Psychopharmacology

, Volume 219, Issue 3, pp 859–873

Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Δ9-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive–compulsive behaviour

Authors

  • Serena Deiana
    • School of Medical Sciences, Institute of Medical SciencesUniversity of Aberdeen
  • Akihito Watanabe
    • School of Medical Sciences, Institute of Medical SciencesUniversity of Aberdeen
    • Qs’ Research InstituteOtsuka Pharmaceutical Co. Ltd
  • Yuki Yamasaki
    • School of Medical Sciences, Institute of Medical SciencesUniversity of Aberdeen
    • Qs’ Research InstituteOtsuka Pharmaceutical Co. Ltd
  • Naoki Amada
    • School of Medical Sciences, Institute of Medical SciencesUniversity of Aberdeen
    • Qs’ Research InstituteOtsuka Pharmaceutical Co. Ltd
  • Marlene Arthur
    • School of Medical Sciences, Institute of Medical SciencesUniversity of Aberdeen
  • Shona Fleming
    • School of Medical Sciences, Institute of Medical SciencesUniversity of Aberdeen
  • Hilary Woodcock
    • School of Medical Sciences, Institute of Medical SciencesUniversity of Aberdeen
  • Patricia Dorward
    • School of Medical Sciences, Institute of Medical SciencesUniversity of Aberdeen
  • Barbara Pigliacampo
    • School of Medical Sciences, Institute of Medical SciencesUniversity of Aberdeen
  • Steve Close
    • School of Medical Sciences, Institute of Medical SciencesUniversity of Aberdeen
  • Bettina Platt
    • School of Medical Sciences, Institute of Medical SciencesUniversity of Aberdeen
    • School of Medical Sciences, Institute of Medical SciencesUniversity of Aberdeen
Original Investigation

DOI: 10.1007/s00213-011-2415-0

Cite this article as:
Deiana, S., Watanabe, A., Yamasaki, Y. et al. Psychopharmacology (2012) 219: 859. doi:10.1007/s00213-011-2415-0

Abstract

Rationale

Phytocannabinoids are useful therapeutics for multiple applications including treatments of constipation, malaria, rheumatism, alleviation of intraocular pressure, emesis, anxiety and some neurological and neurodegenerative disorders. Consistent with these medicinal properties, extracted cannabinoids have recently gained much interest in research, and some are currently in advanced stages of clinical testing. Other constituents of Cannabis sativa, the hemp plant, however, remain relatively unexplored in vivo. These include cannabidiol (CBD), cannabidivarine (CBDV), Δ9-tetrahydrocannabivarin (Δ9-THCV) and cannabigerol (CBG).

Objectives and methods

We here determined pharmacokinetic profiles of the above phytocannabinoids after acute single-dose intraperitoneal and oral administration in mice and rats. The pharmacodynamic–pharmacokinetic relationship of CBD (120 mg/kg, ip and oral) was further assessed using a marble burying test in mice.

Results

All phytocannabinoids readily penetrated the blood–brain barrier and solutol, despite producing moderate behavioural anomalies, led to higher brain penetration than cremophor after oral, but not intraperitoneal exposure. In mice, cremophor-based intraperitoneal administration always attained higher plasma and brain concentrations, independent of substance given. In rats, oral administration offered higher brain concentrations for CBD (120 mg/kg) and CBDV (60 mg/kg), but not for Δ9-THCV (30 mg/kg) and CBG (120 mg/kg), for which the intraperitoneal route was more effective. CBD inhibited obsessive–compulsive behaviour in a time-dependent manner matching its pharmacokinetic profile.

Conclusions

These data provide important information on the brain and plasma exposure of new phytocannabinoids and guidance for the most efficacious administration route and time points for determination of drug effects under in vivo conditions.

Keywords

Phytocannabinoids Systemic administration Bioavailability Area under curve Elimination half-life Pharmacokinetic Pharmacodynamic Rats Mice

Copyright information

© Springer-Verlag 2011