The analgesic effect of oral delta-9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions

Naef, Myrtha; Curatolo, Michele; Petersen-Felix, Steen; Arendt-Nielsen, Lars; Zbinden, A. M.; Brenneisen, Rudolf

doi:10.1016/s0304-3959(03)00163-5

Cited by 189 publications

(174 citation statements)

References 40 publications

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“…Furthermore, the analgesic effects of oral THC, morphine or their combination were reported in healthy subjects under experimental pain conditions in a randomized, placebo-controlled, double-blind, cross-over study involving 12 healthy cannabis-naïve volunteers. 6 Each subject received orally either 20 mg THC (dronabinol), 30 mg morphine, a mixture of 20 mg THC and 30 mg morphine or placebo as a single dose. In a heat test, neither morphine nor THC produced an analgesic effect.…”

Section: Discussionmentioning

confidence: 99%

“…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. 7 The results of these trials were disappointing, as cannabinoids were no more effective than placebo in relieving pain.…”

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

confidence: 99%

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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: 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

144

118

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“…In contrast, no synergistic or additive antinociceptive interaction has been detected between D 9 -THC and the m-opioid receptor agonist, piritramide, in patients suffering from acute post-operative pain [95] or between D 9 -THC and morphine in human volunteers subjected to noxious electrical or thermal stimulation of the skin or to painful digital pressure [96,97]. However, together (but not separately), these drugs did reduce the affective response to cutaneous thermal stimulation [97].…”

Section: Potential Adjunctive Strategies For Cannabinoid Receptor Actmentioning

confidence: 95%

Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities

Pertwee

2012

Phil. Trans. R. Soc. B

311

269

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Human tissues express cannabinoid CB 1 and CB 2 receptors that can be activated by endogenously released 'endocannabinoids' or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB 1 /CB 2 receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; D 9 -tetrahydrocannabinol (D 9 -THC)) and Sativex (D 9 -THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB 2 receptors, and/or (v) adjunctive 'multi-targeting'.

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“…Morphine is generally effective towards pain from many different stimulus modalities [37,51,81,94,95]. However, the results are not as clear-cut as seen with alfentanil and this could be due to the complex pharmacokinetic profile of morphine.…”

Section: Figurementioning

confidence: 99%

Assessing analgesic actions of opioids by experimental pain models in healthy volunteers – an updated review

Staahl

Olesen

Andresen

et al. 2009

Brit J Clinical Pharma

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111

131

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AIMExperimental pain models may help to evaluate the mechanisms of action of analgesics and target the clinical indications for their use. This review addresses how the efficacy of opioids can be assessed in human volunteers using experimental pain models. The drawback with the different study designs is also discussed. METHODA literature search was completed for randomized controlled studies which included human experimental pain models, healthy volunteers and opioids. RESULTSOpioids with a strong affinity for the m-opioid receptor decreased the sensation in a variety of experimental pain modalities, but strong tonic pain was attenuated more than short lasting pain and non-painful sensations. The effects of opioids with weaker affinity for the m-opioid receptor were detected by a more narrow range of pain models, and the assessment methods needed to be more sensitive. CONCLUSIONThe way the pain is induced, assessed and summarized is very important for the sensitivity of the pain models. This review gives an overview of how different opioids perform in experimental pain models. Generally experimental pain models need to be designed with careful consideration of pharmacological mechanisms and pharmacokinetics of analgesics. This knowledge can aid the decisions needed to be taken when designing experimental pain studies for compounds entering phase 1 clinical trials.

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The analgesic effect of oral delta-9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions

Cited by 189 publications

References 40 publications

Effects of nabilone, a synthetic cannabinoid, on postoperative pain

Effects of nabilone, a synthetic cannabinoid, on postoperative pain

Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities

Assessing analgesic actions of opioids by experimental pain models in healthy volunteers – an updated review

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