Neuropathy (Nerve Pain)

Neuropathy (nerve pain) is a condition that is associated with many different conditions, including:

• Diabetes
• Multiple sclerosis (MS)
• Cancer
• trigeminal neuralgia
• HIV/AIDS
• Parkinson’s Disease
• Stroke
• Shingles
• Complex regional pain syndrome (CRPS)
• Traumatic brain injuries (TBIs)

The underlying causes of neuropathy are often inflammation, infectious disease, or a metabolic disorder. Some antibiotics, such as ciprofloxacin, and exposure to certain toxins may cause neuropathy.

Unfortunately, we have few medications that can effectively treat neuropathy and nerve pain. Gabapentin and pregabalin, often prescribed for nerve pain, can be harsh and addictive when used long-term. Medical cannabis could be an excellent way to treat nerve pain and may be more effective than current treatment methods.

What is Neuropathy/Peripheral Neuropathy (PN)?

Neuropathy is damage or dysfunction to one or more nerves, resulting in pain (often called “neuropathic pain”), numbness, tingling, headaches/migraines, and muscle weakness. If the motor nerves are affected, then lack of coordination and possibly even paralysis may occur. Some also have an extreme sensitivity to touch.

Neuropathy is often called peripheral neuropathy (PN). Peripheral nerves are found in the muscles, skin, and internal organs. The most common cause of neuropathy is nerve damage from diabetes, called “diabetic neuropathy.” Injuries and infections are also common causes of neuropathy.

Neuropathy affects an estimated 20 million Americans. Although there are more than 100 types of neuropathy, they can be broken down into four major categories:

1. Motor neuropathy: damage to nerve cells that control muscles and movement. This can result in losing coordination and control of limbs or trouble speaking.
2. Sensory neuropathy: The nerves that sense touch or pain become damaged, resulting in a loss of sensation.
3. Autonomic nerve neuropathy: damage to nerve cells controlling unconscious bodily functions such as breathing and heartbeat.
4. Combination neuropathies: a combination of two or more of the above neuropathies. The most common variety is motor neuropathy and sensory neuropathy.

Neuropathy can affect just one nerve (mononeuropathy), two or more nerves in different areas (multiple neuropathies), or multiple nerves (polyneuropathy). Although a wide range of diseases can cause neuropathy, there are three patterns of degeneration they all follow:

1. Segmental demyelination: degeneration of the myelin sheath, sparing the nerve axon.
2. Wallerian degeneration: degeneration of the nerve axon due to the lack of nutrients from the cell body.
3. Axonal degeneration, aka the dying-back phenomenon: The far point (distal) of a nerve fiber (axon) degenerates and progresses proximally, causing further decline as time passes, eventually reaching the neuron.

Brief Summary of Current Treatments

Medications prescribed for nerve pain are sometimes called “neuropathic pain agents.” The medications prescribed for chronic pain differ from those prescribed for neuropathic pain. Opioids and opiate-based drugs are rarely wholly effective for neuropathic pain, whereas anti-convulsant medications such as pregabalin and gabapentin are used instead.

Tricyclic antidepressants are also used for neuropathic pain. Other antidepressants, most notably serotonin and norepinephrine reuptake inhibitors (SNRIs) like venlafaxine and duloxetine, may also help manage neuropathic pain associated with fibromyalgia.

As neuropathic pain can often be felt at specific sites on the skin, capsaicin cream may help. High vitamin diets may also help, and steroids may also be prescribed. For headaches and migraines associated with neuropathy, amitriptyline may be prescribed.

Non-drug treatments include physiotherapy and the use of walking aids.

How Might Medical Cannabis Help?

The endocannabinoid system (ECS) modulates inflammation and pain transmission in the nociceptive pathway. CB1 receptors are abundant in the regions of the brain implicated in the conduction and modulation of pain signals. CB2 receptors are found in the immune system and help regulate inflammation.

Following a nerve injury, neurons along the nociceptive pathway may become more reactive and responsive. This process is known as “sensitization,” where a cascade of cellular events results in painful nerve endings. Cannabinoids can reduce pain by modifying these cellular events, reducing the strength of pain signals sent through the nerve fiber. Medical cannabis is also full of phytocannabinoids and terpenes with anti-inflammatory properties.

Cannabinoids

• Tetrahydrocannabinol (THC) = provides analgesic (painkilling) effects.
• Cannabidiol (CBD) = has anti-inflammatory effects.
• Cannabigerol (CBG) = has neurogenic (brain cell building) effects.
• Cannabichromene (CBC) = has neurogenic effects.
• Cannabinol (CBN) = has sedative effects that can aid sleep.
• Tetrahydrocannabivarin (THCV) = could be particularly useful for diabetic neuropathy, as THCV has been shown to restore insulin sensitivity in mice.

Cannabinoid Ratios

• THC:CBD 1:20
• THC:CBD 1:18
• THC:CBD 2:5
• THC:CBD 1:1
• THC:CBD 2:1

Terpenes and Terpenoids

• Beta-caryophyllene

• Myrcene

• Linalool
• Humulene
• Pinene
• Limonene
• Camphene

Flavonoids

• Cannflavin A, B, and C
• Quercetin
• Kaempferol

Effective Ways of Taking Medical Cannabis for Neuropathy (Nerve Pain)

Routes of Administration

• Inhalation (oral)
• Ingestion (oral)
• Sublingual
• Topical
• Transdermal
• Rectal

Special Formulations

One study found that neuropathy patients treated with a THC/CBD nasal spray reported significantly improved levels of pain, sleep quality, and quality of life according to an enhanced Subject Global Impression of Change (SGIC) scale. A 2013 study published in The Journal of Pain showed that even a low dose of vaporized, THC-rich cannabis significantly reduced neuropathic pain.

Patients with neuropathic pain respond well to THC-rich, CBD-rich, and THC:CBD equal ratios. Products with more balanced THC:CBD profiles can reduce the chances of adverse effects.

Products rich in beta-caryophyllene, linalool, pinene, eugenol, and myrcene may help reduce pain and inflammation associated with neuropathy.

Dosing Methods

• Vaporizer
• Inhaler
• Tincture
• Edible
• Topical cream or salve
• Transdermal patch
• Suppository

What are the Pros and Cons of Taking Medical Cannabis for Neuropathy and Cannabis?

Potential Pros

• Neuropathic pain may have something to do with dysfunction of the vanilloid receptor (TRPV1, the capsaicin receptor) and the ability of the body to keep a consistent internal temperature. CBD desensitizes the TRPV1 receptor and may work as a painkiller similarly to ibuprofen but with fewer adverse side effects.

• Many medications used for PN and neuropathy have many harmful side effects.
• CBD may help induce bone growth and neurogenesis, which may help manage or even possibly reverse nerve pain and neurodegeneration.
• Cannabinoids and terpenes like beta-caryophyllene may work together to help beat nerve pain caused by neuroinflammation, which is hard to treat and target.
• Topicals and creams can be used to target pain in specific areas.
• Medical cannabis may help manage conditions that lead to nerve pain, such as diabetes, rheumatoid arthritis, and multiple sclerosis (MS).
• “Medical cannabis is among the most effective treatments for people with long-term, problematic neuropathic pain.” Medical cannabis provides pain relief and improves the quality of life for many patients with neuropathic pain.

Potential Cons

• The efficacy of medical cannabis depends on the cause of the nerve pain. Some kinds of nerve pain may not respond well to cannabinoids, so the correct ratio is needed for actual effectiveness.
• Most studies have small sample sizes, so a lack of power and the potential for bias still exists.

Useful Anecdotal Information

Jeff Seidel, “I swore I’d never touch marijuana. Here’s why I finally did.” Detroit Free Press

Scientific Data Overview and Studies

• Total Studies = 78 (peripheral neuropathy, diabetic neuropathy, drug-induced polyneuropathy, inflammatory polyneuropathy)
• Positive Studies = 75
• Inconclusive Studies = 2
• Negative Studies = 1
• 28 Meta-analyses (27 positive, 1 negative); 31 animal studies (all positive); 11 double-blind human trials (9 positive, 2 inconclusive); 3 human trials (all positive); 4 lab studies (all positive)
• 21 studies include CBD (20 positive, 1 inconclusive); 20 studies include THC (14 positive, 5 inconclusive, 1 negative); 2 studies include CBC (both positive); 1 study includes CBG (positive); 1 study includes CBN (positive); 2 studies include CBDA (both positive); 1 study includes THCA (positive); 8 studies include a 1:1 THC:CBD ratio (7 positive, 1 inconclusive); 6 studies include the endocannabinoid, anandamide (all positive)
• No. of Leafwell Patients (2021) = 900
• Possible Overall Efficacy: High

Quotes from Studies

“Whether drugs capable of exploiting the differences between the various cannabinoid receptors can yield greater analgesia with fewer adverse effects remains to be seen. This capability would be of substantial benefit in treating neuropathic pain, particularly that of central origin, because existing treatments are far from perfect. In the meantime, the current trial adds to the trickle of evidence that cannabis may help some of the patients who are struggling at present.”

McQuay, Henry J., “More evidence cannabis can help in neuropathic pain,” CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne vol. 182,14 (2010): 1494-5. doi:10.1503/cmaj.100799

“Use of marijuana for chronic pain, neuropathic pain, and spasticity due to multiple sclerosis is supported by high-quality evidence. Six trials that included 325 patients examined chronic pain, 6 trials that included 396 patients investigated neuropathic pain, and 12 trials that included 1600 patients focused on multiple sclerosis. Several of these trials had positive results, suggesting that marijuana or cannabinoids may be efficacious for these indications.”

Hill KP. “Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review.” JAMA. 2015;313(24):2474–2483. doi:10.1001/jama.2015.6199

Conclusion

There are few effective treatments available for neuropathic pain. Medical cannabis is effective for reducing nerve pain and is preferred by many over current prescription medications as it has fewer adverse side effects, reduces nerve pain, and improves the quality of life with improved sleep and appetite.

Related Articles

Medical Cannabis for Nerve Pain (Neuropathy)

Medical Cannabis and Diabetes

CBD and the Brain: The Impact of Cannabidiol on Brain Health

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