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Medical Marijuana Treatment for Pain Management

At Spine Institute of North America, our goal is to relieve your pain and revive your life. Our physicians travel the globe looking for cutting edge treatments that will address your spinal issues and bring much-needed relief. However, there is a treatment you may have heard of that’s a lot closer to home — medical marijuana. We now offer cannabis medication as a pain management technique for patients who qualify.

While medical marijuana remains a controversial topic throughout the U.S., New Jersey’s Compassionate Use Medical Marijuana Act has made it a legal treatment option for qualified candidates. We are registered with the state to approve this treatment if it’s clinically indicated.

Read on to find out more about using medical marijuana as a viable and effective pain medication.

The Use of Medical Marijuana

Medical marijuana has many names, such as medical cannabis, medical weed and medical pot. They all refer to a plant-based medication derived from the Cannabis sativa or Cannabis indica species of marijuana.

The history of using cannabis for medicinal purposes goes back thousands of years. Ancient cultures in China, Egypt, India and Greece used it as a treatment for a variety of maladies. In fact, before marijuana was made illegal in 1937, American physicians used it as a sleep aid, anti-convulsive, analgesic and more.

The active ingredients in marijuana are what give the plant its medical potency — these chemicals are called cannabinoids. While there are dozens of cannabinoids found in the marijuana plant, most physicians focus on two major compounds that contribute to the plant’s medical properties — THC and CBD.

Cannabinoids are what make marijuana for pain an effective treatment. However, the effects and effectiveness will differ depending on the cannabinoid composition of a medical marijuana treatment. Tetrahydrocannabinol or THC is what gives the plant its psychoactive side effects. Cannabidiol or CBD, on the other hand, has many medicinal uses while not causing users to get “high.”

How Does Medical Cannabis Work?

The cannabinoids or chemical compounds secreted by the cannabis flower are what makes medical marijuana an effective treatment for a variety of maladies, including chronic pain. While researchers are unsure how many cannabinoids are found in the plant, they’ve identified at least 85 separate compounds, many of which have medicinal value.

Cannabinoids for pain relief, such as CBD and THC, imitate compounds naturally produced by the human body. These endocannabinoids help stabilize a variety of bodily systems and impact your overall health. Their main job is to help cells communicate with each other. Adverse symptoms can arise when your body is experiencing disease, or there is a deficiency or problem with the endocannabinoid system.

Marijuana cannabinoids bind to endocannabinoid receptors found throughout your brain and body. Depending on the cannabinoid profile of a certain medical marijuana treatment, you can find effective relief for a variety of adverse symptoms.

Many patients struggling with chronic pain from a musculoskeletal condition find that medical marijuana pain management helps them more effectively manage their symptoms.

Who Is a Candidate for Medical Marijuana Treatment?

Candidacy for medical marijuana treatment varies from state to state. Your doctor cannot just prescribe cannabis-based medications. You must first become a patient in New Jersey’s medical marijuana program. The doctors at Spine Institute of North America can evaluate your condition to determine if your painful symptoms qualify you for medical marijuana treatment.

The debilitating medical diagnoses approved under the New Jersey Compassionate Use Medical Marijuana Act include:

  • Chronic pain related to musculoskeletal disorders
  • Chronic pain of visceral origin
  • Lou Gehrig’s disease or ALS
  • Multiple sclerosis
  • Terminal illness with a prognosis of 12 months or less
  • Muscular dystrophy
  • Severe migraines
  • Inflammatory bowel disease
  • Anxiety
  • Post-Traumatic Stress Disorder (PTSD)
  • Tourette’s syndrome
  • Opioid use disorder
  • HIV, AIDS and cancer accompanied by chronic pain, serve nausea, vomiting or wasting syndrome

Some patients do not respond to conventional medical therapies. For those who fall under this category, the following conditions may also be approved for medical marijuana treatment:

  • Glaucoma
  • Seizure disorders, such as epilepsy
  • Intractable skeletal muscular spasticity

What do we do?

Providing a thorough diagnosis to know the cause of your pain

Using the least invasive procedure that will relieve your pain quickly

Providing effective follow-up to ensure fast recovery

Ensuring that you remain fit so that you can enjoy long-term relief from pain

Things to Be Aware of Before Using Medical Cannabis

How Cannabis Use Impacts Day to Day Life

There are different strains of medical marijuana. The main classifications you usually find are sativa, indica and high CBD strains. Depending on which strain you choose will affect how cannabis impacts your everyday life.

  • Sativa marijuana strains have more stimulating side effects, making them better for day time use. However, because many are high in THC, they can make you feel intoxicated.
  • Indica is preferred by patients who need to relax or sleep better at night, as this strain generally causes intense relaxation.
  • High CBD strains can treat a variety of medical conditions with little to no psychoactive side effects.

Cannabis Medication Delivery Methods

While most people associate marijuana with smoking, you can use cannabis medications in many different ways. Dosing is not a precise science and varies depending on the patient, preparation and delivery method.

Before choosing how you would like to use your medical marijuana treatment, talk to your doctor at Spine Institute of North America. There are several ways to consume cannabis, including options far healthier than smoking. Some of the most common delivery methods you can choose from include:

  • Topical medications
  • Edibles and teas
  • Oil capsules
  • Vapor
  • Tinctures

Potential Side Effects and Risks Associated With Medical Marijuana

Cannabis, like any medical treatment, has potential side effects and risks associated with its use. Effects tend to vary depending on what type of strain you medicate with. However, the most common side effects include:

  • Dry mouth
  • Euphoria
  • Confusion
  • Dizziness
  • Sedation
  • Nausea

When using sativa strains, patients sometimes experience mild anxiety, paranoia or panic attacks. Indica strains, on the other hand, can lead to a depressed mood or feeling unmotivated.

Some of the potential risks of marijuana use include a raised heart rate, increasing the risk of a heart attack in those already prone. Smoking cannabis is associated with breathing issues, cough and the risk of lung infection.

Even when used medicinally, marijuana can be addicting. So, patients should only use treatments as directed by their doctor.

NJ State Laws About Medical Marijuana

Federal law has classified marijuana as a Schedule I drug. This means that the drug does not have any accepted medical use and also has a high potential for addiction and abuse. This is why your doctor cannot just write you a prescription for medical marijuana. However, each state is allowed to determine whether cannabis can treat medical conditions.

In 2010, New Jersey’s state government approved and established The New Jersey Compassionate Use Medical Marijuana Act. This removed criminal penalties on a state-level for those approved to use and possess medical cannabis.

You must be accepted into the state’s medical-marijuana program to receive medical marijuana treatments in New Jersey. Then you have to apply for an identification card issued by the New Jersey Department of Health and Senior Services that allows you to purchase and use medical cannabis. However, the law states that patients can only obtain a limited amount of marijuana from state-monitored dispensaries. Patients physically unable to obtain their own cannabis treatment can designate a registered caregiver to assist them.

In 2019, the New Jersey State Assembly and the Senate voted in favor of a bill that expanded access to qualifying patients. It also removed several common barriers related to obtaining medical marijuana treatments.

How to Become A Medical Marijuana Patient in Central New Jersey

If you feel that your medical condition qualifies you to become a medical marijuana patient in New Jersey, there are a few steps to go through first. You can make an appointment at Spine Institute of North America if you would like help understanding this process.

  • You must be a New Jersey state resident with proof of residency. This could be your state-issued ID card or another government-issued ID along with proof of residency such as a bank statement or bill.
  • You must have an established, bonafide relationship with a doctor who is registered with the state to recommend medical marijuana treatment. Doctors at Spine Institute of North America are approved by the state as recommending physicians.
  • Your doctor must diagnose you with one of the qualifying debilitating medical conditions.
  • Once your physician has certified your condition, you must register with New Jersey’s Medicinal Marijuana Program. You can complete this process online, and it includes a fee.

Find Out How We Can Treat Your Chronic Pain at Spine Institute of North America

If you’ve been experiencing pain for some time, you can count on the team at Spine Institute of North America to find a pain management solution that works for you.

If pain is impacting your life and keeping you from doing the things you love, schedule your appointment with one of our highly trained and compassionate physicians. Medical marijuana is just one of the minimally invasive treatments we may recommend, so you can get back to living your life to the fullest.

Cannabinoids and spinal cord stimulation for the treatment of failed back surgery syndrome refractory pain

This study aimed to evaluate pain and its symptoms in patients with failed back surgery syndrome (FBSS) refractory to other therapies, treated with a combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in association with spinal cord stimulation (SCS).

Settings

Outpatients referred at Pain Unit of San Vincenzo Hospital in Taormina (Italy), between September 2014 and January 2016.

Subjects

Eleven FBSS patients diagnosed with neuropathic pain using the Douleur Neuropathique 4 questionnaire and suffering from moderate to severe chronic refractory pain, and undergoing treatment with SCS and a combination of THC/CBD for 12 consecutive months.

Materials and methods

All the included patients discontinued previous unsuccessful therapy at least 2 months before the beginning of the cannabinoid therapy, with the exception of the SCS that was continued. Patients received a fixed dosage of cannabinoid agonists (THC/CBD) that could be increased subjective to pain control response. A Brief Pain Inventory questionnaire was administered to measure pain and its interference with characteristic dimensions of feelings and functions. The duration of treatment with SCS and THC/CBD combination was 12 months.

Results

Effective pain management as compared to baseline result was achieved in all the cases studied. The positive effect of cannabinoid agonists on refractory pain was maintained during the entire duration of treatment with minimal dosage titration. Pain perception, evaluated through numeric rating scale, decreased from a baseline mean value of 8.18±1.07–4.72±0.9 by the end of the study duration (12 months) (P<0.001).

Conclusion

The results indicate that cannabinoid agonists (THC/CBD) can have remarkable analgesic capabilities, as adjuvant of SCS, for the treatment of chronic refractory pain of FBSS patients.

Introduction

Failed back surgery syndrome (FBSS) is defined by the International Association for the Study of Pain as “a spinal pain of unknown origin either persisting despite surgical intervention or appearing after surgical intervention for spinal pain originally in the same topographical location”. 1 Several conditions have been identified as underlying causes for FBSS, such as epidural fibrosis, global or lateral canal stenosis, foraminal stenosis, retained disc fragment, recurrent disc herniation or degeneration, spinal instability, facet joint pain, sacroiliac joint pain, discitis, adhesive arachnoiditis, and others. 2 The percentage of the insurgency of chronic pain after spinal surgery varies significantly ranging from 5% to 74.6%, and the percentage of the need for re-operation is between 13.4% and 35%. 3 Up to 20%–40% of patients who have undergone lumbar spine surgery experience FBSS. 4 Nowadays, this syndrome affectŝ0.02%–2% of the general population. 5 The FBSS patients frequently suffer from moderate to severe chronic pain, associated with sensory and/or motor deficits, as well as other severe chronic pain syndromes associated with the persistence of low back pain, deterioration or recurrence of radiculopathy, and sphincter dysfunction. 6 , 7 The current therapeutic strategies for FBSS include antidepressant medications, antiepileptic medications, 8 deep brain stimulation, spinal cord stimulation (SCS), 9 , 10 epidural and intrathecal injections, 11 , 12 spine surgery, 13 counseling, 14 and exercise therapy. 15 FBSS is considered an intractable syndrome when various combinations of the existing therapeutic strategies prove ineffective. Opioids and their major adjuvants usually produce positive results in the treatment of chronic pain, especially when other therapeutic approaches fail. There is an increasing demand for alternative therapeutic strategies by patients and clinicians when available therapies are marginally effective, or not well tolerated. In this context, the authors assessed the effectiveness of an alternative approach for chronic refractory pain associated with FBSS, using cannabinoids as a multimodal treatment approach to neuropathic pain. The plant Cannabis sativa L. has been used for centuries, both for recreational and medicinal purposes. Only in recent times, studies about exogenous cannabinoids have been performed to evaluate their therapeutic value and to investigate the role of endogenous cannabinoids (endocannabinoids) in physiology and pathophysiology of many neurologic and neuropsychiatric diseases. 16 – 18 Several types of insults which can damage the peripheral or central somatosensory nervous system, including FBSS, can cause neuropathic pain. It is estimated that 7%–8% of the population in developed nations is suffering from neuropathic pain. 19 To date, therapeutic options for neuropathic pain induced by FBSS achieve effective analgesia in only less than 50% of the cases. 20 This pain could, however, be effectively treated by drugs modulating endocannabinoid system. 21 This system is highly expressed in neurons and immune cells, and it plays a crucial role in the development of neuropathic pain. 22 This pilot study aimed to evaluate the effect of a combination of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) in FBSS refractory to other available therapeutic strategies, including opioids, adjuvant drugs, radio frequency neuromodulating treatments, and SCS alone. The SCS, a treatment modality for chronic pain that has been in use since 1967, 9 is an expensive therapy and careful selection for its suitability is recommended. Remarkable technological advances over the years have resulted in electrodes transitioning from single to multi-contact arrays and stimulators from external radiofrequency coupled to implantable rechargeable devices. Current implantable SCS electrodes can be inserted percutaneously through a Tuohy needle using essentially the same technique as that used for an epidural catheter. 23 In this context, a retrospective study documenting the results obtained with oral administration of cannabinoids agonists, namely a combination of THC/CBD, in eleven refractory FBSS patients is presented.

Materials and methods

This article reports a retrospective study, performed at Pain Therapy Unit of San Vincenzo Hospital of Taormina, in collaboration with the Anesthesiology and Pain Therapy Unit and the Department of Biomedical and Dental Sciences and Morphofunctional Imaging of the University Hospital “G. Martino” of Messina. All outpatients included in the study were referred at the Pain Unit of San Vincenzo Hospital, during the period between September 2014 and January 2016. Treatments were performed in accordance with rules and ethical standards on human experimentation and the Declaration of Helsinki of 1964 (further revised in 2013). All the study participants gave written informed consent (including information on possible risks and side effects) for participation in the research study. Every precaution was taken to protect the privacy of patients. The retrospective study was approved by the Local Ethics Committee (Comitato Etico Interaziendale della Provincia di Messina) with protocol number 61/17, and the clinical study is registered with the number <"type":"clinical-trial","attrs":<"text":"NCT03210766","term_id":"NCT03210766">> NCT03210766 (www.clinicaltrials.org). Between November 2014 and December 2015, authors included the clinical records of eleven FBSS patients suffering from moderate to severe chronic pain not responsive to other treatment regimens (including neuromodulating techniques), and considered eligible according to the inclusion and exclusion criteria established for the study. The patients, aged between 49 and 77 years (median age 61.18±10.26 years), were equally distributed (six males and five females) ( Table 1 ). Primary inclusion criteria in this study were the diagnosis of FBSS refractory to other standard treatments. Patients who had not discontinued their previous oral analgesic therapy, at least 2 months before the beginning of the treatment with cannabinoid agonists, were excluded. The SCS therapy, unsatisfactory in terms of pain perception as observed from baseline numeric rating scale (NRS) values, was not discontinued ( Table 1 ). Cannabinoid agonists (THC/CBD) were administered in association with SCS for a treatment period of 12 consecutive months.

Table 1

Characteristics of patients, DN4 score, and BPI’s NRS score before (baseline) and after (final) treatment with THC/CBD combination for 12 consecutive months

Patient’s characteristics and questionnaires
Sex (M/F) 6/5
Age range (years) 49–77
Median age (years) 61.18±10.26
DN4 score 8.90±1.37
BPI baseline NRS score (no therapy, only SCS) 8.15±0.98
BPI final NRS score (SCS and cannabinoid agonists) 4.72±0.9 a

Note:

Abbreviations: DN4, Douleur Neuropathique 4; BPI, Brief Pain Inventory; NRS, numeric rating scale; SCS, spinal cord stimulation; THC, delta-9-tetrahydrocannabinol; CBD, cannabidiol.

The neuropathic pain was assessed using the Douleur Neuropathique 4 (DN4) questionnaire in all the cases studied. The DN4 questionnaire consists of a total of ten items, of which seven items are related to the characteristics of pain (burning, painful cold, electric shocks) and its association with abnormal sensations (tingling, pins and needles, numbness, itching), and three items are related to neurological examination in the painful area (touch hyperesthesia, pinprick hyperesthesia, tactile allodynia). The value of 1 was given to each positive item, and 0 value to each negative item. The total score was calculated as the sum of all ten items and the cutoff value for the diagnosis of neuropathic pain was established as a total score of 4/10. 24 Basal DN4 scores of patients ranged from 7/10 to 10/10 (mean =8.9±1.37). The Brief Pain Inventory (BPI) allows patients to rate and refer the severity of their pain and the degree by which pain interferes with common dimensions of feelings and functions. The BPI was performed by all the patients both at the first visit and at the end of treatment (after 12 months). Initially developed to assess pain related to cancer, the BPI has shown to be an appropriate measure of pain caused by a wide range of clinical conditions. The BPI is a eleven-item questionnaire that consists of four 0–10 NRS items asking patients to rate their pain at its “worst in the last 24 hours”, “least in the last 24 hours”, “average”, and “actually”, with 0 indicating “no pain” and 10 representing “pain as bad as you could imagine”. The remaining seven BPI items probe the degree to which pain interferes with general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life, again using a 0–10 value scale. For these interference items, 0 (zero) represents “does not interfere” and 10 indicates “interferes completely”. 25 Baseline NRS scores for average pain at visit ranged from 7 to 10 (mean =8.15±0.98) ( Table 1 ). Patients were visited weekly in the first month and every 2 weeks for the entire study duration. All patients received an oleic suspension of THC (19%) and CBD (<1%), 25 mg/day for oral administration. The dosage of cannabinoid agonists could be increased, depending on the positive response to pain control.

Statistical analysis

The numerical data were expressed as the mean ± standard deviation (SD). For each numerical parameter for basal observation and after treatment, we separately performed statistical comparison using the Mann–Whitney test. For each numerical parameter, considered separately for basal and final values, we performed a comparison between basal observation and after treatment to evaluate the existence of a statistically significant difference using the Wilcoxon test.

Results

In FBSS patients treated with the THC/CBD combination, an analgesic effect was achieved in four cases within the first month of treatment. The effect of cannabinoid agonists on refractory pain was maintained during the entire observation time with minimal dosage titration. The mean pain perception calculated using the NRS decreased from 8.18±1.07 at first visit to 4.72±0.9 at the end of the observational time in all cases ( Table 2 ), thus indicating marked analgesia with the treatment. The THC/CBD combination significantly reduced burning sensation and paresthesia linked to FBSS. The BPI interference examination showed that all the patients reported improvement in the quality of sleep (11/11; P<0.01). Additionally, THC/CBD combination enhanced mood as indicated by the rise in baseline mean level of 5.54±0.52–3.63±0.5 by the end of the study period (P<0.001). Remarkably, similar results were obtained with every item on the questionnaire.

Table 2

Brief Pain Inventory in failed back surgery syndrome (FBSS) among eleven patients treated with spinal cord stimulation alone, before (baseline) and after (final) 12 months, and treatment with THC/CBD, (N=11).

Brief Pain Inventory items Baseline values Final values Statistics
General activities 6.72±0.90 3.63±0.67 P<0.001
Mood 5.54±0.52 3.63±0.50 P<0.001
Walking abilities 6.45±0.82 3.27±0.78 P<0.001
Normal work 5.90±0.94 3.27±0.46 P<0.001
Relations with other people 6.09±1.04 3.09±0.94 P<0.001
Sleep 6.09±1.44 3.90±1.30 P<0.01
Enjoyment of life 6.18±0.87 3.54±1.03 P<0.001

Note: Data shown as mean ± SD.

Abbreviations: THC, delta-9-tetrahydrocannabinol; CBD, cannabidiol.

The maximum THC/CBD combination dose prescribed for all patients was 100 mg/day, while the minimum was 50 mg/day, with a mean dose of 68.5 mg/day. All adverse events were transient lasting from 30 minutes to a few hours, and not requiring medical care or suspension of therapy ( Table 3 ). There were no reports of any severe adverse events.

Table 3

Adverse events related to treatments

Adverse events Cases (N)
Drowsiness 4
Attention/concentration disorders 3
Dry mouth 2
Headache 2
Nausea/vomiting 2
Apathy 1
Puffy lips 1
Palpitations 1
Dizziness 1
Subjective sense of facial dysmorphism 1
Mood disorders 1
Forgetfulness 1
Increased urinary retention 1

Discussion

FBSS is a symptomatological syndrome, influenced by physical, psychological, and psychosocial factors that contribute to worsening individual quality of life. The pathological mechanism of intractable pain related to FBSS is complex and includes permanent inflammatory, neuropathic, and compressive processes, and in some cases are not susceptible to medical or surgical resolution. 26 Treatment for this category of patients aims to achieve relief from pain and consequently improve quality of life and daily activities. The diagnosis of FBSS through clinical history or history of spine operation is not always easy. Physicians should find the underlying causes of the pain and the mechanisms responsible for its maintenance and enforcement. Only an accurate diagnosis can potentially lead to the implementation of appropriate pain management strategies; this is particularly true for neuropathic pain (of radicular, ganglion, or spine origin) which is initiated by nervous system lesions or dysfunction and can be maintained by several different mechanisms. Moreover, neuropathic pain is more likely to be caused either by surgical treatment or associated diseases (comorbidity) and is more difficult to treat than nociceptive pain. 4 Successful treatment outcomes are difficult to achieve for chronic pain which can, in the long run, adversely affect the patient, health care services, and eventually the society. Although SCS can successfully induce analgesia initially, this has been observed to be relatively temporary, with the analgesia usually wearing out after 12–24 months, 9 as in the presented study. In this scenario, the quick onset and prolonged analgesic effects obtained with cannabis-derived products seem to be independent of the effect of prior SCS therapy. From the results obtained, the superior analgesia combined with the low incidence of adverse events suggests that cannabis-derived products may be a valuable therapeutic option for chronic refractory pain associated with FBSS, in comparison to other drug classes including opioids. Cannabis-derived products have been used historically for chronic pain, and are attracting renewed pharmaceutical interest for analgesia. Epidemiological studies show that 10%–15% of patients suffering from chronic pain use cannabis to improve pain, sleep, and mood. 18 Cannabinoid compounds mediate their pharmacological actions by binding to the cannabinoid receptors, namely cannabinoid type 1 receptor CB1 and cannabinoid type 2 receptor CB2. The CB1 receptors are located predominantly in the nervous system, while CB2 receptors are present in the immune cells. 17 Moreover, several authors have described cannabinoid neurophysiological system as distinct but functionally similar to the opioid pain modulation system. 27 Recent clinical trials, investigating the effects of the newest formulations of synthetic and naturally derived cannabinoids, demonstrated their analgesic properties for refractory neurogenic pain, brachial plexus injuries, and chronic neuropathic pain. 16 These studies suggest that the administration of cannabinoid agonists should be considered in patients suffering from chronic moderate to severe pain, especially when other less invasive treatments and opioid therapies fail, or when extreme adverse events are reported. 28 The plant genus Cannabis contains a complex mixture of phytochemicals (over 60 compounds) known as cannabinoids. Among the cannabinoids, the most investigated are the two major active chemical constituents, namely THC and CBD. Cannabinoids are mixed polyketides derived biosynthetically from malonyl-CoA and hexanoyl-CoA units prenylated with geranyl phosphate. 29 THC is the main psychoactive type of cannabinoid, whereas CBD is the major component of cannabis with a distinct pharmacological and psychotropic profile to THC. CBD (C21H30O2) is a resorcinol-based compound devoid of the psychoactive effects of THC and, on the contrary, is believed to be able to attenuate the psychotomimetic effects induced by high dosages of THC. Selective CB2 agonists may reduce central effects, but these are not clinically available. The mechanism of action of CBD is complex and not fully known since this molecule is a “multifaceted-target” drug interacting with several non-endocannabinoid systems such as receptors, ion channels, enzymes, and transporters. 30 CBD modulates the activity of many cellular effectors, including the receptors CB1 and CB2, 31 GPR55, 32 5HT1A, 33 μ- and δ-opioid, 34 peroxisome proliferator-activated receptor gamma (PPARγ), 35 the transient receptor potential subfamily V member 1 (TRPV1) cation channels, 36 and fatty acid amide hydrolase (FAAH). 37

In Italy and other European countries, only a single product consisting of a THC/CBD oromucosal spray has been authorized by the regulatory agency for the treatment of multiple sclerosis spasticity. However, other cannabis flower preparations may be prescribed for patients suffering from chronic pain conditions, refractory to conventional therapy. In the present study, orally administered oleic suspension of THC (19%) and CBD (<1%) was chosen chiefly because the pharmacokinetic data indicate that intake of “high content” of THC cannabis oil results in detectable plasma concentrations of THC as compared to ingestion of “low content” of THC cannabis oil or “mid-content” THC oil-containing capsules. 38 Additionally, the availability of the product and the simplicity offered by the oral route of administration for the oil suspension, in comparison to vaporization, were favorable factors in choosing this formulation. Due to the lack of precise information on efficacy and safety of the product, the study protocol involved an initial low dosage to be increased according to the patient response.

In the cases described in the present study, the analysis of results confirms the positive effects of treatment with THC/CBD in patients with refractory FBSS pain. Moreover, results from BPI examination show an improvement in mood and general activities as well (P<0.001). Overall, THC/CBD combination was well tolerated and not associated with any severe side effects. However, the small number of cases and the lack of a control group are limiting factors for this study to assess a definitive effect and/or for the identification of patient population for which treatment with THC/CBD may be appropriate. The positive effect of THC on the quality of sleep, reported in our study, has already been observed by other authors, 39 and could perhaps positively influence pain perception. To the best of our knowledge, this is the first study reporting the beneficial effects of a combination of THC/CBD in FBSS refractory pain. Preliminary studies on cannabis and sleep suggest that CBD may have therapeutic effects on insomnia. Similar effects favoring sleep were observed with THC; however, contradictory findings revealed that this compound decreases sleep latency and could impair sleep quality in the long term. 40 As a consequence, in our opinion, the effects of THC on pain may be independent of an effect on sleep. Finally, cannabis-derived products should be used cautiously in patients with a history of, or current anxiety or panic disorder, as well as for those with potential for reported dependence or abuse. Additionally, careful monitoring is advised for patients with depression and other psychiatric disorders. 41

Conclusion

This is the first study that underlines the beneficial effects of cannabinoids for the treatment of FBSS. The results suggest that THC/CBD combination may represent an innovative and valid strategy to treat disabling symptoms represented by pain, nausea, and sleep disorders in FBSS patients. Furthermore, in these patients, cannabinoid treatment could positively contribute to an improved quality of life. Though cannabinoids can have common side effects such as dry mouth and drowsiness, the side effects profile of THC/CBD combination seems to be milder and well tolerated. The chief limiting factors of this study are the small number of cases of FBSS patients with intractable refractory pain and the lack of a control group, even though it is a general opinion that interpretation of results obtained with placebo-controlled trials may encounter difficulties because of the psychoactive effects of cannabis. Additionally, it must be noted that ethical rules in Italy are very restrictive, especially in the context of pain treatment.

Albeit the limitations, in all the cases reported, the beneficial effect obtained with cannabinoids in association with SCS demonstrate that SCS therapy alone may be not sufficient to provide adequate analgesia.

Finally, we believe that prospective clinical studies are required to assess the real safety and efficacy of THC/CBD combination for chronic FBSS refractory pain. In conclusion, the current study suggest that THC/CBD combination represents an alternative treatment strategy in FBSS patients with chronic and severe pain, refractory to neuromodulating techniques, and is a valuable adjuvant to SCS.

Acknowledgments

Authors presented an earlier version of the abstract as a poster at the 38th Italian Society of Pharmacology (SIF) National Meeting in Rimini (Italy) in October 2017, prior to the actual completion or publication of the work.

Footnotes

Author contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.