Abstract
Objective
To investigate the effect of cannabidiol (CBD) on sevoflurane minimum alveolar concentration
(MACSEV) reduction produced by morphine in rats.
Study design
Randomized, blinded trial.
Animals
A total of 75 male Wistar Han rats weighing 276 ± 23 g (mean and standard deviation),
aged 3 months.
Methods
Cannabidiol (CBD) was prepared in an ethanol-solutol-saline vehicle. Animals were
randomly divided into 15 groups and given an intraperitoneal bolus of 1, 3, 5, 6.5,
7.5 or 10 mg kg−1 of CBD alone (CBD1, CBD3, CBD5, CBD6.5, CBD7.5 and CBD10 respectively) or combined
with 5 mg kg−1 of morphine (MOR+CBD1, MOR+CBD3, MOR+CBD5, MOR+CBD6.5, MOR+CBD7.5 and MOR+CBD10).
While three controls groups: MOR+saline, MOR+vehicle and vehicle were given an intraperitoneal
bolus of morphine with saline, morphine with vehicle or vehicle alone respectively.
The MACSEV was determined from alveolar gas samples at the time of tail clamp application. The
MACSEV reduction was analyzed using a one-way ANOVA followed by Tukey’s test. Additionally,
Kruskal-Wallis test for non-normally-distributed data was performed. Data are presented
as mean ± standard deviation. P < 0.05
Results
The mean MACSEV was not reduced by the action of CBD administered alone, but the addition of morphine
to the different doses of CBD significantly reduced the MACSEV. That reduction was greatest in the MOR+CBD1, MOR+CBD7.5 and MOR+CBD10 groups (29
± 5%, 32 ± 5% and 30 ± 6% respectively), less in MOR+CBD3 and MOR+CBD6.5 groups (24
± 3% and 26 ± 4% respectively) and least in MOR+CBD5 group (17 ± 2%). However, only
the MOR+CBD5 group was statistically significantly different from MOR+CBD1, MOR+CBD7.5
and MOR+CBD10 groups.
Conclusions and clinical relevance
MACSEV in rat was unaltered by the action of CBD alone, the reduction in MACSEV produced by morphine was not enhanced by the addition of CBD at the doses studied.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Veterinary Anaesthesia and AnalgesiaAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Reduction of the sevoflurane minimum alveolar concentration induced by methadone, tramadol, butorphanol and morphine in rats.Lab Anim. 2012; 46: 200-206
- Direct inhibition by cannabinoids of human 5-HT3A receptors: probable involvement of an allosteric modulatory site.Br J Pharmacol. 2002; 137: 589-596
- Positive allosteric modulators of the opioid receptor: a novel approach for future pain medications.Br J Pharmacol. 2015; 172: 277-286
- Central nervous system effects of acetate: contribution to the central effects of ethanol.J Pharmacol Exp Ther. 1991; 259: 403-408
- Synergistic interactions between cannabinoid and opioid analgesics.Life Sci. 2004; 74: 1317-1324
- Reduction of isoflurane MAC with buprenorphine and morphine in rats.Lab Anim. 2000; 34: 252-259
- Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Delta(9)-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour.Psychopharmacology. 2012; 219: 859-873
- Opioids and cannabinoids interactions: involvement in pain management.Curr Drug Targets. 2010; 11: 462-473
- Women appear to have the same minimum alveolar concentration as men: a retrospective study.Anesthesiology. 2003; 99: 1059-1061
- Implications of experimental technique for analysis and interpretation of data from animal experiments: outliers and increased variability resulting from failure of intraperitoneal injection procedures.Lab Anim. 2007; 41: 312-320
- Cannabidiol is a potential therapeutic for the affective-motivational dimension of incisión pain in rats.Front Pharmacol. 2017; 8: 391https://doi.org/10.3389/fphar.2017.00391.eCollection2017
- Cannabidiol and endogenous opioid peptide-mediated mechanisms modulate antinociception induced by transcutaneous electrostimulation of the peripheral nervous system.J Neurol Sci. 2014; 347: 82-89
- Disposition and analgesic effects of systemic morphine, morphine-6-glucuronide and normorphine in rat.Pharmacol Toxicol. 1996; 79: 40-46
- Intraoperative use of opioids.in: Stein C. Opioids in pain control: basic and clinical aspects. Cambridge University Press, New York1999: 234-246
- First-pass effect of morphine in rats.J Pharmacol Exp Ther. 1977; 203: 365-376
- Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors.Naunyn Schmiedebergs Arch Pharmacol. 2006; 372: 354-361
- US Veterinarians’ knowledge, experience, and perception regarding the use of cannabidiol for canine medical conditions.Front Vet Sci. 2019; 5: 338https://doi.org/10.3389/fvets.2018.00338eCollection2018
- Cannabinoids: a new approach for pain control?.Curr Opin Oncol. 2019; 31: 275-279
- Effect of age on MAC in humans: a meta-analysis.Br J Anaesth. 1996; 76: 179-185
- Cannabidiol: an overview of some pharmacological aspects.J Clin Pharmacol. 2002; 42: 11S-19S
- An analgesic circuit activated by cannabinoids.Nature. 1998; 395: 381-383
- CB(2) cannabinoid receptor antagonist SR144528 decreases mu-opioid receptor expression and activation in mouse brainstem: Role of CB(2) receptor in pain.Neurochem Int. 2008; 53: 309-316
- Cannabidiol administration after hypoxia-ischemia to newborn rats reduces long-term brain injury and restores neurobehavioral function.Neuropharmacology. 2012; 63: 776-783
- Determination and applications of MAC.Anesthesiology. 1980; 53: 315-334
- Large concentrations of nitrous oxide decrease the isoflurane minimum alveolar concentration sparing effect of morphine in the rat.Anesth Analg. 2005; 100: 404-408
- The blood count and body temperature in normal rats.J Physiol. 1926; 61: 329-336
- Effects of delta-9-tetrahydrocannabinol on halothane MAC in dogs.Anesthesiology. 1973; 38: 521-524
- A review of morphine and morphine-6-glucuronide’s pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain.Eur J Pharm Sci. 2015; 74: 45-62
- Effect of arterial hypotension on anaesthetic requirement in dogs.Br J Anaesth. 1976; 48: 947-951
- Modulation of rat brain opioid receptors by cannabinoids.J Pharmacol Exp Ther. 1987; 241: 534-539
- Molecular and cellular basis of cannabinoid and opioid interactions.Pharmacol Biochem Behav. 2005; 81: 360-368
- Effects of delta-9-tetrahydrocannabinol on cyclopropane MAC in the rat.Anesthesiology. 1973; 38: 525-527
- The effect of hyperoxia on cerebral blood flow: a study in healthy volunteers using magnetic resonance phase-contrast angiography.Eur J Anaesthesiol. 2000; 17: 152-159
- A simplified method for endotracheal intubation in the rat.Eur J Appl Physiol. 1994; 76: 1823-1825
- Hypothermia decreases ethanol MAC in rats.J Anesth. 2006; 20: 247-250
Article info
Publication history
Published online: October 15, 2020
Accepted:
April 5,
2020
Received:
April 4,
2019
Identification
Copyright
© 2020 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.
