Cited by 209Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsPain Management and Opioid Use

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, Alex, Brenneisen, Rudolf·2003·Pain

Abstract

From folk medicine and anecdotal reports it is known that Cannabis may reduce pain. In animal studies it has been shown that delta-9-tetrahydrocannabinol (THC) has antinociceptive effects or potentiates the antinociceptive effect of morphine. The aim of this study was to measure the analgesic effect of THC, morphine, and a THC-morphine combination (THC-morphine) in humans using experimental pain models. THC (20 mg), morphine (30 mg), THC-morphine (20 mg THC+30 mg morphine), or placebo were given orally and as single doses. Twelve healthy volunteers were included in the randomized, placebo-controlled, double-blinded, crossover study. The experimental pain tests (order randomized) were heat, cold, pressure, single and repeated transcutaneous electrical stimulation. Additionally, reaction time, side-effects (visual analog scales), and vital functions were monitored. For the pharmacokinetic profiling, blood samples were collected. THC did not significantly reduce pain. In the cold and heat tests it even produced hyperalgesia, which was completely neutralized by THC-morphine. A slight additive analgesic effect could be observed for THC-morphine in the electrical stimulation test. No analgesic effect resulted in the pressure and heat test, neither with THC nor THC-morphine. Psychotropic and somatic side-effects (sleepiness, euphoria, anxiety, confusion, nausea, dizziness, etc.) were common, but usually mild.

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Crossref · 10.1016/s0304-3959(03)00163-5

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  • In Naef 2003, there was no significant analgesic effect of dronabinol or morphine-dronabinol combination on heat, pressure or cold tests; there was an additive effect of morphine on the transcutaneous electrical stimulation test; potentiation of analgesia was not observed.

    “No significant analgesic effect of dronabinol or morphine-dronabinol combination on heat, pressure or cold tests.Additive effect of morphine on transcutaneous electrical stimulation test Potentiation of analgesia not observed in this experimental pain study”

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Authors
Naef, M., Curatolo, M., Petersen-Felix, S., Arendt-Nielsen, L., Zbinden, A., & Brenneisen, R.
Affiliations
  • University of Bern (CH)
  • University Hospital of Bern (CH)
Corresponding author
Brenneisen, Rudolf
Venue
Pain
Published
2003-09
Volume
105
Issue
1
Pages
79-88
ISSN
0304-3959 (ISSN-L)
OpenAlex
W2091487276
Cited by
209
References
52
Citations by year
2026: 5 · 2025: 3 · 2024: 14 · 2023: 12 · 2022: 4 · 2021: 15 · 2020: 12 · 2019: 7 · 2018: 17 · 2017: 11 · 2016: 7 · 2015: 6 · 2014: 5 · 2013: 7 · 2012: 13
FWCI
6.36
Type
journal article
Language
en
Open access
closed
Locations
  • Pain (publishedVersion)
  • PubMed (publishedVersion)
  • VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
Funders
Novartis Foundation
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Keywords
delta-9-tetrahydrocannabinol, morphine, analgesia, experimental pain, antinociception, hyperalgesia, transcutaneous electrical stimulation, cannabis, opioid analgesics, adverse effects, pharmacokinetics
MeSH terms
Adult, Analgesics, Opioid, Cold Temperature, Double-Blind Method, Drug Combinations, Transcutaneous Electric Nerve Stimulation, Female, Hot Temperature, Humans, Male, Morphine, Pain, Palliative Care, Pressure, Dronabinol, Pain Threshold, Cross-Over Studies, Analgesics, Non-Narcotic

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