Effective treatment of fibromyalgia-associated chronic pain with cannabidiol (Epidyolex) in two cases

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CASE REPORT

Hippokratia 2025, 29(1): 39-41

Papacostas SS
Department of Neurophysiology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus

Abstract

Background: Fibromyalgia is a chronic condition characterized by musculoskeletal pain and gastrointestinal and neuropsychiatric symptoms that currently lacks a consistently effective symptomatic treatment.

Description of the cases: We present the cases of two patients with fibromyalgia in whom the use of cannabidiol (Epidyolex) in relatively low doses was effective in significantly ameliorating their symptoms, which were previously resistant to other pharmacological interventions.

Conclusion: The reported cases illustrate that cannabidiol may have a significant role in the therapeutic armamentarium of fibromyalgia.HIPPOKRATIA 2025, 29 (1):39-41.

Keywords: Fibromyalgia, chronic pain, cannabidiol, Epidyolex

Corresponding author: Savvas S Papacostas, Department of Neurophysiology, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, P.O.Box 23462, 1683 Nicosia, Cyprus, tel: +35722358600, e-mail: savvas@cing.ac.cy

Introduction

Fibromyalgia (FM) is a condition of unknown cause characterized by chronic widespread pain, often associated with fatigue, cognitive dysfunction, migraine headaches, lower abdominal pain, cramps, and psychological problems, mainly depression and insomnia1,2. The pain is thought to result from central nervous system processes and affects females twice as often as males3,4. It is estimated to occur in about 4 % of the population5. Specific diagnostic criteria have been proposed, and nine trigger points have been identified that produce pain with pressure on the scalp, trunk, arms, and legs6.

Treatment is challenging involving a combination of medications, exercise, psychotherapy and physical therapies7. Commonly used medications include selective serotonin reuptake or serotonin-norepinephrine reuptake inhibitors (SSRI/SNRI), nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants8, among others. It is, therefore, crucial to develop more effective therapies for pain control and improving quality of life. Recently, cannabis and its derivatives have been used; however, their efficacy remains controversial, and results of clinical trials or meta-analyses remain inconclusive9. In contrast, well-established uses include chemotherapy-induced nausea and vomiting, spasticity in multiple sclerosis, epilepsy and neuropathic pain.

Recently, active substances in cannabis have been removed, resulting in the development of cannabinoid products, which are mostly devoid of psychoactive effects and, in addition to cannabis, have been used in chronic pain conditions. Efficacy in FM is still limited, and their use remains controversial. We present the cases of two patients with FM who attained significant symptom improvement following the administration of Epidyolex, a drug currently approved for epilepsy. 

Description of cases

First case

A right-handed woman weighing 60 kg presented at the age of 31 with a three-year history of intermittent low back and cervical pain associated with left-sided hemi-numbness and transient left arm tremor. She had a history of migraine attacks characterized by nausea, visual disturbance, and throbbing headache, occasionally accompanied by hemisensory disturbance and treated with NSAIDs, codeine-containing preparations, and muscle relaxants.

Family history was significant for migraines in her mother, sister, and two maternal aunts. She was single and worked in a bank. There was no history of tobacco, alcohol, or illicit drug use. Neurological examination revealed a 4+/5 strength, postural tremor in her left triceps, and a subjective feeling of left hemi-body sensory deficit. A complicated migraine was diagnosed.

Brain imaging was normal. Electromyography revealed mild chronic radiculopathy at the C6 spinal vertebra level. A spine magnetic resonance imaging (MRI) scan revealed minimal spondylotic changes in the cervical and lumbar regions. Her treatment continued, and she was referred for physical therapy, to which she had a poor response.

Over the subsequent 12 years, she continued to experience symptom exacerbations and remissions, namely migraine headaches, spinal pain, and diffuse tenderness. Following her wedding, medications were tapered, and she conceived. Symptoms persisted during pregnancy and became worse after delivery. Subsequent treatments included topiramate, valproic acid, gabapentin, amitriptyline, pregabalin, SSRIs/SNRIs, in combination with muscle relaxants, vitamins, physical therapy, and an FM diet following this diagnosis by a rheumatologist. Zolmitriptan was administered on an as-needed basis for breakthrough migraine attacks, whereas melatonin was used for insomnia without significant help. Due to frequent absences from work, she was eventually laid off.

Cannabidiol (CBD) in the form of Epidyolex was subsequently given as a last resort at a dose of 0.8 mg/kg and titrated to 1.6 mg/kg twice daily (BID) as an off-label treatment approved by the pharmaceutical services at the Ministry of Health of Cyprus based on a compassionate protocol. On follow-up, she reported a 50 % improvement in her chronic pain. She was able to gradually withdraw other medications and remained on CBD in combination with duloxetine, zolmitriptan as needed, and topiramate 100 mg BID. She continued to have fluctuations in her symptoms but remained overall improved for the subsequent three years, especially following titration of CBD to 1.6 mg/kg BID. Following a gradual worsening of her symptoms, the dose of cannabidiol was titrated to 2.4 mg/kg BID, achieving good symptom control. Tolerability was good, with minimal side effects, including dizziness and cough. Blood testing parameters remained unchanged from baseline.

Second case

A right-handed woman weighing 70 kg presented at the age of 51, complaining of diffuse pains and frequent migraines. A rheumatologist had previously diagnosed FM and was treating her with duloxetine 60 mg at night and paracetamol/codeine preparations. She had been previously treated with multiple classes of medications, including NSAIDs, tricyclic antidepressants, piracetam, benzodiazepines, and paracetamol with or without codeine. In addition to her migraine, she also reported gastrointestinal symptoms, anxiety, intermittent depression, and insomnia. She described her headache as mostly right hemicranial, associated with photophobia, phonophobia, and nausea since the age of 16 and occurring three to four times per month. She also complained of bilateral hand numbness, especially at night.

Past medical history was significant for congenital nystagmus. Family history was significant for the presence of focal onset epilepsy in her daughter. On presentation, she was taking duloxetine 60 mg nocte and paracetamol/codeine preparations. She denied drug allergies. She worked as a school cleaner and denied smoking, alcohol or drug abuse.

On examination, she appeared tense and anxious. Nystagmus was noted especially with right-sided gaze. Diffusely increased reflexes were noted. Positive trigger points were found corroborating the diagnosis of fibromyalgia, and a Tinnel sign was elicited. A nerve conduction study revealed the presence of bilateral carpal tunnel syndrome, whereas a brain MRI scan was normal.

She was treated with pregabalin 25 mg BID and gradually titrated to 75 mg three times daily in combination with duloxetine. She was also placed on an FM diet, resulting in some improvement; however, her depression worsened. At that point, duloxetine was switched to venlafaxine 75 mg daily. She was administered low dose benzodiazepines and melatonin for insomnia. Over the following five years, she tried various combinations of SSRIs with pregabalin, simple analgesics, and benzodiazepines. Exacerbations and remissions characterized her symptoms, and she also developed cognitive problems, namely decreased concentration and short-term memory dysfunction. Subsequently, she was given a low dose CBD in the form of Epidyolex 1 mg/kg BID on a compassionate protocol. A month later, she reported approximately 40 % improvement in symptoms overall. The dose was titrated to 2 mg/kg BID, and on that regimen, she achieved approximately 75 % improvement, which persisted thereafter. No significant side effects were reported.

Discussion

Previous studies highlighted the fact that CBD use is common among FM patients, with many reporting a beneficial effect across multiple symptom domains10. Clinicians should, therefore, discuss CBD use with patients and consider its possible interactions with other drugs. Cannabis use carries risks as well, including developmental, cognitive, and psychiatric, as well as the risks of addiction9 resulting from components such as tetrahydrocannabinol (THC) whereas CBD lacks such effects. These two components exhibit significant pharmacodynamic differences accounting for their differential actions11. Another issue is the inconsistent concentration of various commercially available preparations, making evaluating efficacy difficult. CBD in the form of Epidyolex on the other hand, has nearly 100 % consistent concentration and is the first prescription formulation of plant-derived CBD approved by regulatory bodies in the US and Europe12; as such, its therapeutic value in FM and other conditions such as epilepsy, neuropathic pain and spasticity11 may be assessed accurately. CBD may play a role in modulating intracellular Ca2+ and adenosine-mediated signaling. In contrast, THC acts as a partial agonist at the cannabinoid receptor CB1, located mainly in the central nervous system, and the CB2 receptor, located in the immune system. The different mechanisms of action of the two compounds explain the lack of psychoactive effects of CBD in contrast to THC11.

The two cases of patients with FM presented demonstrate that the use of CBD (Epidyolex) in low doses relative to other conditions, such as epilepsy where the recommended dose ranges between 10-20 mg/kg, was effective in nearly ameliorating symptoms which had previously proved resistant to other interventions. CBD is currently used as an antiseizure medication12 and may therefore have an additional significant role in the therapeutic armamentarium of FM. The two cases described had no significant side effects, but further research is required to define appropriate patient selection and treatment regimens.

Conflict of interest

The author declares no conflicts of interest. 

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