The analgesic effect of oral delta-9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions
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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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”
From Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis (2017) · cites this paper as Naef 2003
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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
- ORCID
- Curatolo, Michele
- 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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