Combining a Sleep Aid With a THC Pill Reduced Cannabis Withdrawal Symptoms and Relapse in a Lab Setting | Research

The takeaway

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.

Read this if you are interested in potential medications for managing cannabis withdrawal or reducing cannabis use.

Zolpidem + nabilone reduced cannabis self-administration during simulated relapse

What the researchers 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.

Why it 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 numbers in context

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 the study worked

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.

What this study cannot 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.

How to read the evidence

Within-subject controlled design in an inpatient setting provides strong internal validity, but very small sample limits generalizability.

When this study was published

Published in 2016. Research on pharmacotherapies for cannabis use disorder has continued, with nabilone among the more promising candidates.

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.

Questions still open

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?

Common 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.

Read the original research

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

View on PubMed ↗Publisher’s paper ↗

Citation

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