| Title |
Enhanced Brain Disposition and Effects of Δ9-Tetrahydrocannabinol in P-Glycoprotein and Breast Cancer Resistance Protein Knockout Mice
|
|---|---|
| Published in |
PLOS ONE, April 2012
|
| DOI | 10.1371/journal.pone.0035937 |
| Pubmed ID | |
| Authors |
Adena S. Spiro, Alexander Wong, Aurélie A. Boucher, Jonathon C. Arnold |
| Abstract |
The ABC transporters P-glycoprotein (P-gp, Abcb1) and breast cancer resistance protein (Bcrp, Abcg2) regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ(9)-tetrahydrocannabinol (THC) has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT) mice. Abcb1a/b (-/-), Abcg2 (-/-) and wild-type (WT) mice were injected with THC before brain and blood were collected and THC concentrations determined. Another cohort of mice was examined for THC-induced hypothermia by measuring rectal body temperature. Brain THC concentrations were higher in both Abcb1a/b (-/-) and Abcg2 (-/-) mice than WT mice. ABC transporter knockout mice exhibited delayed elimination of THC from the brain with the effect being more prominent in Abcg2 (-/-) mice. ABC transporter knockout mice were more sensitive to THC-induced hypothermia compared to WT mice. These results show P-gp and Bcrp prolong the brain disposition and hypothermic effects of THC and offer a novel mechanism for both genetic vulnerability to the psychoactive effects of cannabis and drug interactions between CNS therapies and cannabis. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Egypt | 1 | 33% |
| Montenegro | 1 | 33% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 33% |
| Practitioners (doctors, other healthcare professionals) | 1 | 33% |
| Science communicators (journalists, bloggers, editors) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 2% |
| Unknown | 60 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 9 | 15% |
| Student > Bachelor | 9 | 15% |
| Student > Ph. D. Student | 8 | 13% |
| Student > Master | 7 | 11% |
| Other | 4 | 7% |
| Other | 11 | 18% |
| Unknown | 13 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 18% |
| Pharmacology, Toxicology and Pharmaceutical Science | 9 | 15% |
| Agricultural and Biological Sciences | 9 | 15% |
| Biochemistry, Genetics and Molecular Biology | 6 | 10% |
| Neuroscience | 4 | 7% |
| Other | 6 | 10% |
| Unknown | 16 | 26% |