Panax Ginseng
Panax Ginseng is a plant species native to asia that has been used extensively in traditional medicines. There have been numerous double blind placebo controlled trials that demonstrate cognitive benefits particularly in relation to serial 3 and seven tests which test for mental arithmetic, concentration and short term memory.
Effective for - healthy adults
Effective dose - 200 to 400mg of extract
Length of action - 60 minutes to 6 hours
Type cognition effected - memory quality, secondary memory, mental arithmetic, mental fatigue, abstract thinking, simple reaction times and speed of attention have reported improvement
Type of cognition impeded - speed of attention has reported interference
Enhancers - Guarana and Ginkgo Biloba
Supporting Human Studies
Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity (Reay et al, 2005)
Using a double-blind, placebo-controlled, balanced crossover design, 30 healthy young adults completed a 10min test battery at baseline, and then six times in immediate succession commencing 60min after the day’s treatment (placebo, 200mg G115 or 400mg G115). The 10 min battery comprised a Serial Threes subtraction task (2min); a Serial Sevens task (2min); a Rapid Visual Information Processing task (5min); then a ‘mental fatigue’ visual analogue scale. Blood glucose was measured prior to each day’s treatment, and before, during and after the post-dose completions of the battery. Both the 200mg and 400mg treatments led to significant reductions in blood glucose levels at all three post-treatment measurements (p 0.005 in all cases). The most notable behavioural effects were associated with 200mg of ginseng and included significantly improved Serial Sevens subtraction task performance and significantly reduced subjective mental fatigue throughout all (with the exception of one time point in each case) of the post-dose completions of the 10min battery (p 0.05).
Dose dependent changes in cognitive performance and mood following acute administration of Ginseng to healthy young volunteers (Kennedy et al, 2001)
Recent evidence suggests that chronic administration of Ginseng can improve cognitive performance in animals and in humans. No previous study has examined the possibility of cognitive effects following single doses of Ginseng in healthy adults. The present study investigated whether acute administration of Ginseng (G115, Pharmaton SA) had any consistent effect on mood and four aspects of cognitive performance ("Quality of Memory", "Speed of Memory", "Quality of Attention" and "Speed of Attention") that can be derived by factor analysis of the Cognitive Drug Research computerised assessment battery. The study followed a placebo-controlled, double-blind, balanced, crossover design. Twenty healthy young adult volunteers received 200, 400, and 600 mg of G115, and a matching placebo, in counterbalanced order, with a 7 day wash-out period between treatments. Following a baseline cognitive assessment, further test sessions took place 1, 2.5, 4 and 6 h after the day's treatment. The most striking result was a significant improvement in "Quality of Memory" and the associated "Secondary Memory" factor at all time points following 400 mg of Ginseng. Both the 200 and 600 mg doses were associated with a significant decrement of the "Speed of Attention" factor at later testing times only. Subjective ratings of alertness were also reduced 6 h following the two lowest doses. To the best of our knowledge this represents the first demonstration of a modulation of mood and cognitive performance by acute administration of Ginseng.
Effects of Panax ginseng, consumed with and without glucose, on blood glucose levels and cognitive performance during sustained ‘mentally demanding’ tasks (Reay et al, 2006)
Using a double-blind, placebo-controlled, balanced-crossover design, 27 healthy young adults completed a 10 minute “cognitive demand” test battery at baseline. They then consumed capsules containing either ginseng (extract G115) or a placebo and 30 minutes later a drink containing glucose or placebo. A further 30 minutes later they completed the “cognitive demand” battery six times in immediate succession. Depending on the condition to which the participant was allocated on that particular day, the combination of capsules/drink treatments corresponded to a dose of: 0mg G115/0mg glucose (placebo); 200mg G115/0mg glucose (ginseng); 0mg G115/25g glucose (glucose) or 200mg G115/25g glucose (ginseng/glucose combination). The 10 minute “cognitive demand” battery comprised a Serial Threes subtraction task, a Serial Sevens subtraction task, a Rapid Visual Information Processing task, and a “mental fatigue” visual analogue scale. Blood glucose levels were measured prior to the day's treatment, and before and after the post-dose completions of the battery. The results showed that both Panax ginseng and glucose enhanced performance of a mental arithmetic task and ameliorated the increase in subjective feelings of mental fatigue experienced by participants during the later stages of the sustained, cognitively demanding task performance. Accuracy of performing the Rapid Visual Information Processing task (RVIP) was also improved following the glucose load. There was no evidence of a synergistic relationship between Panax ginseng and exogenous glucose ingestion on any cognitive outcome measure.
A double masked study of the effects of ginseng on cognitive functions (Sorensen and Sonne, 1996)
The effects of a pure ginseng preparation on a variety of cognitive functions was compared with those of placebo in a double-masked, randomized, test-retest design. The subjects were healthy volunteers older than 40 years of age who were given the ginseng preparation or placebo for 8 to 9 weeks. Of the 112 subjects who completed the study, 55 received ginseng and 57 received placebo. The ginseng group showed a tendency to faster simple reactions and significantly better abstract thinking than the controls. However, there was no significant difference between the two groups in concentration, memory, or subjective experience.
The effect of acute administration of 400mg of Panax ginseng on cognitive performance and mood in healthy young volunteers (Sunram-Lea et al, 2005)
Recent evidence suggests that single dose administration of ginseng can improve certain aspects of cognitive performance and mood in healthy young volunteers in a dose and time dependent manner. The aim of this study was to investigate the effect of acute administration of 400 mg of a standardized Panax ginseng extract (G115 .,Pharmaton SA)on mood and cognitive performance. Following a double-blind, placebo controlled, balanced, cross-over design, thirty healthy young adult volunteers received 400 mg of ginseng, and a matching inert placebo, in a counterbalanced order, with a 7-day washout period between treatments. Following baseline evaluation of cognitive performance and mood measures, participants9 cognitive performance and mood was assessed again 90 minutes after drug ingestion. Ginseng improved speed of attention, indicating a beneficial effect on participants9 ability to allocate attentional processes to a particular task. No significant effect was observed on any other aspect of cognitive performance and on self-reported mood measures. Previous research demonstrated no improvement on attentional processes, but significant improvements on tasks associated with episodic memory performance following administration of 400 mg of ginseng when participants were tested 1h,2.5h,4,h and 6h post ingestion. Consequently, it may be the case that ginseng offers alternative windows of therapeutic opportunity on different aspects of cognitive performance at different time points.
Panax ginseng (G115) improves aspects of working memory performance and subjective ratings of calmness in healthy young adults (Reay et al, 2010)
There is a lack of research into the cognitive and mood effects of repeated ginseng ingestion. The present study assessed the effects ofPanax ginseng (G115) on subjective mood and aspects of ‘working’ memory processes, following a single dose and following sub-chronic (7 days) ingestion, in healthy volunteers. A placebo-controlled, double-blind, randomised, crossover was utilised. Thirty volunteers (mean age 22.87 years; SD 4.01) received each treatment (200 mg; 400 mg; placebo) for 8 days, in a counter balanced order, with a 6-day wash-out period. Testing was on days 1 and 8 of each treatment period, at pre-dose, 1, 2.5 and 4 h post-dose. Results revealed dose-related treatment effects (p < 0.05). Two hundred milligrams slowed a fall in mood at 2.5 and 4 h on day 1 and at 1 and 4 h on day 8, but slowed responding on a mental arithmetic task across day 1 and at 1 and 2.5 h on day 8. The 400 mg dose also improved calmness (restricted 2.5 and 4 h on day 1) and improved mental arithmetic across days 1 and 8. We found no evidence of additional benefits, nor attenuation of acute effects following repeated ingestion of Panax ginseng (G115).
Supporting Animal Studies
Panax ginseng extract improves the performance of aged Fischer 344 rats in radial maze task but not in operant brightness discrimination task (Nitta et al, 1995)
The effect of Panax ginseng extract on the learning performance of aged Fischer 344 rats using the 8-arm radial maze task and the operant discrimination task was examined. Aged rats showed significantly impaired learning performance in both tasks. Daily administration of ginseng extract (8 g/kg/d, p.o. for 12-33 d) ameliorated the impairment of learning performance in the radial maze task but not in the operant discrimination task. These results suggest that subchronic treatment with ginseng extract improves spatial cognitive impairment in aged rats.
Memory effects of standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK 501) and their combination Gincosan (Petkov et al, 1993)
In experiments on young (aged 3 months) and old (aged 26 months) rats, using some conditioned-reflex methods with punishment or positive reinforcement for active and passive avoidance (shuttle-box, step-down, step-through, and water maze), we studied the effects of the standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK501) and their combination Gincosan (PHL-00701). The extracts were administered orally for 7 days before training at three increasing doses: 17, 50, and 150 mg/kg for G115; 10, 30, and 90 mg/kg for GK501; and 27, 80, and 240 mg/kg for PHL-00701. The two extracts and their combination improved the retention of learned behavior. This effect varied considerably with the extracts, with the dose and with the behavioral method used. The results suggest that the Panax ginseng G115 and the Ginkgo biloba GK501 extracts possess properties similar in every respect to those of nootropic drugs.
Effects of Standarized Ginseng Extract on Learning, Memory and Physical Capabilites (Petkov and Mosharrof, 1987)
Standardized ginseng extract (G115, Pharmaton, Lugano) was administered orally at doses of 3,10,30,100 and 300 mg/kg for 10 days as ten rats were used wtih each dose. With the "shuttle-box" method for active avoidance most pronounced effect on learning and memory was obtained by the dose of 10 mg/kg. With the "step-down" method for passive avoidance the dose of 30 mg/kg significantly improved retention. In the staircase maze training with positive (alimentary) reinforcement only the dose of 10 mg/kg significantly improved learning and memory. The dose of 100 mg/kg greatly increased the locomotor activity of mice.
Beneficial effects of S-113m, a novel herbal prescription, on learning impairment model in mice (Nishiyama et al, 1995)
The effects of S-113m, a novel herbal prescription consisting of Biota orientalis, Panax ginseng and Schisandra chinensis, were studied regarding learning and memory performance in the step-down and lever-press tests in normal, as well as in learning-impaired, mice. The prescription had no effect on memory registration, consolidation and retrieval processes or on motor activity in normal mice. However, a single oral administration of S-113m at doses of 250 and 500 mg/kg reduced the ethanol-induced and scopolamine-induced impairment of memory registration in the step-down test. The preparation also improved the electroconvulsive shock-induced impairment of memory consolidation in the same test. S-113m did not, however, attenuate the ethanol-induced impairment of memory retrieval. These results suggest that S-113m has a preferential beneficial effect on the impairment of memory registration and memory consolidation rather than on memory retrieval in mice, through direct action on the learning and memory processes.
Ginsenoside Rb1 improves spatial learning and memory by regulation of cell genesis in the hippocampal subregions of rats (Liu et al, 2011)
Ginsenoside Rb1 (Rb1) is known to improve learning and memory in hippocampus-dependent tasks. However, the cellular mechanism remains unknown. Cell genesis in hippocampus is involved in spatial learning and memory. In the present study, Rb1 was orally administrated to adult rats for 30days. The behavioral training tests indicated that Rb1 improved spatial cognitive performance of rats in Morris water maze (MWM). Furthermore, we investigated the effects of Rb1 on cell genesis in adult rats' hippocampus, using thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. It has been shown that hippocampal cell genesis can be influenced by several factors such as learning and exercise. In order to avoid the effects of the interfering factors, only the rats treated with Rb1 without training in MWM were used to investigate cell genesis in hippocampus. When BrdU was given to the rats 30days prior to being killed, it was shown that oral administration of Rb1 significantly increased cell survival in dentate gyrus and hippocampal subregion CA3. However, when BrdU was injected 2h prior to sacrifice, the results indicated that Rb1 had no significant influence on cell proliferation in the hippocampal subregions. Thus, an increase of cell survival in hippocampus stimulated by Rb1 may be one of the mechanisms by which ginseng facilitates spatial learning and memory. Our study also indicates that Rb1 may be developed as a therapeutic agent for patients with memory impairment.
Contradictory Studies
Gincosan (A Combination of Ginkgo biloba and Panax ginseng ): The Effects on Mood and Cognition of 6 and 12 Weeks' Treatment in Post-menopausal Women (Hartley et al, 2004)
In a double-blind placebo controlled study, post-menopausal women aged 51-66 were randomly assigned to 12 weeks treatment with Gincosan (320 mg/day), containing 120 mg Ginkgo biloba , and 200 mg Panax ginseng ( n =30), or matched placebo ( n =27). They were given measurements of mood, somatic anxiety, sleepiness, and menopausal symptoms and a battery of cognitive tests before treatment and after 6 and 12 weeks of treatment. There were no significant effects of Gincosan treatment on ratings of mood, bodily symptoms of somatic anxiety, menopausal symptoms, or sleepiness or on any of the cognitive measures of attention, memory or frontal lobe function. Thus, after chronic administration, Gincosan appeared to have no beneficial effects in post-menopausal women.
Combinational Studies
The Memory enhancing effects of a Ginkgo Biloba/Panax Ginseng combination in healthy middle aged volunteers (Wesnes et al, 2000)
The effects of capsules containing 60 mg of a standardised extract of Ginkgo biloba (GK501) and 100 mg of a standardised extract of Panax ginseng (G115) on various aspects of cognitive function were assessed in healthy middle-aged volunteers. A double blind, placebo controlled, 14 week, parallel group, repeated assessment, multi-centre trial of two dosing regimens, 160 mg b.i.d. and 320 mg o.d. was conducted. Two hundred and fifty-six healthy middle-aged volunteers successfully completed the study. On various study days (weeks 0, 4, 8, 12 and 14) the volunteers performed a selection of tests of attention and memory from the Cognitive Drug Research computerised cognitive assessment system prior to morning dosing and again, at 1, 3 and 6 h later. The volunteers also completed questionnaires about mood states, quality of life and sleep quality. The Ginkgo/ginseng combination was found significantly to improve an Index of Memory Quality, supporting a previous finding with the compound. This effect represented an average improvement of 7.5% and reflected improvements to a number of different aspects of memory, including working and long-term memory. This enhancement to memory was seen throughout the 12-week dosing period and also after a 2-week washout. This represents the first substantial demonstration of improvements to the memory of healthy middle-aged volunteers produced by a phytopharmaceutical.
Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and a ginkgo/ginseng combination to healthy young adults (Kennedy et al, 2002)
The present study directly compared the effects of single doses of G. biloba, ginseng, and a product combining the two on aspects of mood and cognitive performance in the same cohort of healthy, young adult volunteers. The study followed a randomised placebo-controlled, double-blind, balanced, cross-over design. Twenty participants received 360 mg of ginkgo, 400 mg of ginseng, 960 mg of a product combining the two extracts, and a matching placebo. Treatment order was dictated by random allocation to a Latin square, with a 7-day wash-out period between treatments. Cognitive testing comprised completion of the Cognitive Drug Research (CDR) computerised assessment battery and two serial subtraction mental arithmetic tasks. Mood was assessed with Bond-Lader visual analogue scales. Following a baseline cognitive assessment, further test sessions took place 1, 2.5, 4, and 6 h after the day's treatment was taken. The results largely supported previous findings. All three treatments were associated with improved secondary memory performance on the CDR battery, with the ginseng condition evincing some improvement in the speed of performing memory tasks and in the accuracy of attentional tasks. Following ginkgo and the ginkgo/ginseng combination performance of both the Serial Threes and Serial Sevens, subtraction tasks was also improved at the later testing sessions. No modulation of the speed of performing attention tasks was evident.
Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng (Kennedy et al, 2004)
In this double-blind, counterbalanced, placebo-controlled study, the cognitive and mood effects of separate single doses of: 75 mg of a dried ethanolic extract of guarana (approx 12% caffeine), 200 mg of Panax ginseng (G115), and their combination (75 mg/200 mg), were assessed in 28 healthy young (18-24) participants. On each day of the study (separated by a 7-day washout), cognitive performance and subjective mood were assessed pre-dose and at 1, 2.5, 4 and 6 h post-dose using the Cognitive Drug Research computerised assessment battery, Serial subtraction tasks and Bond-Lader mood scales. In comparison to placebo, all three treatments resulted in improved task performance throughout the day. In the case of guarana, improvements were seen across 'attention' tasks (but with some evidence of reduced accuracy), and on a sentence verification task. While also increasing the speed of attention task performance, both ginseng and the ginseng/guarana combination also enhanced the speed of memory task performance, with little evidence of modulated accuracy. Guarana and the combination, and to a lesser extent ginseng, also led to significant improvements in serial subtraction task performance.
Acute, dose-dependent cognitive effects of Ginkgo biloba, Panax ginseng and their combination in healthy young volunteers: differential interactions with cognitive demand (Scholey and Kennedy, 2002)
The present paper describes three studies examining the acute effects of single doses of Ginkgo biloba (GK501), Ginseng (G115) and their combination (Ginkoba M/E, Pharmaton SA) on the performance of healthy young adults (mean age 21 years) during serial arithmetic tasks with differing cognitive load. In each double-blind, placebo-controlled study three different treatment doses and a placebo were administered, according to a balanced crossover design, with a 7-day washout period between each dose. Participants' scores on two computerised serial subtraction tasks (Serial Threes and Serial Sevens) were assessed pre-dosing and at 1, 2.5, 4 and 6 h thereafter. A number of significant time, dose and task-specific effects were associated with each treatment. There was a dose-dependent improvement in speed of responding during Serial Threes following Ginkgo biloba. Different doses of Ginseng improved accuracy and slowed responses during Serial Sevens. The most striking result, however, was a highly significant and sustained increase in the number of Serial Sevens responses following 320 mg of the Ginkgo–Ginseng combination at all post-treatment testing times. This was accompanied by improved accuracy during Serial Sevens and Serial Threes following the 640 mg and the 960 mg dose, respectively.
Differential, dose dependent changes in cognitive performance following acute administration of a Ginkgo biloba/Panax ginseng combination to healthy young volunteers (Kennedy et al, 2001)
The present study investigated whether acute administration of a combination of standardised extracts of Ginkgo biloba (GK501, Pharmaton SA) and Ginseng (G115, Pharmaton SA) had any consistent effect on mood and aspects of cognitive performance (quality of memory, secondary memory, working memory, speed of memory, quality of attention and speed of attention) that can be derived by factor analysis of the cognitive drug research computerised assessment battery. The study followed a placebo-controlled, double blind, balanced, crossover design. Twenty healthy young adult volunteers received 320, 640, and 960 mg of the combination, a matching placebo with a seven-day wash-out period between treatments. Following a baseline cognitive assessment, further test sessions took place 1, 2.5,4 and 6 h after the day's treatment. The most striking result was a dose-dependent improvement in performance on the quality of memory factor for the highest dose. Further analysis revealed that this effect was differentially targeted at the secondary memory rather than the working memory component. There was also a dose dependent decrement in performance of the speed of attention factor for both the 320 and 640 mg doses.
The cognitive, subjective, and physical effects of a ginkgo biloba/panax ginseng combination in healthy volunteers with neurasthenic complaints (Wesnes et al, 1997)
Sixty-four healthy volunteers (aged 40 to 65 years) were assigned randomly to four equal dosing groups, receiving 80, 160, or 320 mg of the combination ginkgo biloba/ginseng or placebo. Assessments were performed on the day before dosing, and again at Days 1, 30, and 90 at 1 hour after the morning dose and 1 hour after the afternoon dose. The assessments included the Cognitive Drug Research (CDR) computerized assessment system, the Vienna Determination Unit, cycle ergometry, and various questionnaires. The treatments were well tolerated by all volunteers. On Day 90 at 1 hour post morning dosing, dose-related improvements were seen on the CDR tests, the 320 mg dose being significantly superior to placebo. These effects, however, were reversed 1 hour after the afternoon dose, possibly suggesting that a longer inter-dosing interval would be preferable.
Effective for - healthy adults
Effective dose - 200 to 400mg of extract
Length of action - 60 minutes to 6 hours
Type cognition effected - memory quality, secondary memory, mental arithmetic, mental fatigue, abstract thinking, simple reaction times and speed of attention have reported improvement
Type of cognition impeded - speed of attention has reported interference
Enhancers - Guarana and Ginkgo Biloba
Supporting Human Studies
Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity (Reay et al, 2005)
Using a double-blind, placebo-controlled, balanced crossover design, 30 healthy young adults completed a 10min test battery at baseline, and then six times in immediate succession commencing 60min after the day’s treatment (placebo, 200mg G115 or 400mg G115). The 10 min battery comprised a Serial Threes subtraction task (2min); a Serial Sevens task (2min); a Rapid Visual Information Processing task (5min); then a ‘mental fatigue’ visual analogue scale. Blood glucose was measured prior to each day’s treatment, and before, during and after the post-dose completions of the battery. Both the 200mg and 400mg treatments led to significant reductions in blood glucose levels at all three post-treatment measurements (p 0.005 in all cases). The most notable behavioural effects were associated with 200mg of ginseng and included significantly improved Serial Sevens subtraction task performance and significantly reduced subjective mental fatigue throughout all (with the exception of one time point in each case) of the post-dose completions of the 10min battery (p 0.05).
Dose dependent changes in cognitive performance and mood following acute administration of Ginseng to healthy young volunteers (Kennedy et al, 2001)
Recent evidence suggests that chronic administration of Ginseng can improve cognitive performance in animals and in humans. No previous study has examined the possibility of cognitive effects following single doses of Ginseng in healthy adults. The present study investigated whether acute administration of Ginseng (G115, Pharmaton SA) had any consistent effect on mood and four aspects of cognitive performance ("Quality of Memory", "Speed of Memory", "Quality of Attention" and "Speed of Attention") that can be derived by factor analysis of the Cognitive Drug Research computerised assessment battery. The study followed a placebo-controlled, double-blind, balanced, crossover design. Twenty healthy young adult volunteers received 200, 400, and 600 mg of G115, and a matching placebo, in counterbalanced order, with a 7 day wash-out period between treatments. Following a baseline cognitive assessment, further test sessions took place 1, 2.5, 4 and 6 h after the day's treatment. The most striking result was a significant improvement in "Quality of Memory" and the associated "Secondary Memory" factor at all time points following 400 mg of Ginseng. Both the 200 and 600 mg doses were associated with a significant decrement of the "Speed of Attention" factor at later testing times only. Subjective ratings of alertness were also reduced 6 h following the two lowest doses. To the best of our knowledge this represents the first demonstration of a modulation of mood and cognitive performance by acute administration of Ginseng.
Effects of Panax ginseng, consumed with and without glucose, on blood glucose levels and cognitive performance during sustained ‘mentally demanding’ tasks (Reay et al, 2006)
Using a double-blind, placebo-controlled, balanced-crossover design, 27 healthy young adults completed a 10 minute “cognitive demand” test battery at baseline. They then consumed capsules containing either ginseng (extract G115) or a placebo and 30 minutes later a drink containing glucose or placebo. A further 30 minutes later they completed the “cognitive demand” battery six times in immediate succession. Depending on the condition to which the participant was allocated on that particular day, the combination of capsules/drink treatments corresponded to a dose of: 0mg G115/0mg glucose (placebo); 200mg G115/0mg glucose (ginseng); 0mg G115/25g glucose (glucose) or 200mg G115/25g glucose (ginseng/glucose combination). The 10 minute “cognitive demand” battery comprised a Serial Threes subtraction task, a Serial Sevens subtraction task, a Rapid Visual Information Processing task, and a “mental fatigue” visual analogue scale. Blood glucose levels were measured prior to the day's treatment, and before and after the post-dose completions of the battery. The results showed that both Panax ginseng and glucose enhanced performance of a mental arithmetic task and ameliorated the increase in subjective feelings of mental fatigue experienced by participants during the later stages of the sustained, cognitively demanding task performance. Accuracy of performing the Rapid Visual Information Processing task (RVIP) was also improved following the glucose load. There was no evidence of a synergistic relationship between Panax ginseng and exogenous glucose ingestion on any cognitive outcome measure.
A double masked study of the effects of ginseng on cognitive functions (Sorensen and Sonne, 1996)
The effects of a pure ginseng preparation on a variety of cognitive functions was compared with those of placebo in a double-masked, randomized, test-retest design. The subjects were healthy volunteers older than 40 years of age who were given the ginseng preparation or placebo for 8 to 9 weeks. Of the 112 subjects who completed the study, 55 received ginseng and 57 received placebo. The ginseng group showed a tendency to faster simple reactions and significantly better abstract thinking than the controls. However, there was no significant difference between the two groups in concentration, memory, or subjective experience.
The effect of acute administration of 400mg of Panax ginseng on cognitive performance and mood in healthy young volunteers (Sunram-Lea et al, 2005)
Recent evidence suggests that single dose administration of ginseng can improve certain aspects of cognitive performance and mood in healthy young volunteers in a dose and time dependent manner. The aim of this study was to investigate the effect of acute administration of 400 mg of a standardized Panax ginseng extract (G115 .,Pharmaton SA)on mood and cognitive performance. Following a double-blind, placebo controlled, balanced, cross-over design, thirty healthy young adult volunteers received 400 mg of ginseng, and a matching inert placebo, in a counterbalanced order, with a 7-day washout period between treatments. Following baseline evaluation of cognitive performance and mood measures, participants9 cognitive performance and mood was assessed again 90 minutes after drug ingestion. Ginseng improved speed of attention, indicating a beneficial effect on participants9 ability to allocate attentional processes to a particular task. No significant effect was observed on any other aspect of cognitive performance and on self-reported mood measures. Previous research demonstrated no improvement on attentional processes, but significant improvements on tasks associated with episodic memory performance following administration of 400 mg of ginseng when participants were tested 1h,2.5h,4,h and 6h post ingestion. Consequently, it may be the case that ginseng offers alternative windows of therapeutic opportunity on different aspects of cognitive performance at different time points.
Panax ginseng (G115) improves aspects of working memory performance and subjective ratings of calmness in healthy young adults (Reay et al, 2010)
There is a lack of research into the cognitive and mood effects of repeated ginseng ingestion. The present study assessed the effects ofPanax ginseng (G115) on subjective mood and aspects of ‘working’ memory processes, following a single dose and following sub-chronic (7 days) ingestion, in healthy volunteers. A placebo-controlled, double-blind, randomised, crossover was utilised. Thirty volunteers (mean age 22.87 years; SD 4.01) received each treatment (200 mg; 400 mg; placebo) for 8 days, in a counter balanced order, with a 6-day wash-out period. Testing was on days 1 and 8 of each treatment period, at pre-dose, 1, 2.5 and 4 h post-dose. Results revealed dose-related treatment effects (p < 0.05). Two hundred milligrams slowed a fall in mood at 2.5 and 4 h on day 1 and at 1 and 4 h on day 8, but slowed responding on a mental arithmetic task across day 1 and at 1 and 2.5 h on day 8. The 400 mg dose also improved calmness (restricted 2.5 and 4 h on day 1) and improved mental arithmetic across days 1 and 8. We found no evidence of additional benefits, nor attenuation of acute effects following repeated ingestion of Panax ginseng (G115).
Supporting Animal Studies
Panax ginseng extract improves the performance of aged Fischer 344 rats in radial maze task but not in operant brightness discrimination task (Nitta et al, 1995)
The effect of Panax ginseng extract on the learning performance of aged Fischer 344 rats using the 8-arm radial maze task and the operant discrimination task was examined. Aged rats showed significantly impaired learning performance in both tasks. Daily administration of ginseng extract (8 g/kg/d, p.o. for 12-33 d) ameliorated the impairment of learning performance in the radial maze task but not in the operant discrimination task. These results suggest that subchronic treatment with ginseng extract improves spatial cognitive impairment in aged rats.
Memory effects of standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK 501) and their combination Gincosan (Petkov et al, 1993)
In experiments on young (aged 3 months) and old (aged 26 months) rats, using some conditioned-reflex methods with punishment or positive reinforcement for active and passive avoidance (shuttle-box, step-down, step-through, and water maze), we studied the effects of the standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK501) and their combination Gincosan (PHL-00701). The extracts were administered orally for 7 days before training at three increasing doses: 17, 50, and 150 mg/kg for G115; 10, 30, and 90 mg/kg for GK501; and 27, 80, and 240 mg/kg for PHL-00701. The two extracts and their combination improved the retention of learned behavior. This effect varied considerably with the extracts, with the dose and with the behavioral method used. The results suggest that the Panax ginseng G115 and the Ginkgo biloba GK501 extracts possess properties similar in every respect to those of nootropic drugs.
Effects of Standarized Ginseng Extract on Learning, Memory and Physical Capabilites (Petkov and Mosharrof, 1987)
Standardized ginseng extract (G115, Pharmaton, Lugano) was administered orally at doses of 3,10,30,100 and 300 mg/kg for 10 days as ten rats were used wtih each dose. With the "shuttle-box" method for active avoidance most pronounced effect on learning and memory was obtained by the dose of 10 mg/kg. With the "step-down" method for passive avoidance the dose of 30 mg/kg significantly improved retention. In the staircase maze training with positive (alimentary) reinforcement only the dose of 10 mg/kg significantly improved learning and memory. The dose of 100 mg/kg greatly increased the locomotor activity of mice.
Beneficial effects of S-113m, a novel herbal prescription, on learning impairment model in mice (Nishiyama et al, 1995)
The effects of S-113m, a novel herbal prescription consisting of Biota orientalis, Panax ginseng and Schisandra chinensis, were studied regarding learning and memory performance in the step-down and lever-press tests in normal, as well as in learning-impaired, mice. The prescription had no effect on memory registration, consolidation and retrieval processes or on motor activity in normal mice. However, a single oral administration of S-113m at doses of 250 and 500 mg/kg reduced the ethanol-induced and scopolamine-induced impairment of memory registration in the step-down test. The preparation also improved the electroconvulsive shock-induced impairment of memory consolidation in the same test. S-113m did not, however, attenuate the ethanol-induced impairment of memory retrieval. These results suggest that S-113m has a preferential beneficial effect on the impairment of memory registration and memory consolidation rather than on memory retrieval in mice, through direct action on the learning and memory processes.
Ginsenoside Rb1 improves spatial learning and memory by regulation of cell genesis in the hippocampal subregions of rats (Liu et al, 2011)
Ginsenoside Rb1 (Rb1) is known to improve learning and memory in hippocampus-dependent tasks. However, the cellular mechanism remains unknown. Cell genesis in hippocampus is involved in spatial learning and memory. In the present study, Rb1 was orally administrated to adult rats for 30days. The behavioral training tests indicated that Rb1 improved spatial cognitive performance of rats in Morris water maze (MWM). Furthermore, we investigated the effects of Rb1 on cell genesis in adult rats' hippocampus, using thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. It has been shown that hippocampal cell genesis can be influenced by several factors such as learning and exercise. In order to avoid the effects of the interfering factors, only the rats treated with Rb1 without training in MWM were used to investigate cell genesis in hippocampus. When BrdU was given to the rats 30days prior to being killed, it was shown that oral administration of Rb1 significantly increased cell survival in dentate gyrus and hippocampal subregion CA3. However, when BrdU was injected 2h prior to sacrifice, the results indicated that Rb1 had no significant influence on cell proliferation in the hippocampal subregions. Thus, an increase of cell survival in hippocampus stimulated by Rb1 may be one of the mechanisms by which ginseng facilitates spatial learning and memory. Our study also indicates that Rb1 may be developed as a therapeutic agent for patients with memory impairment.
Contradictory Studies
Gincosan (A Combination of Ginkgo biloba and Panax ginseng ): The Effects on Mood and Cognition of 6 and 12 Weeks' Treatment in Post-menopausal Women (Hartley et al, 2004)
In a double-blind placebo controlled study, post-menopausal women aged 51-66 were randomly assigned to 12 weeks treatment with Gincosan (320 mg/day), containing 120 mg Ginkgo biloba , and 200 mg Panax ginseng ( n =30), or matched placebo ( n =27). They were given measurements of mood, somatic anxiety, sleepiness, and menopausal symptoms and a battery of cognitive tests before treatment and after 6 and 12 weeks of treatment. There were no significant effects of Gincosan treatment on ratings of mood, bodily symptoms of somatic anxiety, menopausal symptoms, or sleepiness or on any of the cognitive measures of attention, memory or frontal lobe function. Thus, after chronic administration, Gincosan appeared to have no beneficial effects in post-menopausal women.
Combinational Studies
The Memory enhancing effects of a Ginkgo Biloba/Panax Ginseng combination in healthy middle aged volunteers (Wesnes et al, 2000)
The effects of capsules containing 60 mg of a standardised extract of Ginkgo biloba (GK501) and 100 mg of a standardised extract of Panax ginseng (G115) on various aspects of cognitive function were assessed in healthy middle-aged volunteers. A double blind, placebo controlled, 14 week, parallel group, repeated assessment, multi-centre trial of two dosing regimens, 160 mg b.i.d. and 320 mg o.d. was conducted. Two hundred and fifty-six healthy middle-aged volunteers successfully completed the study. On various study days (weeks 0, 4, 8, 12 and 14) the volunteers performed a selection of tests of attention and memory from the Cognitive Drug Research computerised cognitive assessment system prior to morning dosing and again, at 1, 3 and 6 h later. The volunteers also completed questionnaires about mood states, quality of life and sleep quality. The Ginkgo/ginseng combination was found significantly to improve an Index of Memory Quality, supporting a previous finding with the compound. This effect represented an average improvement of 7.5% and reflected improvements to a number of different aspects of memory, including working and long-term memory. This enhancement to memory was seen throughout the 12-week dosing period and also after a 2-week washout. This represents the first substantial demonstration of improvements to the memory of healthy middle-aged volunteers produced by a phytopharmaceutical.
Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and a ginkgo/ginseng combination to healthy young adults (Kennedy et al, 2002)
The present study directly compared the effects of single doses of G. biloba, ginseng, and a product combining the two on aspects of mood and cognitive performance in the same cohort of healthy, young adult volunteers. The study followed a randomised placebo-controlled, double-blind, balanced, cross-over design. Twenty participants received 360 mg of ginkgo, 400 mg of ginseng, 960 mg of a product combining the two extracts, and a matching placebo. Treatment order was dictated by random allocation to a Latin square, with a 7-day wash-out period between treatments. Cognitive testing comprised completion of the Cognitive Drug Research (CDR) computerised assessment battery and two serial subtraction mental arithmetic tasks. Mood was assessed with Bond-Lader visual analogue scales. Following a baseline cognitive assessment, further test sessions took place 1, 2.5, 4, and 6 h after the day's treatment was taken. The results largely supported previous findings. All three treatments were associated with improved secondary memory performance on the CDR battery, with the ginseng condition evincing some improvement in the speed of performing memory tasks and in the accuracy of attentional tasks. Following ginkgo and the ginkgo/ginseng combination performance of both the Serial Threes and Serial Sevens, subtraction tasks was also improved at the later testing sessions. No modulation of the speed of performing attention tasks was evident.
Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng (Kennedy et al, 2004)
In this double-blind, counterbalanced, placebo-controlled study, the cognitive and mood effects of separate single doses of: 75 mg of a dried ethanolic extract of guarana (approx 12% caffeine), 200 mg of Panax ginseng (G115), and their combination (75 mg/200 mg), were assessed in 28 healthy young (18-24) participants. On each day of the study (separated by a 7-day washout), cognitive performance and subjective mood were assessed pre-dose and at 1, 2.5, 4 and 6 h post-dose using the Cognitive Drug Research computerised assessment battery, Serial subtraction tasks and Bond-Lader mood scales. In comparison to placebo, all three treatments resulted in improved task performance throughout the day. In the case of guarana, improvements were seen across 'attention' tasks (but with some evidence of reduced accuracy), and on a sentence verification task. While also increasing the speed of attention task performance, both ginseng and the ginseng/guarana combination also enhanced the speed of memory task performance, with little evidence of modulated accuracy. Guarana and the combination, and to a lesser extent ginseng, also led to significant improvements in serial subtraction task performance.
Acute, dose-dependent cognitive effects of Ginkgo biloba, Panax ginseng and their combination in healthy young volunteers: differential interactions with cognitive demand (Scholey and Kennedy, 2002)
The present paper describes three studies examining the acute effects of single doses of Ginkgo biloba (GK501), Ginseng (G115) and their combination (Ginkoba M/E, Pharmaton SA) on the performance of healthy young adults (mean age 21 years) during serial arithmetic tasks with differing cognitive load. In each double-blind, placebo-controlled study three different treatment doses and a placebo were administered, according to a balanced crossover design, with a 7-day washout period between each dose. Participants' scores on two computerised serial subtraction tasks (Serial Threes and Serial Sevens) were assessed pre-dosing and at 1, 2.5, 4 and 6 h thereafter. A number of significant time, dose and task-specific effects were associated with each treatment. There was a dose-dependent improvement in speed of responding during Serial Threes following Ginkgo biloba. Different doses of Ginseng improved accuracy and slowed responses during Serial Sevens. The most striking result, however, was a highly significant and sustained increase in the number of Serial Sevens responses following 320 mg of the Ginkgo–Ginseng combination at all post-treatment testing times. This was accompanied by improved accuracy during Serial Sevens and Serial Threes following the 640 mg and the 960 mg dose, respectively.
Differential, dose dependent changes in cognitive performance following acute administration of a Ginkgo biloba/Panax ginseng combination to healthy young volunteers (Kennedy et al, 2001)
The present study investigated whether acute administration of a combination of standardised extracts of Ginkgo biloba (GK501, Pharmaton SA) and Ginseng (G115, Pharmaton SA) had any consistent effect on mood and aspects of cognitive performance (quality of memory, secondary memory, working memory, speed of memory, quality of attention and speed of attention) that can be derived by factor analysis of the cognitive drug research computerised assessment battery. The study followed a placebo-controlled, double blind, balanced, crossover design. Twenty healthy young adult volunteers received 320, 640, and 960 mg of the combination, a matching placebo with a seven-day wash-out period between treatments. Following a baseline cognitive assessment, further test sessions took place 1, 2.5,4 and 6 h after the day's treatment. The most striking result was a dose-dependent improvement in performance on the quality of memory factor for the highest dose. Further analysis revealed that this effect was differentially targeted at the secondary memory rather than the working memory component. There was also a dose dependent decrement in performance of the speed of attention factor for both the 320 and 640 mg doses.
The cognitive, subjective, and physical effects of a ginkgo biloba/panax ginseng combination in healthy volunteers with neurasthenic complaints (Wesnes et al, 1997)
Sixty-four healthy volunteers (aged 40 to 65 years) were assigned randomly to four equal dosing groups, receiving 80, 160, or 320 mg of the combination ginkgo biloba/ginseng or placebo. Assessments were performed on the day before dosing, and again at Days 1, 30, and 90 at 1 hour after the morning dose and 1 hour after the afternoon dose. The assessments included the Cognitive Drug Research (CDR) computerized assessment system, the Vienna Determination Unit, cycle ergometry, and various questionnaires. The treatments were well tolerated by all volunteers. On Day 90 at 1 hour post morning dosing, dose-related improvements were seen on the CDR tests, the 320 mg dose being significantly superior to placebo. These effects, however, were reversed 1 hour after the afternoon dose, possibly suggesting that a longer inter-dosing interval would be preferable.