Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review

Campbell, Fiona

doi:10.1136/bmj.323.7303.13

Cited by 360 publications

(229 citation statements)

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“…Psychostimulants, excitatory amino acids, and a heterogeneous group of compounds of diverse chemical composition that allegedly facilitate learning and memory or overcome natural or induced cognitive impairments 50 might someday be useful in combination with cannabis or cannabinoids currently thought to be undesirable because of the depressant effects on the central nervous system that limit their use. 15 In addition to the issues discussed above, the noxious pyrolytic byproducts released through combustion remain a public health deterrent to the use of smoked cannabis. 42,51 However, a method has been devised to provide a safer and more efficient delivery system.…”

Section: Discussionmentioning

confidence: 99%

A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

Wilsey

Marcotte

Tsodikov

et al. 2008

The Journal of Pain

272

244

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The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use "medical marijuana," and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. KeywordsNeuropathic pain; analgesia; cannabis; clinical trial; neuropsychological testingThe case for the clinical utility of cannabis as an analgesic derives from experimental studies as well as anecdotal reports. Activation of the endocannabinoid system suppresses HHS Public AccessAuthor manuscript J Pain. Author manuscript; available in PMC 2016 August 01. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript behavioral responses to acute and persistent noxious stimulation through both central 71 and peripheral 45 mechanisms. Cannabinoid receptors are localized in neuroanatomic regions intimately involved with transmission and modulation of pain signals: The periaqueductal gray (PAG), the rostral ventromedial medulla (RVM), 40,66 and the dorsal horn of the spinal cord. 66 Animal experimentation has clearly demonstrated that synthetic and endogenous cannabinoids not only produce analgesia but also interact in some manner to potentiate opioids, 18,70 particularly in neuropathic pain. 41 Surveys involving the use of medicinal marijuana reveal that pain, sleep, and mood improve with only modest side effects. 72,73 In one human pain experiment, subjects had a significant dose-dependent antinociception (increased finger withdrawal latency) effect that was not reversed by opioid antagonism. 31 In a somewhat contradictory manner, hyperalgesic activity and enhancement of the perception of pain on acute exposure in chronic users of marijuana was reported. 20 Experience with cancer pain revealed that 120 mg codeine and 20 mg delta-9-tetrahydrocannabinol (9-THC) were similar to each other and significantly superior to placebo for the sum of the pain intensity differences and total pain relief. 55,56 However, there was a clear dose-response relationship for sedation, mental clouding, and other central nervous system (CNS) related side effects f...

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Section: Discussionmentioning

confidence: 99%

A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

Wilsey

Marcotte

Tsodikov

et al. 2008

The Journal of Pain

272

244

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“…Nevertheless, SCI patients with chronic pain have reported substantial pain relief from marijuana, suggesting the possibility that cannabinoids may be of particular value as a treatment option for this indication (Cardenas and Jensen, 2006). As alluded to earlier, the somnolence and psychotropic side-effects associated with nonselective CB ligands may not appeal to all chronic pain patients (Campbell et al, 2001;Svendsen et al, 2004). These issues only highlight the need for a well characterized and selective ligand to directly answer the question of whether CB 1 receptor agonists can attenuate neuropathic pain in general and specifically, SCI pain.…”

Section: Effect Of Cannabinoid Antagonists On the Antinociceptive Effmentioning

confidence: 99%

“…A review of the clinical literature regarding the use of presently available nonselective CB ligands in chronic pain, including some types of neuropathic pain, suggests that their efficacy is no better than codeine (Attal et al, 2004;Campbell et al, 2001). Although other studies indicate efficacy in neuropathic pain, the analgesic effect of the drug may be due to a combination of non-CB as well as CB receptor activity (Karst et al, 2003).…”

Section: Effect Of Cannabinoid Antagonists On the Antinociceptive Effmentioning

confidence: 99%

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Antinociceptive effect of cannabinoid agonist WIN 55,212-2 in rats with a spinal cord injury

Hama

Sagen

2007

Experimental Neurology

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Spinal cord injury (SCI) pain exhibits many symptoms associated with peripheral neuropathic pain, including increased tactile hypersensitivity. One novel approach to ameliorate SCI pain is the use of cannabinoid (CB) ligands. The current study evaluated the efficacy of the nonselective CB receptor agonist WIN 55,212-2 on tactile hypersensitivity in rats following a brief compression to the thoracic spinal cord. The withdrawal thresholds of the hind paws following SCI were significantly decreased, indicating tactile hypersensitivity. Systemic injection of WIN 55,212-2 increased withdrawal thresholds in a dose-dependent manner. Pretreatment with the CB 1 receptor subtype-selective antagonist AM 251 completely abolished the antinociceptive effect of WIN 55,212-2 whereas pretreatment with the CB 2 receptor subtype-selective antagonist AM 630 did not alter the antinociceptive effect of WIN 55,212-2. These data indicate that a CB 1 selective agonist may be novel therapeutic treatment for clinical SCI pain. KeywordsAM 251; AM 630; allodynia; chronic pain; CB 1 receptor; neuropathic pain Trauma or disease to either the peripheral or central nervous system leads to persistent pain. There are few effective treatments for patients with chronic neuropathic pain. The cannabinoids show promise in alleviating peripheral neuropathic pain, which in turn, may have efficacy on central neuropathic pain states.Studies in rats indicate that the cannabinoid receptors (subtypes CB 1 and CB 2 ) have key roles in modulating pain, especially neuropathic pain. The CB 1 receptor has been identified in the rat dorsal root ganglia, spinal cord, and brain areas relevant to the processing of pain-related information (Farquhar-Smith et al., 2000;Hohmann et al., 1999;Tsou et al., 1998). There are numerous studies in rat models of peripheral neuropathic pain that demonstrate significant suppression of thermal and mechanical hypersensitivity with a non-selective CB receptor agonist, which is attenuated with a selective CB 1 receptor antagonist (Bridges et al., 2001;Fox et al., 2001;Herzberg et al., 1997;Pascual et al., 2005;Ulugol et al., 2004). However, a role for the CB 1 receptor in rats with central neuropathic pain caused by a spinal cord injury (SCI) has not been examined. The current study evaluated the effect of the non-selective CB receptor agonist WIN 55,212-2 in a rat model of neuropathic pain induced by compression of the spinal Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Gatley et al., 1996;Pertwee et al., 1995). NIH Public AccessSurgical and behavioral testing procedures were revi...

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“…1 However, the use of cannabis or cannabinoids in the treatment of acute pain in humans has not been as widely reported. 2 A previous clinical trial examined the acute postoperative analgesic effects of cannabinoids using im levonantradol, 3 a synthetic analogue of Δ 9 -tetrahydrocannabinol (Δ 9 -THC), the main psychoactive constituent of cannabis. 4 Since 1990, only three other clinical studies have evaluated the effects of cannabinoids in acute pain, two with human volunteers 5,6 and one in postsurgical patients.…”

Section: Résultats : Quarante Et Un Patients (Moyenne D'âge De 52 ± 2mentioning

confidence: 99%

Effects of nabilone, a synthetic cannabinoid, on postoperative pain

Beaulieu

2006

Can J Anesth/J Can Anesth

146

118

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Purpose:Cannabinoids have been shown to have analgesic properties in animal studies, but a potential role for these drugs in acute pain management has not been established. It was hypothesized that nabilone, an oral cannabinoid synthetic tetrahydrocannabinol analogue, decreases morphine consumption, pain scores, nausea and vomiting following major surgery. Methods:A double-blind, randomized, placebo-controlled, parallel-group pilot trial compared the effects of two different doses, 1 mg (n = 11) and 2 mg (n = 9) of nabilone, ketoprofen 50 mg (n = 11) or placebo (n = 10), given at eight-hour intervals for 24 hr. Outcomes included morphine consumption, pain scores and emesis after major surgery. Secondary outcomes included patient tolerability of the study medication.Results: Forty-one patients (mean age 52 ± 2 yr) undergoing gynecologic (46%), orthopedic (44%), or other (10%) surgery were recruited. Cumulative 24-hr morphine consumption was not different between the four groups, but pain scores at rest and on movement were significantly higher in the 2 mg nabilone group compared to the other groups. There were no significant differences between groups with respect to episodes of nausea and vomiting, quality of sleep, sedation, euphoria, pruritus, or the number and severity of adverse events. No serious adverse event was recorded.Conclusions: Contrary to the main hypothesis, high dose nabilone in the presence of morphine patient controlled analgesia is associated with an increase in pain scores in patients undergoing major surgery.

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Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review

Cited by 360 publications

References 28 publications

A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

Antinociceptive effect of cannabinoid agonist WIN 55,212-2 in rats with a spinal cord injury

Effects of nabilone, a synthetic cannabinoid, on postoperative pain

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