The arthritis drug celecoxib did not ease cannabis withdrawal and actually increased craving | Research

The takeaway

A placebo-controlled study in 15 daily cannabis smokers found that the COX-2 inhibitor celecoxib did not reduce withdrawal symptoms, did not change endocannabinoid levels, and increased cannabis craving.

Addiction researchers, pharmacologists, and clinicians looking for cannabis use disorder treatments.

Celecoxib increased cannabis craving compared to placebo

What the researchers found

Compared to placebo, celecoxib improved some subjective sleep measures but did not affect mood, cannabis self-administration, or circulating endocannabinoid levels. Celecoxib increased cannabis craving, suggesting it does not show promise as a pharmacotherapy for cannabis use disorder.

Why it matters

There are currently no FDA-approved medications for cannabis use disorder. Blocking COX-2 was hypothesized to increase endocannabinoid levels and reduce withdrawal, but this study found the approach ineffective.

The numbers in context

15 participants (12M, 3F). Celecoxib 200 mg twice daily. Cannabis abstinence produced characteristic withdrawal (negative mood, anorexia, dreaming). Cannabis abstinence was associated with increased OEA and oleic acid but no change in endocannabinoid levels.

How the study worked

Placebo-controlled crossover study with 15 daily, non-treatment-seeking cannabis smokers (12 male, 3 female). Each participant completed two 11-day phases (placebo vs. celecoxib 200 mg BID) with a washout period of at least 14 days.

What this study cannot tell us

Very small sample (15 participants, only 3 female). Non-treatment-seeking population may not represent those trying to quit. Single dose of celecoxib tested.

How to read the evidence

Placebo-controlled crossover design but very small sample size of 15 participants.

When this study was published

Published in 2022.

The bigger picture

While blocking FAAH (a different enzyme) has shown promise for cannabis withdrawal in earlier studies, blocking COX-2 does not appear to be a viable alternative pathway, narrowing the pharmacological options being explored.

Questions still open

Why did celecoxib increase craving? Would higher doses or different COX-2 inhibitors produce different results? Is the FAAH pathway more promising than COX-2 for cannabis withdrawal treatment?

Common questions

Are there medications for cannabis withdrawal?

No FDA-approved medications exist for cannabis withdrawal. This study tested celecoxib (a COX-2 inhibitor) and found it ineffective, though FAAH inhibitors have shown more promise in other research.

What does cannabis withdrawal look like?

In this study, four days without cannabis produced negative mood, reduced appetite, and increased dreaming in daily smokers, consistent with established withdrawal patterns.

Read the original research

Impact of cyclooxygenase-2 inhibition on cannabis withdrawal and circulating endocannabinoids in daily cannabis smokers.

Addiction biology, 27(4), e13183

View on PubMed ↗Publisher’s paper ↗

Citation

Haney, Margaret; Bedi, Gillinder; Cooper, Ziva D; Herrmann, Evan S; Reed, Stephanie Collins; Foltin, Richard W; Kingsley, Philip J; Marnett, Lawrence J; Patel, Sachin. (2022). Impact of cyclooxygenase-2 inhibition on cannabis withdrawal and circulating endocannabinoids in daily cannabis smokers.. Addiction biology, 27(4), e13183. https://doi.org/10.1111/adb.13183