How Oral THC (Dronabinol) Affects Blood Cannabinoid Levels in Daily Cannabis Smokers | Research

The takeaway

High-dose oral THC increased blood cannabinoid levels in a dose-dependent manner, but smoked cannabis could only be distinguished from oral THC for about one hour after smoking.

Read this if you want to understand how oral THC replacement therapy works at the pharmacological level.

Smoked cannabis was distinguishable from oral THC for only ~1 hour in blood tests

What the researchers found

During placebo dosing periods, blood THC and its metabolites consistently decreased, supporting the withdrawal symptoms observed. During active dronabinol dosing, all cannabinoid blood levels increased in a dose-dependent fashion. At the 120 mg/day dose, the metabolite THCCOOH increased significantly, and at 60 mg/day, the metabolite 11-OH-THC increased significantly.

After a smoked cannabis challenge (5.9% THC cigarette), peak blood concentrations occurred within 15 minutes. However, the spike from smoking was only distinguishable from oral THC blood levels for about one hour, making it impractical to detect cannabis relapse during dronabinol treatment.

The ratio of THCCOOH to THC was higher after overnight dronabinol abstinence but could not reliably distinguish oral dosing from smoked cannabis.

Why it matters

Understanding the pharmacokinetics of oral THC during substitution therapy is essential for developing cannabis dependence treatments. The finding that relapse to smoked cannabis is nearly undetectable during dronabinol therapy has implications for clinical monitoring in treatment settings.

The numbers in context

11 participants. Dronabinol doses: 0, 30, 60, 120 mg/day. Challenge cigarette: 5.9% THC. THC peak within 15 minutes of smoking. Smoked cannabis distinguishable from oral THC for approximately 1 hour only.

How the study worked

Eleven daily cannabis smokers participated in a within-subject design with four 5-day medication sessions receiving 0, 30, 60, or 120 mg/day oral THC (dronabinol). Sessions were separated by 9 days of ad libitum cannabis smoking. On day 5 of each session, participants smoked one 5.9% THC cigarette. Blood samples were collected and analyzed for THC, 11-OH-THC, and THCCOOH using two-dimensional gas chromatography mass spectrometry.

What this study cannot tell us

Only 11 participants were included. All were chronic, daily cannabis smokers, so results may not generalize to lighter users. The cannabis challenge used a relatively low-potency cigarette (5.9% THC). The study examined pharmacokinetics only, not clinical outcomes like sustained abstinence.

How to read the evidence

This is a controlled pharmacokinetic study with a within-subject design, but the sample size was very small (n=11).

When this study was published

Published in 2014. Research on cannabinoid substitution therapy for cannabis dependence continues.

The bigger picture

Dronabinol (oral THC) has been studied as a substitution therapy for cannabis dependence, similar to methadone for opioid dependence. This pharmacokinetic data helps explain both its therapeutic effects (withdrawal suppression) and its limitations (inability to monitor for relapse through blood testing).

Questions still open

Can alternative biomarkers better detect cannabis relapse during dronabinol therapy? What is the optimal dronabinol dose for balancing withdrawal suppression with side effects? Would newer oral cannabinoid formulations offer better pharmacokinetic profiles for dependence treatment?

Common questions

What is dronabinol?

Dronabinol is synthetic THC in capsule form, FDA-approved for nausea and appetite stimulation. It has also been studied as a substitution therapy for cannabis dependence, similar to how methadone is used for opioid dependence.

Why can't blood tests detect relapse during dronabinol treatment?

Because both oral dronabinol and smoked cannabis produce the same compound (THC) and metabolites in the blood. The spike from smoking is brief and blends into the background levels from oral dosing within about an hour.

Read the original research

Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence.

Therapeutic drug monitoring, 36(2), 218-24

View on PubMed ↗Publisher’s paper ↗

Citation

Milman, Garry; Bergamaschi, Mateus M; Lee, Dayong; Mendu, Damodara R; Barnes, Allan J; Vandrey, Ryan; Huestis, Marilyn A. (2014). Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence.. Therapeutic drug monitoring, 36(2), 218-24. https://doi.org/10.1097/FTD.0b013e3182a5c446