Reintoxication: the release of fat-stored delta(9)-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure.
Nathan Gunasekaran, L E Long, B L Dawson, G H Hansen, D P Richardson, K M Li, Jonathon C Arnold, Iain S. Mcgregor
British Journal of Pharmacology November 2009 DOI: 10.1111/j.1476-5381.2009.00399.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study (in vitro and in vivo experiments) Peer reviewed |
|---|---|
| Population | Rats and freshly isolated rat adipocytes |
| Interventions | Delta(9)-tetrahydrocannabinol (THC) adrenocorticotrophic hormone (ACTH) food deprivation |
| Dose | 10 mg.kg(-1) THC for 10 consecutive days |
| Duration | 10 consecutive days of THC injections; 24 h food deprivation |
| Topics | Cannabis |
| Key findings | Lipolysis triggered by ACTH or food deprivation released stored THC from fat cells and raised blood levels of THC and its metabolite THC-COOH in rats repeatedly injected with THC. The authors propose this indicates a possible 'reintoxication' mechanism whereby stress or fasting could raise blood THC in chronically exposed animals, but they state further research is needed to confirm functional consequences. |
Abstract
Delta(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in adipose tissue where it is stored for long periods of time. Here we investigated whether conditions that promote lipolysis can liberate THC from adipocytes to yield increased blood levels of THC. In vitro studies involved freshly isolated rat adipocytes that were incubated with THC before exposure to the lipolytic agent adrenocorticotrophic hormone (ACTH). A complementary in vivo approach examined the effects of both food deprivation and ACTH on blood levels of THC in rats that had been repeatedly injected with THC (10 mg.kg(-1)) for 10 consecutive days. Lipolysis promoted by ACTH or food deprivation was indexed by measurement of glycerol levels. ACTH increased THC levels in the medium of THC-pretreated adipocytes in vitro. ACTH also enhanced THC release from adipocytes in vitro when taken from rats repeatedly pretreated with THC in vivo. Finally, in vivo ACTH exposure and 24 h food deprivation both enhanced the levels of THC and its metabolite, (-)-11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) in the blood of rats that had been pre-exposed to repeated THC injections. The present study shows that lipolysis enhances the release of THC from fat stores back into blood. This suggests the likelihood of 'reintoxication' whereby food deprivation or stress may raise blood THC levels in animals chronically exposed to the drug. Further research will need to confirm whether this can lead to functional effects, such as impaired cognitive function or 'flashbacks'.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 5
- Does acute stress induced via cold water immersion increase blood THC concentrations in regular cannabis users? Psychopharmacology December 2025
- Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol. ACS Chemical Neuroscience May 15, 2019
- Selective effects of Δ9-tetrahydrocannabinol on medium spiny neurons in the striatum. PLoS One 2018
- The Differential Binding of Antipsychotic Drugs to the ABC Transporter P-Glycoprotein Predicts Cannabinoid-Antipsychotic Drug Interactions. Neuropsychopharmacology October 2017
- Cannabidiol potentiates Δ⁹-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats. Psychopharmacology November 2011