AAS – CNS Effects

[Michael Scally MD]

Healthcare Professionals' Stigmatization of Men with Anabolic Androgenic Steroid Use and Eating Disorders

Highlights
· We present healthcare providers with four clinical vignettes.
· We examine providers’ attitudes toward men presenting with different clinical problems.
· Providers’ exhibited negative attitudes toward the male eating disorder patient and steroid user.
· Results may help explain steroid users’ documented distrust of healthcare professionals.

Yu J, Hildebrandt T, Lanzieri N. Healthcare professionals' stigmatization of men with anabolic androgenic steroid use and eating disorders. Body Image. 2015;15:49-53. https://www.sciencedirect.com/science/article/pii/S174014451500087X

Building upon previous research on the stigmatization of individuals with eating disorders (EDs), the present study sought to evaluate healthcare providers' attitudes toward male anabolic androgenic steroid (AAS) users.

Healthcare providers (N=148) were first randomly assigned to read one of four vignettes describing a male AAS user, ED patient, cocaine user, or healthy control.

Each provider then rated, on a scale of -3 to +3, how strongly either word in one of 22 word-pairs described his or her feelings toward the person described in the vignette.

Results indicated that providers perceived the ED and AAS use patients less favorably than the cocaine user or healthy adult, suggesting that the two groups may be stigmatized by health providers.

Given the psychiatric and medical risks associated with AAS use and EDs, reducing bias may help reduce the personal suffering and public health burden related to these behaviors.

 

[Michael Scally MD]

[Thesis] Long-term Anabolic-Androgenic Steroid Use, Aggression and Executive Functions
https://www.duo.uio.no/bitstream/handle/10852/44323/1/AAS-ferdig.pdf

Stian Langli

Anabolic-Androgenic steroids (AAS) are synthetic derivatives of testosterone. While they previously were associated mostly with use among professional athletes, the recent decades have seen a spread of AAS use to the general population.

Heightened aggressiveness is one of the most commonly reported side effects of AAS use; however, the reasons behind this association have remained elusive. AAS have recently been shown to lead to neurochemical alterations in brain areas important for the regulation of aggression, as well as frontal areas important for executive functions.

The aims of this study were to investigate aggression and levels of executive functioning in long-term AAS users. AAS users with long-term AAS using careers (defined here as 1 year of cumulative use or more) and non-AAS using exercisers were recruited from local gyms and via online forums.

The assessment included a semi-structured interview concerning demographic data, exercise habits, self-reports of side effects and pattern of AAS use. Based on this data, estimated lifetime doses of AAS were calculated. Other aspects of pattern of AAS use were age of onset, total duration of use, concomitant drug abuse and AAS dependence.

Aggression was assessed using the Buss Perry Aggression Questionnaire (BPAQ), which produces four subscales on different aspects of aggression. Executive functions were assessed using three commonly used neuropsychological tests; the Color Word Interference Test (CWIT), the Trail Making Test (TMT) and the Attentional Network Test (ANT).

The results showed a significant and strong main effect of AAS use on several measures of aggression. AAS users with no history of drug abuse displayed significantly higher levels of aggression than controls. Furthermore, estimated lifetime dose, age of onset and duration of use correlated with levels of aggression.

Findings on executive functions were somewhat more ambiguous. AAS users performed worse than controls on measures of executive inhibition and executive control. No differences were seen on tests of cognitive flexibility.

It is concluded that AAS users display significantly higher levels of aggression compared to non-AAS using individuals, and that these levels are associated with a more severe pattern of AAS use. Furthermore, this investigation provides evidence that AAS users display lower levels of executive inhibition and control, but not flexibility.

The implications of this finding for the association between AAS use and aggression are discussed, and suggestions for future research are presented.

 

[Michael Scally MD]

Mhillaj E, Morgese MG, Tucci P, Bove M, Schiavone S, et al. Effects of anabolic-androgens on brain reward function. Frontiers in Neuroscience. http://journal.frontiersin.org/article/10.3389/fnins.2015.00295/abstract

Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming the so called androgen anabolic steroids (AAS). These substances were originally synthesized to obtain anabolic effects greater than testosterone.

Although AAS are rarely prescribed compared to testosterone, the off-label utilization is very wide. Furthermore, combination of different steroids, and doses largely higher than those used in therapy are common.

Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia. Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse.

Among the AAS abusers, the frequency of side effects is higher, with psychiatric complications such as labile mood, lack of impulse control and high violence.

On the other hand, AAS addiction studies are complex because the collection of data is very difficult due to reticent subjects and can be biased by many variables, including physical exercise, that alter the reward system.

Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in reward process, leading to an increased sensitivity toward opioid narcotics and central stimulants.

The aim of this review is to discuss what is present in literature in regard to steroid abuse and alteration of reward system in preclinical and clinical studies.

 

[Michael Scally MD]

 

[Michael Scally MD]

Mhillaj E, Morgese MG, Tucci P, Bove M, Schiavone S, et al. Effects of anabolic-androgens on brain reward function. Front Neurosci. 2015;9:295. http://journal.frontiersin.org/article/10.3389/fnins.2015.00295/full

Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids (AAS).

These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common.

Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia. Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse.

The frequency of side effects is higher among AAS abusers, with psychiatric complications such as labile mood, lack of impulse control and high violence.

On the other hand, AAS addiction studies are complex because data collection is very difficult due to the subjects' reticence and can be biased by many variables, including physical exercise, that alter the reward system.

Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in the reward process, leading to increased sensitivity toward opioid narcotics and central stimulants.

The goal of this article is to review the literature on steroid abuse and changes to the reward system in preclinical and clinical studies.

 

[Michael Scally MD]

[Rats] Cross-Sensitization between Testosterone and Cocaine

Highlights

• Repeated testosterone increased cocaine-induced hyperlocomotion in adolescent rats. [ten once-daily subcutaneous (s.c.) injections of testosterone (10mg/kg)]
• Acute testosterone did not change the locomotor response to cocaine.
• Cross-sensitization between testosterone and cocaine in adolescent rats.

Engi SA, Cruz FC, Crestani CC, Planeta CS. Cross-sensitization between testosterone and cocaine in adolescent and adult rats. Int J Dev Neurosci 2015;46:33-7. https://www.sciencedirect.com/science/article/pii/S0736574815004323

Cocaine and anabolic-androgenic steroids are substances commonly co-abused. The use of anabolic steroids and cocaine has increased among adolescents. However, few studies investigated the consequences of the interaction between anabolic-androgenic steroids in animals' model of adolescence. We examined the effects of acute and repeated testosterone administration on cocaine-induced locomotor activity in adult and adolescent rats.

Rats received ten once-daily subcutaneous (s.c.) injections of testosterone (10mg/kg) or vehicle. Three days after the last testosterone or vehicle injections rats received an intraperitoneal (i.p.) challenge injection of either saline or cocaine (10mg/kg). A different subset of rats was treated with a single injection of testosterone (10mg/kg) or vehicle and three days later was challenged with cocaine (10mg/kg, i.p.) or saline. Immediately after cocaine or saline injections the locomotor activity was recorded during forty minutes.

Our results demonstrated that repeated testosterone induced locomotor sensitization to cocaine in adolescent but not adult rats.

 

[Millard]

"Cocaine and anabolic-androgenic steroids are substances commonly co-abused."

WTF? They must mean 'commonly' in the same way that suicides, exploding hearts, violent rampages, cancer and death are commonly seen side effects of AAS.

 

[anonymous_475692]

Like the title, I feel AAS dependency/ addiction is real and is indeed a fact

 

[Excallibro]

How long is a receptor sensitized or desensitized by un-natural tickling? What are the feedback mechanisms involved, inside the cell?

These are things we still have to learn.

In the mean time, it's useful to think of your androgen receptors as your balls.

 

[Michael Scally MD]

Anabolic Steroids Alter the Physiological Activity of Aggression Circuits in the Lateral Anterior Hypothalamus [Blah Blah Blah]

Highlights
· Adolescent AAS exposure alters neuronal firing parameters in the hypothalamus.
· LAH neuronal activity and aggressive behavior are correlated in AAS animals.
· AAS increases the proportion of responsive cells that are excited by AVP.
· AAS lowers the proportion of cells that respond to DA D2 receptor antagonists.

Morrison TR, Sikes RW, Melloni RH, Jr. Anabolic Steroids Alter the Physiological Activity of Aggression Circuits in the Lateral Anterior Hypothalamus. Neuroscience. Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus

Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies.

Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations.

For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression.

To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior.

The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular).

AAS treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP.

Both DA D2 antagonists and 5HT increased the firing frequency of AVP responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone.

These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding.

More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure.

 

[Dr JIM]

I am puzzled (not a sarcastic comment, but a literal one) at what is behind these.

Why, when anabolic steroids don't fit the established criteria for addictive drugs, would researchers wish to find alternative definitions or mechanisms of addiction?

The academic interest is somewhat escaping me, as is medical utility.

But on the other hand I'm not ready to jump on a conspiracy explanation of a desire to push the square peg of anabolic steroids into the round hole of addictive controlled substances. While I wouldn't doubt that there are parties that would like to do it, I wouldn't assume that these researches have that as their motivation. But how exactly their career tracks could have taken them in this direction, I really have no idea and find it kind of odd.

I know this thread and Bills post are somewhat dated but as is usually the case in academia the dictum is and essentially always has been, publish of perish.

It matters little what one publishes, why it's published, whether it alters medical practice, physician practice patterns, or medical therapeutics just get it print, and while the NEJM is certainly preferred the Haitian Journal of Rodent Drug Interdiction will suit the calling just fine.

Regs
Jim

 

[Michael Scally MD]

[GMAFB! MYTH!] The Neurobiology and Addiction Potential of Anabolic Androgenic Steroids and The Effects of Growth Hormone

Highlights
· Anabolic androgenic steroids (AAS) have an impact on the central nervous system.
· AAS affect the mesolimbic reward system in the brain.
· The prevalence of dependence among AAS users is approximately 30%.
· Polysubstance abuse including hormones, stimulants, and opiates is common among AAS users.
· Growth hormone and insulin-like growth factor are often used in combination with AAS.

Anabolic androgenic steroids (AAS) are substances that mimic the hormone testosterone, and primarily act via the androgen receptor. In addition to their physiological effect on muscle tissue and growth, research from the last decade has shown that AAS have a pronounced impact on the central nervous system.

A large number of studies have demonstrated that AAS affect the mesolimbic reward system in the brain. However, whether the direct effects of AAS on endorphins, dopamine, serotonin and GABA etc. and on the corresponding and related systems lead to dependence needs to be further elucidated.

According to recent studies, the prevalence of AAS dependence among AAS users has been estimated to be approximately 30%, and polysubstance use, of both pharmaceutical drugs and narcotics, within this group is common.

The present review primarily discusses AAS in the context of addiction and dependence, and further addresses the issue of using multiple substances, i.e. stimulants and opiates in combination with AAS. In addition, aspects of the treatment of AAS dependence, the connection between AAS abuse and cognition, and AAS-induced neurotoxicity are presented.

Currently, performance enhancing drugs are frequently used in combination with AAS. Therefore, a large section on growth hormone and insulin-like growth factor is also included.

Gronbladh A, Nylander E, Hallberg M. The neurobiology and addiction potential of anabolic androgenic steroids and the effects of growth hormone. Brain Res Bull. Elsevier: Article Locator

 

[Dr JIM]

I've never believed "addiction" fits the AAS profile for drug abuse.

But it's clear many do become "dependent" upon their physiologic and/or psychological effects.

 

[anonymous_475692]

I've never believed "addiction" fits the AAS profile for drug abuse.

But it's clear many do become "dependent" upon their physiologic and/or psychological effects.

well what physiologic/psychological effects do users experience to make them become dependent on AAS ?

 

[Dr JIM]

[GMAFB! MYTH!] The Neurobiology and Addiction Potential of Anabolic Androgenic Steroids and The Effects of Growth Hormone

Highlights
· Anabolic androgenic steroids (AAS) have an impact on the central nervous system.
· AAS affect the mesolimbic reward system in the brain.
· The prevalence of dependence among AAS users is approximately 30%.
· Polysubstance abuse including hormones, stimulants, and opiates is common among AAS users.
· Growth hormone and insulin-like growth factor are often used in combination with AAS.

Anabolic androgenic steroids (AAS) are substances that mimic the hormone testosterone, and primarily act via the androgen receptor. In addition to their physiological effect on muscle tissue and growth, research from the last decade has shown that AAS have a pronounced impact on the central nervous system.

A large number of studies have demonstrated that AAS affect the mesolimbic reward system in the brain. However, whether the direct effects of AAS on endorphins, dopamine, serotonin and GABA etc. and on the corresponding and related systems lead to dependence needs to be further elucidated.

According to recent studies, the prevalence of AAS dependence among AAS users has been estimated to be approximately 30%, and polysubstance use, of both pharmaceutical drugs and narcotics, within this group is common.

The present review primarily discusses AAS in the context of addiction and dependence, and further addresses the issue of using multiple substances, i.e. stimulants and opiates in combination with AAS. In addition, aspects of the treatment of AAS dependence, the connection between AAS abuse and cognition, and AAS-induced neurotoxicity are presented.

Currently, performance enhancing drugs are frequently used in combination with AAS. Therefore, a large section on growth hormone and insulin-like growth factor is also included.

Gronbladh A, Nylander E, Hallberg M. The neurobiology and addiction potential of anabolic androgenic steroids and the effects of growth hormone. Brain Res Bull. Elsevier: Article Locator

This citation unfortunately typifies how deranged some AAS users are.

NO and I'm NOT suggesting "steroids made them do it" (use other recreational drugs narcotics in particular) but some in the BB world refuse to accept the FACT lifting heat will eventually take its toll on the human body!

You know the mantra "lift heavy or leave', which by its very nature implies if narcotics are required so be it!

 

[Redrum42]

As somebody that used to be legit addicted to many drugs I can see the parallels. But not nearly as bad.

I use TRT legit from a doc, but occasionally take a couple weeks off due to not having money (no insurance) or just to kind of reset my "tolerance"

I feel shitty off, even with PCT hcg, many weeks off. There is just missing that energetic, masculine, confident drive.

Definitely not true addiction. Kind of like weed is "addicting". Technically yes but not in the true sense of an all encompassing soul eating addiction.

Hope I don't derail the train mentioning weed ..

 

[Michael Scally MD]

[Rats] Chronic Administration of Nandrolone Increases Susceptibility to Morphine Dependence Without Correlation with LVV-Hemorphin 7

Highlights
· LVV-H7 activates opioid receptors and dose-dependently reduced locomotor activity.
· Nandrolone pretreatment prior to CPP testing potentiated the reward of morphine.
· LVV-H7 antiserum coadministered with nandrolone did not have any blocking effect.
· AAS increases susceptibility to morphine dependence without correlation with LVV-H7.

LVV-hemorphin 7 (LVVYPWTQRF; LVV-H7), an N-terminal fragment of the beta-chain of hemoglobin cleaved by cathepsin D/pepsin, is an atypical endogenous opioid peptide that is found in high concentration in blood. LVV-H7 acts as a mu-opioid agonist and an inhibitor of insulin-regulated aminopeptidase. Subchronic administration of anabolic androgenic steroids (AAS) has been clinically proven to induce the synthesis of erythrocytes and increase hemoglobin concentrations.

Patients with a history of AAS abuse are more susceptible to opioid abuse. We hypothesized that this association could be at least partially attributed to the sensitization of the mesocorticolimbic dopaminergic pathway by LVV-H7. Using the conditioned place preference test and neurochemical analysis, we investigated the possible mechanism underlying the effect of chronic nandrolone administration on morphine-induced reward and its correlation with LVV-H7 in rats. Either LVV-H7 may not sensitize the rewarding neural circuits or its inhibition on locomotor activity could mask reward-related behaviors.

Chronic nandrolone pretreatment indeed caused a significant reward by low dose morphine, which did not cause any reward in control rats. However, coadministration of anti-LVV-H7 antiserum with nandrolone did not block this effect. This may rule out the possibility of the involvement of LVV-H7 in the action of nandrolone to intensify morphine-induced reward. Moreover, the serum level of LVV-H7 was mildly increased in response to chronic nandrolone administration in our animal model.

According to the current clinical observations, we may conclude that the chronic administration of nandrolone can increase susceptibility to morphine dependence, but that this effect is not related to elevated LVV-H7.

Huang EY, Chen YH, Huang TY, Chen YJ, Chow LH. Chronic administration of nandrolone increases susceptibility to morphine dependence without correlation with LVV-hemorphin 7 in rats. Neuropeptides. Chronic administration of nandrolone increases susceptibility to morphine dependence without correlation with LVV-hemorphin 7 in rats

 

[Redrum42]

Now as trying to taper down on methadone while being on TRT because of methadone induced hypogonadism.. I find the above very interesting ...

Hope I'm not screwing myself.

 

[Dr JIM]

Now as trying to taper down on methadone while being on TRT because of methadone induced hypogonadism.. I find the above very interesting ...

Hope I'm not screwing myself.

Your presupposed cause and effect relationship is a stretch fella as it's seemingly based on the notion causation and association are equivalent in this instance.

That's to say while opiates have been associated with suppressed gonadotropin levels, especially with chronic use, whether said narcs are directly responsible for symptomatically reduced TT levels is another matte.

 

[Redrum42]

Well methadone is one of the worst as far as suppression.

As I lower my dose my natural levels are slowly rising.

Yeah I guess that's not proof but there's a dickload of studies and anecdotal evidence out there that seems to prove my point.

Who knows maybe I misinterpreted it all but I thought opiates=bad for your balls was kind of widely accepted.