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Study breakdown

Synthetic THC Shows Modest Ability to Suppress Opioid Withdrawal but Causes Too Many Side Effects

Randomized Controlled TrialModerate evidence
The takeaway

In an inpatient study of 12 opioid-dependent adults, higher doses of dronabinol (20-30 mg) produced modest opioid withdrawal suppression but with concerning side effects including tachycardia, sedation, and feeling high.

Read this if you are interested in whether cannabinoids could help treat opioid withdrawal.

Modest withdrawal suppression at 20-30 mg, but with tachycardia and psychoactive effects

What the researchers found

The cannabinoid system shares neural circuitry with the opioid system, making it a rational target for treating opioid dependence. This proof-of-concept study tested whether dronabinol (synthetic THC) could suppress opioid withdrawal.

Twelve opioid-dependent adults maintained on oxycodone underwent controlled withdrawal sessions, receiving single test doses of dronabinol (5, 10, 20, or 30 mg), oxycodone (30 or 60 mg), or placebo.

Lower dronabinol doses (5-10 mg) had minimal effects. Higher doses (20-30 mg) showed modest withdrawal suppression signals, but these were accompanied by dose-related increases in feeling high, sedation, feeling of heart racing, and actual tachycardia. Participants did not like dronabinol more than placebo and identified it as marijuana. Some cognitive impairment occurred at higher doses.

The authors concluded that while CB1 activation is a reasonable withdrawal treatment strategy, dronabinol's narrow therapeutic window and cardiovascular effects make it a poor candidate.

Why it matters

The opioid epidemic demands new treatment approaches. While this study finds dronabinol itself is not the answer, it establishes proof-of-concept that CB1 receptor activation can reduce opioid withdrawal, pointing to the need for cannabinoid drugs with better therapeutic windows.

The numbers in context

12 opioid-dependent adults. Dronabinol doses: 5, 10, 20, 30 mg (reduced from planned 40 mg). 5-10 mg: similar to placebo. 20-30 mg: modest withdrawal suppression with tachycardia, sedation, and feeling high. Oxycodone produced expected withdrawal suppression.

How the study worked

5-week inpatient, double-blind, randomized, placebo-controlled study. 12 opioid-dependent adults maintained on oxycodone 30 mg QID. Oxycodone was withheld for 21 hours to produce measurable withdrawal. Single test doses were administered in 7 experimental sessions. Observer and participant ratings assessed withdrawal suppression, agonist effects, and cognition.

What this study cannot tell us

Very small sample (12 participants). Single-dose design may underestimate effects of repeated dosing. Only oxycodone dependence was studied. The highest planned dose (40 mg) had to be reduced to 30 mg due to adverse effects. Short withdrawal challenge may not reflect sustained withdrawal.

How to read the evidence

Well-controlled inpatient proof-of-concept study with multiple dose comparisons, but very small sample size.

When this study was published

Published in 2016. Research on cannabinoid approaches to opioid withdrawal has continued with different compounds.

The bigger picture

This study fits into a broader effort to find non-opioid treatments for opioid withdrawal. The modest but real withdrawal suppression signal supports continued investigation of cannabinoid approaches, perhaps with drugs that provide CB1 activation without the psychoactive and cardiovascular effects of THC.

Questions still open

  • Would a non-psychoactive CB1 partial agonist provide withdrawal relief without side effects? Could CBD or other cannabinoids address opioid withdrawal through different mechanisms? Would repeated dosing produce better withdrawal suppression than single doses?

Common questions

Can THC help with opioid withdrawal?
In this small study, higher doses of synthetic THC (dronabinol) showed modest ability to suppress opioid withdrawal symptoms, but the side effects (rapid heart rate, sedation, feeling high) made it impractical.
Is the cannabinoid system still a target for opioid treatment?
Yes. While dronabinol specifically is not a good candidate, the proof-of-concept that CB1 activation reduces opioid withdrawal supports continued development of better-targeted cannabinoid-based approaches.

Read the original research

Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.

Drug and alcohol dependence, 164, 143-150

Citation

Lofwall, Michelle R; Babalonis, Shanna; Nuzzo, Paul A; Elayi, Samy Claude; Walsh, Sharon L. (2016). Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.. Drug and alcohol dependence, 164, 143-150. https://doi.org/10.1016/j.drugalcdep.2016.05.002

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