Nandrolone Decanoate …brain damage and drug dependance

Most scientifical research towards brain damage and drug dependence is focused on nandrolone; one of the most commonly (ab)used AAS. Nandrolone is a synthetic modification of the testosterone molecule and lacks a methyl (CH3) group at the C19 position.

Apart from elite athletes aiming for increased performance during competition, both professional and amateur bodybuilders administer AASs to gain maximal muscle volume. During the past decade their use has spread to colleges and high schools as well. Over the last years, several studies examining substance use-patterns have shown an increase in anabolic-androgenic steroids (AASs) in all user groups, not only in athletes. The use of AASs is no longer limited to professional power training athletes and body builders, but a large number of young adolescents take AASs in high doses with the intention of improving their physical fitness, appearance, increasing of confidence levels, and even pleasure.

However, this misuse probably involves more than a desire to enhance the user’s appearance or sporting performance: it also appears to have much in common with the use of alcohol and tobacco. According to recent surveys, people who abuse AASs also tend to abuse psychotropic drugs such as cocaine, heroin, amphetamine and MDMA (“ecstasy”). One explanation for the popularity of stimulant drugs among steroid users could be the fact that they increase fat burning and induce a sensation of an “energy burst” that makes the user train even harder. This trend is alarming because, while the side effects of both anabolic steroids and stimulants have been well documented, very few studies have been performed to assess the potential effects resulting from the concomitant use of these drugs. For example, it has been hypothesized that steroid hormones are important determinants of cocaine’s effects on behavior by influencing neuronal activity and plasticity.

Synergism

Most of us know the word synergy, it means that two different compound enhance each other’s effect. It’s like 1 +1 = 3. We also know that many bodybuilders, probably the majority, stacks in polypharmacy. Mostly these compounds fit nicely together. It’s so good to smoke cigarettes if you drink a lot of beer. Just as oral steroids complete the injectables. I know many young bodybuilders that don’t want to use alcohol, because it will make them fat, but they do snort “speed” to be able to party all week-ends and use “coke” to feel good. Some smoke marihuana to sleep. Do we even think about the fact that some of these recreational drugs could work synergistically on the side effects?

I know guys that started as bodybuilders but along the way they visited the gym no more. They became lethargic and only wanted to use drugs in their spare time. It’s not only a thing for young bodybuilders, but society as a whole is using much drugs. It has become kind of common. On the discussion-boards we try to warn members for these dangers.

Researches try to find answers to these questions and we will discuss some to make you all aware. Common sense will tell you that a combination of AAS and “coke” isn’t good. But what does it do exactly? And with Growth hormone? I think I saw to many guys that have debilitating themselves. Nice guys that liked to party, now in their thirties, you can see it in their faces in their eyes. You don’t need to be an MD to see that they have damaged their brain. Just like to much alcohol can damage your brain. No one will deny that.

The mental side effects associated with AASs have been observed more frequently as the use of AASs has become more widespread. Changes in mood, euphoria, delusions, depression and violent behavior, are reported to be associated with the prolonged use of AASs. The neurochemical mechanisms behind AAS-induced mental side effects are not clear. Nevertheless, on the basis of animal studies, it has been suggested that AAS abuse may constitute a risk factor in aggressive behavior, partly by affecting the serotonergic system and drug dependence by affecting the dopaminergic system in the brain.

AAS Dependence

No cases of abuse or dependence have been described in men or women who received or self-administered therapeutic doses of AASs for medical indications. However, when used for enhancing physical appearance, AASs can lead to abuse and dependence in both men and women has proposed a two-stage model of AAS dependence. According to this hypothesis, anabolic effects on muscle growth account for the first stage of steroid use. However, with chronic exposure, users can develop physical and psychological dependence on AASs, as defined by DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders, 1987). Regarding the background literature AASs abusers share personality factors with the abusers of psychotropic substances, such as cannabis, amphetamine and cocaine.

Animal models

While it is clear that AASs are abused, defining the potential for addiction in humans has been problematic because it is difficult to separate direct psychoactive effects the drugs in humans from the user’s psychological dependence on the anabolic effects of AASs. Thus, studies in laboratory animals are a useful tool to explore androgen reward. Several experimental models have been developed to study reward in laboratory animals, where conditioned place preference (CPP) and self-administration are the most important methodologies. Testosterone, like many drugs of abuse, will increase rates of bar pressing for electrical brain stimulation, which is considered an indication of a drug’s rewarding effects. Male hamsters preferentially self-administer testosterone orally, and in many studies the testosterone induces conditioned place preference. To the author’s knowledge, there is only one CPP-study carried out with nandrolone, and it shows that nandrolone is able to induce CPP in mice. Both hamsters and rats self-administer testosterone intravenously (i.v.). Syrian hamsters have also been shown to self-administer nandrolone. As seen, AASs are self-administered by rodents, although the effect is known to be rather modest. Still, it is comparable with other mild reinforcers such as benzodiazepines and nicotine.

Pre-exposure to AASs has been demonstrated to affect the response to other substances of abuse in experimental animals. Nandrolone decanoate is shown to block CPP induced by food, tetrahydrocannabinol and morphine. Male adult rats have been shown to increase voluntary alcohol intake after cessation of AAS-administration.

Steroids users need more XTC pills

Recreational drugs like XTC or amphetamines have less effect on steroids users than on non-users. Researchers at the Finnish National Public Health Institute concluded this from experiments they did on rats.

The researchers wanted to know more about the relationship between steroids and drugs, because studies have shown that drugs use is higher among steroids users than non-users. They wondered whether it had anything to do with the way in which the combination of substances affects the brain.

XTC and amphetamines both increase the concentration of dopamine in the nucleus accumbens, in brain’s pleasure centre. The more dopamine released in the nucleus accumbens, the better you feel. What’s more, XTC also raises the concentration of serotonin in the nucleus accumbens. And serotonin contributes to feelings of pleasure and enjoyment too.

The figure below shows the concentration of serotonin in the nucleus accumbens of rats that had been given XTC [the arrow indicates when this happened, Ed.] and in rats that had been given a ten-day course of nandrolone decanoate or Deca-Durabolin. The Deca-rats received an injection containing 5 or 20 mg nandrolone decanoate per kg bodyweight every other day for 10 days.

XTC causes a serotonin peak; Deca does not. Deca did, however, cause a dopamine peak, as did amphetamines and nandrolone. It’s the peaks that give XTC users that temporarily ecstatic feeling .

The combination of deca and XTC works out differently than you might expect.

Deca flattens off the serotonin peak. And the steroid does the same to the dopamine peak.

Rats that have been given XTC are more active than normal. They are high, and this is reflected in their behavioural score. The graph below shows that Deca suppresses that behaviour.

How androgens cause this effect the researchers don’t know. They exclude the possibility that steroids speed up the breakdown of dopamine and serotonin. They looked at that, and observed no change. They suspect that steroids have a negative effect on the brain cells that manufacture serotonin and dopamine.

"Abusers of AAS may require larger doses of drugs to achieve the desired effects", the Finns conclude. The potentially harmful effect of steroids on the cells that produce neurotransmitters may explain why steroids users are relatively frequent drugs users. Steroids users feel unwell more often and use recreational drugs as a form of self-medication.

Nandrolone and Cocain

The abuse of anabolic androgenic steroids (AASs) is not only a problem in the world of sports but is associated with the polydrug use of nonathletes. Investigations of the neurochemical effects of AAS have focused in part on the monoaminergic systems, involving, among other things, the development of dependence. We have previously shown that pretreatment with nandrolone decanoate attenuates dose-dependently the increase in extracellular dopamine (DA) concentration evoked by amphetamine and 3,4-methylenedioyxymethamphetamine in the nucleus accumbens (NAc). The aim of this study was to investigate whether the nandrolone pre-exposure modulates the acute neurochemical and behavioral effects of cocaine in rats and whether the effects are long lasting. DA, 5-hydroxytryptamine (5-HT), and their metabolites were measured from samples collected from the NAc by microdialysis. The behavior of the animals was recorded. The present study demonstrates that five injections of nandrolone (5 and 20 mg/kg) inhibited cocaine-evoked DA and 5-HT outflow in the NAc, locomotor activity (LMA), and stereotyped behavior in experimental animals, and that these effects are seen even after elimination of nandrolone from bloodstream. Given that accumbal outflow of DA and 5-HT, as well as LMA and stereotyped behavior, is related to gratification of stimulant drugs, this study suggests that nandrolone, at the doses tested, has a significant effect on the pleasurable properties of cocaine. Furthermore, because neurochemical and behavioral responses were still attenuated after a fairly long recovery period, it seems that nandrolone may induce long-lasting changes in the brains of rat.

Nandrolone decanoate and DA

The impact of AASs, particularly Nandrolone Decanoate, on the brain dopaminergic systems has been studied to some extent in rodents. Two-week dosing of Nandrolone Decanoate at 15 mg/kg daily decreased density of dopamine D1-like receptor protein in the caudate putamen and NAc core and shell. Similar results were later obtained for mRNA levels. On the other hand, the densities of dopamine D2-like receptors were upregulated in the caudate putamen, VTA and NAc core, while downregulated in the shell. Sub-chronic Nandrolone administration to rats causes alterations in mRNA expression of DA receptors. An increase was detected in the D1 –receptor in amygdala and the D4 in the NAc, and a decrease in D 1 receptor in the hippocampus. In these studies, no changes in gene expression of TH or AADC were detected.

The daily dosing of Nandrolone at 1, 5 and 15 mg/kg for 14 days increased amounts of DAT in the caudate putamen and treatment with Nandrolone (15 mg/kg/day for 14 days) caused an up-regulation of the binding potential of the DAT in the striatum. This could explain some of the alterations seen in DA receptors after Nandrolone dosing, since receptor number or activity could be affected by Nandrolone’s actions on increased DA up-take by DAT.

Nandrolone pre-treatment (15 mg/kg/day for 14 days) has been shown to attenuate amphetamine-induced decreases of the DA metabolite levels. Furthermore, Nandrolone Decanoate pre-treatment is shown to abolish the effect of amphetamine on the hippocampal DOPAC/DA ratio and the hypothalamic DOPAC level and DOPAC/DA ratio. This reduced metabolism might possibly be a compensation for increased DA uptake, since the DA baseline levels remains unchanged. This is in line with earlier findings of DAT up-regulation. Nandrolone has not been shown to change the MAO-A or MAO-B activity in rats.

Steroid use found to damage brain's spatial functioning

Long-term use of anabolic-androgenic steroids (AAS) appears to severely impact a user's ability to accurately recall the shapes and spatial relationships of objects, say medicos from McLean Hospital and Harvard Medical School. Their study, appearing in the journal Drug and Alcohol Dependence, used a variety of tests to determine whether steroid users developed cognitive defects due to their admitted history of abuse.

The subjects in the study were aged between 29 and 55 and had been using steroids for an average of seven years. Each participant was asked to complete five cognitive tests that assessed a wide range of brain functions, including memory for shapes and locations of objects, memory for lists of words, reaction time, ability to maintain attention, and speed of information processing.

Researcher Harrison Pope and his colleagues discovered that those participants who were long-term AAS users did significantly worse than nonusers on a test called "Pattern Recognition Memory," where participants are asked to try to remember a collection of patterns that they have been presented on a computer screen. The scores on this test declined noticeably with increasing lifetime AAS use. Importantly, the results remained stable in sensitivity analyses addressing potential confounding factors, indicating that the findings were unlikely to be attributable to some factor other than AAS use.

"Our work clearly shows that while some areas of brain function appear to be unaffected by the use of AAS, users performed significantly worse on the visuospatial tests that were administered. Those deficits directly corresponded to their length of use of anabolic-androgenic steroids," explained Pope. "Impaired visuospatial memory means that a person might have difficulty, for example, in remembering how to find a location, such as an address on a street or a room in a building."

Pope said the visuospatial deficits observed in steroid users were similar to those only previously seen in elderly people with dementia, who can become easily become lost or disoriented. "The magnitude of our findings was quite shocking and we hope that they will lead to larger studies and increased awareness regarding the possible dangers of the use and abuse of AAS," he concluded.

Erythropoietin (EPO) on Nandrolone Decanoate induced brain injury

Tugyan et all undertook a study in order to investigate the possible neuroprotective and anti-apoptotic role of EPO treatment on Nandrolone Decanoate induced brain injury.

Apoptosis is a programmed cell death. In recent years, many experimental studies have examined the relation of apoptosis and AAS usage in different tissues and organs.

Shokri et al. investigated the apoptotic effects of nandrolone on testis tissue and found a significant increase in apoptotic cells after nandrolone injection. Other researchers investigated the apoptotic effects of three kinds of AAS on ventricular myositis, and they also demonstrated that these compounds increased apoptotic cell count in a dose dependent manner. To our knowledge, there is no study evaluating the effects of Nandrolone Decanoate on brain tissue. Their study demonstrated that Nandrolone Decanoate caused a significant increase in apoptotic cells and a significant decrease in neuronal count in the parietal cortex, prefrontal cortex and hippocampal regions of the brain.

Because of the high sensitivity of the brain, the ongoing damage and increasing amount of reactive oxygen species (ROS) lead to pathological changes in brain tissue. Previous studies show the antioxidant effect of EPO in different brain regions. The present study shows that Nandrolone Decanoate induced the oxidative stress and apoptotic cell death in several regions of the brain including parietal cortex, prefrontal cortex and hippocampal regions and indicates that EPO decreases the apoptotic and antioxidant stress induced by Nandrolone Decanoate usage in brain tissue in the parietal cortex, prefrontal cortex and hippocampal regions of the brain.

The present study indicates for the first time that EPO has neuroprotective effects against Nandrolone Decanoate induced-brain injury by its anti-apoptotic and anti-oxidant effects. It has been previously demonstrated that EPO can cross the brain–blood-barrier by active translocation through capillary endothelium. It reaches its peak concentration in the brain 4 h after the first administration and subsequently decays slowly to baseline levels over the next 20–30 h

The study of Tugyan et all shows that Nandrolone Decanoate administration led to a decrease in neuronal count and apoptotic cell death as well as an increase in oxidative stress in the brain. Additionally, the improving effects of H-EPO are shown against Nandrolone Decanoate induced brain damage in a dose dependent manner. In the light of the present results we conclude that H-EPO is neuroprotective and may be useful in AAS induced damage in brain tissue.

Growth Hormone and AAS

GH improves spatial memory and reverses certain anabolic androgenic steroid-induced effects in intact rats

GH has previously been shown to promote cognitive functions in GH-deficient rodents. In this study we report the effects of GH on learning and memory in intact rats pretreated with the anabolic androgenic steroid nandrolone. Male Wistar rats received nandrolone decanoate (15 mg/kg) or peanut oil every third day for 3 weeks and were subsequently treated with recombinant human GH (1.0 IU/kg) or saline for 10 consecutive days. During the GH/saline treatment spatial learning and memory were tested in the Morris water maze (MWM). Also, plasma levels of IGF1 were assessed and the gene expression of the GH receptors (Ghr), Igf1 and Igf2, in hippocampus and frontal cortex was analyzed. The results demonstrated a significant positive effect of GH on memory functions and increased gene expression of Igf1 in the hippocampus was found in the animals treated with GH. In addition, GH was demonstrated to increase the body weight gain and was able to attenuate the reduced body weight seen in nandrolone-treated animals. In general, the rats treated with nandrolone alone did not exhibit any pronounced alteration in memory compared with controls in the MWM, and in many cases GH did not induce any alteration. Regarding target zone crossings, considered to be associated with spatial memory, the difference between GH- and steroid-treated animals was significant and administration of GH improved this parameter in the latter group. In conclusion, GH improves spatial memory in intact rats and can reverse certain effects induced by anabolic androgenic steroids.

AAS or Marijuana as a 'gateway ' to other drug usage

Some studies point to AAS as a “gateway” drug to other drug use, but a study from 2010 proved different.

The addiction rate for marijuana is lower than that of alcohol, and there is little scientific evidence that it acts as a trigger for harder drugs.

While teen marijuana use is not to be encouraged, the real "gateway drug" risk might be from abusing prescription opioids and stimulants, like OxyContin, Vicodin and Adderall, or with inhalant drug use. These have strong addictive properties and more accessible to teens.

A 2010 study by the National Institute on Drug Abuse found that among 12th graders, 8% abused Vicodin and 5.1% abused OxyContin. Inhalant use peaks in the 8th grade at around 17%, far earlier than all other drugs.

The result of the survey will not really come as a surprise for us, but it is rather unpleasant for authorities and “Big Pharma”: 17% of high schoolers drink, smoke, use drugs during school day

Steroids use doesn’t lead to drugs

The gateway theory has fallen. The use of steroids doesn’t lead to drug addiction. That’s the message of a study from 2010 by anthropologists Nina Garevik and Anders Rane of the Swedish Karolinska University published in Drug and Alcohol Dependence.

Ten years ago the psychiatrist Harrison Pope wrote a letter to the New England Journal of Medicine proposing a theory that steroids use can lead to drug addiction. Pope based this on a study done in a clinic where a quarter of the opiate addicts had started out as chemical athletes, and had bought their first drugs from a steroids dealer. At that time Nubain was a used drug on the American steroids scene. Nubain is an opiate intended for junkies going through withdrawal, but chemical athletes used it occasionally to enable them to train harder.

Other researchers picked up quickly on Pope’s discovery, and suggested that steroids may lead to changes in the brain that would make steroids users more susceptible to addiction. Some governments were so alarmed at the hard drugs – steroids link that they stepped up their war on steroids even further. Other governments, such as the Swedish, decided to finance research on the phenomenon. Thanks to that – and a subsidy from the WADA – we have the study that will be published soon in Drug and Alcohol Dependence.

The Swedish researchers interviewed 56 men in 2007-2008 who had been picked up by the Stockholm narcotics police. The men had drugs on them, and steroids as well, or had confessed to using steroids as well.

First the researchers selected the men in the group who used both drugs and steroids: there were 33 of them. Then the researchers tried to determine which came first: use of steroids or of drugs. "Only a minority (21%), of these individuals started their drug use with AAS and 55% with narcotic agents. Data about the first-used substance was missing for 24% of subjects", the Swedes write. "The most commonly co-used substances were cannabis (35%), cocaine (28%), diazepam (26%) and amphetamine (15%)."

These findings don’t support the gateway theory, but when the researchers enquired about the co-users’ lifestyles the theory was put to rest for good. However, a small number of men who used both drugs and steroids did also do weight training. The same was true of some of the men who only used steroids.

"Since supraphysiologic doses of AAS may increase fat-free mass and muscle size even without strength training, it may appeal to some potential users who are uninterested in training but want to become stronger for aesthetic or other reasons", write the Swedes. "AAS are also known to increase aggressiveness and inhibit impulse control, and this may make them desirable among users who intend to commit criminal acts."

So the group that the researchers studied was a criminal subgroup from the drugs scene, which had discovered the potential of steroids – but which has nothing in common with the vast majority of steroids users in gyms and fitness centres.

This blogpost is far from complete research towards drugdependence and the interactions and side effects of all these different dugs used in poly-pharmacy will continue for a while since more and more people start using AAS for different reasons.