Related Experiment Video
Updated: Jun 4, 2025

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Morphine-induced side effects can be differentially modulated by cannabidiol in male and female rats
Carlos Henrique Alves Jesus1, Jaqueline Volpe2, Bruna Bittencourt Sotomaior1
1Department of Pharmacology, Biological Sciences Sector, Federal University of Paraná.
Abstract:
Opioid use disorder is a public health problem that includes symptoms such as withdrawal syndrome and opioid-induced hyperalgesia. Currently, drugs to treat side effects of opioids also have undesirable effects, which lead to limitations. This study investigated the effect of a treatment with cannabidiol in morphine-induced hyperalgesia and withdrawal behavior in morphine-dependent rats. Male and female rats were submitted to a morphine-induced physical dependence protocol consisting of a twice daily treatment with morphine (filtered solution, dose of 7.89 mg/kg, 1 ml/kg, s.c.) for 10 days. Nociception was measured using the hot plate test and morphine-induced thermal hyperalgesia was equally achieved following 7-10 days of morphine administration in male and female rats. Repeated treatment with cannabidiol (30 mg/kg) was sufficient to prevent thermal hyperalgesia in male and female rats. Subsequently, rats received an acute administration of naloxone (2 mg/kg. s.c.), 90 min after the morphine treatment on day 11, the number of withdrawal behaviors was scored. Rats that received treatment exclusively with morphine presented significant withdrawal behaviors compared to control (Water). Morphine-dependent female rats showed a prevalent stereotyped behavior of rearing, whereas male rats had teeth chattering behavior as the most preeminent. Treatment with cannabidiol on day 11 partially attenuated withdrawal behavior in morphine-dependent male rats, with mild effects in female rats (high withdrawal responders only). Altogether, our data provide evidence of an anti-hyperalgesic effect of cannabidiol in rats. Male and female rats treated chronically with morphine exhibited withdrawal behaviors in different ratios, and cannabidiol treatment attenuated withdrawal behavior in a sex-dependent manner.
Related Concept Videos
Chemotherapy-Induced Nausea and Vomiting: Cannabinoids
Two synthetic agonists of THC,...
Analgesia and Pain Management
Opioid Analgesics: Synthetic and Semisynthetic Opioids
Opioid Receptors: Overview
CNS Stimulants: Cocaine, Amphetamines and Cannabinoids
Opioid Analgesics: Morphine and Other Natural Cogeners

