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American Ginseng Extract Improves Working Memory in Schizophrenia Patients

Reviewed: Chen EYH, Hui CLM. HT1001, a proprietary North American ginseng extract, improves working memory in schizophrenia: a double-blind, placebo-controlled study. Phytother Res. December 2011; 26(8):1166-1172.

Schizophrenia affects cognitive function and causes memory impairment. In particular, working memory — temporary memory storage for language comprehension, learning, and reasoning — is severely affected in patients with schizophrenia. The cognitive dysfunction may be caused by cholinergic abnormalities (deficits in working memory and other cognitive domains associated with reductions in production of the neurotransmitter acetylcholine and resultant nerve transmission) and therapeutic options are limited. Ginsenosides, the major bioactive components of American ginseng (Panax quinquefolius, Araliaceae) root, are thought to help cognition by working on the cholinergic system. The purpose of this randomized, double-blind, placebo-controlled study was to evaluate a proprietary American ginseng product, HT1001 (Afexa Life Sciences Inc.; Edmonton, Alberta, Canada*), on working memory in patients with schizophrenia. HT1001 is claimed to be unique because it has undergone a chemical fingerprinting and biological characterizing technology (ChemBioPrint®; Afexa Life Sciences Inc.) that ensures consistency between batches, that its primary active ingredients are quantitated, and that impurities are eliminated. (HT1001 is different chemically and hence biologically from the CVT-E002 [aka COLD-FX®] extract made by the same company, the latter being standardized to primarily polysaccharides from the ginseng root, with little to no ginsenosides.)

Patients (n=64; aged 18-55 years) with stable schizophrenia (defined as having no significant change in medication or symptoms over the previous 3 months) were recruited from in- and outpatient facilities in Hong Kong. Patients were excluded if they had a history of significant medical illness, mental retardation, comorbid substance abuse, recent (within 2 years) electroconvulsive therapy, required a change in medication, or if they were at risk of violence or suicide. Patients received either placebo or 200 mg/day HT1001 along with their regular medication for 4 weeks. This dose was equivalent to 1000 mg dried American ginseng root. A battery of tests was conducted at baseline and after 4 weeks of treatment to assess efficacy. The Positive and Negative Syndrome Scale (PANSS) was used to assess the positive and negative symptoms of schizophrenia. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess depressive symptoms. The Abnormal Involuntary Movement Scale, the Barnes Akathisia Rating Scale, and the Simpson-Angus Scale were used to assess dyskinesia, akathisia, and extrapyramidal symptoms, respectively. The Letter-Number Span Test of the Wechsler Adult Intelligence Scale–3rd Edition (WAIS-III) was used to assess verbal working memory. The Visual Pattern Test was used as a test of visual working memory.

At baseline, there were no significant differences between groups in the overall cognitive profile, working memory, severity of illness symptoms, or medication side effects. On the Visual Pattern Test performance, the HT1001-treated patients had a significant improvement over baseline (P<0.006); in contrast, the placebo-treated group had no significant change. The HT1001-treated patients had no significant improvement over baseline on the Letter-Number Span Test; however, the placebo-treated group had a significant decline on the test compared with baseline (P<0.01). Both groups had similar changes, or lack of changes, in clinical symptoms, except for extrapyramidal side effects (abnormalities in gait, excessive muscle rigidity, muscle spasms, and tics). The HT1001-treated patients had a significant improvement over baseline in extrapyramidal side effects (P<0.015).

The authors conclude that HT1001 significantly improved visual working memory function in patients with stable schizophrenia and prevented a decline in verbal working memory function. Another important finding was that HT1001 reduced extrapyramidal side effects caused by schizophrenia medication. These symptoms are a major cause of distress, morbidity, and treatment noncompliance. The authors think that this is the first study to examine the effects of an American ginseng extract on cognition in patients with schizophrenia. Herb-drug interactions are important considerations, and studies suggest that American ginseng should not be used with the anticoagulant warfarin (Coumadin®) Future studies are needed to assess the potential for HT1001 and conventional drug interactions. This study shows promise for patients with schizophrenia.

—Heather S. Oliff, PhD

*Purchased by Valeant Pharmaceuticals, Inc., in October 2011.