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

• Published in: Pain (Amsterdam) Vol. 105; no. 1; pp. 79 - 88
• Main Authors: Naef, Myrtha, Curatolo, Michele, Petersen-Felix, Steen, Arendt-Nielsen, Lars, Zbinden, Alex, Brenneisen, Rudolf
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.09.2003; Elsevier
• Subjects: Adult; Analgesics; Analgesics, Non-Narcotic - adverse effects; Analgesics, Non-Narcotic - blood; Analgesics, Non-Narcotic - therapeutic use; Analgesics, Opioid - adverse effects; Analgesics, Opioid - blood; Analgesics, Opioid - therapeutic use; Antinociception; Biological and medical sciences; Cold Temperature; Cross-Over Studies; Delta-9-tetrahydrocannabinol; Double-Blind Method; Dronabinol - adverse effects; Dronabinol - blood; Dronabinol - therapeutic use; Drug Combinations; Experimental pain; Female; Hot Temperature; Humans; Male; Medical sciences; Morphine; Morphine - adverse effects; Morphine - blood; Morphine - therapeutic use; Neuropharmacology; Pain - drug therapy; Pain - etiology; Pain - physiopathology; Pain Threshold; Palliative Care; Pharmacokinetics; Pharmacology. Drug treatments; Plasma levels; Pressure; Transcutaneous Electric Nerve Stimulation; Experimental pain; Delta-9-tetrahydrocannabinol; Morphine; Antinociception; Plasma levels; Pharmacokinetics; Human; Affect affectivity; Psychotropic; Antinociception: Plasma levels; Opiates; Cannabidaceae; Transcutaneous stimulation; Hyperalgesia; Analgesia; Cannabis; Analgesic; Pain; Treatment; Folk medicine; Dicotyledones; Angiospermae; Double blind study; Reaction time; Spermatophyta; Anxiety
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/S0304-3959(03)00163-5

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.