Synthetic THC Shows Modest Ability to Suppress Opioid Withdrawal but Causes Too Many Side Effects
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Modest withdrawal suppression at 20-30 mg, but with tachycardia and psychoactive effects
- Evidence Grade:
- Well-controlled inpatient proof-of-concept study with multiple dose comparisons, but very small sample size.
- Study Age:
- Published in 2016. Research on cannabinoid approaches to opioid withdrawal has continued with different compounds.
- Original Title:
- Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.
- Published In:
- Drug and alcohol dependence, 164, 143-150 (2016)
- Authors:
- Lofwall, Michelle R(3), Babalonis, Shanna(8), Nuzzo, Paul A(2), Elayi, Samy Claude, Walsh, Sharon L
- Database ID:
- RTHC-01215
Evidence Hierarchy
Participants are randomly assigned to treatment or placebo groups to test cause and effect.
What do these levels mean? →Frequently Asked 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.
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Cite This Study
https://rethinkthc.com/research/RTHC-01215APA
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
MLA
Lofwall, Michelle R, et al. "Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.." Drug and alcohol dependence, 2016. https://doi.org/10.1016/j.drugalcdep.2016.05.002
RethinkTHC
RethinkTHC Research Database. "Opioid withdrawal suppression efficacy of oral dronabinol in..." RTHC-01215. Retrieved from https://rethinkthc.com/research/lofwall-2016-opioid-withdrawal-suppression-efficacy
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.