Combining a Sleep Aid With a THC Pill Reduced Cannabis Withdrawal Symptoms and Relapse in a Lab Setting
Combining zolpidem (a sleep medication) with nabilone (a synthetic THC pill) reduced cannabis withdrawal-related mood disruption, appetite changes, and self-administration of cannabis more than zolpidem alone.
Quick Facts
What This Study Found
Eleven daily cannabis users completed three 8-day inpatient stays testing different medication conditions during monitored cannabis withdrawal.
Both zolpidem alone and zolpidem plus nabilone improved sleep during withdrawal. However, only the combination reduced withdrawal-related mood disruption and changes in food intake.
The most significant finding was about relapse: when active cannabis was made available on days 5-8, participants given the zolpidem-nabilone combination self-administered less cannabis than those on placebo. Zolpidem alone did not reduce cannabis self-administration.
The combination did produce small increases in some abuse-related subjective ratings, a potential concern. Neither medication condition affected cognitive performance.
Key Numbers
11 daily cannabis users. 8-day inpatient phases. Nabilone 3 mg twice daily + zolpidem 12.5 mg at bedtime. Combination reduced cannabis self-administration vs. placebo. Both medication conditions improved sleep. Only combination improved mood and food intake.
How They Did This
Placebo-controlled, within-subject, counter-balanced inpatient study. Eleven non-treatment-seeking daily cannabis users completed three 8-day phases testing placebo, zolpidem alone (12.5 mg at bedtime), and zolpidem (12.5 mg) plus nabilone (3 mg twice daily). Cannabis withdrawal was assessed on days 3-4 and relapse on days 5-8.
Why This Research Matters
There are no approved medications for cannabis use disorder. This study provides evidence that a combination pharmacotherapy targeting both sleep (zolpidem) and cannabinoid withdrawal (nabilone) may be more effective than targeting sleep alone, and suggests nabilone could reduce relapse.
The Bigger Picture
This study supports the agonist replacement approach to cannabis use disorder, similar to how methadone (an opioid agonist) helps treat opioid dependence. Nabilone, as a synthetic THC analog, may reduce withdrawal and relapse by partially satisfying cannabinoid receptor demand without the reinforcing pattern of smoked cannabis.
What This Study Doesn't Tell Us
Very small sample of 11 non-treatment-seeking users. The inpatient lab setting does not replicate real-world conditions. The slight abuse-related subjective effects of the combination warrant monitoring. Short study duration.
Questions This Raises
- ?Would nabilone alone (without zolpidem) be sufficient to reduce withdrawal and relapse?
- ?Would treatment-seeking patients respond differently?
- ?Is the abuse potential of the combination clinically significant?
Trust & Context
- Key Stat:
- Zolpidem + nabilone reduced cannabis self-administration during simulated relapse
- Evidence Grade:
- Within-subject controlled design in an inpatient setting provides strong internal validity, but very small sample limits generalizability.
- Study Age:
- Published in 2016. Research on pharmacotherapies for cannabis use disorder has continued, with nabilone among the more promising candidates.
- Original Title:
- Effects of zolpidem alone and in combination with nabilone on cannabis withdrawal and a laboratory model of relapse in cannabis users.
- Published In:
- Psychopharmacology, 233(13), 2469-78 (2016)
- Authors:
- Herrmann, Evan S(10), Cooper, Ziva D(28), Bedi, Gillinder(10), Ramesh, Divya, Reed, Stephanie C, Comer, Sandra D, Foltin, Richard W, Haney, Margaret
- Database ID:
- RTHC-01177
Evidence Hierarchy
Participants are randomly assigned to treatment or placebo groups to test cause and effect.
What do these levels mean? →Frequently Asked Questions
Is there a medication that helps with cannabis withdrawal?
No medications are approved, but this study found that combining a sleep aid (zolpidem) with a synthetic THC pill (nabilone) reduced withdrawal-related mood problems and decreased the desire to use cannabis.
Does treating sleep problems during withdrawal help prevent relapse?
Treating sleep alone (zolpidem only) improved sleep but did not reduce cannabis use. Adding nabilone to address the broader withdrawal syndrome was what reduced self-administration.
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Cite This Study
https://rethinkthc.com/research/RTHC-01177APA
Herrmann, Evan S; Cooper, Ziva D; Bedi, Gillinder; Ramesh, Divya; Reed, Stephanie C; Comer, Sandra D; Foltin, Richard W; Haney, Margaret. (2016). Effects of zolpidem alone and in combination with nabilone on cannabis withdrawal and a laboratory model of relapse in cannabis users.. Psychopharmacology, 233(13), 2469-78. https://doi.org/10.1007/s00213-016-4298-6
MLA
Herrmann, Evan S, et al. "Effects of zolpidem alone and in combination with nabilone on cannabis withdrawal and a laboratory model of relapse in cannabis users.." Psychopharmacology, 2016. https://doi.org/10.1007/s00213-016-4298-6
RethinkTHC
RethinkTHC Research Database. "Effects of zolpidem alone and in combination with nabilone o..." RTHC-01177. Retrieved from https://rethinkthc.com/research/herrmann-2016-effects-of-zolpidem-alone
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.