THC and CBD blood and brain concentrations following daily administration to adolescent primates

S L Withey; J Bergman; M A Huestis; S R George; B K Madras

doi:10.1016/j.drugalcdep.2020.108129

THC and CBD blood and brain concentrations following daily administration to adolescent primates

Drug Alcohol Depend. 2020 Aug 1:213:108129. doi: 10.1016/j.drugalcdep.2020.108129. Epub 2020 Jun 18.

Authors

S L Withey¹, J Bergman², M A Huestis³, S R George⁴, B K Madras⁵

Affiliations

¹ Laboratory of Addiction Neurobiology, McLean Hospital, 115 Mill St, Belmont, MA, 02478, USA; Department of Psychiatry, Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
² Behavioral Biology Program, McLean Hospital, 115 Mill St, Belmont, MA, 02478, USA; Department of Psychiatry, Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
³ Institute of Emerging Health Professions, Thomas Jefferson University, 130 S. 9th Street, Philadelphia, PA, 19107, USA.
⁴ Department of Pharmacology, University of Toronto, Toronto, ON, M5S 1A8, Canada; Department of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
⁵ Laboratory of Addiction Neurobiology, McLean Hospital, 115 Mill St, Belmont, MA, 02478, USA; Department of Psychiatry, Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA. Electronic address: bertha_madras@hms.harvard.edu.

Abstract

Background: Cannabis availability with high concentrations of Δ-9-tetrahydrocannabinol (THC) and a range of THC to cannabidiol (CBD) ratios has increased in parallel with a rise in daily cannabis consumption by adolescents. Unanswered questions in adolescents include: 1) whether THC blood concentrations and THC metabolites remain stable or change with prolonged daily dosing, 2) whether CBD modulates THC pharmacokinetic properties and alters THC accumulation in brain, 3) whether blood THC levels reflect brain concentrations.

Methods: In adolescent squirrel monkeys (Saimiri boliviensis), we determined whether a four-month regimen of daily THC (1 mg/kg) or CBD (3 mg/kg) + THC (1 mg/kg) administration (IM) affects THC, THC metabolites, and CBD concentrations in blood or brain.

Results: Blood THC concentrations, THC metabolites and CBD remained stable during chronic treatment. 24 h after the final THC or CBD + THC injection, blood THC and CBD concentrations remained relatively high (THC: 6.0-11 ng/mL; CBD: 9.7-19 ng/mL). THC concentrations in cerebellum and occipital cortex were approximately twice those in blood 24 h after the last dose and did not significantly differ in subjects given THC or CBD + THC.

Conclusions: In adolescent monkeys, blood levels of THC, its metabolites or CBD remain stable after daily dosing for four months. Our model suggests that any pharmacological interactions between CBD and THC are unlikely to result from CBD modulation of THC pharmacokinetics. Finally, detection of relatively high brain THC concentrations 24 h after the final dose of THC suggests that the prolonged actions of THC may contribute to persistent cognitive and psychomotor disruption after THC- or cannabis-induced euphoria wane.

Keywords: 11-OH-THC, THC-COOH; Adolescent monkeys; CBD; CBD blood; CBD brain; Cannabidiol; Cannabis; Marijuana; Pharmacokinetics; THC; THC blood; THC brain; THC metabolites.

Grants and funding

R01 DA042178/DA/NIDA NIH HHS/United States