Download PDF
Planta Med 2018; 84(04): 221-224
DOI: 10.1055/s-0043-117838
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Effects of Cannabidiol on Morphine Conditioned Place Preference in Mice

James Roland Markos
1   Department of Psychology, University of Mississippi, University, MS, USA
,
Hannah M. Harris
1   Department of Psychology, University of Mississippi, University, MS, USA
,
Waseem Gul
2   Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS, USA
4   ElSohly Laboratories Inc., Oxford, MS, USA
,
Mahmoud A. ElSohly
2   Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS, USA
3   Department of BioMolecular Science, University of Mississippi, University, MS, USA
4   ElSohly Laboratories Inc., Oxford, MS, USA
,
Kenneth J. Sufka
1   Department of Psychology, University of Mississippi, University, MS, USA
2   Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS, USA
› Author Affiliations
Further Information

Publication History

received 19 April 2017
revised 11 July 2017

accepted 25 July 2017

Publication Date:
09 August 2017 (online)

Also available at
    Permissions and Reprints

Abstract

This study sought to determine whether the cannabis constituent cannabidiol attenuates the development of morphine reward in the conditioned place preference paradigm. Separate groups of mice received either saline or morphine in combination with one of four doses of cannabidiol using three sets of drug/no-drug conditioning trials. After drug-place conditioning, morphine mice displayed robust place preference that was attenuated by 10 mg/kg cannabidiol. Further, when administered alone, this dose of cannabidiol was void of rewarding and aversive properties. The finding that cannabidiol blocks opioid reward suggests that this compound may be useful in addiction treatment settings.

Key words

Cannabaceae - Cannabis sativa - abuse deterrent - cannabidiol - conditioned place preference - opioid addiction
 

  • References

  • 1 Dart RC, Surratt HL, Cicero TJ, Parrino MW, Severtson SG, Bucher-Bartelson B, Green JL. Trends in opioid analgesic abuse and mortality in the United States. N Engl J Med 2015; 372: 241-248
    CrossrefPubMedGoogle Scholar
  • 2 Kalso E, Edwards JE, Moore AR, Mcquay J. Opioids in chronic non-cancer pain: Systematic review of efficacy and safety. Pain 2004; 112: 372-380
    CrossrefPubMedGoogle Scholar
  • 3 Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, Glaser S, Vallejo R. Opioid complications and side effects. Pain Physician 2008; 11: S105-S120
    CrossrefPubMedGoogle Scholar
  • 4 Højsted J, Sjøgren P. Addiction to opioids in chronic pain patients: a literature review. Eur J Pain 2007; 11: 490-518
    CrossrefPubMedGoogle Scholar
  • 5 Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths – United States, 2010–2015. MMWR Morb Mortal Wkly Rep 2016; 65: 1445-1452
    CrossrefPubMedGoogle Scholar
  • 6 Jayawant S, Balkrishnan R. The controversy surrounding OxyContin abuse: issues and solutions. Thera Clin Risk Manag 2005; 1: 77-82
    PubMedGoogle Scholar
  • 7 Cicero TJ, Ellis MS. Abuse-deterrent formulations and the prescription opioid abuse epidemic in the United States: lessons learned from OxyContin. JAMA Psychiatry 2015; 72: 424-430
    CrossrefPubMedGoogle Scholar
  • 8 Schneider J, Matthews M, Jamison RN. Abuse-deterrent and tamper-resistant opioid formulations: what is their role in addressing prescription opioid abuse?. CNS Drugs 2010; 24: 805-810
    CrossrefPubMedGoogle Scholar
  • 9 Simon K, Worthy M, Barnes M, Tarbell B. Abuse-deterrent formulations: transitioning the pharmaceutical market to improve public health and safety. Ther Adv Drug Saf 2015; 6: 1-13
    PubMedGoogle Scholar
  • 10 Carroll F, Carlezon W. Development of kappa opioid receptor antagonists. J Med Chem 2013; 56: 2178-2195
    CrossrefPubMedGoogle Scholar
  • 11 Parker L, Burton P, Sorge R, Yakiwchuk C, Mechoulam R. Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. Psychopharmachology 2004; 175: 360-366
    PubMedGoogle Scholar
  • 12 Katsidoni V, Anagnostou I, Panagis G. Cannabidiol inhibits the reward-facilitating effect of morphine: involvement of 5-HT1A receptors in the dorsal raphe nucleus. Addict Biol 2013; 18: 286-296
    CrossrefPubMedGoogle Scholar
  • 13 Tzschentke TM. Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Prog Neurobiol 1998; 56: 613-672
    CrossrefPubMedGoogle Scholar
  • 14 Parker L, Tomlinson T, Horn D, Erb SM. Relative strength of place conditioning produced by cocaine and morphine assessed in a three-choice paradigm. Learn Motiv 1994; 25: 83-94
    CrossrefPubMedGoogle Scholar
  • 15 Gaiardi M, Bartoletti M, Gubellini C, Bacchi A, Babbini M. Modulation of the stimulus effects of morphine by d-amphetamine. Pharmacol Biochem Behav 1998; 59: 249-253
    CrossrefPubMedGoogle Scholar
  • 16 Hand T, Stinus L, Le Moal M. Differential mechanisms in the acquisition and expression of heroin-induced place preference. Psychopharmacology (Berl) 1989; 98: 61-67
    CrossrefPubMedGoogle Scholar
  • 17 Tierney C, Nadaud D, Koenig-Berard E, Stinus L. Effects of two alpha 2 agonists, rilmenidine and clonidine, on the morphine withdrawal syndrome and their potential addictive properties in rats. Am J Cardiol 1988; 61: 35D-38D
    CrossrefPubMedGoogle Scholar
  • 18 Finlay J, Jakubovic A, Phillips A, Fibiger H. Fentanyl-induced conditional place preference: lack of associated conditional neurochemical events. Psychopharmacology (Berl) 1988; 96: 534-540
    CrossrefPubMedGoogle Scholar
  • 19 Pchelintsev M, Gorbacheva E, Zvartau E. Simple methodology of assessment of analgesicsʼ addictive potential in mice. Pharmacol Biochem Behav 1991; 39: 873-876
    CrossrefPubMedGoogle Scholar
  • 20 Morgan CJA, Schafer G, Freeman TP, Curran HV. Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study. Br J Psychiatry 2010; 197: 285-290
    CrossrefPubMedGoogle Scholar
  • 21 Mechoulam R, Parker L, Gallily R. Cannabidiol: an overview of some pharmacological aspects. J Clin Pharmacol 2002; 42: 11S-19S
    CrossrefPubMedGoogle Scholar
  • 22 Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus L. Cannabidiol – recent advances. Chem Biodivers 2007; 4: 1678-1692
    CrossrefPubMedGoogle Scholar
  • 23 Hurd YL, Yoon M, Manini AF, Hernandez S, Olmedo R, Ostman M, Jutras-Aswad D. Early phase in the development of cannabidiol as a treatment for addiction: opioid relapse takes initial center stage. Neurotherapeutics 2015; 12: 807-815
    CrossrefPubMedGoogle Scholar
  • 24 Townsend EA, Naylor JE, Negus SS, Edwards SR, Qureshi HN, McLendon HW, McCurdy CR, Kapanda CN, do Carmo JM, da Silva FS, Hall JE, Sufka KJ, Freeman KB. Effects of nalfurafine on the reinforcing, thermal antinociception, and respiratory-depressant effects of oxycodone: modeling an abuse-deterrent opioid analgesic in rats. Psychopharmacol 2017; DOI: 10.1007/s00213-017-4652-3.
    PubMedGoogle Scholar
  • 25 Neelakantan H, Tallarida RJ, Reichenbach ZW, Tuma F, Ward SJ, Walker EA. Distinct interactions of cannabidiol and morphine in three nociceptive behavioral models in mice. Behav Pharmacol 2015; 26: 304-314
    CrossrefPubMedGoogle Scholar