How THC and CBD from an oral spray move through the body | Research

The takeaway

A THC/CBD mouth spray produced blood levels well below those seen with smoking, with no drug buildup after nine days of repeated use.

Read this if you want to understand how pharmaceutical cannabinoid sprays compare to smoking in terms of blood levels and drug accumulation.

Peak THC levels stayed below 12 ng/mL, well under levels seen with smoking

What the researchers found

In this Phase I pharmacokinetic trial, healthy male volunteers received a THC/CBD oral spray at three dose levels (2, 4, or 8 sprays) either as single doses or daily for nine days. Both THC and CBD were rapidly absorbed after spraying.

Peak blood concentrations stayed below 12 ng/mL across all dose levels, well below the levels typically reported in people who smoke or inhale cannabis. THC showed greater bioavailability than CBD at every dose tested.

Importantly, there was no evidence of accumulation with repeated daily dosing for any of the compounds measured. Variability between individuals ranged from moderate to high for all pharmacokinetic measures. The spray was well tolerated, with no serious adverse events reported.

Why it matters

Understanding how quickly cannabinoids are absorbed and whether they accumulate with repeated use is essential for medical formulation development. The finding that peak blood levels stayed far below those from smoking suggests oral spray delivery may carry a lower risk of the acute psychoactive effects associated with high-peak THC exposure.

The numbers in context

Peak THC blood concentrations stayed below 12 ng/mL across all dose levels. Three dose tiers were tested: 2 sprays (5.4 mg THC, 5.0 mg CBD), 4 sprays (10.8 mg THC, 10.0 mg CBD), and 8 sprays (21.6 mg THC, 20.0 mg CBD). Nine consecutive days of dosing showed no accumulation.

How the study worked

This was a Phase I, within-subject crossover study in healthy male volunteers. Participants received single or multiple doses of THC/CBD oromucosal spray (containing 2.7 mg THC and 2.5 mg CBD per spray) after overnight fasting. Plasma samples were analyzed using gas chromatography-mass spectrometry for THC, CBD, and the THC metabolite 11-hydroxy-THC.

What this study cannot tell us

The study included only healthy male participants, so results may not generalize to females or people with medical conditions. Fasting conditions may not reflect real-world use. The controlled clinical setting differs from typical patient use patterns.

How to read the evidence

Controlled Phase I trial with systematic pharmacokinetic measurements, though limited to healthy male volunteers.

When this study was published

Published in 2013, this study informed the regulatory pathway for THC/CBD oral spray products.

The bigger picture

Pharmaceutical cannabinoid products need reliable pharmacokinetic profiles to gain regulatory approval. This study helped establish the dosing framework for THC/CBD oral spray (later marketed as Sativex), demonstrating predictable absorption patterns and a safety margin compared to inhaled cannabis.

Questions still open

How do these pharmacokinetic profiles change in patients with multiple sclerosis or other conditions for which the spray is indicated? Does food intake meaningfully alter absorption? Would longer-term dosing beyond nine days reveal any accumulation effects?

Common questions

Does THC build up in the body with daily oral spray use?

In this nine-day study, there was no evidence of THC, CBD, or THC metabolite accumulation with once-daily dosing at any of the three dose levels tested.

How do THC blood levels from oral spray compare to smoking?

Peak concentrations from the spray stayed below 12 ng/mL, which researchers noted was well below levels typically reported in people who smoke or inhale cannabis.

Read the original research

A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray.

European journal of clinical pharmacology, 69(5), 1135-47

View on PubMed ↗Publisher’s paper ↗

Citation

Stott, C G; White, L; Wright, S; Wilbraham, D; Guy, G W. (2013). A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray.. European journal of clinical pharmacology, 69(5), 1135-47. https://doi.org/10.1007/s00228-012-1441-0