A Set Back for Probiotics, but Other Supplements Have a Role in Addictions
REVIEW OF: Mosavat SH et al, BMC Psychiatry 2026
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
EVIDENCE GRADE: Moderate (7/10), small size
Background
Probiotics improved psychiatric symptoms in dozens of small placebo-controlled trials, mainly in depression (n=20) and anxiety (n=30). They work better in clinically diagnosed patients, reducing depression with a large effect size (0.6–1.3) and anxiety with a moderate one (0.2–1.0). They also improve cognitive symptoms in depressed patients and have at least one study in treatment-resistant depression.
What we don’t know is whether they work in substance-induced depression. Research on gut-brain axis suggests possible benefits, and this small pilot trial from Iran put that question to a direct test.
The Study
40 adults with DSM-5 substance-induced depressive disorder were randomized to four weeks of a Lactobacillus helveticus and Bifidobacterium longum probiotic (Moodamin, two capsules daily) or placebo, added to standard care including therapy and antidepressants as clinically indicated. The paper lacks details on what type of substances were involved, but imply opium. Depression was measured with the BDI and anxiety with the HAM-A. Inflammatory cytokines including IL-6, IFN-gamma, IL-17, and IL-22 were also assessed.
Both groups improved substantially. BDI scores dropped from roughly 43 to 10 in the probiotic group and from 40 to 14 in the placebo group — neither the depression nor anxiety outcomes differed between groups. Cytokine changes were also nonsignificant, though there were small downward trends in IL-6 in the probiotic arm.
The negative results dispute the cynicism that “Iran only publishes positive trials,” but why did probiotics fail? Either the study was too small, the placebo response was too big, or they don’t work in this population.
Practice Implications
- When patients with substance-induced depression want to try a natural approach, don’t reach for probiotics
- N-Acetylcysteine (NAC) has more positive in various substance-induced mood symptoms, though the data there is still weak
- In opioid use disorder, saffron has positive trials and a biological mechanism, modulating opioid transmission
- In cocaine and methamphetamine use disorders, citicoline improves mood and cognitive symptoms
- In alcohol use disorders, acetyl-l-carnitine treats depression, while magnesium protects the liver (and may improve depression. These patients often have low magnesium levels inside the liver even when they are normal in the bloodstream. B vitamins provide essential protection against anemia and brain damage in alcohol use disorder (typical preventative doses are vitamin B1 100 mg qd, vitamin B9 1 mg qd, Vitamin B12 1 mg po qd, though higher or IV doses may be needed in severe or inpatient populations).
- Stick with lab-tested products when using supplements in psychiatry
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
Share Your Input in Comments
- Are you seeing responses to probiotics in practice?
- Which supplements do you find effective in substance use disorders?
