Hey guys, i haven't been around much, since i just started college a few months ago and have been wicked busy, but I just wrote this up, since i have nothing better to do and I've been studying neuroscience and stuff. i'm gonna take more courses in this type of stuff and possibly do some research on my own in the future 
but this is just a summary article for now, since most of you guys don't have access to the full article, which is linked in the "Medicinal Mushroom Research" post at the top of this forum.
I tried to write it kind of scientifically, so it might be a bit tedious to read. if you don't know what "p-values" are, they are the things that look like "(p<0.05)" - These basically tell you the probability that your results are due to chance. the lower the p value, the more statistically significant
This is Your Brain on Cordyceps sinensis
by "ABC"
December 18, 2009INTRODUCTION There is a growing amount of literature and ongoing research on the bodily effects of
Cordyceps sinensis, an entomopathogenic fungus that is highly valued in traditional Chinese and Tibetan medicine. For example, consuming
C. sinensis is believed to increase energy, sexual stamina, and vitality (Halpern, 2007; Stengler, 2005). Also,
C. sinensis can be used to help treat cardiovascular disease and fatigue, as well as to modulate the immune system and blood glucose levels (Halpern, 2007; Nishizawa, Torii, Kawasaki, Katada, Ito, Terashita, Aiso, and Matsuoka, 2007; Stengler, 2005). In contrast to the bodily effects, there are relatively fewer primary research reports on the neuropsychological effects of
C. sinensis. Nishizawa and colleagues (2007) have suggested that
C. sinensis has an antidepressant-like effect by upregulating the expression of monoaminergic neurotransmitters, which are widely believed to be involved in the pathophysiology of psychiatric diseases, such as depression and anxiety. Though the main focus of medical
C. sinensis research has been on its effects on the body, the potential psychological effects must also be further studied to understand the fungus' full effects.
WHY IS IT IMPORTANT? Major depressive disorder (MDD) is a debilitating and potentially life-threatening psychiatric disorder that affects about 121 million people worldwide (“Depression,” World Health Organization). The costs of depression are a burden to the patient, their family, and their community. Depression can disrupt occupational functioning and social relationships. The “monoamine hypothesis” suggests that the pathophysiology of MDD involves monoaminergic neurotransmitters, including dopamine, noradrenaline/norepinephrine, and serotonin (5-HT) (Nishizawa et al., 2007). Populations with MDD exhibit lower monoaminergic neurotransmitter expression, while antidepressant treatments upregulate amounts of synaptic monoaminergic neurotransmitters.
METHODOLOGY The tail suspension test (TST) is a widely used test for model depression in animal research with rodents. The TST was used by Nishizawa and colleagues (2007) with laboratory mice. Mice were individually suspended by their tail with adhesive tape, in a box (35x35x40 cm high) (Nishizawa et al., 2007). The TST lasted for six minutes, in which the mice were observed for immobility (Nishizawa et al., 2007). In the TST, immobility is defined as the amount of time the mouse spends hanging passively and completely motionless. Immobility in the TST is a model of behavioral despair. The TST has been used to consistently reflect the therapeutic effects of antidepressant medications in rodents (Nishizawa et al., 2007).
The open field test (OFT) is often used to check the locomotor activity of test rodents who may also be subject to testing in the TST. In the OFT, mice were placed in a rectangular walled arena and allowed to explore freely (Nishizawa et al., 2007). Movement was recorded by observing the number of times the mouse crossed evenly spaced marking lines on the floor of the arena. The OFT is important to check if the antidepressant-like effects observed in the TST were truly a measure of decreased despair or merely caused by locomotor stimulation, such as what might be caused by caffeine, for example (Nishizawa et al., 2007).
The head twitch response (HTR) test is used to evaluate drugs' effects on the serotonergic system in vivo (Nishizawa et al., 2007). An administration of clorgyline (1 mg/kg), a monoamine oxidase inhibitor (MAOI), and 5-HTP (150 mg/kg), a precursor of 5-HT, were used to induce an increased number of head twitches (Nishizawa et al., 2007). The number of head twitches was counted for 2 minutes at 10 minute intervals from 10-50 minutes after the injection of 5-HTP. Nishizawa and colleagues (2007) suggest that these head twitches can be used to observe the activity of 5-HT in the central nervous system.
Nishizawa and colleagues (2007) tested
C. sinensis extract in two forms. For the first extract, a hot water extract (HWCS) was made of 20g
C. sinensis in 400g water, which was then freeze-dried and diluted to various concentrations (500, 1000, 2000 mg/kg) in distilled water to be administered orally at 10 ml/kg (Nishizawa et al., 2007). The other tested extract was a supercritical fluid extract (SCCS) obtained from 52.2 kg of
C. sinensis, resulting in 4.82 kg of extract which was administered orally at 2.5, 5.0, or 10.0 ml/kg (Nishizawa et al., 2007). Plain water was administered orally as a control (Nishizawa et al., 2007). Mice tested in the TST were administered with HWCS, SCCS, or water for 5 consecutive days, while mice tested in the OFT were administered with HWCS, SCCS, or water for 6 consecutive days before testing (Nishizawa et al., 2007).
BEHAVIORAL EFFECTS The supercritical fluid extract of
C. sinensis (SCCS) significantly reduced immobility time, in the mouse TST, in comparison to controls (Nishizawa et al., 2007). The reduction of immobility seems to be dose dependent, with only the administration of SCCS at 5.0 and 10.0 ml/kg significantly reducing immobility, in comparison to controls (p<0.05; Nishizawa et al., 2007). However, administration of the hot water extract of
C. sinensis (HWCS) did not significantly change the duration of immobility time during the mouse TST, in comparison to controls. Though the comparison was not analyzed, the control group for the SCCS administered group had a higher average expression of immobility than the control group for the HWCS administered group, even though both groups were treated with only water (Nishizawa et al., 2007). This difference in immobility time among the control groups may have affected the statistical outcome of the trials.
Neither SCCS nor HWCS had significant effects on locomotor activity, rearing, or grooming in the mouse OFT, in comparison to controls (Nishizawa et al., 2007). This suggests that
C. sinensis does not affect immobility time in the TST by directly stimulating locomotor activity, but reduces immobility time through other, possibly antidepressant-like, mechanisms (Nishizawa et al., 2007).
NEUROLOGICAL EFFFECTS Desipramine, a tricyclic antidepressant known to be a noradrenaline reuptake inhibitor, bupuropion, a dopamine reuptake inhibitor, and fluoxetine, a selective serotonin reuptake inhibitor, were used as positive controls (Nishizawa et al., 2007). By inhibiting the reuptake of monoamines, these drugs increase levels of synaptic monoaminergic neurotransmitters. Respectively, these positive controls increased levels of noradrenaline, dopamine, and serotonin in the synapses, resulting in significantly decreased immobility time (Desipramine, p<0.01; bupuropion, p<0.01; fluoxetine, p<0.001; Nishizawa et al., 2007).
A respective pretreatment with a noradrenaline receptor antagonist (NRA), a dopamine receptor antagonist (DRA), or a serotonin synthesis inhibitor (SSI) were able to significantly block the anti-immobility actions of desipramine (p<0.01), bupuropion (p<0.05), fluoxetine (p<0.05; Nishizawa et al., 2007). The anti-immobility action of SCCS was significantly inhibited by NRA (p<0.05) and DRA (p<0.01), but not by SSI (Nishizawa et al., 2007). This evidence suggests that the reduction of immobility by SCCS relies on an upregulation of synaptic noradrenaline and dopamine, but not serotonin (Nishizawa et al., 2007).
Furthermore, SCCS did not significantly affect the number of 5-HTP-induced head twitches in the HTR (Nishizawa et al., 2007). The positive control, fluoxetine, significantly increased HTR at 10-12 minutes (p<0.001) and significantly reduced HTR at 30-32 minutes (p<0.05) after administration, in comparison to controls (Nishizawa et al., 2007). This evidence further suggests that the actions of a supercritical fluid extract of
C. sinensis (SCCS) do not involve the serotonergic (5-HT) system (Nishizawa et al., 2007).
CONCLUSIONS SCCS had significant antidepressant-like effects in the mouse tail suspension test (TST). However, a hot water extract of
C. sinensis did not have significant effects in the mouse TST. The anti-immobility effects of SCCS seem to be associated with the upregulation of synaptic noradrenaline/norepinephrine and dopamine, but not with serotonin (Nishizawa et al., 2007).
QUESTIONS AND FURTHER RESEARCH This initial research by Nishizawa and colleagues (2007) has posed many questions to address in future research. Further research is needed to identify the bioactive chemicals of
C. sinensis that have antidepressant-like effects (Nishizawa et al., 2007). A variety of tests should be conducted to confirm the antidepressant-like actions of
C. sinensis.
Further research might be conducted on the antidepressant-like effects of
C. sinensis on neurogenesis and stress hormones, which have been widely associated with the pathophysiology of depression. The measurement of brain-derived neurotrophic factor (BDNF) has been used to observe the effects of drugs on neurogenesis. Future research might be conducted to study possible neurogenerative effects of
C. sinensis. Further research on the effects of
C. sinensis on corticosterone, a stress hormone, should be done to show how
C. sinensis affects rodents exposed to chronic mild stress, an animal model of depression. Likewise, research should be done on the effects of
C. sinensis on human salivary cortisol, reflecting levels of stress, compared to a placebo control group. Another suggestion for further research is to scientifically quantify possible alteration of noradrenaline, dopamine, and serotonin by
C. sinensis, as opposed to using the head twitch response.
A limitation of this research was that it was not double-blind (Nishizawa et al., 2007). Since the researchers knew what they were administering to the mice, it is possible that experimenter bias influenced the measurement of immobility in the TST. Until further research confirms the antidepressant-like actions of SCCS in the mouse TST, it is possible to speculate that the increased immobility in the control group for the SCCS groups was a main statistical cause of SCCS' seemingly significant effects, which in reality might have made no significant changes.
Another thing that was not addressed was the administration of
C. sinensis for 5 or 6 days in the TST and the OFT, respectively (Nishizawa et al., 2007). Further research should conduct these tests in parallel, as different durations of treatment may impact the results.
Without further research, it will be difficult to form a more conclusive answer to the question of
C. sinensis as an antidepressant treatment option. Furthermore, fluoxetine, an SSRI commercially known as Prozac, reduced immobility more effectively than SCCS in the mouse TST (Nishizawa et al., 2007). Though SCCS showed a significant decrease in immobility time in the mouse TST, it still seems to be less effective than Western medicine.
ReferencesDepression. (n.d.). Retrieved December 18, 2009, from http://www.who.int/mental_healt
h/management/depression/definition/
Halpern, G. (2007). Healing Mushrooms. Garden City Park, NY: Square One Publishers.
Nishizawa, K., Torii, K., Kawasaki, A., Katada, M., Ito, M., Terashita, K., Aiso, S., Matsuoka, M. (2007). Antidepressant-like effects of Cordyceps sinensis in the mouse tail suspension test. Biological & Pharmaceutical Bulletin, 30(9), 1758-1762.
Stengler, M. (2005). The Health Benefits of Medicinal Mushrooms. North Bergen, NJ: Basic Health Publications.
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