The dose per capsule is 1 mg but we found that this could be excessive for some patients. Therefore, some were started at 0.25 mg by opening the capsule and dividing the resultant powder into four.
The initial time for nabilone use has been at night to reduce the potential discomfort of any side effects. Once the patient’s confidence has been developed, the dosage has been increased where appropriate. Those patients who have benefited from nabilone have been through a period of discontinuation to help evaluate the benefits of this drug.
The age range of the 43 patients who have used nabilone is from 25–82 years with 75% between the ages of 30 and 50. More women than men were treated, mainly reflecting a large sex difference in the group with multiple sclerosis.
The diagnoses of the patients were categorised into 6 groups as the most convenient method of presenting the information from such an heterogeneous group. No attempt has been made to do anything more than describe the effects of using nabilone on each individual patient and thereby evaluate whether it might be of value in pain control.
Multiple Sclerosis is characterised by widespread and varied damage to the central nervous system. Part of the pain experienced is neuropathic (i.e. pain that results from damage to the nerves) and is often resistant to conventional analgesics. However, patients also experience nociceptive pain (i.e. arising from damaged or dysfunctional tissues where the nervous system is intact). This may be secondary to muscle spasm, mechanical strain or bladder spasm. Patients often present with a cluster of pain symptoms in a variety of sites of their bodies.
Patients will often receive a wide variety of agents to try and treat their pain. They may also have had to come to terms with the progressive and often relentless deterioration of their physical health. The psychological and social effects of this process may add to or complicate the pain experience.
Six out of 13 patients obtained benefit from nabilone and 3 have continued for periods between 2 and 3 years. Two of these long term patients have a varied cluster of sites and types of pain. They have achieved substantial pain relief with nabilone. Their intake of other analgesics and psychotropic agents has become minimal. The third patient with mainly leg pain has maintained an improvement in pain and in sleep.
Three patients have discontinued in spite of benefit. One, with mainly spinal pain, had obtained much better pain relief with smoked cannabis and also improvement in his appetite and well-being. As he had a reliable supply, he has opted to continue with this mode of administration. He is able to provide a precise control of his pain, smoking just as much as he needs. A second patient found that cannabis provided better pain relief than nabilone with less side effects. The final patient was discontinued from nabilone due to difficulties with assessment and drug compliance. However, it was clear that she had gained some benefit with her sleeping.
Seven patients found nabilone either ineffective or suffered side effects without any observed benefit.
Back pain is the commonest problem presenting to Pain Relief Clinics. Many of these patients have major problems with their pain, complicated by a multitude of factors. Surgery and other invasive treatment have not only a very limited scope but also a significant failure rate.
The group included a mixture of neuropathic and nociceptor pains in a broad group of patients but with one common factor. There was no other treatment to offer.
Two patients have continued with nabilone. One has both lumbar arachnoiditis and sympathetically mediated pain in her limbs (complex regional pain syndrome). For her, nabilone has acted as an adjuvant to her other analgesics, relieving pain and misery and improving sleep. However, it is dysphoria that prohibits the use of nabilone when she wants to drive. The second patient has scarring of her S1 nerve root, established at 2 operations. She gets pain in the S1 dermatome and has been unable to control it adequately with opioids and a variety of other agents. Nabilone produces a substantial reduction in her pain and improvement in her sleep.
Five other patients with a variety of spinal problems have benefited from using nabilone but have had to stop either because of side effects or because of difficulties in assessment.
Two patients found nabilone completely ineffective to manage the pain. Both of them had had multiple spinal operations and suffered both mechanical spinal pain and neurogenic pain from nerve scarring.
The pain arising from damage to peripheral nerves can be extremely difficult to control satisfactorily. Patients will commonly describe their pain as a constant burning, tearing or pricking sensation. Diabetic neuropathy is a good example and for some patients the use of tricyclic antidepressants or anticonvulsants is satisfactory. However, for others, these may be ineffective. Conventional analgesics are often of little use.
One patient with anaesthesia dolorosa of her face, a condition that can occur after therapeutic damage to the trigeminal nerve, seems to have been cured of her problem. The severe burning, thumping pain that she experienced in her face was uncontrollable with analgesics and a range of psychotropic drugs. Not only did her pain recede completely but she was able to wean herself off all her medication. At 15 months she also discontinued nabilone and a year later has not had any recurrence of the pain in her face. She still has numbness though. Unfortunately, at the point at which nabilone was discontinued, she was discovered to have a metastatic carcinoma of the kidney. There is no evidence that this is anything more than coincidental. She subsequently went on to use nabilone to control the pain from a metastatic lesion in her spine (see below).
Two patients with diabetic neuropathy achieved good pain relief with nabilone but only one continues to use it. The other has found that the dysphoric side effects interfered too much with her daily life. She therefore opted for less satisfactory pain relief, using tramadol. However, from a functional point of view, she was better.
Four other attempts to treat neuropathies with nabilone have not been successful (sensori-motor, diabetic, post-chemotherapy, post herpetic).
Central Neurogenic Pain
This group of 5 patients had pain arising from within the central nervous system. For each of them the underlying cause is very different.
A patient who was tetraplegie following a spinal injury, had some benefit from nabilone. Previously he was smoking cannabis to control pain in his scapula region and in his sacral dermatomes. However, he achieved much better pain control for his distal body pain from regular cannabis use and consequently opted to continue smoking.
Four other patients obtained no benefit (post trigeminal tractotomy for post herpetic neuralgia, thalamic pain post CVA, cervical myelopathy, central cord syndrome post trauma).
Three patients with malignant disease have used nabilone for pain management. The first, a young woman with advanced cervical cancer, supplemented her opiate analgesia with nabilone before dying a few weeks later. A second patient using morphine to control the pain of a spinal metastasis reached the limit with opiates due to side effects. Her pain control substantially improved with a small amount of nabilone. She had used nabilone previously for anaesthesia dolorosa (see above). A third patient with bronchial carcinoma and a tracheo-oesophageal fistula and severe chest pain has used nabilone as an adjuvant to opiate analgesia. He improved sleep and well-being. Previously he was a frequent cannabis user.
Most Pain Relief Clinics have their collection of patients who are best described as “Heartsinks” from the feelings engendered in the clinician trying to support them. Hence they are often ready and willing candidates for any new treatment.
Of six patients with a wide variety of complex physical, psychological and social problems, 1 definitely obtained benefit from nabilone, whilst 3 others probably were helped. The former preferred smoking cannabis for his neck pain and insomnia opted for this approach. The other 3 were discontinued due to difficulties with assessment.
Benefits and Side Effects of Nabilone and Cannabis
As time has passed we have observed many patients using nabilone and/or cannabis. The effects and side effects have been the same although the effects of cannabis have always been preferred.
From our observations the benefits can probably be divided into 3 categories with possibly a variety of mechanisms:
- For pain directly arising from nerve damage (neuropathic) pain a direct reduction in pain was observed. Therefore effects on the receptors within the pain pathways can be proposed.
- For muscle spasms and bladder cramps there has been a reduction, presumably by a direct effect on the neural control of muscle tension.
- The adjuvant effects of improved sleep, “pain compressing”, “pain distancing”, anxiolysis, relaxation, euphoria, and relief of depression all have benefits on the patient’s perception and management of pain. These will be mediated through cortical and limbic system mechanisms.
- There are probable peripheral effects on inflammation which would influence pain although all of the patients here have visited NSAID therapy in the past.
Side effects seem to have occurred with a similar frequency to many other psychoactive drugs. Drowsiness and dysphoria have been the major problems for patients. A dry mouth has been reported. No other side-effects of nabilone have been noted.
Cannabis Use in Chronic Pain
Many patients self-report their use of cannabis for the relief of their chronic pain and a record of these has been kept recently. Two specific observations have been made. Firstly, a significant number of these patients have spinal pain as a result of trauma. The injuries have never been severe enough to cause neurological damage. However, all have experienced soft tissue damage and including one with a vertebral crush fracture. A common feature has been a combination of muscle spasm, excessive superficial spinal tenderness (hyperalgesia, allodynia) and lack of sleep.
Secondly, a patient with an established prolapsed intervertebral disc could relieve all his pain with cannabis. His prolapsed disc was later surgically treated with substantial relief of symptoms.
Occasionally patients in the clinic will ask for advice on their use of cannabis and its interaction with other drugs. In parts of London where cannabis is widely used socially, discussion of this issue is the norm for certain health workers.
Nabilone is a very expensive drug because of its current limited use. It is producing budgeting problems within our Hospital. Cannabis grown commercially is extremely cheap. Nabilone possibly costs 10 times as much as the equivalent amount of cannabis bought on the street. Cannabis can be grown to yield a cocktail of cannabinoids of known and repeatable concentrations. The illogicalities are evident.
There are many possible uses for cannabinoids in pain relief. Not only is the whole field of chronic pain open to such a new potential analgesic, but also its place in palliative care needs exploring. Acute pain, particularly acute back pain may be another valuable use of it. Sedation in Intensive Care is another possibility although this area is littered with agents that have come and gone. The anti-inflammatory effects may preclude its use here. Perhaps the traditional use of benzodiazepines for premedication prior to surgery could be challenged!
Leaving aside the flights of fancy described above, and focusing just on chronic pain, the issue of drug trials must be addressed. All trials of treatment for chronic pain are fraught with difficulty and commonly yield conflicting or ambiguous results. There are many reasons but two will suffice. Firstly, pain cannot be directly measured. Secondly these patients are a heterogenous group often with a multitude of physical, psychological and social problems. No two patients with multiple sclerosis are the same. Therefore treating these patients as a group can be a statistical nightmare when one comes to analyse the results. Conducting trials on cannabinoids will be worse due to the variety of effects they produce. It may be that the trial of the drug(s) in single individuals is the only way forward at the current time (an “N of 1” trial).
Trials of cannabinoids will require not only the current oral forms that are essentially of slow onset and long acting, but also a fast release variant. The nasal or inhalational route may be optimal providing a route for breakthrough pain and also a method of “fine tuning” the drug. In the past asthma has been treated with inhaled cannabinoids.
The experiences described above have been just that. No attempt has been made to try and prove benefit or compare effects. The purpose has been to define some areas for future studies. The challenge is now for clinicians to start clinical research in this area.
However, we must not lose sight of the fact that there are a large number of patients with chronic pain who might benefit from this group of drugs. Currently their options for analgesia are limited or non-existent. This is particularly poignant when one considers the history and safety of cannabis.
Of the patients continuing on nabilone evidence relating to their tolerance of the side effects of dysphoria and drowsiness was conflicting, this was also true of their tolerance of the analgesic capability of the drug, and it is on this basis why further investigative work is needed.
Selections from the book: “Cannabis. The Genus Cannabis”. Edited by David T.Brown. Series: “Medicinal and Aromatic Plants — Industrial Profiles”. 1998.