Abstract
A randomized, double-blinded, placebo controlled crossover study was conducted in
16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy
and tolerability of inhaled cannabis. In a crossover design, each participant was
exposed to 4 single dosing sessions of placebo or to low (1% tetrahydrocannabinol
[THC]), medium (4% THC), or high (7% THC) doses of cannabis. Baseline spontaneous
pain, evoked pain, and cognitive testing were performed. Subjects were then administered
aerosolized cannabis or placebo and the pain intensity and subjective “highness” score
was measured at 5, 15, 30, 45, and 60 minutes and then every 30 minutes for an additional
3 hours. Cognitive testing was performed at 5 and 30 minutes and then every 30 minutes
for an additional 3 hours. The primary analysis compared differences in spontaneous
pain over time between doses using linear mixed effects models. There was a significant
difference in spontaneous pain scores between doses (P < .001). Specific significant comparisons were placebo versus low, medium, and high
doses (P = .031, .04, and <.001, respectively) and high versus low and medium doses (both
P < .001). There was a significant effect of the high dose on foam brush and von Frey
evoked pain (both P < .001). There was a significant negative effect (impaired performance) of the high
dose on 2 of the 3 neuropsychological tests (Paced Auditory Serial Addition Test,
Trail Making Test Part B.
Perspective
This small, short-term, placebo-controlled trial of inhaled cannabis demonstrated
a dose-dependent reduction in diabetic peripheral neuropathy pain in patients with
treatment-refractory pain. This adds preliminary evidence to support further research
on the efficacy of the cannabinoids in neuropathic pain.
Key words
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References
- Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial.Neurology. 2007; 68: 515-521
- Vaporization as a smokeless cannabis delivery system: A pilot study.Clin Pharmacol Ther. 2007; 82: 572-578
- Diabetic somatic neuropathies.Diabetes Care. 2004; 27: 1458-1486
- The synthetic cannabinoid WIN55,212-2 attenuates hyperalgesia and allodynia in a rat model of neuropathic pain.Br J Pharmacol. 2001; 133: 586-594
- Effects of moderate and high doses of marihuana on thermal pain: A sensory decision theory analysis.J Clin Pharmacol. 1981; 21: 299S-310S
- A longitudinal assessment of painful diabetic peripheral neuropathy on health status, productivity, and health care utilization and cost.Pain Med. 2011; 12: 118-126
- The breeding of cannabis cultivars for pharmaceutical end uses.in: Guy G.W. Whittle B.A. Robson P. Medicinal Uses of Cannabis and Cannabinoids. Pharmaceutical Press, London2004: 55-70
- 3-[2-Cyano-3-(trifluoromethyl)phenoxy]phenyl-4,4,4-trifluoro-1-butanesulfonate (BAY 59-3074): a novel cannabinoid Cb1/Cb2 receptor partial agonist with antihyperalgesic and antiallodynic effects.J Pharmacol Exp Ther. 2004; 310: 3221-3233
- Cannabinoids block tactile allodynia in diabetic mice without attenuation of its antinociceptive effect.Neurosci Lett. 2004; 368: 82-86
- A psychometric evaluation of the Beck Depression Inventory–II.Psychol Assess. 1998; 10: 83-89
- Impact of postherpetic neuralgia and painful diabetic peripheral neuropathy on health care costs.J Pain. 2010; 11: 360-368
- Recommendations for the pharmacological management of neuropathic pain: An overview and literature update.Mayo Clin Proc. 2010; 85: S3-S14
- The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: The Rochester Diabetic Neuropathy Study.Neurology. 1993; 43: 817-824
- Smoked medicinal cannabis for neuropathic pain in HIV: A randomized, crossover clinical trial.Neuropsychopharmacology. 2009; 34: 672-680
- Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale.Pain. 2001; 94: 149-158
- Consequences of dichotomization.Pharm Stat. 2009; 8: 50-61
- Bias reduction of maximum likelihood estimates.Biometrika. 1993; 80: 27-38
- The Design and Analysis of Clinical Experiments.John Wiley and Sons, Inc, New York, NY1999
- Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory.Appetite. 1988; 11: 1-14
- Efficacy, safety, and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy: Findings from seven randomized, controlled trials across a range of doses.Diabetes Care. 2008; 31: 1448-1454
- Painful diabetic polyneuropathy: Epidemiology, pain description, and quality of life.Diabetes Res Clin Pract. 2000; 47: 123-128
- Isolation, structure and partial synthesis of an active constituent of hashish.J Am Chem Soc. 1964; 86: 1646-1647
- The health care costs of diabetic peripheral neuropathy in the US.Diabetes Care. 2003; 26: 1790-1795
- A comparative study on some chemical and biological characteristics of various samples of cannabis resin.Bull Narc. 1962; 3: 37-46
- Paced auditory serial-addition task: A measure of recovery from concussion.Percept Mot Skills. 1977; 44: 367-373
- Pharmacokinetics and pharmacodynamics of cannabinoids.Clin Pharmacokinet. 2003; 42: 327-360
- Cannabidiol potentiates pharmacological effects of Delta(9)-tetrahydrocannabinol via CB(1) receptor-dependent mechanism.Brain Res. 2008; 1188: 157-164
- Characterization and localization of cannabinoid receptors in rat brain. A quantitative in vitro autoradiographic study.J Neurosci. 1991; 11: 563-583
- Localization of central cannabinoid CB1 receptor messenger RNA in neuronal subpopulations of rat dorsal root ganglia: A double-label in situ hybridization study.Neuroscience. 1999; 90: 923-931
- Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC: CBD extract and THC extract in patients with intractable cancer-related pain.J Pain Symptom Manage. 2010; 182: E694-E701
- Pregabalin relieves symptoms of painful diabetic neuropathy: A randomized controlled trial.Neurology. 2004; 63: 2104-2110
- Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats.Pain. 2003; 105: 275-283
- Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain.Eur J Neurosci. 1999; 11: 4213-4225
- An examination of the central sites of action of cannabinoid-induced antinociception in the rat.Life Sci. 1995; 56: 2103-2109
- Validation of Michigan Neuropathy Screening Instrument for diabetic peripheral neuropathy.Clin Neurol Neurosurg. 2006; 108: 477-481
- Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: A randomized, placebo-controlled, graded-dose trial.J Pain. 2012; 13: 438-449
- Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain.BMC Neurol. 2009; 9: 6
- Anxiety mediates the association between cannabis use and attenuated positive psychotic symptoms.Psychiatry Res. 2014; 218: 180-186
- Neuropsychology: Current Status and Application.Winston and Sons, Washington, DC1974
- National Institute of Mental Health Diagnostic Interview Schedule.Arch Gen Psychiatry. 1981; 140: 201-206
- Statistical Issues in Drug Development.John Wiley & Sons Ltd, West Sussex, England2007
- Cannabinoid CB(1) receptor upregulation in a rat model of chronic neuropathic pain.Eur J Pharmacol. 2001; 415: R5-R7
- Responder analyses and the assessment of a clinically relevant treatment effect.Trials. 2007; 8: 31
- Impact of painful diabetic polyneuropathy on patients.in: Lawson E.F. Backonja M. Painful Diabetic Polyneuropathy: A Comprehensive Guide for Clinicians. Springer Science, New York2013: 155-166
- Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system.Neuroscience. 1998; 83: 393-411
- The effect of WIN 55,212-2, a cannabinoid agonist, on tactile allodynia in diabetic rats.Neurosci Lett. 2004; 371: 167-170
- Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers.Anesthesiology. 2007; 107: 785-796
- Smoked cannabis for chronic neuropathic pain: A randomized controlled trial.CMAJ. 2010; 182: E694-E701
- Low-dose vaporized cannabis significantly improves neuropathic pain.J Pain. 2013; 14: 136-148
- A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain.J Pain. 2008; 9: 506-521
- Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models.Eur J Neurosci. 2003; 17: 2750-2754
Article info
Publication history
Published online: April 02, 2015
Accepted:
March 23,
2015
Received in revised form:
March 17,
2015
Received:
January 17,
2015
Footnotes
Supported by Grant C00-SD-107 from the University of California Center for Medicinal Cannabis Research, La Jolla, California, United States of America.
None of the authors have conflict of interests to report.
Clinicaltrial.gov ID: NCT00781001.
Identification
Copyright
© 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.
