About hordenine

Nootropics

Hordenine is a naturally-occurring atypical stimulant that is found in barley, bitter orange and cacti such as Echinopsis candicans. Sometimes it is found in weight loss or athletic performance enhancement supplements in larger amounts and sometimes it is found in fake “bitter orange extracts”, which may actually be a mixture of different synthetic phenylethylamine stimulants [1]. Is hordenine a good enhancer of coffee or a good alternative to it? Indeed, in the first place it is not very well researched. It is one of the many atypical minor phenylethylamine stimulants that is considered reasonably safe in smaller doses. In higher doses, is also sold as a supplement for weight loss or athletic performance enhancer. Are there any concerns?

Hordenine is no doubt bioactive. It is a relatively poor but selective inhibitor of monoamine oxidase B that breaks down dopamine [2] and phenylethylamine (PEA), prolonging their effect in the brain, heart and kidneys. While it does not mimic noradrenaline itself, it inhibits the removal of noradrenaline from synapses, and thus increases noradrenergic tone [2]. Therefore, it is a stimulant. Inhibiting breakdown of dopamine might reduce oxidative stress and might be useful for some neural conditions (mood disorders, Parkinson’s disease) and potentially disadvantageous in others (schizophrenia, anxiety disorders). Inhibition of noradrenaline uptake may be useful in the context of mood and attention disorders while it is reasonable to speculate that it may be dangerous in the context of hypertension and related diseases as well as anxiety disorders. The combined effect of these with other stimulants with different mechanisms may be greater than sum of their parts, and thus more potent as well as more dangerous.

It has been found that hordenine blocks synthesis of melanin, which is a molecule that protects the skin from the damaging effects of the sunlight [3]. The paper discussed that this property of hordenine might have potential pertinent to hyperpigmentation disorders. In the same time, it seems wise to consider that inhibition of normal tanning might increase the risk of skin cancer in some contexts.

An animal study has found that hordenine may be a kidney-friendly substance in mice with chemically induced diabetes. More specifically, hordenine reduced inflammation mediators IL-1beta and IL-6 as well as (in this context) harmful tissue remodeling enzyme MMP-9 [4]. Reduction of oxidative stress indicates normalization of haywire metabolism in the kidneys (ROS). While this is just one study made in animals, it is of great interest because it is not so easy to find molecules that are beneficial for kidneys (or liver).

High doses of hordenine have been investigated in the horse [5]. The responses of the horses were flehmen response (expression of intestinal discomfort, probably), defecation within 60 seconds, respiratory distress and doubling of heart rate. These responses to 2 mg/kg injection were transient and animals biological signs returned to normal within 30 minutes. When the same dose was given to animals orally, no such responses were recorded; the concentration of hordenine returned to baseline within 24 h.

Hordenine reduces the disease causing capacity of certain Pseudomonas aeruginosa or Serratia marcescens strains [6,7]. These bacteria are not so often found from healthy persons. It is unknown whether hordenine has any useful or harmful effect on the healthy persons’ beneficial bacteria that are mostly quite different from these two species.

Hordenine has weak dopamine D2 agonist properties. Consumption of beer is insufficient source of hordenine for this to become pertinent but higher doses found in food supplements with high concentrations might [8]. D2 receptor is pertinent for goal maintenance during mental tasks [9], less receptors are linked to better working memory and task switching.

While increased dopaminergic tone via MAO B inhibition might be beneficial for cognitive enhancement, substantial activation of D2 receptors might reduce cognitive performance, instead. Therefore, while it is clear that hordenine is a cardiovascular, nervous system and metabolism stimulant, nootropic properties are debatable – while it might me mildly nootroopic, the opposite may be true, instead.

 

[1] https://pubmed.ncbi.nlm.nih.gov/32497396/
[2] https://pubmed.ncbi.nlm.nih.gov/2570842/
[3] https://pubmed.ncbi.nlm.nih.gov/23768344/
[4] https://pubmed.ncbi.nlm.nih.gov/29775900/
[5] https://pubmed.ncbi.nlm.nih.gov/2269269
[6] https://pubmed.ncbi.nlm.nih.gov/29353476/
[7] https://pubmed.ncbi.nlm.nih.gov/30609368/
[8] https://pubmed.ncbi.nlm.nih.gov/31984737/
[9] https://pubmed.ncbi.nlm.nih.gov/30125286//

Effects of Ibutamoren on brain

Nootropics, SARMs

It seems that short-term use of ibutamoren after short-term stress reduces anxiety while long-term use during chronic stress increases anxiety.  A new paper [1] describes a mechanism wherein a ghrelin mimetic (ibutamoren mesylate) can enhance fear learning in rats in the context of chronic stress. The said mechanism showed that a ghrelin agonist did not activate HPA stress axis, whose downstream effector hormone is cortisol. Ghrelin is a stress hormone by itself. Growth hormone receptors were up-regulated during repeated stressful events, ghrelin agonist increased growth hormone levels and the fear learning of the rats grew in response to growth hormone. The mechanism was confirmed by using ghrelin antagonist that blocked the enhanced fear learning. In case of the short time frame, the opposite seems to be true, as short time stress followed by ghrelin agonist reduces stress symptoms in mice [2]. Fourth study also demonstrated that ghrelin weakens fear learning in generally unstressed rodents while chronically stressed rats had elevated levels of hunger hormone and fear learning ended up with fewer ghrelin receptors. High expression of ghrelin receptors reduces anxiety [3], while low levels have the opposite effect. Hence, it seems that long-term ibutamoren may exacerbate long-term stress, and brain ghrelin receptor down-regulation is the probable explanation. It seems likely, that transient or occasional increases in ghrelin receptor activation (such as after interval exercise [4]) may be more adaptive than chronic elevation regime.

[1] https://www.nature.com/articles/mp2013135

[2] https://www.ncbi.nlm.nih.gov/pubmed/22521145

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886665/

Summary of SARMs doses used in human studies

Nootropics, SARMs

Overview of SARMs dosages used in human studies.

SARM/Nootropic and dosage used:
Ostarine 3 mg [1]
Ligandrol 1 mg [2]
YK-11 Unknown
RAD120 Unknown
Cardarine Unknown
SR9009 Unknown
SR9011 Unknown
Unifiram Unknown
PRL-5-83 5 mg [3]
Yohimbine Usually 5…30 mg [4],[5]
Hordenine Unknown but present in beer 1…6 mg [6]
PEA Unknown but see [6],[7]

[1] https://www.ncbi.nlm.nih.gov/pubmed/27138015
[2] https://www.ncbi.nlm.nih.gov/pubmed/27138015
[3] https://www.ncbi.nlm.nih.gov/pubmed/?term=PRL-8-
[4]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430403
[5] https://www.ncbi.nlm.nih.gov/pubmed/9315493
[6] https://www.ncbi.nlm.nih.gov/pubmed/30409657
[7] https://www.ncbi.nlm.nih.gov/pubmed/26481102
[8] https://www.ncbi.nlm.nih.gov/pubmed/26481102

How does yohimbine interact with caffeine?

Nootropics

In 1989 there was a study that investigated the behavior of animals. Caffeine was anxiogenic in the context of exploration and social interaction while yohimbine was anxiogenic in the context of exploration but displayed anti-conflict properties in social interaction [1]. Unexpectedly, caffeine and yohimbine cancelled each others’ effects out.

An interesting study investigated rat vocalizations under the influence of either caffeine, yohimbine or amphetamine. 22 kHz sounds were interpreted as signals of alarm or distress while 50 kHz voice were interpreted as response to rewarding stimuli while mentioning that it is unknown whether the same signal is associated with anxiety [2]. Caffeine and amphetamine increased 50 kHz calls, yohimbine did not. In addition, it was shown that while caffeine and amphetamine were locomotor stimulants, yohimbine was not.

Yohimbine can promote fat loss by mildly increasing lipolysis when not counteracted by eating because after a meal the lipolysis-enhancement does not work [3]. In lower doses it does not increase blood pressure, heart rate or cause anxiety as much as ephedrine but larger doses have both cardiovascular and anxiogenic effects.

A human cardiology study [4]investigated caffeine, ephedrine and yohimbine in obese women during exercise (handgrip and cycloergometer). Caffeine and ephedrine increased heart ejection fraction during cycling (amount of blood pumped out of left ventricle, an increase may be considered usually beneficial) and did not alter the hemodynamics while resting. Addition of yohimbine increased diastolic blood pressure (that may be considered quite undesirable in this context) and heart rate (same interpretation) but decreased ejection fraction (same interpetation) and stroke index during rest (same interpretation). During exercise, yohimbine decreased ejection fraction during both exercises and increased cardiac load during exercise.

 

Bottom line: while yohimbine seems useful for fasted long-duration low-intensity fat burning training, it seems that combining it with substantial amounts of caffeine may be asking for trouble. Most importantly, yohimbine seems a very unwise choice for hard exercise (weightlifting, sprint, high-intensity interval training, intense cardio, and, if I may suggest, also pushing the limits with rough sex).

[1] https://www.ncbi.nlm.nih.gov/pubmed/2707309
[2] https://www.ncbi.nlm.nih.gov/pubmed/29909426
[3] https://www.ncbi.nlm.nih.gov/pubmed/12323115
[4] https://www.ncbi.nlm.nih.gov/pubmed/9545623

New review for Unifiram

Nootropics

We have updated overview article of Unifiram. 

Unifiram (CAS# 272786-64-8) is a substance that was reported in year 2000 to have similar properties to piracetam but more potent in a mouse passive avoidance test. However, unifiram has shown pro-cognitive effects for mice by preventing amnesia induced by scopolamine (muscarinic antagonist), mecamylamine (nicotinic antagonist), baclofen (GABA-B agonist), clonidine (alpha-2 agonist), NBQX (AMPA antagonist) in passive avoidance test. Read more about Unifiram.

Unifiram is also available in our shop.

Effects of yohimbine to mind

Nootropics, SARMs

Yohimbine is usually considered an agent that helps to reduce body fat, increase sexual desire and ability for men as well as a stimulant that may cause unpleasant adverse effect of anxiety together with elevation of blood pressure.

However, according to the literature, yohimbine has some other effects as well, including effects on cognition, memory and sleep that may be of interest. Yohimbine (30 mg) reduced errors on letter flank test [1]. A simple version of letter flank test that shows ability to filter out irrelevant stimuli from detecting target letter is available online [2]. However, it increases rapid response impulsivity and errors in a somewhat more complex immediate memory test that has numbers instead of a single letter; the used dosage was a comparable 30 mg dose for a 75 kg person. The problem that occurred with yohimbine was that the test subjects did not read the number thoroughly and prematurely thought that the number was similar to another number presented just before the current. The test is explained online [4] but is not freely available.

Interestingly, yohimbine seems to have a truly interesting sex-specific effects on both memory and cognition of fear. Without affecting learning, it interrupted ability of women to generalize from learned memories [5]. Furthermore, the effect of yohimbine for processing fear-related signals (alteration of amygdala activity) is opposite for men and women [6].

A small study with medical students as subjects used a low dose. It was found that yohimbine improved following cognitive abilities: reaction time (single choice, not multiple choice), critical flicker fusion threshold and working memory (as measured by 1-back and 2-back tests) [7]. However, during glucocorticoid treatment or during high stress, yohimbine may be counterproductive for higher, flexible thought: yohimbine and cortisol together may reduce goal-directed behavior in favor of habitual behavior [8].

 

References:

[1] https://www.ncbi.nlm.nih.gov/pubmed/15858063
[2] https://www.psytoolkit.org/experiment-library/flanker.html
[3] https://www.ncbi.nlm.nih.gov/pubmed/15866563
[4] http://www.impulsivity.org/measurement/IMTDMT
[5] https://www.ncbi.nlm.nih.gov/pubmed/28253079
[6] https://www.ncbi.nlm.nih.gov/pubmed/23380165
[7] http://www.sciencedomain.org/abstract/7854
[8] https://www.ncbi.nlm.nih.gov/pubmed/22836250

Enhancetech online shop is opened

Nootropics, SARMs, SARMs online shop

We have opened our online shop at ENHANCETECH.eu address. It is possible to buy all products provided by Enhancetech. 

Online shop for nhancetech products is now opened. All our customers can buy now our provided SARMs and other products.

Currently we are offering following products:
Ostarine (MK-2866)
Ligandrol (LGD-4033)
Ibutamoren (MK-677)
Cardarine (GW501516)

All products can be ordered with different ingredient amount.

 

Also we are pointing out, that all products are for research purposes. SARMs are not medicines or food supplements. Please read our sale terms also before buying from e-shop.