THC/CBD spray reduced cannabis withdrawal symptoms in a clinical trial | Research

The takeaway

Nabiximols (a THC/CBD spray) significantly reduced cannabis withdrawal severity and kept patients in treatment longer, but did not improve long-term cannabis use outcomes compared to placebo.

Read this if you are interested in whether medications can help manage cannabis withdrawal and support quitting.

Nabiximols reduced withdrawal severity and tripled the odds of staying in treatment

What the researchers found

In a double-blind clinical trial, 51 cannabis-dependent treatment seekers received either nabiximols (up to 86.4 mg THC and 80 mg CBD daily) or placebo during a 9-day inpatient admission, followed by 28 days of outpatient follow-up. Nabiximols significantly reduced overall withdrawal severity, with notable effects on irritability, depression, and cravings.

Patients receiving nabiximols stayed in treatment significantly longer during the medication phase, with a number needed to treat of 2.84 for successful treatment retention. Importantly, participants could not distinguish between nabiximols and placebo, and those on nabiximols did not report feeling intoxicated.

However, after medication ended, both groups showed similar reductions in cannabis use at follow-up. Nabiximols provided no advantage over placebo for long-term cannabis use, cannabis-related problems, or dependence severity.

Why it matters

No medications are approved for cannabis dependence or withdrawal. This trial, published in JAMA Psychiatry, demonstrated that agonist replacement with nabiximols can manage the acute withdrawal period effectively. The finding that withdrawal relief did not translate to better long-term outcomes echoes patterns seen with other substance use disorders.

The numbers in context

51 participants randomized. Maximum daily dose: 86.4 mg THC + 80 mg CBD. Nabiximols significantly reduced withdrawal severity (P = .01). Treatment retention hazard ratio: 3.66 (95% CI: 1.18-11.37). Number needed to treat: 2.84. No significant differences in adverse events between groups.

How the study worked

Two-site, double-blind, randomized clinical trial with inpatient and outpatient phases. 51 cannabis-dependent adults received a 6-day nabiximols or placebo regimen with standardized psychosocial interventions during a 9-day admission, followed by 28-day outpatient follow-up. Primary outcomes included withdrawal severity (Cannabis Withdrawal Scale), treatment retention, and adverse events.

What this study cannot tell us

Small sample size of 51 participants limits statistical power. The 6-day medication course may have been too short. Inpatient setting does not reflect typical outpatient treatment conditions. Long-term outcomes were based on self-report.

How to read the evidence

Double-blind randomized clinical trial published in JAMA Psychiatry, though with a relatively small sample of 51 participants.

When this study was published

Published in 2014. Research on agonist replacement for cannabis dependence continues.

The bigger picture

This study positioned nabiximols as a potential withdrawal management tool similar to how nicotine replacement is used for smoking cessation. The gap between short-term withdrawal management and long-term use reduction mirrors challenges across addiction medicine and suggests that medication alone may be insufficient without sustained behavioral support.

Questions still open

Would a longer course of nabiximols improve long-term outcomes? Could combining nabiximols with intensive outpatient behavioral therapy bridge the gap between withdrawal management and sustained abstinence? Is there an optimal tapering protocol?

Common questions

Can THC/CBD spray help with quitting cannabis?

In this trial, nabiximols significantly reduced withdrawal symptoms and helped patients stay in treatment longer. However, after the medication ended, long-term cannabis use outcomes were no better than placebo.

Does nabiximols get you high?

Participants in this trial could not reliably distinguish nabiximols from placebo, and those receiving nabiximols did not report greater intoxication, despite receiving up to 86.4 mg of THC daily.

Read the original research

Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial.

JAMA psychiatry, 71(3), 281-91

View on PubMed ↗Publisher’s paper ↗

Citation

Allsop, David J; Copeland, Jan; Lintzeris, Nicholas; Dunlop, Adrian J; Montebello, Mark; Sadler, Craig; Rivas, Gonzalo R; Holland, Rohan M; Muhleisen, Peter; Norberg, Melissa M; Booth, Jessica; McGregor, Iain S. (2014). Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial.. JAMA psychiatry, 71(3), 281-91. https://doi.org/10.1001/jamapsychiatry.2013.3947