks, and implications towards its application in improving muscle control among MS.

Multiple sclerosis and muscle control 

What is multiple sclerosis (MS)?

Multiple Sclerosis (MS) is a chronic autoimmune condition affecting the CNS as your immune system mistakenly attacks your myelin sheaths, the protective covers surrounding your brain (cranial) and spinal nerves become damaged and inflamed, resulting in inflammation. Hence, peripheral nerve signalling to the body is interrupted, affecting various functions such as vision, sensation and movement issues, depending on the attacked nerves.¹

Common MS symptoms related to muscle control

Muscle stiffness, spasticity, and spasms 

Muscle stiffness, spasticity, and spasms are three interrelated symptoms among MS. While muscle stiffness is the increased tone resistance (spasticity) among muscles due to upper motor neuron (UMN) lesion, making them slow and difficult to relax. Spasms are the uncontrollable twitches or jerks during muscle stretch, such as clonus or sudden, repetitive involuntary limb movements, even when muscles are resting.³

Tremors 

Tremors, as involuntary trembling or shaking movements, can be a symptom among 25-60% MS population. While manifesting as either “gross” or “fine” across big or small movements, such as shakiness in hands, feet or bigger on the arms and legs. Intention and postural tremor have been the most common subtypes associated with ataxia of MS, more noticeable than the essential tremor everyone could have, these could impairs active reaching movements and balances when holding body parts against gravity, whereas relives during completely relaxed scenarios, such as lying down or sleeping.⁴

Ataxia

Ataxia is the lack of muscle coordination that occurs at any time among 80% of MS cases during disease course.⁵ Often appears as clumsiness, unsteady gait, impaired eye and limb movements, speech problems, and sometimes dizziness. It may also be accompanied by other symptoms like fatigue, weakness, and sensory or visual disturbances like double vision, impacting daily functioning.⁶

Weakness

Weakness is common among MS. Ranges from reduced strength or energy to complete loss of some/all limbs, even whole body movements, particular during relapses. Fatigue is also closely linked due to the increased energy expenditure needed for basic movements, further impairing walking, seating postural balance, resulting in falls and loss of independence.^7,8

Cannabis and its components 

Overview of cannabis

Cannabis is a generic term referring to the dried leaves, flowers, stems, and seeds of the cannabis sativa L. plant, with terpenes in offering its distinct smell. While there are at least 125 cannabinoids, the cannabinoids and terpenes concentrations and combinations vary from plant to plant and among different cannabis strains.^2,9

Among all there are two major cannabinoids:

• Tetrahydrocannabinol (THC), also known as delta-9-tetrahydrocannabinol, has been the most psychoactive substance among cannabis. With its concentration in cannabis varying from 1-24%, it changes brain functioning by altering perception, mood, consciousness, and/or behaviour
• Cannabidiol (CBD), is the major non-psychoactive cannabinoid, with concentration less than 1%. Often considered as medical cannabis (marijuana), it can be manufactured into multiple forms of products for various purposes

Endocannabinoid system: mechanisms of action

The endocannabinoid system (ECS) is a complex network of receptors, endocannabinoids (cannabinoid-like compounds produced by the body), and enzymes, playing a crucial role of various physiological regulatory processes, such as skeletal muscle functioning, pain control, inflammation and brain development.^10,11

There are two main types of receptors, namely CB1 and CB2 among the ECS. 

• CB1 receptors, primarily found in the central nervous system (CNS), play a key modulating role among functions such as pain perception, memory, mood, and appetite
• CB2 receptors, mainly located among the peripheral nervous system (PNS), especially immune or glial cells, influencing inflammatory and immune responses

As endocannabinoids bind to these receptors, a cascade of neurotransmitter signalling events are triggered to maintain homeostasis in the body. Whereby, endocannabinoids are produced on demand, acting as retrograde messengers that regulate neurotransmitter release for various physiological activities modulation. 

Effects of cannabis on muscle control in MS 

Due to endocannabinoid receptors among the CNS and PNS, and its claimed effectiveness among some MS individuals upon muscle stiffness, spasticity, and pain relief.¹² The several beneficial effect on these symptomatic relief will be mentioned below:

Muscle relaxation and spasticity management 

Cannabis exerts a dual impact on relaxing spastic muscles among MS via the endocannabinoid system through nabiximols. Regarding muscle stiffness, spasticity and spasms as signs of upper motor neuron (UMN) lesion, the THC and CBD compounds among cannabis can effectively interact with the endocannabinoid system in alleviating CNS excitability. 

When THC-CBD compounds among cannabis bind to CB1 receptors in CNS at glutamatergic synapses, it has reduced the release of excitatory glutamatergic neurotransmitters. Thus, CNS’s hyperexcitability to deliver an antispastic effect in alleviating muscle stiffness and spasm. 

The simultaneous release of inhibitory GABAergic neurotransmitters on CB1 could further modulate neurotransmitter activity, to reduce intracortical facilitation. Hence, decreasing moto-neuronal excitability and involuntary muscle contraction, to facilitate spasticity management and muscle relaxation.¹³

Pain relief 

Dronabinol, the synthetic form of THC, is found to offer a certain extent on relieving MS central neuropathic pain in MS, targeting the endocannabinoid system.^14,15 By interacting with the cannabinoid receptors, central neuropathic pain among MS can be alleviated by dronabinol, through pain perception modulation and CNS hyperexcitability reduction.¹⁶ With dronabinol, analgesic properties, mimicking the effect of natural cannabinoids, it helps to alleviate neuropathic pain, muscle spasms, hence improving muscle control.

Anti-inflammatory effects

Concerning MS has long been known to be a chronic low-grade neuronal inflammatory disease, cannabis’s effectiveness to mitigate neuroinflammation has been beneficial.¹⁷ While the anti-inflammatory effects are considered to be cannabinoid’s potential inhibitory on NLRP3, alongside THC and CBD binding to cannabinoid receptors.¹⁷ By modulating cytokine production and immune cell activities, cannabis is effective in dampening neuroinflammation, whilst lessening neuronal damages among MS.^18,19 Hence, alleviating stiffness, spasms, tremors and weaknesses, improves muscle control and potential disease modification.

Neuroprotection 

Cannabis confers neuroprotection among MS by engaging the endocannabinoid system. The interaction of THC and CBD with CB1 and CB2 could have exerted their neuroprotective activities such as the mTOR1 pathway, brain-derived neuropathic factor (BDNF), thus remyelination, glial and axonal preservation among MS. Through the anti-inflammatory and antioxidant effects of neurotransmitter release and cell survival pathway promotion, cannabis helps to combat oxidative stress and neuroinflammation that contributes to neurodegeneration among MS.^18,19 Thereby, capable of slowing down MS progression while securing the muscle strength, tone and control as much as possible.

Comparison to other MS treatments 

Concerning muscle control promotion among MS, cannabis has presented a unique alternative compared to traditional treatments. While cannabis, with its various modulative effects upon THC and CBD interaction with the endocannabinoid system, ultimately improves muscle control. Its multifaceted approach targeting both spasticity and relaxation could offer a comprehensive management vision among MS-related muscle symptoms. 

While the traditional MS treatments for muscle control such as muscle relaxants, corticosteroids, and physiotherapy are effective in leveraging specific symptoms like spasticity, tremor, and ataxia. They may be accompanied by different side effects, like drowsiness, gastrointestinal issues, and weakness. 

Synergistic effects when combined usage 

When used together with traditional treatments, cannabis can act synergistically as the entourage effect, in potentially improving overall responses and therapeutic outcomes. The use of nabiximols (medical cannabis) is combined with physical therapy programs and muscle relaxants in persistent.²⁰ Hence, having a positive effect on potential benefits amplification, leading to improved muscle control among the affected population. 

Risks and side effects of cannabis use 

Potential adverse effects 

While there is an uncertainty of cannabis strength, either when bought illegally or when it is consumed in a mixture, the effectiveness and desirable outcomes might not always be attainable or the same. Potentially causing less welcome changes such as:

• Dizziness 
• Sleepiness 
• Anxiety 
• Feeling sick 
• Increased risk of seizures
• Harmful to unborn babies

Despite the side effects mentioned above, high doses of cannabis may even slow down reaction time, causing blood pressure, heartbeat, visual, and coordination changes. Smoking cannabis can even affect your lungs over time, heightening the risk of heart attack and cancer. 

Furthermore, cannabis consumption could further heighten the risk of contracting or intensify existing mental health problems like schizophrenia or bipolar disorder.

Long-term effect on MS 

While smoking cannabis mixed with tobacco has posed extra risk upon individuals with MS by speeding up the relapses evolving into secondary progressive MS. Smoking of tobacco could further lessen the therapeutic effect of MS drugs.

Despite the worsened memory, reaction time measured and abnormal brain activity in MRI among people with MS that have smoked cannabis, where none of these are seen in those who use the cannabis-based drugs, Sativex.²¹

Though Sativex may still induce some side effects like sleepiness, headache, diarrhoea, even hyperlite from the THC within, making MS fatigue worsen for a period of a few weeks before they fade.²² The long-term adverse effects are still much milder when compared with ordinary forms of cannabis. 

FAQs 

Is Marijuana the same as Cannabis?

Partly yes, while cannabis refers to all products derived from the plant Cannabis sativa, which contains approximately 540 substances. Marijuana are the cannabis parts or products containing substantial THC compounds. 

Summary 

Cannabis has demonstrated both direct or indirect promise in enhancing muscle control upon Multiple Sclerosis (MS). Through active compounds like THC and CBD, cannabis interacts with the endocannabinoid system among the central and peripheral nervous system in alleviating muscle stiffness, promotes relaxation, modulates pain perceptions, reduces inflammation and enhances neuroprotection, ultimately improving muscle function. With cannabis’s holistic approach in addressing both spasticity and relaxing muscles, it offers an all-rounded solution for MS-related muscle symptoms management. Despite the promising efficacy in symptomatic relief, further research into potential side effects, varied individual responses, and long term effects are still necessary to be considered as part of a safe and secure MS treatment.