Oral THC (dronabinol) suppressed cannabis withdrawal in a dose-dependent manner | Research

The takeaway

Dronabinol (oral THC) at doses up to 120 mg per day dose-dependently reduced cannabis withdrawal symptoms with few side effects and no meaningful cognitive impairment.

Read this if you are interested in pharmaceutical approaches to managing cannabis withdrawal during quit attempts.

Dronabinol up to 120 mg/day suppressed withdrawal with no cognitive impairment

What the researchers found

Thirteen daily cannabis smokers completed a within-subject crossover study receiving 0, 30, 60, and 120 mg dronabinol per day for five consecutive days each. Dronabinol dose-dependently reduced cannabis withdrawal symptoms, with higher doses providing greater relief.

The medication produced few adverse side effects and did not cause significant cognitive impairment at any dose tested, including the highest 120 mg dose. On the fifth day of each dosing period, participants smoked cannabis. Dronabinol did not alter the subjective effects of smoked cannabis, though the 60 and 120 mg doses reduced the heart rate increase normally caused by smoking.

The finding that dronabinol did not block the subjective effects of smoked cannabis distinguishes it from substitution therapies like methadone, which reduce the rewarding effects of the target drug.

Why it matters

Cannabis use disorder currently has no FDA-approved pharmacotherapy. Demonstrating that oral THC can suppress withdrawal symptoms safely at doses up to 120 mg/day supports continued development of agonist replacement strategies similar to those used for opioid and nicotine dependence.

The numbers in context

13 daily cannabis users tested. Four dose levels: 0, 30, 60, 120 mg/day. Five-day dosing periods separated by nine-day washouts. Withdrawal was dose-dependently suppressed. No significant cognitive impairment at any dose.

How the study worked

Within-subject crossover study with 13 daily cannabis smokers. Each participant received all four dose levels (0, 30, 60, 120 mg/day) for five consecutive days in counterbalanced order, separated by nine-day washout periods of ad libitum cannabis use. Withdrawal symptoms, craving, sleep quality, vital signs, and cognitive performance were assessed.

What this study cannot tell us

Very small sample of 13 participants. Five-day dosing periods may not reflect the longer durations needed clinically. The nine-day ad libitum cannabis use between conditions complicates interpretation. Real-world treatment involves more variables than this controlled setting.

How to read the evidence

Controlled crossover design with within-subject comparisons, but very small sample size limits generalizability.

When this study was published

Published in 2013. Dronabinol continues to be studied for cannabis use disorder treatment.

The bigger picture

Agonist replacement therapy has been successful for opioid (methadone, buprenorphine) and nicotine (patch, gum) dependence. This study contributes to evidence that a similar approach could work for cannabis, using oral THC to manage the transition away from smoked cannabis.

Questions still open

Would longer treatment with dronabinol during a complete quit attempt improve abstinence rates? Is 120 mg the ceiling dose, or could higher doses be more effective? Would combining dronabinol with behavioral therapy improve outcomes beyond either alone?

Common questions

Can oral THC help with cannabis withdrawal?

In this small study, dronabinol (oral THC) dose-dependently reduced withdrawal symptoms at doses up to 120 mg/day, with few side effects. Larger clinical trials are needed to confirm these findings.

Does dronabinol block the high from smoking cannabis?

No. In this study, dronabinol did not alter the subjective effects of smoked cannabis. It reduced withdrawal but did not prevent users from feeling the effects of smoking.

Read the original research

The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

Drug and alcohol dependence, 128(1-2), 64-70

View on PubMed ↗Publisher’s paper ↗

Citation

Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong. (2013). The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.. Drug and alcohol dependence, 128(1-2), 64-70. https://doi.org/10.1016/j.drugalcdep.2012.08.001