Pharmacokinetics and Central Accumulation of Delta-9-Tetrahydrocannabinol (THC) and its Bioactive Metabolites Are Influenced by Route of Administration and Sex
Bibliographic record
Abstract
Abstract Up to a third of North Americans over 16 years old report using cannabis in the prior month, most commonly through inhalation. Animal models that reflect human cannabis consumption are critical to study its impacts on brain and behaviour. Nevertheless, most animal studies to date examine effects of cannabis through injection of delta-9-tetrahydrocannabinol (THC; primary psychoactive component of cannabis). THC injections produce markedly different physiological and behavioural effects than inhalation, likely due to distinctive pharmacokinetics of each administration route. The current study directly examined if administration route (injection versus inhalation), with dosing being matched on peak THC blood levels, alters the metabolism of THC, and the central accumulation of THC and its metabolites over time. Adult male and female Sprague-Dawley rats received either a single intraperitoneal injection of THC (2.5 mg/kg) or a single (15 min) session of inhaled exposure to THC distillate (100 mg/mL) vapour. Blood and brains were collected at 15, 30, 60, 90 and 240 minutes post-exposure for analysis of THC and metabolites through mass spectrometry-liquid chromatography. Inhalation results in immediate hypothermia, whereas injection results in delayed hypothermia. Despite achieving comparable peak concentrations of blood THC in both groups, our results indicate higher initial brain THC concentration following inhalation, whereas injection resulted in dramatically higher 11-OH-THC concentrations, a potent THC metabolite, in blood and brain that increased over time. Our results provide evidence that THC and its metabolites exhibit different pharmacokinetic profiles following inhalation versus injection, which could have significant impacts for data interpretation and generalizability. Accordingly, we suggest that translational work in the realm of THC and cannabis strongly consider using inhalation models over those that employ injection. Highlights Body temperature as well as blood and brain levels of THC and metabolites differ based on administration route THC inhalation results in immediate hypothermia, whereas THC injection results in delayed hypothermia THC inhalation results in higher initial brain THC levels than injection THC injection results in higher blood & brain 11-OH-THC levels than inhalation Translational cannabis work should strongly consider using inhalation over injection
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".