Condition category
Signs and Symptoms
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Dilip Kapur


Contact details

Pain Management Unit
Flinders Medical Centre
Flinders Drive
Bedford Park

Additional identifiers

EudraCT number number

Protocol/serial number

CL0014 Version 5

Study information

Scientific title


Study hypothesis

To compare the efficacy and tolerability of nabilone with dihydrocodeine when used in the treatment of neuropathic pain based upon the following null hypotheses:
1. The analgesic activity of nabilone is not different from that of dihydrocodeine when used in the treatment of neuropathic pain over a six-week period
2. The patient tolerability of nabilone is not different from that of dihydrocodeine when used in the treatment of neuropathic pain over a six-week period
3. The antidepressant effect of nabilone is not different from that of dihydrocodeine when used in the treatment of neuropathic pain over a six-week period
4. Anxiety reducing effects of nabilone are not different from dihydrocodeine when used in the treatment of neuropathic pain over a six-week period

Ethics approval

Approval received from:
1. South Tees Local Research Ethics Committee on the 20th April 2001 (ref: 00/53)
2. West Ethics Committee Glasgow on the 23rd November 2001 (ref: 01/95)
3. Newcastle and North Tyneside Joint Ethics Committee on the 20th June 2001 (ref: 2000/137)

Study design

Randomised, double blind, crossover trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Mixed neuropathic pain


The medication was given in identical tablets either containing 240 µg nabilone or 30 mg dihydrocodeine. The dose schedule was one capsule in the first week, two capsules in the third week, four capsules in the third and fourth week and then eight capsules in week five and six. After a two week washout the treatment was crossed over. If there were side effects the dose was not increased further. During the washout rescue medication in the form of eight tablets 30/500 codeine with paracetamol was permitted. So each treatment arm was six weeks with a two week washout after six weeks and in the end. Patients with benefit went then into the open label trial (see ISRCTN38408594: A one year open label assessment of the use of nabilone in the treatment of chronic neuropathic pain). Visual Analogue Scale (VAS) scores and hours slept were recorded in a diary daily and then averaged per week. Only pain scores for the last two weeks were used for the analyses.

Intervention type



Not Specified

Drug names

Nabilone, dihydrocodeine

Primary outcome measure

Mean pain score as measured by VAS 0 - 10 for the last two weeks on treatment.

Secondary outcome measures

1. Sleep was measured as hours slept and if the sleep was interrupted or not in the diary
2. Depression and anxiety were measured with the Hospital Anxiety and Depression Score (HAD) at baseline and after each treatment period
3. Quality of life was measured with the 36-item Short Form questionnaire (SF-36) at baseline and after each treatment period
4. Six psychometric tests were performed at baseline and after each treatment period on a Apple Newton device
5. Side effects were assessed every two weeks with a eight-point questionnaire rating the severity of the side effects on a five point scale plus a field for open comments

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Patients entering the study will be recruited following written informed consent from pain clinics at participating centres
2. Patients will be in the age range 18 - 90 years with a diagnosis of neuropathic pain made according to the criteria set out below
3. Patients may be taking stable dose regimens of paracetamol, anticonvulsants, antidepressants, opioids or Non-Steroidal Anti-Inflammatory Srugs (NSAIDs)
4. Patients taking excluded medications (see exclusion criteria below) may enter the study after a two week period without these medications

Diagnosis of neuropathic pain:
The term "neuropathic pain" is loosely applied to a variety of heterogeneous conditions and strict diagnostic criteria are difficult to apply. However, for the purposes of this study, the diagnosis will be made on the basis of the following:
1. Pain secondary to an identifiable injury or disease process where damage to the central or peripheral nervous system is suspected
2. Pain persisting for more than three months in the absence of any continuing nociceptive stimulus
3. Pain that is documented as responding poorly to either opioid analgesics or NSAIDs
4. Pain associated with at least two of the following signs/symptoms:
4.1. Abnormal sensation on clinical examination, including sensory loss, paraesthesia, dysaesthesia
4.2. Mechanical allodynia (static or dynamic)
4.3. Pain of a burning character
4.4. Pain of a stabbing or lancinating character
4.5. Signs of sympathetic dysfunction (discolouration, abnormal vasomotor activity, skin trophic changes)

Many conditions may present with neuropathic pain. However, in some conditions the
distinction between primary nociceptive and neuropathic pain is extremely difficult. An
important example of this is in mechanical low back pain where radiation of pain into the legs is commonly reported in the absence of identifiable nerve injury. Given this diagnostic difficulty, for the purpose of this study, patients with lumbar radiculopathy will not be recruited to the study.

The Central Post-Stroke Pain Syndrome seems to have features that are significantly different to other types of neuropathic pain. For this reason, patients with this syndrome will not be included in this study.

Participant type


Age group

Not Specified


Not Specified

Target number of participants


Participant exclusion criteria

Patients may not enter the study if they have a history of any of the following conditions:
1. Epilepsy
2. Liver disease
3. Psychosis
4. Bipolar disorder
5. Substance misuse
6. Renal failure
7. Adverse reactions to either dihydrocodeine or nabilone
8. Pregnant women, lactating women or women of childbearing potential not using effective methods of contraception
9. Patients involved in ongoing legal action against a third party in which financial compensation is being sought for personal injury alleged to be the cause of the presenting condition

Excluded medications:
Patients may not take the following medications during the study:
1. Dihydrocodeine
2. Antipsychotic drugs
3. Benzodiazepine drugs (excepting stable doses of night-time sedatives)
4. Monoamine oxidase inhibitors

Patients taking dihydrocodeine may enter the study after a washout period of two weeks. Analgesia during this time will be provided with co-proxamol. Patients taking cannabinoid preparations of any kind may not be included in the study.

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Pain Management Unit

Sponsor information


Cambridge Laboratories Ltd (UK)

Sponsor details

Deltic House Newcastle
Kingfisher Way
Silverlink Business Park
NE28 9NX
United Kingdom

Sponsor type




Funder type


Funder name

Cambridge Laboratories Ltd (UK) - supported by a grant

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

The sponsors/funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Results in

Publication citations

  1. Results

    Frank B, Serpell MG, Hughes J, Matthews JN, Kapur D, Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study., BMJ, 2008, 336, 7637, 199-201, doi: 10.1136/bmj.39429.619653.80.

Additional files

Editorial Notes