Evaluation of Intramuscular Levonantradol and Placebo in Acute Postoperative Pain

Jain, Adesh; Ryan, Jerome R.; McMahon, F. Gilbert; Smith, Gladys

doi:10.1002/j.1552-4604.1981.tb02610.x

Cited by 138 publications

(108 citation statements)

References 4 publications

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“…Significant pain relief was obtained with levonantradol, but commonly associated with drowsiness. 3 In 2002, Greenwald et al reported the acute antinociceptive properties of inhaled cannabis in recreational drug users. 5 Only five male volunteers completed the study which consisted of three test sessions during which they smoked cigarettes containing 0% (placebo) and 3.55% THC (active).…”

Section: Discussionmentioning

confidence: 99%

“…Despite these challenges, we were able to recruit similar numbers of subjects compared to other studies evaluating cannabinoids for postoperative analgesia. 3,7 Furthermore, in these studies, patients received only one dose of study medication compared to three doses in the present study. A practical concern is the use of oral medications during the early postoperative period which may be associated with poor patient tolerance.…”

Section: Limitationsmentioning

confidence: 97%

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Effects of nabilone, a synthetic cannabinoid, on postoperative pain

Beaulieu

2006

Can J Anesth/J Can Anesth

144

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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Section: Discussionmentioning

confidence: 99%

Section: Limitationsmentioning

confidence: 97%

Effects of nabilone, a synthetic cannabinoid, on postoperative pain

Beaulieu

2006

Can J Anesth/J Can Anesth

144

118

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“…In brief, there were contradictory findings in human studies on pain, with some research suggesting that THC relieved cancer pain about as well as 60 mg of codeine [56,57] and that levonantrodol, a synthetic THC-like cannabinoid was effective in post-operative and trauma pain [58]. On the other hand, Raft et al [59] found no effect of THC on the pain of tooth extraction, and Clark et al [60] found some suggestion that moderate to high doses of THC actually produced hyperalgesia.…”

Section: Results Of Earlier Research With Cannabis Thc and Its Syntmentioning

confidence: 99%

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

Grant

Cahn

2005

Clinical Neuroscience Research

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The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol exert some of their effect through binding specific cannabinoid receptor sites has led to the discovery of an endocannabinoid signaling system, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis on the one hand, while opening the possibility of developing novel therapeutic agents on the other. This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well; CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation. This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control.

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“…It has been used in clinical trials to palliate postoperative pain or pain due to trauma and has shown more analgesic efficacy than placebo [70]. Levonantradol causes adverse effects more often than THC in many patients, but none of them is considered serious.…”

Section: Therapeutic Uses Of Cannabinoids In Pain Episodesmentioning

confidence: 99%

Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes

Manzanares¹,

Julián²,

Carrascosa

2006

231

148

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Cannabis extracts and synthetic cannabinoids are still widely considered illegal substances. Preclinical and clinical studies have suggested that they may result useful to treat diverse diseases, including those related with acute or chronic pain. The discovery of cannabinoid receptors, their endogenous ligands, and the machinery for the synthesis, transport, and degradation of these retrograde messengers, has equipped us with neurochemical tools for novel drug design. Agonist-activated cannabinoid receptors, modulate nociceptive thresholds, inhibit release of pro-inflammatory molecules, and display synergistic effects with other systems that influence analgesia, especially the endogenous opioid system. Cannabinoid receptor agonists have shown therapeutic value against inflammatory and neuropathic pains, conditions that are often refractory to therapy. Although the psychoactive effects of these substances have limited clinical progress to study cannabinoid actions in pain mechanisms, preclinical research is progressing rapidly. For example, CB 1 -mediated suppression of mast cell activation responses, CB 2 -mediated indirect stimulation of opioid receptors located in primary afferent pathways, and the discovery of inhibitors for either the transporters or the enzymes degrading endocannabinoids, are recent findings that suggest new therapeutic approaches to avoid central nervous system side effects. In this review, we will examine promising indications of cannabinoid receptor agonists to alleviate acute and chronic pain episodes. Recently, Cannabis sativa extracts, containing known doses of tetrahydrocannabinol and cannabidiol, have granted approval in Canada for the relief of neuropathic pain in multiple sclerosis. Further double-blind placebo-controlled clinical trials are needed to evaluate the potential therapeutic effectiveness of various cannabinoid agonists-based medications for controlling different types of pain.

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Evaluation of Intramuscular Levonantradol and Placebo in Acute Postoperative Pain

Cited by 138 publications

References 4 publications

Effects of nabilone, a synthetic cannabinoid, on postoperative pain

Effects of nabilone, a synthetic cannabinoid, on postoperative pain

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes

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