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  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 . 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 , 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 ) may be more adaptive than chronic elevation regime.
In november 2019, USA started introducing SARMs control act that would make SARMs illegal to sell or possess but it has not become a law, yet (date: 02/14/2020) . While China may have banned export of SARMs in the same time, several SARMs are bidded on alibaba.com . In USA, the aim of SARMs ban is to protect the consumers from unscrupulous vendors that sell SARMs as food supplements as well as buyers that unknowingly buy food supplements unknowingly. On the other hand, it will also mean that selling and buying SARMs becomes criminal, even if these substances are considered as research chemicals by both parties.
The parties that support criminalization include entertainment sports industry, pharmaceutical industry and natural products industry: U.S. Anti-Doping Agency, the American Herbal Products Association, the Consumer Healthcare Products Association, the Council for Responsible Nutrition and the United Natural Products Alliance.
Enhancetech has most of the SARMs back in stock and there shouldn’t be any problem according to our manufacturer. We might not be able to ship to US, after SARMs control act would become a law. So we suggest all US customers to order SARMs as soon as possible.
Overview of SARMs dosages used in human studies.
SARM/Nootropic and dosage used:
Ostarine 3 mg 
Ligandrol 1 mg 
PRL-5-83 5 mg 
Yohimbine Usually 5…30 mg ,
Hordenine Unknown but present in beer 1…6 mg 
PEA Unknown but see ,
We have added new SARM SR9009 to our provided products.
SR9009 also known as Stenabolic is an experimental circadian rhytm modulator (RevErb-alpha agonist). In one hand, SR9009 is said to be attractive as a performance-enhancing agent, yet, in the other hand, its use has been discouraged because it is potentially harmful. The desire to discourage its use has prompted development of its screening methods. So far, SR9009 has revealed anti-inflammatory properties (suppressing activation of several pro-inflammatory cytokines including tumor necrosis factor alfa, whose downstream effect was suppression of tumor necrosis factor alpha). The anti-inflammatory effects have been shown in animal models of endometriosis, heart attack, Alzheimer’s disease and some autoimmune diseases.
Excessive blood cholesterol is considered an important risk factor of cardiovascular diseases. Excessive blood cholesterol has both genetic and dietary component. It is also known that cholesterol is either LDL (low density lipoprotein) HDL, also known as “good cholesterol” and “bad cholesterol”, respectively.
The non-pharmacological strategy to improve blood cholesterol is improving diet (broadly – less junk food and more salad) and exercise, which are aimed at lowering LDL without lowering HDL. The most effective foods for lowering LDL are oatmeal, kidney beans, apples, pears, bananas, berries, fish, nuts, avocados, olive oil, and, good news for body builders, whey protein. On the other hand, dairy fats (cream, butter, cheese) and trans fats (crackers and cakes, especially the cheaper ones) raise the bad cholesterol . Especially in overweight subjects, calorie restriction lowers increased cholesterol . For high risk patients, statins are used. From the field of herbal medicine, several lines of evidence suggest that berberine works similarly well , with the reservation that berberine research lacks the industry-supported large studies. Cocoa is a well-researched food, and while chocolate is suspicious due to huge sugar content, cocoa supplements significantly improve the metabolic profile as well . Of research chemicals, cardarine has been one of the more promising substances: while the research of the substance has been abandoned by the industry, it is used for research. While the original effects revealed very specific effect of raising good cholesterol in very low doses and lowering bad cholesterol in higher doses, later research has revealed that it counteracts especially bad, endothelium-damaging form of cholesterol called oxLDL .
Exercise program of older men showed that after a year or half, there were no improvements in grip strength, body mass index or bad cholesterol but there were improvements in body shape, walking speed, one leg standing and good cholesterol . On the other hand, in children a rather intriguing counter-intuitive association was found: fatter children had more good cholesterol . In addition, higher muscle mass may lower cardiovascular risks for boys only . However, the good news is that for older folks, even two strength training sessions per week helped to lower cardiovascular risks, especially in case of higher blood pressure and elevated cardiovascular inflammation marker hsCRP. Research suggests that for adults, both men and women, hand grip strength (relative to body mass) and relative fat mass (fat mass index) may be the best independent predictors of cardiovascular health .
SARMs are double edged swords. In one hand, SARMS seem to have good safety combined with beneficial effects on muscle and bone, they have some drawbacks similar to steroids: SARMS lower good cholesterol significantly and dose-dependently according to multiple studies ,,,. The effects of androgens on blood profile are not just negative because the triglyceride levels tend to be improved. A monkey study of a novel dermally administered SARM that demonstrated increased muscle mass without lowering good cholesterol by reducing exposure of liver to that SARM, and a SARM that atypically did not lower good cholesterol have been revealed in clinical human studies, as well [Ahv],[Ahv+1].
Time will tell whether newer SARMs will have the same benefits as those that have been investigated for a longer time (i.e. ostarine) without having the drawback of lowering the good cholesterol. The research is improtant, because the effects seem really interesting for older people especially, and the proportion of older people is increasing proportionally almost worldwide.
“Was the government to prescribe to us our medicine and diet, our bodies would be in such keeping as our souls are now.” — Thomas Jefferson
While it is understandable that competitive sports event organizers want to keep their events clear from the performance-enhancing drugs due to their values, the aim to extend that policy to laymen with a threat of a felony level (sic!) criminal offense seems clearly less justified both economically and morally. It can be reasoned that punitive laws are not in the interest of taxpayers. Average cost of per recruit in a cohort study is about ten dollars for offline recruitment and the cost can be further reduced by a third if online recruitment methods such as Facebook are used . On the other hand, cost per year spent in prison is at least 30 000 dollars . It would be more reasonable and cheaper to label the the said performance-enhancing drug users as “test subjects” and investigate them than label the said experimenters as “offenders” and put them into the jail. If the nonmedical use of substances could be epidemiologically monitored with compulsory following of a study protocol, then it should satisfy both moderate authoritarians and libertarians. If the use of SARMs is positioned clearly as that of performance-enhancement rather than that of medical, it should unburden medical and pharmaceutical regulatory authorities from some of the responsibility. On the other hand, it would position the sports authorities as major stakeholder, as seems to be the case (pharmaceutical industry does not seem to be major stakeholder because use of SARMs is not at odds with their major economic interests). In order to draw the boundaries that would allow the laypersons to use SARMs, the concerns of sports authorities must be taken into the account, and We suggest that science would be perfect arbiter while observation with the right to cancel the study due to health concerns is not sufficient means of regulation.
There is new bill in Congress that would ban SARMs. Should possession of SARMs become a dangerous criminal act then?
United States senators are pushing a bill that would reclassify SARMs as illegal substances (Schedule III) that would be treated similarly with anabolic steroids and some other drugs such as ketamine or buprenorphine. The parties that are interested in banning SARMs in USA are US Anti-Doping Agency, Council for Responsible Nutrition and Federal Law Enforcement Officers Association. While it is already clear that FDA has not approved SARMs as pharmaceuticals, the parties that are interested in enacting punitive laws pertinent to SARMs capitalize on possible negative health consequences. On the other side of the coin, a more plausibly benevolent argument is that under the less strict laws it is more difficult to stop the unscrupulous vendors who include SARMs as unlisted ingredients in their “food supplements”, which has been the concern of Council of Responsible Nutrition. Without saying, such cheating of consumers is already illegal. The bill aimed at making possession of a SARM a felony did not pass in April 24, 2018 . What are the probable implications of this bill passing? “Once that happens, state and local police can arrest for SARMs, so that possessors are only one unexpected car stop or one bitter ex-spouse phone call away from a set of handcuffs.”.
We have added new SARM SR9011 to our product list.
SR9011 is a novel circadian clock amplifier not yet tested in humans but is already a suspected performance enhancing agent. In mice, it has reduced blood fat and sugar levels while it increased energy expenditure and appetite. SR9011 had mild or nightlong interaction with wakefulness depending on light conditions, has anti-inflammatory properties and does not have overt toxicity. In a few cell lines it did not interfere with proliferation of normal cell lines specifically. Hence, Rev-ErbA? agonists, as shown by at least four lines of evidence, seem to have a broad spectrum of effects.
Ibutamoren (MK-677) has been researched with aims of increasing muscle mass, improving healing of injures and increasing quality of sleep. But there are also some side-effects related to blood pressure.
Growth hormone deficiency, if present, is associated with lower blood pressure independent of the time of the day  with normal response to exercise in humans. In rats whose hypophysis (part of brain that produces growth hormone) was removed, growth hormone lowered blood pressure, instead . Mechanistically, alterations of growth hormone level may modify the blood pressure indeed but the exact dose relationship is unknown, and human studies must be considered more informative.
Growth hormone release amplifier MK-677 or ibutamoren is also relevant from the perspective of cardiovascular health: a study with obese humans has shown that ibutamoren moderately but significantly increased both diastolic blood pressure (mean 84 vs 79) and heart rate (mean 61 vs 56) . In the first administration of ibutamoren, a transient elevation of prolactin and cortisol was observed, while the long term result was increase of fat free mass. On the other hand, ibutamoren moderately decreased glucose tolerance in the long term, which reduces its potential utility for diabetic (as indicated by elevated glucose levels and glucose intolerance) and pre-diabetic (as indicated by elevated glycosylated hemoglobin levels in blood) humans. The effects of ibutamoren may be dependent on age and duration of administration. The negative effects may be more prominent in the elderly, as it was associated with congestive heart failure and elevated blood pressure in a study of elderly patients with hip fracture . While there were some improvements in the gait speed and prevention of falling, the study was terminated early due to this side effect.
There were 135 PubMed-indexed Studies about SARMs (steroid androgen receptor modulators) at the end of January 2019.
SARMs were a hot topic in American Society of Bone and Mineral Research conference held in Quebec, Canada. The established technologies for improvement of bone function are high dose vitamin D, bisphosphonate drugs and somewhat more novel combination therapy of monoclonal antibodies that attack osteoclasts (cells that normally remodel the bone but cause osteoporosis if their proportion is out of balance) and recombinant parathyroid hormone that supports osteoblasts (bone-building cells) if used intermittently . However, the SARMs were the most interesting from the novelty perspective.
A really interesting study published in 2019 discusses a SARM found from the nature (wild bitter gourd extract) and compared the SARM with testosterone in castrated mice (to unmask the effects of treatment from endogenous male steroid hormones). While testosterone increased the mass of both muscles and male accessory glands (prostate and seminal vesicles), the bitter gourd extract increased grip strenth and acrobatic/balance performance measured with as measured by the typical rotarod test . Boosting mitochondria and their oxidative capacity as well as negating castration-induced muscle decline was proposed as mechanism of action.
A review paper was also published in 2019. It is somewhat a non-news that no SARMs are available as prescription drugs. In summary, the research has found that these molecules seem to have few if any drug interactions and the clinical studies suggest potential future applications for pathological muscle loss, benign prostate hyperplasia (BPH), hypogonadism and breast cancer  as well as, possibly, Duchenne muscular dystrophy (a disease which causes progressive weakness of muscles that is eventually lethal due to withering of breathing muscles). In contrast to uses related to disease, the use of SARMs as performance-enhancing agents was briefly discussed, as these drugs have anabolic effects with less side effects (without excluding potential for abuse), that make SARMs interesting for bodybuilding community.
In addition to regular additions to the set of studies dedicated to development of methods of doping detection, a few other studies were published in 2018: development of transdermal system of administration of SARM LY305  – it improved the speed of muscle and bone repair without overt adverse effects in laboratory rodents, and was well-tolerated in human volunteers. Another study discovered that SARM S42 inhibited proliferation of prostate cancer cell line PC-3 . Third study, expectedly, found that YK11 supported the function and proliferation of bone-building osteoblast cells of mice , and another study weighed in additional evidence by showing the anti-osteoporosis effects for the currently perhaps the best-known SARM ostarine .
Animal studies (especially optimistic ones for the sake of caution) must be taken with a grain of salt, though. A study found that LGD-4033 (that may also be known as ligandrol) metabolizes moderately differently in humans and horses, which adds a layer of complexity to interpretation of animal studies in general as well as doping detection in different species specifically .
While the aim of this text was to summarize the studies published in 2019 and 2018, a few studies of interest were published in 2017 deserve mentioning. We will cover this in future posts.