Probiotics and Nicotine Dependence: What One RCT Found

A probiotic lowered nicotine-dependence scores in one 12-week randomized trial of smokers. That makes the result worth watching. It does not make probiotics a smoking-cessation treatment.

The study found a statistically significant between-group reduction on the Nicotine Dependence Syndrome Scale (NDSS), a 19-item measure that captures several dimensions of dependence. It found no statistically significant improvement in anxiety or depression. Fasting glucose, triglycerides, and C-reactive protein (CRP) also improved in the probiotic group. These are three separate findings with very different levels of interpretive support.

The dependence result is new, preliminary, and unreplicated. The biomarker results fit a broader probiotic literature. The mood results fit a pattern seen in non-clinical populations: people without diagnosed mood disorders often show little or no measurable benefit.

What the smoker trial tested

In Sadeghi et al.'s 2026 double-blind, placebo-controlled trial, 74 adult smokers in Kashan, Iran, were assigned to a daily multi-strain probiotic or a matched placebo for 12 weeks. The probiotic group included 36 participants and the placebo group 38 participants. Eligibility required a Fagerström Test for Nicotine Dependence (FTND) score of at least 4.

The intervention supplied 1.8 × 10⁹ colony-forming units per day of Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium lactis. Compared with placebo, the probiotic group had a statistically significant reduction in NDSS scores. The published information available here does not provide an effect estimate or confidence interval for that difference, so readers cannot judge its size or precision.

The boundary around the result matters. The trial measured a questionnaire score, not cigarette consumption, quit attempts, relapse, biochemically verified abstinence, or sustained smoking cessation. A lower NDSS score may turn out to predict useful behavior change, but this study did not test that link.

The new endpoint was not the endpoint used to size the trial

Sadeghi's trial appears to be the first human randomized study to test a probiotic against a validated multidimensional nicotine-dependence scale. That is a legitimate research first. It is not confirmation that altering the gut microbiome reduces nicotine dependence.

The researchers calculated sample size from the Beck Depression Inventory (BDI): 36 participants per group, a 7.9-point mean difference, 80% power, and an alpha of 0.05. They did not report a prospective power calculation for the NDSS. The BDI and NDSS assess different constructs and have different psychometric structures. A study large enough for one questionnaire may be too small, or unnecessarily large, for another.

The enrollment and outcome instruments also differed. FTND established who qualified for the study, while NDSS tracked dependence. The scales overlap, but they do not measure identical features of nicotine dependence. The publication did not report a baseline-to-follow-up FTND comparison, so it cannot show whether both measures moved together.

Those limitations do not erase the NDSS result. They prevent a confident estimate of its clinical importance and make replication essential. A future trial should designate NDSS as a primary endpoint, calculate sample size for that endpoint, track FTND alongside it, and measure smoking behavior and abstinence.

Mood did not improve in this cohort

The trial found no statistically significant between-group differences in Beck Anxiety Inventory (BAI) or BDI scores. Its abstract's broader language about anxiety and depression improvement should not be read as evidence of significant mood benefits.

That result fits the enrolled population. The study excluded people with psychiatric diagnoses, which likely limited baseline symptom severity and left less room for a detectable change. In contrast, a 2025 meta-analysis by Moshfeghinia et al. found lower depression and anxiety scores with probiotic, prebiotic, and synbiotic interventions among patients with diagnosed depression. The pooled effects became substantially smaller after the authors excluded trials at high risk of bias.

Results are thinner in people without clinical mood disorders. A 2026 meta-analysis of healthy working adults found limited mental-health effects from probiotics. Similarly, a double-blind crossover trial in healthy older adults found limited cognitive and emotional effects from Lactobacillus rhamnosus and Bifidobacterium lactis (Ruiz-Gonzalez et al.).

These comparisons cannot identify why Sadeghi's mood outcomes were null. They do make the result unsurprising. Smokers with subthreshold depression, anxiety, or diagnosed mood disorders may respond differently, but this trial did not enroll the population needed to answer that question.

A probiotic is not a single intervention

"Probiotic" describes a category, not a predictable psychological treatment. In a 2024 network meta-analysis, Yang et al. found that strain combinations substantially affected depression, anxiety, and stress outcomes. Sadeghi's combination was not among the combinations identified as optimal for those endpoints.

Strain-specific findings add context without supplying an explanation. A 2025 meta-analysis by Cheng et al. found antidepressant effects for Lactobacillus reuteri in randomized depression trials; Sadeghi's supplement did not include that strain. Its absence does not prove why BAI and BDI scores failed to change, nor does it predict what would happen to NDSS scores with a different formula. It simply means this product cannot stand in for every probiotic formulation.

One apparent exception also supports that caution. In Southern Chinese participants with sleep disturbance and mood symptoms, an eight-week multi-strain E3 probiotic improved self-reported sleep quality, depressive symptoms, and anxiety symptoms in a 2023 study by Chan et al.. The formulation, participant characteristics, endpoints, and follow-up differed from the smoker trial. The studies should not be treated as interchangeable.

Biomarkers changed, but they do not reveal a mechanism

Sadeghi's probiotic group had significant improvements in fasting plasma glucose, triglycerides, and CRP. These metabolic findings have more precedent than the dependence signal. A double-blind trial in adults with subthreshold depression also reported psychosocial and biomarker improvements with a probiotic blend (Moschonis et al.). A trial in men with obesity undergoing caloric restriction found improvements in body composition, quality of life, and psychobiological factors with probiotic supplementation in a metabolically dysregulated population (Marques et al.).

CRP is an inflammation marker, not evidence that inflammation caused the NDSS change. A systematic review in inflammatory bowel disease found inconsistent effects of mood interventions on inflammatory biomarkers. That evidence does not establish a simple causal chain from probiotic use to lower CRP to better mood or less nicotine dependence.

The gut-brain explanation remains untested in smokers

The trial did not measure gut microbiome composition, short-chain fatty acids, BDNF, GABA, cortisol, gut-permeability markers, or dopamine-pathway metabolites. It therefore cannot identify a biological route through which the supplement might have affected NDSS scores.

Human research does support the possibility of a gut-to-brain signal. A randomized neuroimaging study by Rode et al. found that a multi-strain probiotic changed brain morphology and resting-state functional connectivity in healthy participants. It did not study smoking, nicotine reward, addiction circuitry, or dopaminergic signaling. Those proposed mechanisms remain speculative in smokers.

One small 12-week trial found lower NDSS scores with a specific low-dose probiotic. It found no significant mood benefit and did not measure smoking cessation, microbiome change, or biological mediators.

The practical verdict is narrow. Probiotics are not established aids for quitting smoking, and this trial does not show that they are. It does justify a larger replication that is powered for NDSS, tracks FTND and smoking outcomes, verifies microbiome change, measures plausible biological intermediates, and includes smokers with subthreshold mood symptoms. Until then, proven smoking-cessation treatments deserve the job.