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A preliminary, randomized, double-blind, placebo-controlled trial of L-carnosine to improve cognition in
K N Roy Chengappa1, Scott R Turkin, Susan DeSanti
1Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, PA 15213-2593, USA. chengappakn@upmc.edu
Background:
Targeting glutamatergic dysfunction provides an exciting opportunity to improve cognitive impairment in schizophrenia. One treatment approach has targeted inadequate antioxidant defenses at glutamatergic synapses. Animal and human data suggest NMDA antagonists worsen executive cognitive controls--e.g. increase perseverative responses and impair set-shifting. We conducted a preliminary study to test the hypothesis that L-carnosine, an antioxidant and anti-glycation agent which is co-localized and released with glutamate would improve executive dysfunction, a cognitive domain associated with glutamate.
Methods:
Seventy-five symptomatically stable adults with chronic schizophrenia were randomly assigned to L-carnosine as adjunctive treatment (2 g/day) or a matched placebo in a double-blind manner for 3 months. Cognitive domains (executive dysfunction, memory, attention and motor speed) were assessed using a computerized battery at baseline, 4 and 12 weeks, along with psychopathology ratings and safety parameters.
Results:
The L-carnosine group performed significantly faster on non-reversal condition trials of the set-shifting test compared with placebo but reversal reaction times and errors were not significantly different between treatments. On the strategic target detection test, the L-carnosine group displayed significantly improved strategic efficiency and made fewer perseverative errors compared with placebo. Other cognitive tests showed no significant differences between treatments. Psychopathology scores remained stable. The carnosine group reported more adverse events (30%) compared with the placebo group (14%). Laboratory indices remained within acceptable ranges.
Conclusions:
These preliminary findings suggest that L-carnosine merits further consideration as adjunctive treatment to improve executive dysfunction in persons with schizophrenia.
Insights
L-carnosine supplementation improved executive dysfunction in schizophrenia patients by enhancing strategic efficiency and reducing perseverative errors. Further research is warranted for this promising adjunctive treatment.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Glutamatergic dysfunction is a key factor in cognitive impairment in schizophrenia.
- Antioxidant strategies targeting glutamatergic synapses offer a potential therapeutic avenue.
- NMDA antagonists exacerbate executive cognitive deficits in schizophrenia.
Purpose of the Study:
- To investigate the efficacy of L-carnosine as an adjunctive treatment for executive dysfunction in schizophrenia.
- To assess L-carnosine's impact on cognitive domains, psychopathology, and safety.
- To test the hypothesis that L-carnosine improves executive dysfunction associated with glutamate.
Main Methods:
- A 3-month, double-blind, placebo-controlled study involving 75 adults with chronic schizophrenia.
- Participants received either L-carnosine (2 g/day) or a placebo as adjunctive therapy.
- Cognitive functions, psychopathology, and safety were assessed using a computerized battery and rating scales.
Main Results:
- L-carnosine significantly improved performance on set-shifting non-reversal trials and strategic target detection.
- The L-carnosine group exhibited enhanced strategic efficiency and fewer perseverative errors.
- No significant differences were observed in other cognitive domains; psychopathology remained stable.
Conclusions:
- L-carnosine shows potential as an adjunctive treatment to improve executive dysfunction in schizophrenia.
- Further investigation into L-carnosine's therapeutic benefits for schizophrenia-related cognitive deficits is recommended.
- While generally safe, L-carnosine was associated with a higher incidence of adverse events compared to placebo.
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