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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.
Psychopharmacology (Berl) 2012; 219(3):859-73P

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), Δ(9)-tetrahydrocannabivarin (Δ(9)-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 Δ(9)-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.

Authors+Show Affiliations

School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21796370

Citation

Deiana, Serena, et al. "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." Psychopharmacology, vol. 219, no. 3, 2012, pp. 859-73.
Deiana S, Watanabe A, Yamasaki Y, et al. 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. Psychopharmacology (Berl). 2012;219(3):859-73.
Deiana, S., Watanabe, A., Yamasaki, Y., Amada, N., Arthur, M., Fleming, S., ... Riedel, G. (2012). 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. Psychopharmacology, 219(3), pp. 859-73. doi:10.1007/s00213-011-2415-0.
Deiana S, et al. 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. Psychopharmacology (Berl). 2012;219(3):859-73. PubMed PMID: 21796370.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Deiana,Serena, AU - Watanabe,Akihito, AU - Yamasaki,Yuki, AU - Amada,Naoki, AU - Arthur,Marlene, AU - Fleming,Shona, AU - Woodcock,Hilary, AU - Dorward,Patricia, AU - Pigliacampo,Barbara, AU - Close,Steve, AU - Platt,Bettina, AU - Riedel,Gernot, Y1 - 2011/07/28/ PY - 2010/12/21/received PY - 2011/07/08/accepted PY - 2011/7/29/entrez PY - 2011/7/29/pubmed PY - 2012/9/25/medline SP - 859 EP - 73 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 219 IS - 3 N2 - 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), Δ(9)-tetrahydrocannabivarin (Δ(9)-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 Δ(9)-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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/21796370/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_ L2 - https://dx.doi.org/10.1007/s00213-011-2415-0 DB - PRIME DP - Unbound Medicine ER -