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Evaluation of the analgesic efficacy and psychoactive effects of AZD 1940, a novel peripherally acting cannabinoid agonist, in human capsaicin‐induced pain and hyperalgesia
Author(s) -
Kalliomäki Jarkko,
Annas Peter,
Huizar Karin,
Clarke Cyril,
Zettergren Annika,
Karlsten Rolf,
Segerdahl Märta
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12051
Subject(s) - medicine , hyperalgesia , capsaicin , analgesic , allodynia , placebo , anesthesia , agonist , visual analogue scale , cannabinoid , pharmacology , nociception , receptor , alternative medicine , pathology
Summary The aim of the present study was to investigate the effects of AZD 1940, a novel peripherally acting cannabinoid CB 1 / CB 2 receptor agonist, on capsaicin‐induced pain and hyperalgesia, as well as on biomarkers of cannabinoid central nervous system ( CNS ) effects. The present study was a randomized, double‐blind, placebo‐controlled, four‐sequence, two‐period, cross‐over study in 44 male healthy volunteers aged 20–45 years. The effects of two single oral doses of AZD 1940 (400 and 800 μg) were compared with placebo. Pain intensity after intradermal capsaicin injections in the forearm was assessed on a continuous visual analogue scale ( VAS ; 0–100 mm). Primary and secondary hyperalgesia induced by application of capsaicin cream on the calf were assessed by measuring heat pain thresholds and the area of mechanical allodynia, respectively. The CNS effects were assessed at baseline and up to 24 h after dosing using a visual analogue mood scales ( VAMS ) for feeling ‘stimulated’, ‘high’, ‘anxious’, ‘sedated’ or ‘down’. AZD 1940 did not significantly attenuate ongoing pain or primary or secondary hyperalgesia compared with placebo. Mild CNS effects for AZD 1940were observed on the VAMS for ‘high’ and ‘sedated’. Dose‐dependent mild‐to‐moderate CNS ‐related and gastrointestinal adverse events were reported following treatment with AZD 1940. No evidence of analgesic efficacy was found for a peripherally acting CB 1 / CB 2 receptor agonist in the human capsaicin pain model. The emergence of mild dose‐dependent CNS effects suggests that the dose range predicted from preclinical data had been attained.