Managing Neuropathic Pain: CBD and Gabapentin Insights

If you’ve ever bumped your elbow, or if a dentist “touched a nerve” with a bur while treating your teeth, you understand what neuropathic pain is. Yet, people with chronic neuropathic pain experience this feeling daily. Unfortunately, doctors are often faced with a situation where a complete cure is impossible, and attention is focused on controlling the symptoms and adapting to life with neuropathic pain. The aim is to ensure an acceptable quality of life and to relieve pain as much as possible in order to sleep, communicate, and lead a social life. Based on the mechanism of action and pharmacokinetics of CBD and Gabapentin, an interaction is unlikely, aside from individual possible side effects. This article reviews how cannabidiol, a cannabis constituent, and Gabapentin, a drug commonly used for epilepsy and peripheral neuropathic pain, manage the pain of various severity and whether cannabis is a potential alternative to old-fashioned pharma. Currently, there is a growing body of research supporting that cannabis, specifically CBD, may effectively treat chronic pain, making it a valuable player in the medical field.

The Importance of Finding the Treatment

The ability to experience pain is an ancient and fundamental protective mechanism that ultimately leads to learning, adaptation and survival in changing environmental conditions. In addition, pain informs about tissue damage and triggers reflex and behavioural responses to minimise and avoid damaging effects. The nervous system is a sensitive and complex structure. Damage to the nervous system is serious, and self-healing of this structure is slow, if at all. As a result, the regenerative capacity of the nervous system is severely limited, and any nerve damage is challenging to treat.

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Neuropathic pain treatment is becoming an increasingly important area of study for clinicians of different profiles because of the widespread prevalence and the difficulties in finding long-lasting treatment. Neuropathic pain can cause suffering and varying degrees of disability for the patient and entail significant medical and social consequences. Despite there being many pharmaceuticals recommended for treating neuropathic pain, picking the optimal treatment regimen is often difficult for clinicians.

What is neuropathic pain, you may ask?

It is defined as “pain directly resulting from injury or disease of the somatosensory system” (Treede R.D. et al., 2008). From a clinical point of view, this means that neuropathic pain can result from damage to both the peripheral and central nervous systems. As defined by the International Association for the Study of Pain (IASP), neuropathic pain is “pain initiated or caused by a primary injury or dysfunction of the nervous system.” Thus, it differs from the pain that travels along healthy nerves from damaged tissue (for example, a fall, cut, or knee arthritis).

The main factors leading to the onset of neuropathic pain include diabetes mellitus, herpes infection, stroke, multiple sclerosis, malignant neoplasms, HIV infection, as well as post-traumatic and postoperative lesions of the peripheral nervous system (Bouhassira D. et al., 2008). In neuropathic pain, the main pathogenetic mechanisms activate peripheral nociceptors and neuronal and receptor disorders, peripheral and central sensitisation. The resulting persistent and often excruciating pain is resistant to drug treatment with conventional analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) (Snegirev F.G., 2010). Neuropathic pain affects the patient’s quality of life significantly, compromising their psychological condition. Unfortunately, most currently available treatments for this pathological condition have low to moderate efficiency and side effects that may limit their use. Henceforth, more effective and safe approaches are needed for individuals suffering from neuropathic pain that can reduce the symptoms of the disease and improve quality of life in general.

Drugs other than those used for pain associated with tissue damage, such as pain relievers, are often used for neuropathic pain. For example, drugs sometimes used for depression or epilepsy may be effective in some patients with neuropathic pain. One of these is Gabapentin. The outcome is defined as good if a patient with high pain levels gets rid of the pain by taking the drug without the side effects that would force the patient to stop taking the medication.

Neuropathic Pain Prevalence

According to official statistics, one in five adults in Europe suffers from moderate to severe chronic pain, and only 2% receive qualified medical care. Furthermore, the prevalence of neuropathic pain syndrome in Europe significantly exceeds most chronic pain without neuropathic characteristics (Breivik H. et al., 2006).

Neuropathic pain affects approximately 7–8% of the European population (Attal N. et al., 2010). However, in the 2011 Guidelines for the Assessment of Neuropathic Pain, the Special Interest Group on Neuropathic Pain (NeuPSIG) noted the lack of sensitivity and specificity of many screening instruments and their failure to identify the true prevalence of this pathology in the general population (Haanpää M . et al., 2011).

Main Symptoms

For some people, light touching clothes or bedding can cause skin discomfort and even pain. For others, any pressure (such as from socks, shoes, or tight clothing) can cause pain. According to patient surveys, here are some of the most prevalent neuropathic symptoms:

Burning pain;
The sensation of electric shock;
Tingling sensation, “needles under the skin”;
Piercing, stitching, cutting pain;
Convulsions;
Numbness;
Having trouble sleeping and resting;
Creeping sensation;
Painful sensations of cold and heat in the limbs;
Symptoms of allodynia (a pain provoked by a stimulus that usually does not cause it.)

Treating Neuropathic Pain

The treatment of neuropathic pain has different areas to target, as listed below.

To reduce or eliminate the cause of pain with the help of:
- Anticonvulsant medications. If you are prescribed these medications, it does not mean that you have a seizure disorder. These medications help calm the nerves that cause pain.
- Antidepressants. If you are prescribed antidepressant medications, it does not mean that you have depression or are being treated for depression. Antidepressants usually help with the psychological side of coping with chronic pain.
- Opioids. A strong prescription medicine is used to relieve pain.
- Local anaesthetics. These numb the skin or a small area on the body.
- Steroid medicines. Used to reduce the nerve inflammation
- In some cases, nerve blockade is necessary. This method of neuropathic pain treatment includes injection of local anaesthetics, steroids, or other medications into the affected nerves that are thought to be responsible for the pain signals. The effect of these nerve blocks is temporary, so they must be repeated to continue to relieve pain.
To maintain an average level of activity.
To improve the quality of life.

What About CBD?

The legalisation of cannabidiol (CBD), a potent plant extract of cannabis, came about primarily because of its beneficial health properties. Numerous studies have highlighted the efficacy of cannabidiol for symptoms of various disorders, such as:

Epilepsy (Epidiolex as an FDA approved drug);
Bipolar disorder;
Multiple sclerosis;
Anxiety, social anxiety disorder;
Neuropathy;
Inflammation;
Dystonia;
Post-cancer treatment nausea (CBD and THC);
Sleep deprivations, insomnia;
Parkinson’s disease.

Currently, two varieties of cannabis are distinguished: marijuana and hemp. The well-known constituent of marijuana, THC – tetrahydrocannabinol, is classified as a controlled substance in most countries around the world. CBD, on the other hand, is a non-psychotropic component of cannabis and does not obscure mind state and lucidity. Studies by A W Zuardi et al., 1995 even showed that CBD possesses an antipsychotic effect, blocking THC psychoactive properties. Research from the British Journal of Psychiatry stated that cannabis users with higher levels of cannabidiol in their hair showed fewer schizophrenic-like symptoms (Morgan CJ et al.,2008). A small preliminary analysis of the effects of cannabidiol on psychosis in Parkinson’s disease also yielded encouraging results (Zuardi A et al., 2008).

Is CBD legal?

Under the newly established system, the hemp that CBD is extracted from should not contain more than 0.2% THC in the UK and 0.3% in most of Europe.

Is CBD safe?

Many studies have shown CBD is safe for most individuals and has an extensive dosage range. Doses ranging from a few milligrams up to 1,500 mg have been taken with few adverse effects for up to four weeks and showed no adverse effects even in such a high amount.

What is Gabapentin?

Gabapentin (1- (aminomethyl) -cyclohexane acetic acid) is a structural analogue of gamma-aminobutyric acid (GABA) and was initially registered in 1994 as an antiepileptic agent. Now it is sold under the brand names Neurontin and Horizant and reported as an anticonvulsant drug helping people with epilepsy control seizures and neuropathic pain of various aetiology. However, the first mention of the ability of Gabapentin to reduce the intensity of pain syndrome dates back to 1996, when in the Journal Neurology AZ. Segal and G. Rordorf described a clinical case with a decrease in the severity of burning postherpetic pain in a 77-year-old patient while receiving Gabapentin at a dose of 900mg per day. Subsequently, the results of many randomised clinical trials confirmed the clinical efficacy of Gabapentin in the treatment of patients with various forms of neuropathic pain, which served as the basis for including this drug in the current European guidelines for the pharmacotherapy of neuropathic pain as a first-line drug.

How does Gabapentin work?

Gabapentin, as it states from the name, has a similar effect as a natural GABA brain neurotransmitter – it inhibits brain neuron activity,thus stopping pain.

To be clear, it does not control the nerves to stop them from being painful, but it can block your brain from registering the signal of pain. The exact mechanism of action is not fully understood yet; however, the effectiveness of drugs in the treatment of neuropathic pain is explained by their ability to bind to voltage-sensitive calcium channels in the central nervous system (CNS), mainly to α2-delta protein. This leads to a decrease in the release of neurotransmitters in the central nervous system due to a reduction in calcium influx through closed channels (Bockbrader et al., 2010). In the context of the current trends in the pharmacotherapy of neuropathic pain and the leading positions that antiepileptic drugs, in particular Gabapentin, it is advisable to consider the advantages of the clinical use of this drug in more detail, as any medication can have potential adverse side effects and risk of overuse.

Possible side effects of Gabapentin

The listed side effects are not observed in all patients who have been prescribed Gabapentin.

Drowsiness;
Increased fatigue or general weakness;
Nausea and vomiting;
Dizziness;
Diarrhoea;
Constipation;
Rash;
Abdominal pain;
Nervous eye tick.

Research on CBD and Gabapentin

Gabapentin

In 2017 Wiffen PJ et al. published a great review of Gabapentin treatment for neuropathic pain of moderate to severe levels. Thirty-seven randomised, double-blind trial studies satisfied the inclusion criteria, randomising 5914 participants to treat using Gabapentin, placebo, or other drugs. After 4 to 12 weeks, more participants (32%) had substantial benefit with Gabapentin at 1200mg daily, or greater than with placebo (17%). More participants (46%) had the moderate benefit with Gabapentin at 1200mg daily or more than with placebo (25%). In painful diabetic neuropathy, more participants (38%) had substantial benefit with Gabapentin at 1200mg daily or more significantly than with placebo (21%). However, participants experiencing at least one adverse event withdrawal with Gabapentin (63%) than with placebo (49%). Adverse event withdrawal included dizziness (19%), somnolence (14%), peripheral oedema (7%), and gait disturbance (14%). Out of all studies, it was concluded that Gabapentin at doses of 1800mg to 3600mg daily could provide good levels of pain relief to some people with postherpetic neuralgia and peripheral diabetic neuropathy. Evidence for other types of neuropathic pain is minimal. However, it is recommended to start at lower doses of Gabapentin and work your way up to a therapeutic dose.

Cannabidiol

CBD became famous as a treatment for epilepsy, but researchers soon discovered that this interesting cannabinoid could help with a wide range of conditions, such as neuropathic pain. So what do we know about cannabinoids and how exactly CBD tackles this problem?

Cannabinoids are categorised into three main types:

Phytocannabinoids – the naturally occurring cannabinoids found in the cannabis plant, including tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV), cannabidiol (CBD), cannabavirin (CBV), cannabichromene (CBA) acid) (CBDa), and tetrahydrocannabinol acid (THCa).
Endogenous cannabinoids – naturally occurring cannabinoids found in the human body (e.g. anandamide, 1-AG).
Synthetic cannabinoids – artificial cannabinoids created in a lab.

Cannabinoids interact with the body’s endocannabinoid system, which plays a role in regulating body functions such as immunity, sleep, and pain. Researchers are just beginning to understand how this hemp extract can help the body cope with pain. CBD helps increase levels of anandamide, a natural compound associated with pain regulation. The cannabinoid increases blood levels of anandamide, a crucial constituent of the endocannabinoid system, which can reduce perceived pain levels.

Other research suggests that CBD can reduce inflammation, which can also help control pain. A 2012 study by Wei Xiong published in the Journal of Experimental Medicine found evidence that CBD can reduce pain and inflammation through targeting α3 glycine receptors. In addition, according to research published in the European Journal, cannabidiol helped people with arthritis cope with their pain symptoms. Another Israel study from 2016 examined the effects of CBD on the number of seizures experienced by children with intractable epilepsy. More than half of the patients who saw improvement, reporting their seizures were reduced by 50% or more. The researchers also noted that the patients were more alert and had an improved quality of life. In a 2020 study by Dixon H Xu et al., a randomised study of 29 people with neuropathy received 250mg CBD oil or a placebo. Participants reported no side effects and a significant reduction in intense pain, sharp pain, plus cold and itchy sensations.

Does CBD Interact with GABA?

GABA is the primary neurotransmitter in our nervous system, contributing to excitatory and inhibitory neurotransmission regulation. It is sometimes known as the firehose for pain and inflammation. Research by Charlotte Marie Pretzsch et al., 2019 found that CBD facilitates glutamate and GABA neurotransmission across the brain through agonism at the transient receptor potential vanilloid type 1 (TRPV1) receptor. MRI scans measured glutamate and GABA in men with and without ASD (autism spectrum disorder) following a single oral dose of 600mg CBD or a matched placebo (at least two weeks apart) in a randomised, double-blind cross-over design study. Generally, CBD was shown to shift GABA levels; however, with autism, it seemed to have less efficacy.

Enzymes break down many drugs in the liver, specifically by the cytochrome P450 system. As the same system breaks down CBD, it may compete or interfere with these enzymes, leading to too much/not enough of the drug in the body, called altered concentration. In turn, altered concentration may lead to the lowered medication efficacy or an increased risk of side effects. Such drug interactions can cause unpleasant and sometimes serious problems.

The unique liver enzyme system metabolises most drugs, but Gabapentin is digested differently. It is eliminated from the systemic circulation by kidneys (renal excretion) as an unchanged drug. Gabapentin elimination rate is constant, and its half-life is 5 to 7 hours and is unaltered by dose or following multiple dosing. In older people and patients with impaired renal function, gabapentin plasma clearance is obviously reduced. In worst cases, Gabapentin can be removed from the plasma by hemodialysis. According to the Pennsylvania State University College of Medicine research, Gabapentin is not on the list of potentially dangerous drugs when co-administered with cannabinoids.

However, you have to be precautious as using Gabapentin and cannabis products with THC may cause the following effects:

Increase side effects such as dizziness, drowsiness, confusion, and difficulty concentrating.
Some people, especially the elderly, may also experience impaired thinking, judgment, and motor coordination.
It is best to avoid or limit alcohol use while using these medications.
Avoid activities requiring mental alertness, such as driving or operating hazardous machinery until you know how the drugs affect you.
If you have any questions or concerns, speak with your doctor. It is essential to describe all medications you use, including vitamins and herbal supplements. Do not stop using any drugs without first talking to your doctor.

Why CBD is still a Good Alternative

Gabapentin has been reported to have several adverse effects, including:

Limb swelling;
Shortness of breath;
Back or chest pain;
Vomiting;
Urinary problems;
Lack of concentration;
Suicidal tendencies, especially in high doses.

The US Food and Drug Administration (FDA) issued a warning about antiepileptic drugs (AEDs), like Gabapentin, for causing severe breathing problems among patients with respiratory comorbidities (like COPD). Another issue with Gabapentin is that it provides only temporary relief, not curing the cause of the problem. Altogether, a growing body of research shows that cannabis is an effective pain treatment with fewer side effects than many other alternatives.

Possible Side Effects of CBD

Side effects for CBD are rare, especially when taken within the recommended dosage. Only minor side effects have been reported from CBD use. These include:

Digestive problems – CBD, including the FDA-approved Epidiolex, may cause nausea and vomiting, diarrhoea, and changes in appetite.

Dry mouth – In a survey of 1,500 people, researchers found that nearly 12% of respondents experienced mild dry mouth after using CBD.

Drowsiness – This side effect of CBD oil was found in studies investigating the chemical’s impact on sleep. Exposure to high doses of CBD may help people sleep more soundly, while lower doses have been shown to promote alertness. However, some people have reported fatigue after exposure.

Whole-plant extracts high in THC may initially be effective pain relievers, but they do not represent the optimal pain-relieving strategy. Consider balanced THC/CBD foods or CBD-rich foods instead, as these may provide the best long-term treatment for chronic pain conditions. CBD does not appear to cause serious adverse side effects, such as affecting your blood pressure, body temperature, or heart rate. This is one of the main reasons why CBD is gaining popularity among scientific researchers and health professionals.

What Type of CBD Product Should I Use?

CBD is found in various products today, from oils and edible to cosmetics, topical and vaping fluids. It is important to choose the product that is right for you. What does this mean in practice? For example, if you suffer from general pain, using ointments or balms will not target the internal cannabinoid system but may ease inflammation on the skin. For headaches, migraines and most types of pain, the most effective way is to use internal products, such as oils, capsules and vapes, which can increase cannabinoids in the body. Products for external and internal use can be combined to increase effectiveness; for example, lubricate the affected joints with balm and carry a bottle of CBD oil or capsules to target the bloodstream.

To Summarise

Many drugs have been developed for pain relief, but most of them are based on artificially synthesised chemical compounds. Not only is CBD natural, but it also has one of the essential advantages – no significant side effects. When consuming CBD, listen to your body: you can start with a small amount, gradually building it up to the one you need to achieve the right results.

Anastasiia Myronenko

Anastasiia Myronenko is a Medical Physicist actively practicing in one of the leading cancer centers in Kyiv, Ukraine. She received her master’s degree in Medical Physics at Karazin Kharkiv National University and completed Biological Physics internship at GSI Helmholtz Centre for Heavy Ion Research, Germany. Anastasiia Myronenko specializes in radiation therapy and is a fellow of Ukrainian Association of Medical Physicists.

Can CBD be an alternative to Gabapentin for Neuropathic Pain? – Alphagreen Academy