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Study breakdown

Head-to-head comparison of Sativex abuse potential versus pure synthetic THC

Randomized Controlled TrialModerate evidence
The takeaway

In 23 recreational cannabis users, Sativex (THC+CBD spray) showed similar or slightly less abuse potential compared to equivalent doses of dronabinol (pure synthetic THC).

Read this if you want to know whether cannabis-based prescription medicines can be abused.

Sativex abuse scores were consistently equal to or lower than dronabinol

What the researchers found

This crossover study gave 23 recreational cannabis users single doses of Sativex (at three dose levels), dronabinol (at two dose levels), or placebo. At the lowest dose (10.8 mg THC), Sativex was not significantly different from placebo on primary abuse potential measures.

At the medium dose (21.6 mg THC), Sativex showed some abuse potential on certain measures. At the highest dose (43.2 mg THC), Sativex showed significant effects on most abuse measures, roughly comparable to dronabinol 40 mg.

Critically, at every dose comparison, Sativex scores were numerically equal to or lower than equivalent dronabinol doses. This confirmed that adding CBD and using oromucosal delivery did not increase abuse potential beyond that of pure THC.

Why it matters

This study directly addressed the regulatory concern about whether a THC-containing medicine could be abused. By showing Sativex had no greater abuse potential than already-approved dronabinol, it supported the case for regulatory approval.

The numbers in context

23 recreational cannabis users. Sativex 10.8 mg: not different from placebo on primary measures. Sativex 43.2 mg and dronabinol 40 mg: generally not statistically different from each other. Sativex scores consistently equal to or lower than equivalent dronabinol.

How the study worked

Single-dose, randomized, double-blind, crossover study. 23 recreational cannabis users received Sativex (10.8, 21.6, and 43.2 mg THC), dronabinol (20 and 40 mg), and matching placebos. Subjective and cognitive measures were assessed over 24 hours post-dose.

What this study cannot tell us

Single-dose design does not capture repeated-use patterns. Recreational cannabis users represent a high-risk population, so abuse potential in pain or MS patients may be lower. The study was funded by GW Pharmaceuticals, Sativex's manufacturer.

How to read the evidence

Well-designed crossover RCT with appropriate comparators and blinding. Moderate sample size for an abuse liability study. Industry-funded.

When this study was published

Published in 2011. This study contributed to Sativex's regulatory approval in multiple countries.

The bigger picture

This was a key regulatory study. By demonstrating that Sativex had no greater abuse potential than dronabinol (which was already classified as Schedule III), it supported appropriate scheduling and prescription access for patients.

Questions still open

  • Does the abuse potential profile change with repeated dosing? Would results differ in non-cannabis-experienced populations? How much of the reduced abuse potential comes from CBD versus the slow delivery route?

Common questions

Is Sativex less addictive than pure THC?
In this study, Sativex showed similar or slightly lower abuse potential compared to dronabinol (pure synthetic THC) at equivalent doses. The CBD content and spray delivery method may reduce the "high" compared to pure THC.
Why test in recreational cannabis users?
Abuse liability studies intentionally use people experienced with the drug class because they can best detect rewarding effects. If abuse potential is low in this high-risk group, it is likely even lower in typical patients.

Read the original research

A randomized, double-blind, placebo-controlled, crossover study to evaluate the subjective abuse potential and cognitive effects of nabiximols oromucosal spray in subjects with a history of recreational cannabis use.

Human psychopharmacology, 26(3), 224-36

Citation

Schoedel, Kerri Alexandra; Chen, Nancy; Hilliard, Annie; White, Linda; Stott, Colin; Russo, Ethan; Wright, Stephen; Guy, Geoffrey; Romach, Myroslava K; Sellers, Edward M. (2011). A randomized, double-blind, placebo-controlled, crossover study to evaluate the subjective abuse potential and cognitive effects of nabiximols oromucosal spray in subjects with a history of recreational cannabis use.. Human psychopharmacology, 26(3), 224-36. https://doi.org/10.1002/hup.1196

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