CBD Oil And Gabapentin

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Clinical studies have shown that the major psychoactive ingredient of Cannabis sativa Δ9-tetrahydrocannabinol (THC) has some analgesic efficacy in neuropathic pain states. However, THC has a significant side effect profile. We examined whether the profile of THC could be improved by co-administering … There is no interaction between CBD oil and gabapentin. However, both may cause sedative effects, which can be additive if used together. 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

THC and gabapentin interactions in a mouse neuropathic pain model

Clinical studies have shown that the major psychoactive ingredient of Cannabis sativa Δ9-tetrahydrocannabinol (THC) has some analgesic efficacy in neuropathic pain states. However, THC has a significant side effect profile. We examined whether the profile of THC could be improved by co-administering it with the first-line neuropathic pain medication gabapentin. This was done using the chronic constriction injury (CCI) model of neuropathic pain in C57BL6 mice. At 8 days post-CCI nerve injury, acute systemic administration of gabapentin produced a dose-dependent decrease in CCI-induced mechanical and cold allodynia, and increased motor incoordination. Coadministration of THC and gabapentin in a fixed-ratio dose-dependently reduced mechanical and cold allodynia, and produced all the side-effects observed for THC, including motor incoordination, catalepsy and sedation. Isobolographic analysis indicated that the ED50 for the THC:gabapentin induced reduction in allodynia was 1.7 times less than that predicted for an additive interaction. The therapeutic window of combination THC:gabapentin was greater than that for THC alone. These findings indicate that gabapentin synergistically enhances the anti-allodynic actions of THC and improves its therapeutic window. Thus, THC may represent a potential adjuvant for neuropathic pain medications such as gabapentin.

Keywords: Cannabinoid; Gabapentin; Isobolograph; Neuropathic pain; Synergy; Tetrahydrocannabinol.

Copyright © 2018 Elsevier Ltd. All rights reserved.

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Neurontin (Gabapentin) With CBD Oil Interaction

In our latest question and answer, the pharmacist discusses the potential interaction between CBD oil and gabapentin.

Sue asked

I have pretty bad neuropathy and have been prescribed gabapentin. Is it safe to also use CBD oil?

Answer

Neurontin (gabapentin) is not known to interact with CBD (cannabidiol) oil. However, there is a lack of data available overall when it comes to potential drug interactions with CBD as it is not well studied (currently at least) in that regard.

Nevertheless, based on what we know about CBD and gabapentin metabolism, an interaction appears to be unlikely, as will be discussed below.

What Is CBD?

Cannabidiol (CBD) is one of the many constituents of the cannabis (i.e. marijuana) plant. In fact, depending on the specific strain of cannabis, CBD can make up over 40% of the total constituents (1).

An interesting characteristic of CBD is that it is ‘non-psychoactive’, meaning it doesn’t cause a “high” or euphoria (2). This is distinct from THC (tetrahydrocannabinol), which is largely responsible for the high that is associated with marijuana.

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Multiple studies have shown CBD to be safe for most individuals and has an extremely wide dosage range. Doses ranging from a few milligrams all the way up to 1,500 mg have been taken with few adverse effects for up to four weeks (3).

CBD has numerous effects on the body, many of which aren’t fully understood. Nevertheless, CBD has been used for several indications, including:

  • Bipolar disorder (4)
  • Dystonia (5)
  • Epilepsy (6)
  • Huntington’s Disease (7)
  • Multiple Sclerosis (8)
  • Parkinson’s Disease (9)
  • Schizophrenia (10)
  • Anxiety (11)
  • Neuropathy (19)
  • Inflammation (20)

CBD certainly looks promising from a medical standpoint, but more studies are needed to determine its effects and overall efficacy.

As CBD may help with various types of pain (e.g. neuropathy), it makes sense to look into its use for those indications and whether or not it is safe with other medications for those indications (like gabapentin).

CBD Drug Interactions

When it comes to drug interactions, many aren’t definitively known but there are some theoretical ones that are proposed based on how CBD is metabolized.

CBD is metabolized by the cytochrome P450 system, the major enzymes involved in drug metabolism. Most drug interactions involve this system of enzymes. When a drug metabolizing enzyme is inhibited, concentrations of a drug may be increased due to decreased metabolism. For example:

  • Drug A is metabolized by CYP 3A4.
  • Drug B inhibits CYP 3A4.
  • Taking Drug B with Drug A may result in increased concentrations of Drug A (due to decreased metabolism). This can potentially increase the risk of side effects.

Studies have shown that CBD can affect numerous enzymes, which could potentially affect how other drugs are metabolized.

Studies have shown that CBD can potentially inhibit:

We say potentially inhibit since lab studies have shown that CBD can inhibit the above enzymes, but several human studies don’t show consistent results.

There is a prescription CBD product known as Epidiolex that offers a little insight unfortunately into potential interactions. It has very few details on specific interactions, and the prescribing information for the drug only theorizes potential interactions based on the potential for CYP metabolizing enzyme inhibition (16). The only drugs it mentions that have confirmed drug interactions are:

  • Diazepam (increases concentrations)
  • Onfi (Clobazam) (increases concentrations)

How Is Gabapentin Metabolized?

The vast majority of drugs are metabolized via the CYP enzyme system. Gabapentin, however, is not. Interestingly, it is not metabolized to any appreciable degree in humans and is excreted intact in the urine (17).

Due to the lack of gabapentin metabolism, CBD isn’t thought to interact with it and should not affect levels of gabapentin in the body if taken at the same time.

The only thing to be aware of is that high doses of CBD can have sedative and slight hypnotic effects (18). Due to this, it is a general warning that CBD be used cautiously with CNS (central nervous system) depressants, like gabapentin, due to the risk of additive sedation.

Can CBD be an alternative to Gabapentin for Neuropathic Pain?

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).

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 di abetes 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.

  1. To reduce or eliminate the cause of pain with the help of:
      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.
  2. To maintain an average level of activity.
  3. To improve the quality of life.
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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).

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.

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.

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