Written by DR. GEORGE TOULIATOS, MD
28 April 2020

 ROID-RAGE

 

 

 

Dr. Testosterone
By George Touliatos, MD

 

ROID RAGE

 

The speculated “roid rage” deals with the consequences of performance-enhancing drugs (PEDs) and anabolic-androgenic steroids (AAS) abuse in the mental status and psychology of bodybuilders. The psychopathological aspect of PEDs/AAS neurotoxicity and dependence can present as a chronic long-term adverse effect, or in the form of episodes-crisis adverse effect.

 

Apart from the fact that bodybuilders have an external appearance way freakier that the average individual, the combination of an extreme low-carbohydrate, low-caloric diet, along with exhausting training along with chemical enhancement abuse, would make an explosive combination, leading eventually to a psychopathologic behavior.

 

Roid rage has been associated with various psychiatric manifestations such as sleep disorders (insomnia), anxiety, mania, depression (bipolar disorder), irritability, aggression, violence, suicidal behavior, psychosis, confusion and delirium. It’s quite common that heavy steroid users have a lower threshold of patience and lose their temper easier, making them act spontaneously, driven by their instinct without thinking logically. Long-term abuse may lead to the development of a dependence syndrome and withdrawal symptoms on cessation.

In terms of cognition, only a handful of studies have investigated the cognitive deficits associated with the long-term use of AAS. They have shown that the abuse of AAS is associated with self-reported retrospective and prospective memory deficits. Furthermore, other studies revealed selective cognitive deficits in AAS users, with specific deficits on cognitive measures of inhibitory control and attention, with no differences in terms of planning or decision making. Taken together, these findings suggest there may be selective cognitive deficits associated with persistent AAS use.

 

Whereas the exact mechanisms of the adverse consequences of AAS use are unclear, they are likely partly reflecting disruptions of brain networks implicated in emotional and cognitive regulation. AAS readily passes the blood-brain barrier and affect central nervous system function. Androgen receptors (AR) are abundantly expressed in the amygdala, hippocampus of the limbic system, brain stem, hypothalamus, and cerebral cortex implicating a wide range of functions, including regulation of emotion and cognition. AR correspond to different chemical substances that are able to cross the blood-brain barrier and the placental barrier as well. As a result, some anabolic steroids with a high level of androgenicity, for instance fluoxymesterone (800 androgenic index) or trenbolone (500 androgenic index), have the ability to bind tighter to the AR.

 

It has being demonstrated that neural junctions transmit signals much faster, reflecting directly to serotonin and dopamine metabolism. However, this is not exclusively linked to the androgenic activity of a particular AAS. Nandrolone decaonate, a 19-nortestosterone derivative AAS prescribed medically for the treatment of osteopenia, muscle wasting and anemia, has been associated with several behavioral disorders in superphysiological treatment doses (>200mg/15 days). Therefore, on-medical use of AAS carries neurodegenerative potential.

 

Recent animal studies have shown this AAS effect, ranging from neurotrophin unbalance to increased neuronal susceptibility to apoptotic stimuli. Experimental and animal studies strongly suggest that apoptotic mechanisms are at least in part involved in AAS-induced neurotoxicity. Furthermore, a great body of evidence is suggesting that increased cellular oxidative stress to cerebral neurons could play a major role in the pathogenesis of many neurodegenerative disorders, such as manic depression, or bipolar effect. Several different studies suggest that a wide range of psychiatric side effects induced by the use of AAS is correlated to the severity of abuse in terms of dosage and time period.

 

In another study, trenbolone was administered to adult and pregnant rats and the primary hippocampus neurons. Hippocampus is a certain area in the mesencephalon (midbrain) belonging to the limbic system, associated with behavior. Trenbolone accumulated in adult rat brain, especially in the hippocampus and fetus brain. Trenbolone induced apoptosis of primary hippocampal neurons. Therefore, 17beta-trenbolone played critical roles in neurodegeneration.

 

Large doses of trenbolone and bodybuilders-powerlifters-strongmen, which are exposed to 17beta-trenbolone by various ways, are all influenced chronically and continually. As a result, it is not only a matter of dose, but duration as well.

Cerebral MRI examinations of persons who chronically abused AAS showed it enlarged the amygdala, a certain area of mesencephalon belonging to the limbic system. Amydgala along with hippocampus determine the emotional status. It’s important to mention that metabolism of glutamic acid was also increased. As well known, glutamine is an important amino acid, taking part in brain’s metabolism. Moreover, it was demonstrated by psychiatric tests that chronic AAS abusers suffered from short-term amnesia and perhaps Alzheimer’s disease.

Some other anabolic steroids, such as methandrostenolone-methandienone (methyltestosterone’s derivative), convert to estrogen.  Aromatization is the production of estrogens by activation of aromatase enzyme in different tissues (breast, liver, adipose, brain). Estrogens are linked directly with neurotransmitters, such as serotonin, thus improving mood. As a result, Dianabol will induce a euphoric effect and addiction is highly to occur, both mentally and physically. image9



On the other hand, testosterone is a naturally existing hormone, which males produce on a daily basis. It is not a synthetic derivative like AAS. However, investigations regarding testosterone’s effect in human behavior revealed that increased levels of circulating testosterone in serum were associated with significant increase in anger and hostility. Testosterone undecaonate, enanthate and cypionate are different types of esters used in hormonal replacement therapy (HRT) in males during andropause.

 

For hypogonadal men who undergo andropause, testosterone supplementation has beneficial effects on mood, self-esteem and sexual desire. Testosterone replacement therapy (TRT) has positive, beneficial effects on depression, anemia, metabolic syndrome, obesity, sarcopenia, osteopenia and fatigue. It improves insulin resistance, physical strength, libido, bone mineral density and red blood cell count. Testosterone application has shown that a single administration of 100mg TU in eugonadal males results in supraphysiological serum testosterone levels, resulting in minor mood changes. On the contrary, hypogonadal males who undergo HRT have no detectable to limited changes in behavior.

The current literature on AAS usage suggests that some users develop episodes of insomnia, aggression (physical and verbal), irritability, anxiety, neurosis, mood swings-emotional instability, hypomania, manic episodes, depression and rarely phychosis-misconcemptions. However, AAS abusers expose themselves to extremely higher doses, quite commonly referred to as stacking cycles of different substances. AAS use has also been proven to unmask behavioral disorders, such as increased aggression, hostility and unprovoked rage attacks. These emotional and behavioral outbursts are referred to as “roid rage,” defined as sudden and exaggerated aggression induced by AAS use that is prone to a subliminal provocation. In addition, AAS users often suffer from a vigilant mindset accompanied by inability to adjust to situations, which then results in frustration and impulsiveness. Moreover, AAS use has also been associated to a wide range of violent crimes and domestic violence, particularly, physical abuse of the partner. The “withdrawal syndrome” induced by AAS abuse has been clearly described, consisting mainly of depressed mood, fatigue, AAS craving, restlessness, anorexia, insomnia, and decreased libido lasting for several weeks or months.

What is most important is to evaluate the psychiatric background of those users, being able to identify if they had a poor genetic predisposition and mental illness history, before they even begun AAS use. We conclude that each person reacts differently under the same circumstances, depending on his character, temper, or level of education. Besides the genetic predisposition of the user, the extent of neurotoxicity of PEDs/AAS also varies with the duration, dosage of abuse, concurrent organic diseases, use of other medications and neurotoxic chemicals, such as marijuana (weed), ethanol or narcotics. Also as a result of their body image concerns, AAS users may abuse a wide range of additional substances to gain muscle, lose fat, or otherwise affect body appearance. These substances include other hormones, beta-agonists (clenbuterol), stimulants (amphetamine, ephedrine, pseudoephedrine) and numerous other agents (diuretics). The habit of polydrug abuse among AAS users makes the neurotoxic effects more severe.

With other drugs that belong to the class of CNS stimulants (ephedrine HCL, clenbuterol HCL, methyloxanthines, amphetamines), as soon as they are discontinued, a rebound effect is more likely to occur. It is a similar case to a hangover, resulting from alcohol abuse, or withdrawal symptoms of cocaine. Remarkably, it was narcolepsy for which amphetamines were manufactured. Therefore, we could make the assumption that amphetamines, ephedrine alkaloids, methyloxanthines, or even beta2 agonists are highly addictive too, when they are ceased abruptly. Another class of narcotics, acting as potent painkillers, has a highly addictive effect on brain’s chemistry. Codeine is an opioid, which belongs to the same family with heroin. Nubain (synthetic morphine) was a widely used painkiller among professional athletes and there are rumors that this kind of drug was claimed to be the reason that IFBB pro Paul DeMayo was pronounced dead at the age of 37.

 

The understanding of the precise underlying mechanisms and the pathophysiology of AAS-induced neuropsychiatric disorders is relatively recent, and appears to be related to chronic AAS exposure. At low concentrations, AAS has trivial effects on the mood, self-esteem and cognitive function, as well as perceived to be clinically beneficial when used in accordance with the treatment protocols for dysthymia or melancholy and refractory depression. Nonetheless, at superphysiological doses, AAS abuse may induce neurochemical or structural alterations in the brain.

George Touliatos, MD is an author, lecturer, champion competitive bodybuilder and expert in medical prevention regarding PED use in sports. Dr. Touliatos specializes in medical biopathology and is the medical associate of Orthobiotiki.gr and Medihall.gr, Age Management and Preventive Clinics in Athens, Greece. Heis the author of four Greek books on bodybuilding, has extensively developed articles for www.anabolic.org and is the medical associate for the book Anabolics, 11th Edition (2017). Dr. Touliatos has been a columnist for the Greek editions of MuscleMag and Muscular Development magazines, and has participated in several seminars across Greece and Cyprus, making numerous TV and radio appearances, doing interviews in print and online. His personal website is https://gtoul.com/

 

 

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