Medical Marijuana for Peripheral Neuropathy

by Jessica Robinson-Papp MD, MS, FAAN Mount Sinai Medical Center, and
Sara Dehbashi, MD, Neuromuscular Fellow, Mount Sinai Medical Center

Medical marijuana use is becoming more common in the U.S. due to legalization in many states. The U.S. federal government still considers all forms of marijuana illegal, however so far they have mostly not interfered with medical marijuana activities that are legal under state laws. Given that peripheral neuropathy and neuropathic pain are complicated conditions that are challenging to treat, we aim to review the effectiveness, roles and risks of medical marijuana in the treatment of peripheral neuropathy in this article.

What is marijuana?

The term marijuana refers to strains of the cannabis plant that contain substances, called cannabinoids, that can have effects on the human body.

What is medical marijuana? 

Medical marijuana refers broadly to marijuana products that are used for medicinal purposes. The exact definition of medical marijuana varies by state. Some states allow actual marijuana (i.e., the plant material) for medicinal use, whereas in other states (e.g. New York), medicinal products are derived from the marijuana plant, and sold in different forms (e.g. tinctures or pills). Marijuana is comprised of over 400 chemical entities with more than 60 cannabinoids. The two main cannabinoids are:

1. Tetrahydrocannabinol, or THC: the psychoactive compound in marijuana (the substance that produces the high). THC occurs naturally in marijuana; there are also synthetic forms of THC that are prescription medications (e.g. dronabinol).
2. Cannabidiol, or CBD: This substance does not produce any psychoactive effects. Since it has low abuse potential, CBD-containing products are less tightly regulated than THC. In some states CBD can be sold as a supplement or topical treatment. A prescription medication form of CBD (Epidiolex) recently became available in the U.S. but is only approved for the treatment of certain forms of epilepsy.

What is recreational marijuana?

Recreational marijuana refers to marijuana that is used for recreational purposes. In most states use of marijuana for recreational purposes is illegal. In states where recreational marijuana is legal, the actual product itself is typically not different from products used for medicinal purposes.

What is synthetic marijuana? 

Synthetic marijuana also sometimes called “fake weed” contains human-made chemicals that are either sprayed on dried, shredded plant material so they can be smoked or sold as liquids to be vaporized and inhaled in e-cigarettes. Some of these products contain chemicals similar to those found in the marijuana plant. However, it is important to know that these drugs may affect the brain much more powerfully than marijuana, and that their effect can be unpredictable, and in some cases dangerous and even life-threatening.

How does medical marijuana work?

The THC and/or CBD contained in medical marijuana binds to specific cannabinoid receptors in the brain and peripheral nervous system which is likely the way in which it is able to alleviate chronic pain (1).

Currently, there is a debate about the so-called “entourage effect” which refers to the idea that compounds other than cannabinoids in marijuana (i.e. terpenes and flavonoids) are important in its therapeutic effects. This idea has wide lay-popularity, but little scientific evidence to support it.

How is medical marijuana administered?

Legal routes of administration vary state by state. For example, in New York state, medical marijuana can be used as a vapor, tincture or pill. In other places the natural leaf form is available and smoking or conversion to an edible product is allowed.

What are the dosing recommendations?(9)

It is important to know that medical marijuana products vary widely and so no consistent recommendations can be made on dosing. A general common sense approach recommended by some doctors is “start low, go slow, and stay low.” One study (8) found that 25 mg herbal cannabis with 9.4% THC, administered as a single smoked inhalation three times daily for five days, significantly reduced average pain intensity compared with a 0% THC cannabis placebo in adult participants with chronic post-traumatic or postsurgical neuropathic pain.

What conditions does medical marijuana treat? 

State laws differ on the conditions that can legally be treated with medical marijuana. The National Academies of Sciences, Engineering and Medicine (NASEM) published a comprehensive review of the literature in 2017 for all indications (not just neurological), which is available here. In summary, medical marijuana is most often allowed to be used in debilitating conditions such as neuropathy, spinal cord injury with spasticity, multiple sclerosis, epilepsy, ALS, chronic pain, Parkinson’s disease, Huntington’s disease, HIV/AIDS, and cancer; and for controlling symptoms and conditions such as muscle spasms, severe nausea, cachexia, PTSD, etc.

For many of these conditions there is inadequate information to conclusively assess the effects of cannabinoids. Studies have shown significant efficacy in 3 main medical conditions, which are: 1) chemotherapy induced nausea and vomiting; 2) chronic pain, including neuropathic pain, and 3) multiple sclerosis related spasticity.

One of the neuropathic pain conditions that has been evaluated by randomized, double-blind studies, is HIV-neuropathy, in which studies have shown promising effects on pain (2).

What are the major risks of taking medical marijuana?

It is important to know that medical marijuana (unlike opioid pain medicines) is not lethal in overdose, and trials done in humans so far have overall shown an acceptable safety profile. The evidence suggests that smoking cannabis (unlike tobacco) does not increase the risk for certain cancers (i.e., lung, head, and neck) in adults, but is associated with chronic cough.

Some other side effects as listed below, have been reported.

• Impairment in learning, attention and memory with acute use, which may persist
• Developing or worsening substance use disorders including alcohol, tobacco and other illicit drugs
• Psychiatric effects, such as development of social anxiety disorder, increased risk of suicidal thoughts, increased risk of schizophrenia and other psychoses, and worsening of pre-existing bipolar symptoms with daily use
• Lower birth weight in pregnancy
• Reduced future achievement in adolescents

What are the laws and regulations surrounding marijuana?

Currently, a total of 34 states in the U.S. have approved a comprehensive, publicly available medical marijuana programs, in addition to approved efforts in 12 states that allow use of medical marijuana products for medical reasons in limited situations (full list available at this website.)

However the U.S. federal government still considers marijuana illegal.

What is the efficacy and cost-effectiveness of medical marijuana in neuropathic pain?

As previously indicated, the scientific literature demonstrates some efficacy of medical marijuana/cannabis in the treatment of chronic neuropathic pain. Clinical trials of different routes of administration (sublingual, oral, smoked, and vaporized) have demonstrated analgesic benefit in the treatment of this costly and disabling condition (3,4,5), and some treatment guidelines for neuropathic pain recommend consideration of cannabinoids as a second or third line agent (6,7).

As expenses for medical marijuana are not covered by health plans and are out-of-pocket, knowing the cost-effectiveness of medical marijuana may impact patients’ decisions regarding its use. Based on a recent published article (7), inhaled cannabis appears to be cost-effective when used as second or third-line treatment in chronic neuropathic pain.

References:

1. Manzanares J et al; Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes; Curr Neuropharmacol. 2006 Jul; 4(3): 239–257
2. Ellis RJ et al; Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial; Neuropsychopharmacology. 2009 Feb;34(3):672-80
3. Wilsey B et al; Low-dose vaporized cannabis significantly improves neuropathic pain; J Pain. 2013 Feb;14(2):136-48.
4. Aviram J et al; Efficacy of Cannabis-Based Medicines for Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials;Pain Physician. 2017 Sep
5. Andreae MH et al; Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data; J Pain. 2015 Dec;16(12):1221-1232.
6. Koppel et al; Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology; Neurology. 2014 Apr 29
7. Tyree GA et al; A Cost-Effectiveness Model for Adjunctive Smoked Cannabis in the Treatment of Chronic Neuropathic Pain; Cannabis Cannabinoid research. 2019 Mar 13
8. Ware Mark A et al; Smoked cannabis for chronic neuropathic pain: a randomized controlled trial; CMAJ. 2010 Oct 5; 182(14): E694–E701.
9. MacCallum CA¹, Russo EB; Practical considerations in medical cannabis administration and dosing; Eur J Intern Med. 2018 Mar;49:12-19.

For more information about medical cannabis and other treatments for peripheral neuropathy, please refer to Peripheral Neuropathy Pain Management and Treatments on the Foundation for Peripheral Neuropathy website.