RAD140 is a selective androgen receptor modulator (SARM) currently under development for potential use in treating muscle wasting disorders and hormone-receptor positive breast cancer.
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What Is RAD140?
RAD140 is a selective androgen receptor modulator (SARM) developed by Radius Health, Inc.
There are several unofficial slang terms for RAD140 in the fitness community, one of the most popular being “Testolone”.
RAD140 has all of the hallmarks of an effective SARM, exhibiting a high affinity for the androgen receptor with tissue selective anabolic effects in muscle in bone, with a relatively minimal effect on prostate, seminal vesicles, and other androgen affected tissues [R].
RAD140 has a high level of oral bioavailability and demonstrated high in vivo tolerability [R].
It is still in the preclinical stages with recruitment occurring right now into its first phase 1 human trial, and has yet to be tested on humans [R].
In addition, it is often referred to as a potential alternative to testosterone replacement therapy in the recreational bodybuilding community.
Its potential efficacy in a hormone replacement therapy context is implied in some of the preclinical animal data, but the scientists also acknowledge the potential limitations of RAD140 when considering it being used in this capacity.
Its lack of aromatization is all that is needed to make a definitive judgment on its overall efficacy profile as a hormone replacement therapy alternative, which I will delve into later.
Recreational users are quick to label RAD140 as the “safe non-steroidal version of testosterone.”
This is because it doesn't require injections and hasn't exhibited any notable side effects in its preclinical data.
Obviously with no human data, it is extremely presumptuous to make a statement like this, and later in the article I will delve further into the limitations of RAD140, and SARMs in general.
RAD140 is purported by many to be a very versatile SARM that provides a complete replacement for testosterone replacement therapy (TRT), without any of the side effects.
Mechanism Of Action
RAD140 doesn’t require any injections as it has a high level of oral bioavailability [R].
After ingestion, RAD140 binds to androgen receptors in different tissues in the body which a high level of selectivity.
After binding to the androgen receptors, RAD140 exerts tissue-specific anabolic effects in muscle tissue and bone, and neuroprotective androgen-like effects in the brain, with a relative lack of stimulation in prostate and seminal vesicles [R].
RAD140 is a potent androgen agonist in the levator ani, and is also a much weaker partial antagonist on the seminal vesicles and possibly the prostate.
RAD140 demonstrated excellent affinity for the androgen receptor (Ki = 7 nM) [R].
To put this in perspective, the affinity for the androgen receptor for Testosterone in this preclinical model was 29 nM, and 10 nM for DHT.
In other words, RAD140 has a greater affinity to bind to the androgen receptor than Testosterone and DHT.
RAD140 does not aromatize into Estrogen, and does not undergo 5-alpha reduction into a more androgenic metabolite.
One thing that needs to be noted is RAD140's preclinical characterization referring to it as a “partial antagonist” in androgen affected tissues [R].
While this implies it is much less androgenic than all other SARMs, this is not necessarily the case.
Most other SARMs are classified as “partial agonists” in androgen affected tissues, and while RAD140 is classified in its preclinical profile as a partial antagonist, partial agonists may also be considered ligands which display both agonistic and antagonistic effects in affected tissues [R].
This is important because at a first glance the majority of readers will assume that RAD140 is the only SARM that has antagonistic effects on the prostate gland, and is therefore the most viable candidate for SARM therapy to date, which is not necessarily the case.
All androgen receptor ligands that have extremely selective functions indicative of a SARM have demonstrated partial agonist activity in the prostate gland, RAD140 included, despite what its preclinical profile may imply.
Increases Muscle Mass
RAD140 is very potent at low dosages and exhibited a mean weight gain of more than 10% in 28 days at only 0.1 mg/kg in a preclinical primate model [R].
In a preclinical rodent model assessing the efficacy of RAD140 in comparison to exogenous Testosterone Propionate, RAD140 significantly outperformed Testosterone in myotrophic/androgenic selectivity.
In this study, rats were castrated and either given placebo, 1 mg/kg of Testosterone Propionate or graded dosages of either 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg of RAD140.
The “sham” group are untreated rats that weren't castrated that serve as a reference guide for how much anabolic/androgenic activity occurs in a normal healthy rat with normal endogenous Testosterone and DHT levels.
After castrating the rats, muscle mass and prostate size decrease because there is no longer sufficient androgen stimulation occurring in the body, as there is no Testosterone or DHT being produced.
By using RAD140 or Testosterone, this study exhibits exactly how effective these two compounds are at replicating the anabolic activity necessary to maintain normal amounts of muscle and bone mass, and how much androgenic activity will occur in the prostate relative to that.
By referring to the figure above you can see that the lowest dosage of RAD140 capable of maintaining normal levels of anabolic activity in the body was the 0.3 mg/kg treated group.
While Testosterone at 1 mg/kg was able to outperform the 0.3 mg/kg RAD140 group in muscle growth, it stimulated prostate growth as well to a much greater extent.
For therapeutic purposes, RAD140 exhibits a greater efficacy profile at low dosages than Testosterone, as it's able to maintain normal amounts of muscle mass, but greatly decrease the amount of androgenic activity in the body.
The 3 mg/kg RAD140 treated group was able to replicate the same level of muscle tissue growth as the 1 mg/kg Testosterone treated group, with about half of the androgenic activity in the prostate.
It would be interesting to see how the same Testosterone treated group would respond if they were given Dutasteride to inhibit the 5-alpha reduction of Testosterone into DHT, and if that group would still exhibit a less favorable selectivity than the RAD140 groups.
For all we know, it could be more beneficial to use Testosterone concurrently with a 5-alpha reductase inhibitor rather than RAD140, especially considering Testosterone aromatizes into Estrogen, which is a severely limiting flaw of SARMs in general, but that all remains to be seen.
In a therapeutic context, RAD140 looks very promising based on the preclinical data given, and it blatantly has the ability to selectively increase muscle tissue, even at supraphysiological levels.
No direct fat loss was noted in the preclinical trials conducted on RAD140, however, as a human accrues more muscle mass, their basal metabolic rate will increase in parallel.
This is a given, therefore anything that can increase lean muscle mass in a human would theoretically increase total daily energy expenditure.
The net result of that would be an increase in the amount of calories expended just by having more muscle tissue via RAD140 usage, and greater overall fat loss.
Therefore, it is very likely that RAD140 can indirectly increase fat loss to some extent, dependent on the amount of muscle growth it induces.
Increases Bone Mineral Density
All SARMs that have reached human trials have shown the ability to inhibit bone turnover, stimulate bone formation, and retain bone mineral density in a state of catabolism [R].
While RAD140 hasn't gone into human testing yet, its tissue selective anabolic effects in bone have been demonstrated in preclinical animal models [R].
Reduces Prostate Size
RAD140 has proven capable of exhibiting tissue selective anabolic effects in muscle and bone equivalent to that of a therapeutic dosage of Testosterone while simultaneously reducing prostate size by approximately 70% [R].
RAD140 has a much lower level of androgenicity in the body and simultaneously suppresses natural Testosterone production.
The net result of this in hypogonadal males would be a fulfilment of Testosterone's important functions, with a lack of androgenic activity.
The net result of this in healthy males with normal testosterone levels would be a drastic decrease in prostate size and androgenic activity, in parallel to natural testosterone suppression.
The reason being that healthy men still operate with a significant amount of androgenic activity occurring via their natural Testosterone production and its 5-alpha reduction to DHT.
When a healthy male has their endocrine system suppressed, they will produce less Testosterone (and consequently DHT as well), which will cause a dose dependent decrease in muscle size, bone mineral density, prostate size and the size of seminal vesicles.
This is what makes RAD140 and other SARMs so interesting, as they will suppress the endocrine system and can reduce systemic androgenic activity, while keep anabolic activity exactly the same, or even increasing it to supraphysiological levels, depending on the dosage used.
There are a variety of therapeutic applications in which a very selective potent agonist in muscle tissue with a far lower level of androgenic activity would be beneficial in a clinical setting, with just one of those being a potentially viable treatment for benign prostatic hyperplasia in men.
Neurodegenerative Disease Protection
SARMs target androgen receptors in different areas of the body, and RAD140 has also shown neuroprotective effects in the brain of androgen deficient rats [R].
Endogenous androgens are responsible for several important functions in the body and brain, the majority of which are mediated via androgen receptor activation [R].
In hormonally deficient rats RAD140 activated those androgen receptors in the brain and prevented neurodegenerative disease progression from occurring in the absence of sufficient endogenous androgens.
RAD140 was able to activate androgen receptors in the brain, protect hippocampal neurons from cell death, and induce anabolic activity in muscle tissue and bone as effectively as Testosterone, all with a near complete absence of stimulation in androgen affected reproductive tissues [R].
Suppresses Breast Cancer
The androgen receptor is frequently expressed in many estrogen receptor (ER)-positive, ER-negative, and triple-negative breast cancers.
As RAD140 facilitates its effects via the androgen receptor, assessing its potential clinical applications in this context was worth exploring.
In a preclinical study RAD140 significantly suppressed the growth and proliferation of breast cancer cells in in vivo and in vitro models of AR/ER+ breast cancer [R].
RAD140 has a promising preclinical profile, and Radius Health is currently in the process of recruiting 40 postmenopausal women with hormone receptor positive breast cancer into its first phase 1 clinical trial on humans [R].
The main goal of the study is to evaluate its safety profile, tolerability, and pharmacokinetic characteristics in hormone receptor positive breast cancer.
RAD140 Clinical Trials
One Phase 1 study on RAD140 has been conducted [R].
The Phase 1 trials are the first stage of testing in human subjects designed to assess safety, side effects, best dosage, and formulation method for the drug.
Dose Escalation Study In Estrogen Receptor Positive, HER2 Negative Breast Cancer
The first Phase 1 trial involving RAD140 was a dose escalation study with a 3 + 3 design conducted in 2017 on 16 postmenopausal women with hormone receptor positive breast cancer.
The primary objective was to determine its safety profile and the maximum tolerated dose of RAD140.
The secondary objectives were to evaluate pharmacokinetics and antitumor activity.
The median age of the 16 patients enrolled in the trial was 58 years old.
88% of them had visceral disease and 94% had androgen receptor positive tumors determined via immunohistochemistry.
6 patients were given 50 mg RAD140 orally once per day.
7 patients were given 100 mg RAD140 orally once per day.
The other 3 patients were given 150 mg RAD140 orally once per day.
The median time on treatment was 8 weeks, with a range of 1-25 weeks for the entire group of patients.
Over 30% of patients experienced an elevation of their ALT/AST levels, decreased weight/appetite, and constipation.
Dose-limiting toxicities (all grade 3 and reversible) included hypophosphatemia and elevated ALT/AST.
2 patients experienced hypophosphatemia, and they were both in the 150 mg dosage group.
2 patients in the 50 mg and 100 mg dosage groups experienced elevated ALT/AST.
No drug-related deaths occurred.
There was 1 partial response in the 100 mg dosage group and 2 patients with stable disease for over 12 weeks.
The time to partial response was 15.9 weeks and the duration was 8.6+ weeks.
SHBG levels decreased in all 12 of the patients evaluated.
PSA levels increased in 10 of the 14 patients evaluated, with the most notable increase occurring in the patient with a partial response to RAD140 treatment.
That patient remained on the treatment at the 7 month mark.
The provisional maximum tolerated dose of RAD140 was determined to be 100 mg dosed once per day orally.
Overall, RAD140 demonstrated an acceptable safety profile and exhibited preliminary evidence of target engagement and antitumor activity [R].
Is RAD140 As Strong As Steroids?
Yes, kind of…
RAD140 purportedly (not officially) has an anabolic:androgenic rating of 90:1 and partially antagonizes the negative effects of testosterone on the prostate.
The anabolic:androgenic ratio is essentially a ratio which exhibits how much anabolic activity a specific compound will exert in the body, and how much androgenic activity it will exert in the body.
Anabolic, meaning that they promote anabolism (cell growth), and androgenic (virilization), meaning that they affect the development and maintenance of masculine characteristics.
The androgenic:anabolic ratio of a compound is a very important factor when determining the potential clinical applications of it.
Initial steroid research sought to synthesize a compound which retained a high degree of anabolic activity, coupled with a lack of androgenic activity, the goal being to produce a compound with a high anabolic yet low androgenic effect.
Because steroids were intended for medical treatment, patients could include men and women, and even children.
The last thing you want to do is give a girl a bunch of testosterone so she can prevent muscle wasting, only to have her end up with a myriad of masculinizing side effects like the deepening of her voice, acne, clitoral enlargement, body hair growth, and all the other negative side effects associated with anabolic androgenic steroids.
The androgenic side effects of steroids in men aren't insignificant either.
The risk of Gynecomastia (man boobs), endocrine shutdown (infertility), testicle shrinkage, negative effects on cholesterol, increased risk of heart disease, among many other side effects are all very real side effects of anabolic androgenic steroids.
I'm not saying that these will absolutely happen at all, but there is a chance of them occurring with steroid use, with some of them still occurring with SARMs to a significant extent.
Considering this, it is obviously very important to synthesize compounds that have as low of a risk of any of these side effects occurring, while still maximizing the anabolic efficacy of the treatment given to patients.
Compounds with a high ratio of androgenic to anabolic effects are the drugs of choice in androgen-replacement therapy, but in the context of muscle and bone wasting prevention, compounds with a much higher anabolic/androgenic ratio are exponentially better candidates for treatment.
Based on the preclinical data, RAD140 has shown that even with a complete absence of testosterone it can still induce just as much anabolic activity in muscle and bone as testosterone would, with several-fold less androgenic activity.
This would consequently eliminate and replace the need for anabolic androgenic steroid use in degenerative musculoskeletal disease treatment.
In addition, RAD140 synergistically works alongside testosterone to induce greater amounts of muscle growth in the body if they are used concurrently, while simultaneously decreasing testosterone’s negative side effects on the prostate [R].
Is RAD140 The Strongest SARM To Date?
This is debatable as different SARMs act on the androgen receptor in different ways in different individuals.
In general, it is undeniable that RAD140 is very strong, and pound for pound it is one of the strongest SARMs on paper with a purported 90:1 anabolic:androgenic ratio.
It is formidable to LGD-4033 in terms of strength gains, although LGD-4033 seems to be a more potent overall muscle builder.
RAD140 seems to have a muscle hardening effect that isn't commonly reported with LGD-4033.
Increased muscular endurance from RAD140 is also reported to be one of its most redeeming traits.
The only SARM that seems to outperform RAD140 in terms of muscle building, strength gains, and muscle hardening simultaneously is S23.
However, S23 is more suppressive and has some odd side effects that aren't reported with RAD140.
RAD140 Reviews (Anecdotal/Recreational Reports)
RAD140 is one of the most popular SARMs in the fitness and bodybuilding community in the context of performance enhancement.
It is most commonly used to gain muscle mass and increase strength.
It is reported to also be very effective at increasing muscular endurance and overall stamina.
While other SARMs help with muscular endurance to some degree, RAD140 in particular seems to excel in its ability to increase endurance, stamina and speed.
This is not to be confused with Cardarine and SR9009, which are not SARMs.
RAD140 is not as effective as Cardarine at increasing cardiovascular endurance.
RAD140 is most commonly used for bulking, or in recomposition phases, and is often referred to as a dry gainer.
It creates a harder, dryer look similar to SARMs like S4 and S23.
Users often report a very noticeable aggression unique to RAD140 that is not notable in any other SARM except S23.
This increased aggression has made RAD140 a fairly popular pre-workout alternative in the bodybuilding community.
Dosages of 10 – 30 mg per day are commonly used in a recreational context for muscle building purposes.
There is no established therapeutic dosage of RAD140.
Pharmacokinetic samples collected for 144 hours after the 100 mg RAD140 single dose showed variable absorption with a half-life of approximately 60 hours [R].
The observed human steady-state pharmacokinetic exposure at 100 mg exceeds the pharmacokinetic exposure of the efficacious dose in mice of 10 mg/kg.
RAD140 Side Effects
One thing you will often read is how there have been no reported side effects of RAD140.
This is not the case, both anecdotally as well as in the limited clinical data.
Potential Ventricular Inflammation
Unpublished preclinical toxicology studies with RAD140 indicated that it induced focal inflammation of the right ventricle in male and female Sprague-Dawley rats [R].
With that being said, the same side effect was not noted in the male or female cynomolgous monkeys treated with RAD140, and preclinical rat models have some underlying issues in regards to cardiovascular risk.
Androgens cause 11beta-hydroxylase inhibition in rat adrenal glands.
Inhibiting this in rats causes an increase in the adrenal output of 11-deoxycorticosterone, which can cause cardiac lesions in rat hearts.
Also, in another preclinical rodent model, high dosages of RAD140 had a protective effect on the heart.
This was the first occurrence of rat cardiotoxicity reported for a SARM.
The data supports that the focal inflammation in the rat studies cannot be extrapolated to primates and humans, so it is very unlikely that this same outcome would occur in humans.
The fact that it didn't occur in monkeys with dosages as high as 1000 mg/kg/day is very reassuring that this outcome would be less likely to occur in humans, but it is notable nonetheless.
While RAD140 exhibits one of the most impressive myotrophic/androgenic preclinical profiles, it cannot be ignored that there was still blatant increasing androgenic activity in a dose dependent manner in all animal models.
Albeit limited due to the high level of tissue selectivity, RAD140 still exhibits androgenic activity in the body and will potentially lead to accelerated hair loss.
However, it could also potentially reduce hair loss if used at a dosage that suppressed endogenous androgens and/or antagonized endogenous androgens at the androgen receptors enough that the androgen load on the body was lower than baseline, while still fulfilling the anabolic functions that would have otherwise been fulfilled via endogenous Testosterone.
This does not exclude temporary shedding (acute telogen effluvium) which can be triggered by a hormonal fluctuation.
This is not to be confused with androgenic alopecia, which is caused by follicular miniaturization induced by androgens.
Based on the efficacy data comparing S1 to Finasteride, it is likely that RAD140 (if anything) would reduce the progression of hair loss at therapeutic dosages based on its tissue selectivity [R].
Anecdotally, recreational users report hair loss quite fairly frequently with RAD140 usage, however, this is with dosages that likely greatly exceed what the therapeutic dosage will be in a clinical setting.
Whether this hair loss in the bodybuilding community is real androgenic alopecia or just temporary shedding is unclear and would require more data.
While the risk is relatively low based on anecdotal reports, it is safe to say that all SARMs can cause gynecomastia (gyno) as they impact the Hypothalamus-Pituitary-Testes-Axis.
By binding harder to the androgen receptors than endogenous androgens, there can be a diversion of more endogenous Testosterone to aromatize into Estrogen.
Also, suppressing Testosterone production in itself can cause an imbalance in the ratio of endogenous androgens relative to endogenous Estrogen in the body, creating a hormone imbalance that encourages gynecomastia development.
Estrogen management would be prudent during any usage of SARMs.
Lowering Of Lipids
Just like any other SARM or anabolic steroid, RAD140 exhibits a dose dependent lowering of lipids (LDL, HDL, triglycerides) [R].
One commonality among all anabolic androgenic compounds is that they will all suppress HDL cholesterol (“good” cholesterol) in a dose dependent manner, and this has been consistently demonstrated in clinical trials conducted on SARMs as well [R, R].
Every single SARM that has been evaluated has exhibited this same dose-dependent suppression of lipids.
Just like anabolic steroids, SARMs have all consistently exhibited suppression of luteinizing hormone (LH) and follicle stimulating hormone (FSH) through the Hypothalamus-Pituitary-Testes-Axis.
The result of this is decreasing natural testosterone production in a dose-dependent manner [R].
Anecdotally, RAD140 is one of the most suppressive SARMs.
In a preclinical primate model assessing its effect on endogenous Testosterone production, young monkeys with testosterone levels between 600-800 ng/dL (similar to the average Testosterone level of 25-54 year old human males) were treated with RAD140 for 28 days.
In all treated monkeys, Testosterone levels dropped to about 50% of baseline, with the average Testosterone level decreasing to 200-300 ng/dL.
This occurred even with dosages as low as 0.01 mg/kg [R].
Increased Estrogen Or Decreased Estrogen
RAD140 does not aromatize into Estrogen, but it still has a large impact on the ratio of Testosterone:Estrogen in the body.
RAD140 binds to androgen receptors harder than endogenous androgens, and can encourage increased amounts of endogenous aromatization of Testosterone to Estrogen by occupying vacant receptor sites.
In addition, dose-dependent suppression of endogenous Testosterone levels can lead to a Testosterone:Estrogen imbalance.
The systemic elevation of Estrogen levels in the body is often misinterpreted as the result of prohormone laced SARMs.
High Estrogen Symptoms
- Acne, oily skin
- Erectile dysfunction
- Low libido
- Gynecomastia (man boobs)
- Water retention
- High blood pressure
- Enlarged prostate
- Shrunken testicles
- Sugar cravings
High dosages and/or long-term use of RAD140 can cause a decrease in systemic Estrogen levels.
This is facilitated through higher levels of endocrine suppression.
Estrogen facilitated physiological functions in the body are mediated through the aromatization of Testosterone into a sufficient amount of Estrogen.
If RAD140 usage suppresses endogenous Testosterone levels too low, it can result in Estrogen levels dropping as a consequence of the lack of aromatization occurring in the body in a suppressed state.
When Estrogen levels get too low, a new set of side effects can occur.
Low Estrogen Symptoms
- Dull weak orgasms
- Dry skin and lips
- Erectile dysfunction
- Low libido
- Mood swings
- Loss of appetite
Even at dosages 10 times higher than the efficacious dosage required to replicate the therapeutic anabolic benefits of Testosterone, RAD140 did not increase liver enzymes or exhibit any liver toxicity [R].
While this was just a preclinical animal model, it is promising for the development of RAD140 as other SARMs have shown potential liver toxicity concerns, albeit minimal at their therapeutic dosage amounts.
RAD140 users commonly report very blatant increases in aggression.
While this is anecdotal, it has occurred consistently enough in the bodybuilding community that it should be considered.
The interesting thing about this is that typically increased aggression only occurs when androgen index increases in the body.
This is why more androgenic steroids are commonly used pre-workout for a quick boost in aggression before training.
The fact that RAD140 is resulting in increased aggression in recreational users could potentially be indicative of some of the following outcomes:
- RAD140 isn't as selective for anabolic activity relative to androgenic activity in humans as it was in the preclinical animal studies
- The dosage humans are using recreationally is far higher than needed
- Their RAD140 is fake and is another hormone entirely
I believe the second potential outcome is the most likely reason.
Potential As A Hormone Replacement Therapy (HRT) Alternative For Men
RAD140 is often labeled in the recreational fitness and bodybuilding community as a potentially safer HRT alternative for men.
This has yet to be proven in clinical trials, and there is one massive inherent flaw that prevents RAD140 from being a standalone effective HRT alternative.
That is its lack of aromatization into Estrogen.
RAD140 does not aromatize into Estrogen, and also greatly suppresses endogenous Testosterone levels.
The net result of this is suboptimal Estrogen levels to support basic physiological functions in the male body, and a myriad of low-estrogen side effects with long term use.
Even if RAD140 was a viable alternative to Testosterone, it would either need to be used in conjunction with exogenous Testosterone, or Estrogen would need to be administered concurrently with RAD140.
RAD140 is not a viable standalone treatment for hormone replacement therapy.
While high levels of Estrogen can cause numerous negative side effects, low Estrogen levels can be just as deleterious in men.
RAD140 Bulking Cycle
In a calorie surplus RAD140 will promote more lean muscle gains than would otherwise be possible to gain naturally.
For use in a performance enhancing context, cycles like the following are commonplace among users.
RAD140 Cutting Cycle
In a calorie deficit RAD140 will retain much more lean muscle mass than would otherwise be possible naturally.
For use in a performance enhancing context, cycles like the following are commonplace among users (the length of this may vary depending on the user's individual timeline constraints for reaching a goal body fat percentage).
RAD140 PCT (Post Cycle Therapy)
RAD140 is very suppressive and undoubtedly requires a PCT phase (post-cycle therapy) for efficient recovery.
The goal of a PCT phase would be to restore natural Testosterone production as quickly as possible and prevent low androgen or high Estrogen side effects from occurring.
Forgoing PCT will greatly increase the risk of muscle loss, fat gain, among all of the other negative side effects associated with low Testosterone levels.
Most RAD140 sources do not third party test their products, nor do they have any satisfactory level of quality control whatsoever.
I strongly advise that before you buy SARMs from a company online you thoroughly evaluate their track record, their third party test results, and how they are marketing their products in general.
These Are My Current Trusted/Go To Companies For Third Party Tested 99%+ Pure RAD140:
Disclaimer: The information included in this article is intended for entertainment and informational purposes only. It is not intended nor implied to be a substitute for professional medical advice. Prior to buying anything, check that it is compliant where you live with your current government laws.