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Nabilone Produced Sustained Positive Effects in Cannabis Smokers and May Be Better Than Dronabinol for Dependence Treatment

Randomized Controlled TrialModerate evidence
The takeaway

In regular marijuana smokers, nabilone produced dose-related positive mood effects with better bioavailability and a slower onset than dronabinol, supporting its potential as a medication for cannabis dependence.

Read this if you are interested in potential medications for cannabis dependence.

Nabilone had better bioavailability and more dose-predictable effects than dronabinol

What the researchers found

Fourteen regular marijuana smokers completed a within-subjects comparison of nabilone (2, 4, 6, 8 mg), dronabinol (10, 20 mg), and placebo across seven sessions. Both drugs increased ratings of feeling good, strong effects, and being "high." Nabilone had a slower onset but more sustained effects, and its effects were more dose-related than dronabinol's.

Nabilone at 6-8 mg modestly reduced psychomotor speed, but overall was well tolerated. Heart rate increased dose-dependently with nabilone. The more predictable dose-response relationship and better bioavailability suggest nabilone may be more suitable than dronabinol as an agonist replacement therapy for cannabis dependence.

Why it matters

Dronabinol (oral THC) has been tested for cannabis dependence but failed to prevent relapse, possibly due to poor bioavailability. Nabilone's better bioavailability and more predictable dose-response could make it a superior agonist therapy, similar to how methadone or buprenorphine work for opioid dependence.

The numbers in context

14 participants smoking 6.6 days/week. Nabilone tested at 2, 4, 6, 8 mg. Dronabinol at 10, 20 mg. Both increased positive mood ratings. Nabilone: slower onset, more dose-related. Nabilone 6-8 mg: modest psychomotor slowing. Dose-dependent heart rate increase with nabilone.

How the study worked

Outpatient, within-subjects, double-blind, randomized protocol. 14 participants (4 female, 10 male) smoking marijuana 6.6 days/week. Seven sessions comparing nabilone (4 doses), dronabinol (2 doses), and placebo. Time-dependent subjective, cognitive, and cardiovascular effects measured.

What this study cannot tell us

Small sample of 14 participants. All were current regular users, not treatment-seeking. Acute effects of single doses do not predict outcomes of sustained treatment. Outpatient setting means compliance and environmental factors were not controlled. The study assessed subjective effects but not actual cannabis reduction.

How to read the evidence

Within-subjects controlled study in current users; moderate evidence for pharmacological profile but no cessation outcomes.

When this study was published

Published in 2013. Nabilone and other agonist therapies for cannabis dependence have continued to be investigated.

The bigger picture

Agonist replacement therapy (replacing the drug of abuse with a controlled, longer-acting version) has been highly successful for opioid dependence. This study took a step toward evaluating whether a similar strategy could work for cannabis dependence, with nabilone as the candidate medication.

Questions still open

  • Would sustained nabilone treatment reduce cannabis use in treatment-seeking individuals? What nabilone dose would balance therapeutic effects with side effects in a clinical trial? Would combining nabilone with behavioral therapy improve outcomes?

Common questions

What is the difference between nabilone and dronabinol?
Both are synthetic cannabinoids that activate the same receptors as THC. Dronabinol is synthetic THC itself, while nabilone is a THC analogue with different pharmacological properties. Nabilone has better bioavailability (more of the drug reaches the bloodstream) and a more predictable dose-response relationship.
How would nabilone help with cannabis dependence?
The concept is agonist replacement therapy, similar to methadone for heroin dependence. By providing a controlled, oral cannabinoid, nabilone could reduce withdrawal symptoms and cravings while avoiding the rapid onset and variable dosing of smoked cannabis. Its slower onset and sustained effects make it potentially suitable for this purpose.

Read the original research

Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers.

Addiction biology, 18(5), 872-81

Citation

Bedi, Gillinder; Cooper, Ziva D; Haney, Margaret. (2013). Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers.. Addiction biology, 18(5), 872-81. https://doi.org/10.1111/j.1369-1600.2011.00427.x

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