Medical Cannabis for Neuropathic Pain – Part 2 of 3

Medical Cannabis for Neuropathic Pain

Welcome back to Part 2 of Medical Cannabis for Neuropathic Pain, a 3 part series.  Before we begin, it is important to recognize that Nov 8, 2016 marked more than a US presidential election.   By the end of the voting, more than half of the states in the union approved the use of cannabis for state qualified medical conditions.

This move, to allow the medical use of marijuana, is supported by a majority of doctors in the U.S. But with that said, it is important to understand cannabis has not yet been analyzed, tested, or approved by the FDA.  There is limited information on the side effects of using medical cannabis; and there may be associated health risks as a result of using marijuana as a medical treatment option. As with all treatments options, you should first discuss the possible use of medical cannabis for neuropathic pain with your doctor.

With the addition of four more states Florida, North Dakota, Montana and Arkansas, voters have now passed bills allowing the medical use of cannabis in 29 states and the District of Columbia (Figure 1). As we mentioned in Part 1, each state has its own laws governing access to the use of medical cannabis which varies to different extents for different conditions.

States were Medical Marijuanna is legal

Figure 1. Marijuana legalization status in the US on Nov 9, 2016.

So let’s get started with Part 2 of Medical Cannabis for Neuropathic Pain with a common question:

Is medical cannabis substantially different from recreational cannabis?

The answer, like most things cannabis, depends on the state in question.

In some states, what can be purchased under the minimum standards for medical cannabis might be identical in form to recreational marijuana because both are derived from the Cannabis plant (called leaf product).

However, one can generalize that medical cannabis has a higher level of testing standards required to meeting the medical standards of dispensing.  These standards do not always apply to recreational use. But even within a state, the product offerings and the company standards will differ between dispensary companies.

Most states do require strict accounting of marijuana products, from seed to sale (figure 2). However, states such as New York do not permit the sale of agricultural leaf for medical use.  Figure 3 illustrates the production process and final product for medical cannabis tincture or oil.

 

Figure 2. Cannabis production: from seed to sale: seeds, seedling, bloom, mature flower, packaged product.

Figure 2. Cannabis production: from seed to sale: seeds, seedling, bloom, mature flower, packaged product.

 

 Figure 3. Processes for Columbia Care product in New York state (no leaf).

Figure 3. Processes for Columbia Care product in New York state (no leaf).

 

Cannabis, also known as hemp, is believed to be one of the earliest crops cultivated by humans nearly 10,000 years ago.  For these civilizations, cannabis crops provided a source of food, fiber, oil and paper. But cultivators recognized that some of the plant varieties had medicinal properties as well.

One variety of the cannabis plant was tall and durable; this became what we now know as industrial hemp. The heavy flowered buds of a second variety were known to have psychoactive effects, and these cannabis plants were grown separate from the hemp plants in order to isolate their “medicinal” characteristics.

The first mention of medical use of marijuana dates back to around 2700 B.C. when the Chinese described the plant as a medicine with many uses, including arthritic pain as well as constipation, malaria, rheumatic pain and female disorders.  Over the next millennium, its use spread to India and the Middle East, eventually to Europe

The famous French naturalist, Jean-Baptiste Lamarck observed in the 1780’s that certain marijuana plants from India were intoxicating and could be made into hashish. But traditional hemp crops, which were more common in Europe, had no mind-altering effect.  In actuality, he was just documenting what cannabis cultivators had known for millennia, that industrial hemp plants have different medicinal qualities from the flowering cannabis buds.  Lamarck named the Indian Cannabis “Indica” to distinguish it from European hemp, which was known at the time as Cannabis “Sativa”.  Cannabis Indica was sold as a therapeutic in Western medicine during the 1800s.

Today, it is widely accepted that marijuana has two different species: Cannabis Indica and Cannabis Sativa.  Scientists have determined that genetic differences between the two strains result in the production of a predominant amount of a particular chemical (called a cannabinoid) such as THC or CBD. These differences determine how the cannabis plants are recommended for different medicinal purposes.

Marijuana Species

Cannabis Sativa

Cannabis Sativa is generally classified as the taller and more robust plant of the Cannabis genera. Traditionally, the medicating effect of a Sativa is often characterized as uplifting and energetic.  Patients often seek Sativas for that experience. Sativas are a good choice for daytime medication and can be effective in the treatment of nausea, headaches and migraines, fatigue, and loss of appetite. Some patients may find Sativas to be intense and may cause certain patients to experience mild anxiety.

Cannabis Indica

Cannabis Indica generally presents with shorter, stockier, plants that have denser leaves and slightly less yielded flower. The medicating effect is most often described as a pleasant full body relaxation –sometimes inducing drowsiness. Indicas are great for relaxation, stress relief, and overall sense of calm and serenity. Cannabis Indicas are also very effective for overall body relief from chronic pain.

Cannabis Hybrids

A Hybrid Genetic is created by selectively breeding the two different genetics (Sativa and Indica) together to create a product that melds the desired individual attributes of the “parent” genetics. Hybrids are a great way to blend various traits that can help provide relief to a qualifying condition that presents a diverse set of symptoms. Hybrids that are an equal balance, 50%/50% of each parent, tend to provide an equivalent measure of each plant.

Cannabis effects on human physiology

It wasn’t until the mid-1990s that scientists discovered why marijuana exerts so many effects in the human body.  It just so happens that the body makes a family of chemicals called endocannabinoids, which are part of a system that moderates physiological processes such as inflammation, immunity, pain sensation, and appetite. These endocannabinoids circulate in the blood stream and bind to cannabinoid receptors (Figure 4) in order to have their effect.  The cannabinoids in agricultural cannabis can bind to, and activate and inactivate, these receptors in the body in much the same way as the endocannabinoids do. Although use of ingested cannabis results in much higher levels than are produced naturally.

Cannabinoid Receptor

Figure 4: Cannabinoid Receptor

As is shown in Figure 4, THC and CBD, the main components of medical cannabis bind specifically to receptors on the surface of nerve cells (neurons).  Animal studies show that the effects (both positive and negative) from medical cannabis are predictable and undeniable.

There are currently two subtypes of cannabinoid receptors that are well characterized. The CB1 receptors are highly concentrated in the brain and nerve endings and the CB2 receptor is expressed mainly on cells of the immune system and blood forming cells.  When THC enters the blood stream and reaches the brain, it binds to CB1 receptors. This type of binding results in changes in the levels of various neurotransmitters (like dopamine and norepinephrine) released from the neurons.  The result for the patient is the acute effects of cannabis ingestion, such as euphoria and anxiety.

Unlike the psychoactive THC, CBD has little binding affinity to either the CB1 or CB2 receptors. Instead, CBD reduces the breakdown of the endocannabinoids the body has already made, indirectly increasing their amount and normal activity at the receptors.  At the same time, CBD opposes the action of THC at the CB1 receptor, thereby muting the psychoactive effects of THC. While many psychoactive drugs clearly fall into the category of stimulant, depressant, or hallucinogen, cannabis hybrids exhibits a mix of all properties.  Some of the short-term physical effects of cannabis use include increased heart rate, dry mouth, reddening of the eyes, muscle relaxation and a sensation of cold or hot.

Active Ingredients of Marijuana

Cannabinoids

Cannabinoids are the biological active ingredients found in the composition of the marijuana flower. These active ingredients interact with your own endocannabinoid system that regulates a variety of different biological receptors. An individual genetic of marijuana for medical use, and even an individual harvest, may present a different variety of cannabinoids and each may affect the way that a particular genetic interacts with your body or treatment. These differences allow a patient and their certifying physician to select a genetic of marijuana with a cannabinoid profile that will best treat an individual’s unique symptoms.  The minor cannabinoids are felt to also interact with CB receptors and the endocannabinoid system, producing an “entourage” effect that is greater than the effects of a synthetic (chemical) preparation.

Tetrahydrocannabinol (THC)

The main active ingredient in marijuana for medical use responsible for the psychoactive properties. THC is reported to be responsible for analgesic pain relief and the euphoric effects of the plant.

Cannabidiol (CBD)

Is an anti-inflammatory and anxiety-relieving compound. CBD may be able to help reduce seizures, blood sugar levels, and suppress muscle spasms. CBD is reported to produce relief in disorders related to rheumatoid arthritis, autoimmune diseases, diabetes, epilepsy, nausea, and neuropathic pain.

Cannabigerol (CBG), a minor cannabinoid

CBG is an anti-fungal compound that is also reported to decrease anxiety and muscle tension. Cannabigerolic Acid has been shown to relieve intra-ocular pressure, which may help treat glaucoma.

Cannabichromene (CBC), a minor cannabinoid

CBC is reported to stimulate new bone growth and help inhibit inflammation and pain.

Effects of Medical Cannabis

Patients should treat marijuana for medical use like they would many prescription drugs and avoid operating a motor vehicle or heavy machinery, performing child or elder care, and making important decisions while under treatment.

Benefits of Medical Cannabis

Although CBD and THC act differently in the body, they seem to have many of the same medical benefits.  Unfortunately, most of this evidence comes from animals, since very few studies on cannabis have been carried out in human patients.  Current human clinical research into the various THC:CBD ratios and efficacy in different diseases will be discussed in Part 3 of this series.  The important result from preclinical animal models for neuropathy patients is that in rats, THC and CBD have been shown to be neuroprotective antioxidants.  Many of the medical benefits of cannabis are attributed to the CBD content, particularly the strong anti-inflammatory and anti-seizure properties.  As mentioned early, through plant genetics, marijuana can be grown richer in THC or CBD, allows growers and patients to select strain types that will give them very specific effects.  That said, many patients find that the results they experience with the “entourage” effect is different from what they expected before using medical cannabis (more on this in the upcoming Part 3).

Appetite When Using Medical Cannabis

The feeling of increased appetite following the use of cannabis has been documented for hundreds of years, and is known colloquially as “the munchies”.   The activation of cannabinoid receptors in the hypothalamus is responsible for maintaining and or increasing food intake.  For many of the conditions where medical cannabis is used, the increased food enjoyment and intake has been seen as a beneficial effect.

Side Effects of Medical Cannabis

Anxiety and paranoia are the most commonly reported side effect of smoking marijuana with a high THC content.   Other effects may include a general alteration of conscious perception, euphoria, feelings of well-being, relaxation or stress reduction, increased sensuality, increased awareness of sensation, increased libido, and creativity.  Cannabis also produces many subjective effects, such as greater enjoyment of food taste and aroma, an enhanced enjoyment of music and comedy, and marked distortions in the perception of time and space.  With very high doses, THC can induce auditory and visual hallucinations.  THC should be used only under the care of a physician by anyone with a mental health history.  In starting out using medical cannabis, users may be better off using cannabis with higher levels of CBD to reduce potential side effects.

As mentioned earlier, there are short-term physical effects of cannabis that include increased heart rate, dry mouth, reddening of the eyes, muscle relaxation and a sensation of cold or hot.

Although cannabis is not addictive in the classic sense, it can result in patient dependence and cannabis “use disorder” is defined as a medical diagnosis in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

Both CBD and THC have been found to present no risk of lethal overdose.  Opioid receptors are present in areas of the brain that control breathing and ingestion of excessive narcotics can cause a person to stop breathing.  Unlike opioid receptors, cannabinoid receptors are not located in these brainstem areas.  Marijuana cannot cause someone to stop breathing, no matter how much they ingest.

Memory

Reliable studies on cannabis and memory are hindered by small sample sizes, confounding drug use, and other factors, however it is agreed generally that cannabis use does affect perception, but does not cause permanent brain damage in adults.  Researchers looking at data from 15 previously published controlled studies involving 704 long-term adult cannabis users and 484 nonusers concluded that long-term cannabis use was only marginally harmful on the memory and learning.

Very heavy use of marijuana is associated with decrements in neurocognitive performance, and any use of marijuana in children and adolescents is to be avoided except in the cases of supervised treatment for severe epilepsy.

Duration of Effects

Peak levels of cannabis-associated intoxication occur approximately 30 minutes after smoking.  The total short-term duration of cannabis effects when smoked is based on the potency, method of smoking (vape) and how much is smoked.  Any acute effects that accompany cannabis use usually abate after 6 hours.

When taken orally (in the form of capsules, food or drink), the effects take longer to manifest initially, and generally last longer, typically for 4–10 hours after consumption.  Taking marijuana in the form of edibles can have unpredictable effects, since they are delayed and thus harder to predict.

Because cannabinoids are lipophilic (fat soluble) compounds that are easily stored in fat, they have a long “elimination half-life” or time they can still be detected in the body. Cannabis and its and related compounds can usually be detectable in the urine or blood for 3 days after episodic use, and up to 10 days with frequent use.  Long-term users can produce positive tests for two to three months after ceasing cannabis use.

Effects of Smoke

Cannabis smoke contains thousands of organic and inorganic chemical compounds, similar to that found in tobacco smoke or cigars.  Smoking any substance will carry the same risk due to carcinogens in all smoke.  Oral ingestion use eliminates the need to inhale toxic combustion products created by smoking and therefore negates the risk of respiratory harm associated with cannabis smoking.

Medical Marijuana Products

Smokable Marijuana

Patients may elect to use marijuana for medical use through traditional methods of inhalation including smoking the product in rolling papers, a pipe, or a water pipe. Additionally, patients can use marijuana for medical use via flower (the dried leaves), oil, or premade cartridges in a variety of commercially available vaporizers or disposable units. These products heat, without burning the medicine, until it vaporizes and allows for the patient to separate the cannabinoids from the plant material.

Edible Marijuana

Marijuana Infused Products (MIP’s), or edible medical marijuana for medical use, are products that have been prepared with oils made from supercritical CO2 fluid extracted marijuana flower. For patients who wish to avoid inhaling the product, eating a MIP is an alternative that provides effective treatment and for some patients necessary additional calories.  The downside is that because edibles take longer to be effective (20-60 minutes at least), they might not be the first choice for patients with pain. 

Concentrated Marijuana

Concentrated marijuana oils and extracts are another alternative format that patients can choose for medicating. These products are produced through a solvent-less extraction process that separates, and concentrates, the essential oils from the marijuana flower. Concentrates allow a patient the ability to select a form of medication that accentuates and intensifies the particular cannabinoid qualities they are looking for. Concentrates can be inhaled either by smoking or through vaporization.

Topical Application of Marijuana

Topical treatments can feature both THC and CBD and come in a variety of different forms including lotions, ointments, and balms. These products can be used to treat a specific medical need or can be used, in conjunction with other topical regimes, as a preventive. All topical products produced will have undergone the necessary formulation to ensure that all the active ingredients will work in their transdermal form.

Comparison of Medical Marijuana to Narcotics

In the clinical setting, opioid painkillers are incredibly potent and can work wonders for certain types of pain.  They are much less effective in cases of nerve pain, however.   In studies, marijuana performs just as well as gabapentin, a leading pharmaceutical used to treat neuropathy.  An additional advantage of cannabis for pain is that whereas narcotics commonly increase nausea and vomiting, marijuana relieves those symptoms.   Of note, the use of monitored drugs including narcotics for pain decreased in states where medical marijuana was approved for those qualified conditions.

 

Medical Cannabis for Neuropathic Pain

Interestingly, there is therapy switching from prescription drugs (which are generally co-paid under insurance plans) to medical cannabis (which is never paid under insurance plans) that is largely driven by the patient rather than the physician.  This fact represents a tangible and powerful example of how patient empowerment directly impacts healthcare spending and therapeutic behavior when given the opportunity to choose superior alternatives to replace the standard of care.

Patients are using medical cannabis to treat a broad range of therapeutic categories including; mental health (anxiety, insomnia), cancer (cachexia, wasting neuropathy),  diabetes (neuropathy), CNS (seizures and sparsity for epilepsy, ALS, MS, etc.) and cardiovascular (inflammation) diseases. These are some of the largest and most critical chronic illness categories today facing the global population.  The majority of patients become repeat purchasers, indicating that they believe they are receiving benefit.

In Conclusion

I hope this gives you some food for thought.  After part 1, most of the questions we received were related to whether THC or CBD predominant formulations were best for certain conditions and symptoms.   The discussion of that will be in the next installment, Part 3.  Just a spoiler, the answer is not simple and things are not as clear-cut as one might believe from the literature.  The fact that the FDA and DEA do not allow current clinical trials with medical cannabis outside of a few formulations that are seeking to have formal FDA approval makes this all the harder to come up with guidelines for physicians to help their patients get the right product.  But the fact that patients are able to change their own formulation and method of use without requiring an additional physician consultation saves a lot of time and money.  Most patients are able to find the right formulation and dose for their symptoms within a month or two.

In Part 1 of this series on “Medical Cannabis for Neuropathic Pain”, we discuss the use of medical cannabis today by neuropathic pain patients. You can read the first of this series “Medical Cannabis for Neuropathic Pain – Part 1 of 3” by clicking here.

In Part 3 of this series on “Medical Cannabis for Neuropathic Pain”, we will discuss which formulation of THC or CBD is best for patients with certain conditions and symptoms, including treating neuropathic pain. You can read the first of this series “Medical Cannabis for Neuropathic Pain – Part 3 of 3” by clicking here.

I hope you find these articles informative and encourage you to contact the Neuropathy Journal, and/or myself, with any questions you may have by clicking here or by commenting below.

About the Author

Rosemary Mazanet, MD PhD - Chair, Scientific Advisory Board Columbia Care

Rosemary Mazanet, M.D. PhD, is Chair of the Scientific Advisory Board for Columbia Care, a board certified oncologist; an alumna of the Dana-Farber Cancer Institute and Brigham and Women’s Hospital; and is a trustee at the University of Pennsylvania Health System. Under her expert supervision Columbia Care is launching clinical trials with one of the largest and most prestigious teaching hospitals in the United States.

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9 Comments

  1. I’m curious, I live in a state that doesn’t approve of medical marijuana,but I live close ro a state that does approve, could I go there to purchase? Do I need a prescription to get some? Are there reprocrections if I did it?
    Thanks for any information on this! Jackie

  2. Thank you for publishing this information. I have been researching this for probably 7 years now and have been reluctant to try it. I am now in the process of getting my medical marijuana card. I have small fiber neuropathy and the pain is excruciating. It has only progressed and I have no options left but this. I’ve failed almost every medication, ivig infusions, I have a spinal cord stimulator which helps a bit and do take a pain medication. I actually took myself off higher doses of pain med three years ago because I was tired of pills. I don’t want to have to increase my medicine since I’ve been on the same dose for over three years but it’s not helping as much anymore. Thank you for all this info, I hope this helps me and anyone else looking into it.

    1. Did you try the medical marijuana yet? I have small fiber neuropathy and it’s all over. It’s a killer. I don’t take any pain meds and couldn’t take neurontin. So I suffer so much. I never smoked marijuana but I have read that it helps with our disease tremendously. I was wondering if a lotion with it in it would work. I burn 24 /7 almost all over

      1. Many patients with small fiber neuropathy are helped by medical cannabis.
        Depending on the state you live in, you might be able to find formulations
        that are more appealing to you than smoking. Most states have edibles (or
        pills), and many states have lotions or creams. If you live in a state
        where medical cannabis is available, your physician should be able to help
        you get a medical recommendation (that is what a cannabis ³prescription² is
        called) to see if it offers you some relief. Just a warning, sometimes the
        creams and lotions take longer (like up to a week) to get enough drug in the
        blood system before you can sense a difference.

  3. Thank you for making this information available to chronic pain suffers. You’ve answered a number of questions I’ve had for many years about THC and CBD.

    Would like to share a couple of things, that you might be able to address, in the hope that it may help others.

    I have been diagnosed with idiopathic Poly Neuropathy. Currently taking Duloxetine (Cymbalta); however, the pain levels have increased over time, as has the frequency of pain episodes.

    A few years ago, I lost 30 lb prior to abdominal surgery. Frequent migraine-like headaches disappeared as did shoulder, and next muscle pain. All came back when I added wheat and gluten products back into my diet. Got off the wheat, but wondered why I had developed this sensitivity after 60 plus years of eating one of my favorite foods.

    Have done a lot of reading on gut health, and leaky gut syndrome. Recently, began serious effort to improve gut health with high quality probiotics and digestive enzymes.

    After two plus months, have noticed significant improvement in pain (less severe, and less frequent) and a reduction in the burning sensation I felt in my feet (that was also beginning to be experienced in my hands). I’ve even been able to walk more than 2 miles a couple of times a week with minimal discomfort (something I have been unable to do for a couple of years — use to walk 4 miles a day, 5 days a week).

    I’ve also noticed that sugar intake seems to impact my pain intensity and frequency. From what I’ve read, sugar isn’t good for gut health (chocolate — an addiction I have yet to beat!!).

    Dr. Mazanet, and Mr. Morrow, is there any information you or your peers are aware of, showing a correlation between gut health and neuropathy in general. I know sugar is a serious issue with diabetics — especially those suffering from peripheral neuropathy; however, I haven’t seen anything in general regarding non-diabetic neuropathy suffers.

    Thanks again for this information, and any answers you might be able to provide regarding gut health and neuropathy.

    And one last questions, any idea when the third installment is due out?

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