Soy isoflavones for the treatment of cocaine use disorder: an open-label pilot study.

2025-12-23
Adicciones 37(4)
- Roser Martínez-Riera
- Francina Fonseca
- Rafael De La Torre
- Nieves Pizarro
- Liliana Galindo
- Joan Ignasi Mestre-Pinto
- Magí Farré
- Marta Torrens

PubMed: 41557447
DOI: 10.20882/adicciones.2428

Study Design

Type: Clinical Trial
Population: 9 subjects with severe cocaine use disorder
Methods: single-center, open, non-controlled trial during 12 weeks of treatment and 4 of follow-up
Blinding: Open-label
Duration: 12 weeks of treatment and 4 of follow-up

Soybeans contain different isoflavones (mainly daidzein) which work as reversible inhibitors of aldehyde-dehydrogenase-2 enzyme (ALDH2). This activity has been related in animal experiments with a reduction of cocaine use. Our aim was to carry out an open-label pilot study to evaluate the possible efficacy of soy isoflavones as natural inhibitor of ALDH2 in cocaine use disorder. Nine subjects with severe cocaine use disorder participated in a single-center, open, non-controlled trial during 12 weeks of treatment and 4 of follow-up. The Substance Use Report (SUR) showed that three subjects (33.3%) reported a cocaine consumption of less than 20% (80% non-use days) from 10 to 12 weeks of the treatment period, from two (22.2%) at baseline, although non-significant. A finding that could not be confirmed by the detection of urine metabolites of cocaine. Seven participants (77.8%) completed the study at 16 weeks and one (1.11%) at 12 weeks. Urine concentrations of isoflavones, demonstrated that eight participants (88.9%) followed the treatment along the study. The Severity Dependence Scale (SDS) score showed a significant decrease between baseline to 12 weeks, baseline to 16 weeks and 12 to 16 weeks; the Brief Substance Craving Scale (BSCS) and Cocaine Selective Severity Assessment (CSSA) decreased their values but not significantly. Significant improvements in different areas of the SF-36 scale were observed: body pain scores decreased from baseline to 16 weeks statistically significant; social function improved its scores from baseline to 12 weeks and from baseline to 16 weeks significantly; the rest of areas increased their scores but not significantly. These findings show lower ratios of cocaine use days, and high retention and adherence to treatment although the acquisition of complete abstinence was not observed. Soy isoflavones could be considered a potential treatment in future research, to be confirmed by placebo-controlled studies with adequate sample size.

Research Insights

Soy→Improved General Health
the rest of areas increased their scores but not significantly
Effect
Neutral
Effect size
Small
Soy→Improved Mental Health
the rest of areas increased their scores but not significantly
Effect
Neutral
Effect size
Small
Soy→Improved Physical Function
the rest of areas increased their scores but not significantly
Effect
Neutral
Effect size
Small
Soy→Improved Role Emotional
the rest of areas increased their scores but not significantly
Effect
Neutral
Effect size
Small
Soy→Improved Role Physical
the rest of areas increased their scores but not significantly
Effect
Neutral
Effect size
Small
Soy→Improved Social Functioning
social function improved its scores from baseline to 12 weeks and from baseline to 16 weeks significantly
Effect
Beneficial
Effect size
Moderate
Soy→Improved Vitality
the rest of areas increased their scores but not significantly
Effect
Neutral
Effect size
Small
Soy→Reduced Bodily Pain
body pain scores decreased from baseline to 16 weeks statistically significant
Effect
Beneficial
Effect size
Moderate
Soy→Reduced Cocaine Consumption Days
three subjects (33.3%) reported a cocaine consumption of less than 20% (80% non-use days) from 10 to 12 weeks of the treatment period, from two (22.2%) at baseline, although non-significant
Effect
Neutral
Effect size
Small
Soy→Reduced Cocaine Withdrawal Severity
the Brief Substance Craving Scale (BSCS) and Cocaine Selective Severity Assessment (CSSA) decreased their values but not significantly.
Effect
Neutral
Effect size
Small
Soy→Reduced Craving
the Brief Substance Craving Scale (BSCS) and Cocaine Selective Severity Assessment (CSSA) decreased their values but not significantly.
Effect
Neutral
Effect size
Small
Soy→Reduced Dependence Severity
The Severity Dependence Scale (SDS) score showed a significant decrease between baseline to 12 weeks, baseline to 16 weeks and 12 to 16 weeks
Effect
Beneficial
Effect size
Small
Soy→Reduced Urine Cocaine Metabolite Level
A finding that could not be confirmed by the detection of urine metabolites of cocaine.
Effect
Neutral
Effect size
Small