CoChat
Sign Up
Cited by 73Cannabis and Cannabinoid ResearchPain Management and Opioid UsePain Mechanisms and Treatments

Nabilone for the Management of Pain

Open access
Tsang, Corey C., Giudice, Mirella G.·2016·Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
DOI 10.1002/phar.1709
Open this paper in CoChat — free accountOpen PDF

Abstract

Nabilone, a synthetic cannabinoid, is approved in many countries including, but not limited to, Canada, the United States, Mexico, and the United Kingdom for the treatment of severe nausea and vomiting associated with chemotherapy. Clinical evidence is emerging for its use in managing pain conditions with different etiologies. We review the efficacy and safety of nabilone for various types of pain as well as its abuse potential, precautions and contraindications, and drug interactions; summarize pertinent clinical practice guidelines; and provide recommendations for dosing, monitoring, and patient education. Citations involving nabilone were identified through systematic reviews evaluating cannabinoids for pain. A systematic search (updated July 23, 2015) of the Ovid MEDLINE, EMBASE, PubMed, and Cochrane Library databases was performed. Eight randomized controlled trials, two prospective cohort trials, and one retrospective chart review were retrieved. Cancer pain, chronic noncancer pain, neuropathic pain, fibromyalgia, and pain associated with spasticity were the pain conditions evaluated. Nabilone was most commonly used as adjunctive therapy and led to small but significant reductions in pain. The most common adverse drug reactions included euphoria, drowsiness, and dizziness. Nabilone was rarely associated with severe adverse drug reactions requiring drug discontinuation, and the likelihood of abuse was thought to be low. Although the optimal role of nabilone in the management of pain is yet to be determined, certain clinical practice guidelines consider nabilone as a third-line agent.

Integrity signals

Registry

Crossref · 10.1002/phar.1709

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

37 of 106 cited sources checked · 15 supported · 2 flagged · accuracy not yet measured

  • Findingcitation

    In that systematic review, the risk of euphoria was RR 10.6 (NNH 3.2).

    “euphoria (relative risk [RR] 10.6, number needed to harm [NNH] 3.2)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [28] 28. Tramer M, Carroll D, Campbell D, et al. Cannabinoids for control of chemotherapy induced nausea and vomiting: quanti- tative systematic review. BMJ 2001;323:16-21. source

      Table 3 lists euphoria at RR 12.5 and a number needed to treat of 7.3, not 10.6 and 3.2. The cited figures belong to the separate “high” sensation row. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Findingcitation

    In that RCT, the overall mean ± SD VAS score was 59.93 ± 24.42 mm for nabilone and 58.58 ± 24.08 mm for dihydrocodeine.

    “However, the overall mean Æ SD VAS score was 59.93 Æ 24.42 mm for nabilone and 58.58 Æ 24.08 mm for dihydrocodeine, respectively.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [15] 15. Frank B, Serpell M, Hughes J, Matthews J, Kapur D. Compar- ison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ 2008;336:199-201. source
  • Study design and conductcitation

    Randomized controlled trials using active comparators are lacking, except in two studies.

    “RCTs using active comparators are lacking, except in two studies.15,20”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [15] 15. Frank B, Serpell M, Hughes J, Matthews J, Kapur D. Compar- ison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ 2008;336:199-201. source
    • cites [20] 20. Ware M, Fitzcharles M, Joseph L, Shir Y. The effects of nabi- lone on sleep in fibromyalgia: results of a randomized con- trolled trial. Anesth Analg 2010;110:604-10. source
  • Findingcitation

    In the RCT comparing nabilone and dihydrocodeine, improvements in anxiety and sleep were comparable between groups.

    “In the RCT comparing NABILONE FOR PAIN MANAGEMENT Tsang and Giudice 281 nabilone and dihydrocodeine, improvements in anxiety and sleep were comparable between groups.15”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [15] 15. Frank B, Serpell M, Hughes J, Matthews J, Kapur D. Compar- ison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ 2008;336:199-201. source

      Table 3 (page not specified in our copy) reports no statistically significant between-drug differences in sleep or anxiety, supporting the comparison. It does not establish that either treatment improved those outcomes, so the claim’s reference to comparable improvements goes beyond the reported results. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Findingcitation

    Nabilone relieved anxiety in smaller RCTs and prospective cohort studies.

    “Nabilone relieved anxiety in smaller RCTs and prospective cohort studies.[17][18][19]25”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [17] 17. Toth C, Mawani S, Brady S, et al. An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo- controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain 2012;153:2073-82. source
    • cites [18] 18. Bestard J, Toth C. An open-label comparison of nabilone and gabapentin as adjuvant therapy or monotherapy in the man- agement of neuropathic pain in patients with peripheral neu- ropathy. Pain Pract 2011;11:353-68. source
    • cites [19] 19. Skrabek R, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain 2008;9:164- 73. source
  • Classified as probably not a substantial claim. 26
  • May combine two claims. 35

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In that RCT, results in the placebo group were not reported.

    “Results in the placebo group were not reported.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [19] 19. Skrabek R, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain 2008;9:164- 73. source

      The Results section reports placebo-group outcomes: no statistically significant changes from baseline at the 2-, 4-, or 8-week visits. It also reports placebo-group withdrawals and comparisons with the treatment group. Thus, the claim that placebo-group results were not reported is contrary to our copy. (LLM, conf=0.93)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    Neither nabilone nor dihydrocodeine reduced pain by a clinically significant amount (>10-mm drop in VAS) in half of the study population.

    “Neither treatment at the end of the treatment period reduced pain by a clinically significant amount (i.e., > 10-mm drop in VAS) in half of the study population.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [15] 15. Frank B, Serpell M, Hughes J, Matthews J, Kapur D. Compar- ison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ 2008;336:199-201. source

      The Results report that 49 of 64 patients in the per-protocol analysis had no clinically relevant (>10-mm) drop in pain score on either treatment. That supports the claim that neither drug achieved this reduction for many patients, but the reported proportion was about 77%, not half, and it applies to the per-protocol group rather than the full study population. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    In a crossover, double-blind RCT comparing nabilone and dihydrocodeine for chronic neuropathic pain, the mean VAS score decreased to a greater extent in the group receiving nabilone first then dihydrocodeine, corresponding to an overall treatment effect of 5.6 mm (95% CI 0.8-10.3, p=0.023).

    “The mean VAS score decreased to a greater extent in the group receiving nabilone first then dihydrocodeine, which corresponded to an overall treatment effect of 5.6 mm (95% confidence interval [CI] 0.8-10.3,p=0.023).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [15] 15. Frank B, Serpell M, Hughes J, Matthews J, Kapur D. Compar- ison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ 2008;336:199-201. source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    Reported adverse drug reactions were generally mild to moderate in intensity, and few serious ADRs were reported.

    “Reported adverse drug reactions (ADRs) were generally mild to moderate in intensity, and few serious ADRs were reported.[15][16][17][18][19][20][21][22]25”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [15] 15. Frank B, Serpell M, Hughes J, Matthews J, Kapur D. Compar- ison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ 2008;336:199-201. source

      The Results (page not specified in our copy) state that no major adverse events occurred with either drug, supporting the claim that serious reactions were few. The Outcome measurements section describes a side-effect questionnaire, but the paper does not classify reported reactions as generally mild to moderate in intensity. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [16] 16. Turcotte D, Doupe M, Torabi M, et al. Nabilone as an adjunctive to gabapentin for multiple-sclerosis-induced neuro- pathic pain: a randomized controlled trial. Pain Med 2015;16:149-59. source
    • cites [17] 17. Toth C, Mawani S, Brady S, et al. An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo- controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain 2012;153:2073-82. source

  • May combine two claims.

    Premisecitation

    Cannabinoids are contraindicated in patients with a history of psychotic disorder, including schizophrenia, or active or unstable cardiovascular disease.

    “Cannabinoids are contraindicated in patients with a history of psychotic disorder, including schizophrenia, or active or unstable cardiovascular disease.29”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [29] 29. Clark A, Lynch M, Ware M, et al. Guidelines for the use of cannabinoid compounds in chronic pain. Pain Res Manag 2005;10:44A-6A. source

      The Abstract lists schizophrenia, uncontrolled hypertension, active ischemic heart disease, and arrhythmias as contraindications. But it calls a history of psychosis a relative contraindication, not an unqualified one, and specifies cardiovascular conditions rather than all active or unstable cardiovascular disease. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    No statistical analysis was conducted for the comparisons of ADRs between nabilone and dihydrocodeine or amitriptyline.

    “No statistical analysis, however, was conducted.15,20”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [15] 15. Frank B, Serpell M, Hughes J, Matthews J, Kapur D. Compar- ison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ 2008;336:199-201. source
    • cites [20] 20. Ware M, Fitzcharles M, Joseph L, Shir Y. The effects of nabi- lone on sleep in fibromyalgia: results of a randomized con- trolled trial. Anesth Analg 2010;110:604-10. source

  • May combine two claims.

    Findingcitation

    The most common ADRs in that systematic review included drowsiness (50%), dizziness (49%), euphoria (14-35%), hypotension (13%), hallucination (10%), and dysphoria or depression (10%).

    “The most common ADRs included drowsiness (50%), dizziness (49%), euphoria (14-35%), hypotension (13%) hallucination (10%), and dysphoria or depression (10%).28”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [28] 28. Tramer M, Carroll D, Campbell D, et al. Cannabinoids for control of chemotherapy induced nausea and vomiting: quanti- tative systematic review. BMJ 2001;323:16-21. source

      Table 3 (in the copy’s “What this study adds” section; page not supplied) reports drowsiness at 50%, dizziness at 49%, a “high” sensation at 35%, and euphoria at 14%. But it reports hypotension at 25%, hallucination at 6%, and dysphoria or depression at 13%—not the percentages claimed. The numbers 13 and 10 in those rows are counts of trials, not event rates. (LLM, conf=0.93)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In 2005, the Canadian Pain Society published guidelines for the use of cannabinoids for chronic pain and recommended that cannabinoids be used only as a last-line therapy.

    “In 2005, the Canadian Pain Society published guidelines for the use of cannabinoids for chronic pain and recommended that cannabinoids be used only as a last-line therapy.29”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [29] 29. Clark A, Lynch M, Ware M, et al. Guidelines for the use of cannabinoid compounds in chronic pain. Pain Res Manag 2005;10:44A-6A. source

      The 2005 paper provides guidelines for cannabinoids in chronic pain. Its treatment algorithm (p. 45A) says traditional approaches should be tried or considered, and recommends considering an oral cannabinoid when other therapies provide inadequate relief or cause unacceptable side effects. That supports a later-line role, but not the absolute claim that cannabinoids should be used only as a last-line therapy. The patient-evaluation section names the Canadian Pain Society in connection with separate opioid guidelines; our copy does not establish that the Society published these cannabinoid guidelines. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Smoked cannabis is more likely to be abused than nabilone, possibly due to a more rapid onset of action and better ease of titration of smoked cannabis.

    “Studies, however, did show that smoked cannabis is more likely to be abused than nabilone, possibly due to a more rapid onset of action and better ease of titration of smoked cannabis.29”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [29] 29. Clark A, Lynch M, Ware M, et al. Guidelines for the use of cannabinoid compounds in chronic pain. Pain Res Manag 2005;10:44A-6A. source

  • May combine two claims.

    Premisecitation

    Nabilone will not give a positive urine test for THC and therefore may be used to ensure that nabilone-treated patients are not also using cannabis.

    “Nabilone will not give a positive urine test for THC and therefore may be used to ensure that nabilone-treated patients are not also using cannabis.35,36”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [35] 35. The cannabinoid checklist. Montreal, QC: Canadian Consortium for the Investigation of Cannabinoids, 2015. Available from http://www.ccic.net/picture/upload/File/ACE%20Resources/CC- IC%20Physician%20Reference%20Card.pdf. Accessed October 2, 2014. source

      The “Diagnosis requires a high index of suspicion” section says synthetic cannabinoids are not detected by urine immunoassay tests for THC. It does not name nabilone or discuss using THC tests to monitor cannabis use in nabilone-treated patients, so those specifics are not established by this paper. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [36] 36. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013 clini- cal practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2013;37:S1-212.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Adverse drug reactions are usually mild to moderate in severity and commonly include drowsiness, dizziness, dry mouth, headache, clumsiness, loss of memory, difficulty concentrating, appetite changes, nausea, euphoria or elevation in mood, confusion, and depression.

    “Adverse drug reactions are usually mild to moderate in severity and commonly include drowsiness, dizziness, dry mouth, headache, clumsiness, loss of memory, difficulty concentrating, appetite changes, nausea, euphoria or elevation in mood, confusion, and depression 15,[17][18][19][22][23][24]”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [15] 15. Frank B, Serpell M, Hughes J, Matthews J, Kapur D. Compar- ison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ 2008;336:199-201. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [17] 17. Toth C, Mawani S, Brady S, et al. An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo- controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain 2012;153:2073-82. source
    • cites [18] 18. Bestard J, Toth C. An open-label comparison of nabilone and gabapentin as adjuvant therapy or monotherapy in the man- agement of neuropathic pain in patients with peripheral neu- ropathy. Pain Pract 2011;11:353-68. source

  • May combine two claims.

    Premisecitation

    Adverse events may be minimized by gradual dose titration, and tolerance will develop to many of these adverse effects.

    “Adverse events may be minimized by gradual dose titration, and tolerance will develop to many of these adverse effects 16,19”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [16] 16. Turcotte D, Doupe M, Torabi M, et al. Nabilone as an adjunctive to gabapentin for multiple-sclerosis-induced neuro- pathic pain: a randomized controlled trial. Pain Med 2015;16:149-59. source
    • cites [19] 19. Skrabek R, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain 2008;9:164- 73. source

      The Discussion (page unavailable) suggests that slower nabilone titration in longer studies may reduce side effects, supporting the first part of the claim. Neither that passage nor the Results establishes that patients develop tolerance to many adverse effects; the reported side effects remained more common with nabilone at both 2 and 4 weeks. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Nabilone theft did occur, although nabilone has no known street value.

    “However, nabilone theft did occur, although nabilone has no known street value.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [32] 32. Moulin D, Boulanger A, Clark A, et al. Pharmacological man- agement of chronic neuropathic pain: revised consensus state- ment from the Canadian Pain Society. Pain Res Manag 2014;19:328-35. source

      The Cannabinoids section (page unavailable) discusses nabilone trials but does not mention theft or street value. Searches for nabilone theft, diversion, and street value found no passage addressing either point. (LLM, conf=0.74)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    The included studies evaluated neuropathic pain in four studies, fibromyalgia in two, spasticity-related pain in two, chronic noncancer pain in two, and cancer pain in one.

    “Neuropathic pain of various etiologies was evaluated in four studies, [15][16][17][18] whereas fibromyalgia, 19,20 spasticity-related pain (one related to spinal cord injury 21 and the other related to chronic upper motor neuron syndrome 22 ), and chronic noncancer pain were each evaluated in two studies.23,24 Cancer pain was examined in one study.25”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In a parallel-group, double-blind, placebo-controlled RCT of adjunctive nabilone in patients with diabetic neuropathic pain, pain as measured by the NRS was significantly reduced in the nabilone group versus placebo (3.5 vs 5.4), with mean differences in NRS scores of 3.0 and 1.1 in the nabilone and placebo groups, respectively (p<0.01).

    “Pain, as measured by the numerical rating scale (NRS), was significantly reduced in the nabilone group versus the placebo group (3.5 vs 5.4), and the mean differences in NRS scores were 3.0 and 1.1 in the nabilone and placebo groups, respectively (p<0.01).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] 17. Toth C, Mawani S, Brady S, et al. An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo- controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain 2012;153:2073-82. source

  • May combine two claims.

    Findingcitation

    In that RCT, despite improvement in pain intensity, the impact on daily activities, as measured by the VAS impact, was not significantly reduced.

    “Despite the improvement in pain intensity, the impact on daily activities, as measured by the VAS impact , was not significantly reduced.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] 16. Turcotte D, Doupe M, Torabi M, et al. Nabilone as an adjunctive to gabapentin for multiple-sclerosis-induced neuro- pathic pain: a randomized controlled trial. Pain Med 2015;16:149-59. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The updated systematic search (to July 23, 2015) yielded 771 citations, of which 594 remained after deduplication and were screened; no full-text results were eligible for full-text review.

    “The updated systematic search yielded 771 citations.After removal of duplications, 594 citations were screened for eligibility.No full-text results were eligible for full-text review (Figure 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Nabilone was most commonly used as adjunctive therapy and led to small but significant reductions in pain.

    “Nabilone was most commonly used as adjunctive therapy and led to small but significant reductions in pain.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    In that RCT, the majority of patients in the nabilone group increased their dosage at week 3; two patients did not tolerate this dose increase.

    “The majority of patients in the nabilone group increased their dosage at week 3; however, two patients did not tolerate this dose increase.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] 21. Pooyania S, Ethans K, Sztum T, Casey A, Perry D. A random- ized, double-blinded, crossover pilot study assessing the effect of nabilone on spasticity in persons with spinal cord injury. Arch Phys Med Rehabil 2010;91:703-7. source

  • May combine two claims.

    Findingcitation

    In a crossover, double-blind, placebo-controlled RCT of adjunctive nabilone in patients with spinal cord injuries, nabilone significantly reduced the score on the Ashworth Scale in both the most involved muscle group and in the eight-muscle group compared to placebo.

    “Nabilone significantly reduced the score on the Ashworth Scale in both the most involved muscle group as well as in the eightmuscle group compared to placebo.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] 21. Pooyania S, Ethans K, Sztum T, Casey A, Perry D. A random- ized, double-blinded, crossover pilot study assessing the effect of nabilone on spasticity in persons with spinal cord injury. Arch Phys Med Rehabil 2010;91:703-7. source

  • May combine two claims.

    Findingcitation

    Sleep duration and quality improved with nabilone in a small RCT, a retrospective chart review, and a larger prospective cohort study.

    “Sleep duration and quality improved with nabilone in a small RCT, a retrospective chart review, and a larger prospective cohort study.17,18,24”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [17] 17. Toth C, Mawani S, Brady S, et al. An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo- controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain 2012;153:2073-82. source
    • cites [18] 18. Bestard J, Toth C. An open-label comparison of nabilone and gabapentin as adjuvant therapy or monotherapy in the man- agement of neuropathic pain in patients with peripheral neu- ropathy. Pain Pract 2011;11:353-68. source
    • cites [24] 24. Berlach D, Shir Y, Ware M. Experience with the synthetic cannabinoid nabilone in chronic noncancer pain. Pain Med 2006;7:25-9. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Anxiety and sleep disturbances were commonly assessed as secondary outcomes in the clinical trials discussed.

    “Anxiety and sleep disturbances were commonly assessed as secondary outcomes in the clinical trials discussed above.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In that chart review, the average duration of nabilone use was 1.5 years, and half of the patients reported using nabilone for its positive effects on quality or duration of sleep, rather than its effect on pain.

    “The average duration of use was 1.5 years, and half of the patients reported using nabilone for its positive effects on quality or duration of sleep, rather than its effect on pain.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] 24. Berlach D, Shir Y, Ware M. Experience with the synthetic cannabinoid nabilone in chronic noncancer pain. Pain Med 2006;7:25-9. source

  • May combine two claims.

    Findingcitation

    Despite a lack of change on the NRS, the study reports many subjective patient anecdotes of mild, but noticeable improvements.

    “Despite a lack of change on the NRS, the study reports many subjective patient anecdotes of mild, but noticeable improvements.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] 24. Berlach D, Shir Y, Ware M. Experience with the synthetic cannabinoid nabilone in chronic noncancer pain. Pain Med 2006;7:25-9. source

  • May combine two claims.

    Findingcitation

    One case each of multiple sclerosis relapse and weakness in the lower limbs were documented, but only the weakness was attributed to nabilone.

    “One case each of multiple sclerosis relapse and weakness in the lower limbs were also documented, but only the weakness was attributed to nabilone.22”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] 22. Wissel J, Haydn T, Muller J, et al. Low dose treatment with the synthetic cannabinoid nabilone significantly reduces spas- ticity-related pain: a double-blind placebo-controlled cross- over trial. J Neurol 2006;253:1337-41. source

  • May combine two claims.

    Findingcitation

    One of the patients with confusion required hospitalization, and the confusion was reversed on cessation of nabilone.

    “One of the patients required hospitalization, and the confusion was reversed on cessation of nabilone.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] 17. Toth C, Mawani S, Brady S, et al. An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo- controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain 2012;153:2073-82. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    No head-to-head safety comparisons between cannabinoids and smoked cannabis were identified.

    “No head-to-head safety comparisons between cannabinoids and smoked cannabis were identified.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Limited data are available on drug interactions with nabilone.

    “Limited data are available on drug interactions with nabilone.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    No tapering schedules for nabilone discontinuation were found.

    “Therefore, nabilone discontinuation should be done gradually, although no tapering schedules were found.31”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] 31. Ware M, St Arnaud-Trempe E. The abuse potential of synthetic cannabinoid nabilone. Addiction 2010;105:494-503. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Few guidelines discuss the use of nabilone for treatment of pain.

    “Few guidelines discuss the use of nabilone for treatment of pain (Table 4).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Other trials found no benefit.

    “Other trials, on the other hand, found no benefit.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    Dosing recommendations for pain are not firmly established and vary slightly based on the source.

    “Dosing recommendations for pain are not firmly established and vary slightly based on the source.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    In that RCT, a higher proportion of females received the active treatment and concomitant analgesics were not reported.

    “A higher proportion of females received the active treatment and concomitant analgesics were not reported.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] 17. Toth C, Mawani S, Brady S, et al. An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo- controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain 2012;153:2073-82. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Flexible dosing schedules were used in the studies, i.e., there were no dose-effect studies.

    “Flexible dosing schedules were used (i.e., no dose-effect studies).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    In that RCT, the final mean gabapentin dose was not reported between groups, and it was unclear if changes in gabapentin doses were allowed during the trial.

    “The final mean gabapentin dose was not reported between groups, and it was unclear if changes in gabapentin doses were allowed during the trial.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] 16. Turcotte D, Doupe M, Torabi M, et al. Nabilone as an adjunctive to gabapentin for multiple-sclerosis-induced neuro- pathic pain: a randomized controlled trial. Pain Med 2015;16:149-59. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Concomitant analgesics were generally not listed in the studies.

    “Concomitant analgesics were generally not listed.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Nabilone was used as adjunctive therapy in all except one study.

    “Nabilone was used as adjunctive therapy in all except one study.18”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] 18. Bestard J, Toth C. An open-label comparison of nabilone and gabapentin as adjuvant therapy or monotherapy in the man- agement of neuropathic pain in patients with peripheral neu- ropathy. Pain Pract 2011;11:353-68. source

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The optimal role of nabilone in the management of pain is yet to be determined.

    “Although the optimal role of nabilone in the management of pain is yet to be determined”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Lack of randomization and blinding in that trial may have led to selection bias, and direct comparison of nabilone and gabapentin must be done cautiously.

    “Lack of randomization and blinding may have led to selection bias, and direct comparison of these agents must be done cautiously.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Anxiety and sleep disturbances are often comorbid conditions in different chronic pain states.

    “These are important because they are often comorbid conditions in different chronic pain states.26,27”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [26] 26. Lautenbacher S, Kundermann B, Krieg JC. Sleep deprivation and pain perception. Sleep Med Rev 2006;10:357-69. source
    • cites [27] 27. Gerrits MM, Vogelzangs N, van Oppen P, et al. Impact of pain on the course of depressive and anxiety disorders. Pain 2012;153:429-36. source

  • May combine two claims.

    Premisecitation

    Both anxiety and sleep disturbances may exacerbate pain and vice versa.

    “Furthermore, both anxiety and sleep disturbances may exacerbate pain and vice versa.26,27”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [26] 26. Lautenbacher S, Kundermann B, Krieg JC. Sleep deprivation and pain perception. Sleep Med Rev 2006;10:357-69. source
    • cites [27] 27. Gerrits MM, Vogelzangs N, van Oppen P, et al. Impact of pain on the course of depressive and anxiety disorders. Pain 2012;153:429-36. source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    It may not be appropriate to extrapolate the ADRs reported in the chemotherapy-induced nausea and vomiting setting to pain management.

    “However, it may not be appropriate to extrapolate the ADRs reported in this setting.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Updated guidelines (2014) from the Canadian Pain Society now recommend cannabinoids (nabilone or a 50:50 mixture of THC and cannabidiol buccal spray) as third-line agents, rather than fourth-line agents, for managing neuropathic pain.

    “Updated guidelines (2014) from the Canadian Pain Society now recommend cannabinoids (nabilone or a 50:50 mixture of THC and cannabidiol buccal spray) as third-line agents, rather than fourth-line agents, for managing neuropathic pain.33”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] 33. Neron A, ed. Care beyond cure: management of pain and other symptoms. 4th ed. Montreal, ON: Canadian Society of Hospital Pharmacists, 2009.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationnone given

    A number of trials show modest, but significant, reductions in pain scores and improvement in secondary outcomes of sleep and anxiety.

    “A number of trials show modest, but significant, reductions in pain scores and improvement in secondary outcomes of sleep and anxiety.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The Canadian Agency for Drugs and Technologies in Health concluded that nabilone significantly reduced pain in patients with chronic noncancer pain compared to placebo but was not better than the comparator analgesics (dihydrocodeine and amitriptyline).

    “They concluded that nabilone significantly reduced pain in patients with chronic noncancer pain compared to placebo but was not better than the comparator analgesics (dihydrocodeine and amitriptyline).45”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] 45. Nabilone. Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc., 2015. Available from http://online.lexi.com. Accessed August 8 2015.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The onset of pain relief may be as soon as 1 wk, but the full effect may take up to 6 mo.

    “The onset of pain relief may be as soon as 1 wk, but the full effect may take up to 6 mo 18”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] 18. Bestard J, Toth C. An open-label comparison of nabilone and gabapentin as adjuvant therapy or monotherapy in the man- agement of neuropathic pain in patients with peripheral neu- ropathy. Pain Pract 2011;11:353-68. source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The potential for abuse of nabilone appears low.

    “Although the potential for abuse appears low, patients should be screened before therapy is initiated and then monitored appropriately.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Certain patients require higher doses of nabilone, reflected in a maximum daily dose of 6 mg divided into two or three doses.

    “Certain patients require higher doses, and this is reflected in a maximum daily dose of 6 mg divided into two or three doses.31,33”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [31] 31. Ware M, St Arnaud-Trempe E. The abuse potential of synthetic cannabinoid nabilone. Addiction 2010;105:494-503. source
    • cites [33] 33. Neron A, ed. Care beyond cure: management of pain and other symptoms. 4th ed. Montreal, ON: Canadian Society of Hospital Pharmacists, 2009.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationnone given

    Nabilone is an emerging treatment for various types of pain including neuropathic pain, fibromyalgia, chronic noncancer pain, and spasticity related to multiple sclerosis.

    “Nabilone is an emerging treatment for various types of pain including neuropathic pain, fibromyalgia, chronic noncancer pain, and spasticity related to multiple sclerosis.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Nabilone is generally well tolerated and has a favorable drug interaction profile.

    “Nabilone is generally well tolerated and has a favorable drug interaction profile.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    After oral administration, nabilone's onset of action occurs within 60-90 minutes, and effects persist for 8-12 hours.

    “After oral administration, nabilone's onset of action occurs within 60-90 minutes, and effects persist for 8-12 hours.7”
    • Also stated in: § Counseling recommendations · plain
      “With each nabilone dose, the onset of effect is within 60-90 min, and the duration of action is 8-12 hrs.31”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] 7. Twycross R, Wilcock A. Palliative care formulary. 4th ed. Not- tingham, UK: Hayward House Study Centre, 2011.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [31] 31. Ware M, St Arnaud-Trempe E. The abuse potential of synthetic cannabinoid nabilone. Addiction 2010;105:494-503. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    This change reflects the results from recent clinical trials.

    “This change reflects the results from recent clinical trials.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Nabilone may be taken without regard to food.

    “The agent may be taken without regard to food.11”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] 11. Nabilone. Micromedex 2.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

53 of 53

  • The paper relies on this without support.

    Certain clinical practice guidelines consider nabilone as a third-line agent for the management of pain.

    “Although the optimal role of nabilone in the management of pain is yet to be determined, certain clinical practice guidelines consider nabilone as a third-line agent.”

  • The paper relies on this without support.

    The likelihood of abuse of nabilone is low.

    “the likelihood of abuse was thought to be low”

  • The paper relies on this without support.

    The urine drug test for THC cannot distinguish between smoked cannabis and THC-containing prescription medications.

    “The urine drug test for THC cannot distinguish between smoked cannabis and THC-containing prescription medications.”
3 of 3

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • The abuse-potential study is assigned the wrong reference number

    Minor

    The text identifies reference 32 as a study of nabilone abuse, but reference 32 is a neuropathic-pain guideline. The bibliography lists the nabilone abuse-potential study as reference 31.

  • Trial completion count differs from the reported treatment denominators

    Minor

    Of 96 patients, 33 reportedly failed to complete the crossover trial, leaving 63 completers. The table nevertheless uses 64 patients as the denominator for each treatment's reduction in pain.

    Reported 64 · recomputed 63

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Ware MA, 2009, What are the needs of physicians considering medical cannabinoids?, Pain Res Manag, 14, 165
  2. Canadian Agency for Drugs and Technologies in Health.Nabilone for chronic pain management: a review of clinical effectiveness safety and guidelines.Ottawa ON:CADTH 2011. Available fromhttp://www.cadth.ca/media/pdf/htis/oct-2011/RC0306-000%20Nabilone%20for%20chronic%20pain.pdf. Accessed October 2 2014.
  3. Valent Canada, 2009, Cesamet (nabilone) product monograph
  4. Buckhardt CS, 2005, Guideline for the management of fibromyalgia syndrome pain in adults and children, 109

Cited by

Sorted by citations

Related

Authors
Tsang, C. C., & Giudice, M. G.
Affiliations
Ottawa Hospital (CA)
Corresponding author
Tsang, Corey C.
ORCID
Tsang, Corey C.
Venue
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
Publisher
Wiley
Published
2016-02-29
Volume
36
Issue
3
Pages
273-286
ISSN
  • 0277-0008 (ISSN-L)
  • 1875-9114
DOI
10.1002/phar.1709
OpenAlex
W2290484125
Cited by
73
References
38
Citations by year
2026: 6 · 2025: 8 · 2024: 7 · 2023: 6 · 2022: 9 · 2021: 7 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 9 · 2016: 1
FWCI
0.87
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
nabilone, cannabinoids, pain management, cancer pain, chronic non-cancer pain, neuropathic pain, fibromyalgia, adjunctive therapy, adverse drug reactions, abuse liability, drug interactions
MeSH terms
Analgesics, Clinical Trials as Topic, Humans, Pain, Dronabinol, Treatment Outcome, Disease Management, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review