Came across this 2003 thread from a hairloss forum, the user “Moeman” pulled together a bunch of research about Finasteride’s effects on GABA-A, anxiety and mental function. Have a read through, it only further confirms what some of us experienced - brain fog.
I have pasted his words verbatim below, in case that forum goes offline there will be a record here.
This is a followup to my initial post asking for feedback on the mental/emotional side effects of finasteride. Someone on HLH mentioned a possible link between GABA, mental function and finasteride. I followed up with some research. This is what I could piece together- i don’t want to be alarmist but as far as I’m concerned it’s not positive news…
Why is this a concern to me… as i mentioned i have felt a little cloudy mentally for sometime… i’m a professional, finished my undergraduate degree at a decent university with a 3.9 GPA, high school with a 97% average… i thought i’d do an IQ test yesterday to give me an idea of whether i was just imagining this… I scored 105 (roughly consistent on 3 different tests). Lots of things can affect your IQ and i’m not necessarily attributing it all or at all to finasteride but my subjective decline seemed to onset with my use of proscar. (FYI i’m in otherwise good health and on no other medications, and use no illicit drugs… the rare toke aside)
Even for those who haven’t noticed any negative effects- read the summary at least. It’s important to know how finasteride impacts on your central nervous system.
I do not have any particular expertise in the subject material I present here so take it with a grain of salt. Any feedback would be appreciated.
Summary- this might initially seem overly technical but it’s not that hard to follow.
DOC, an adrenal steroid whose synthesis is enhanced during stress, undergoes sequential metabolic reduction by 5a-reductase and 3-hydroxysteroid oxidoreductase to form 5-dihydrodeoxycorticosterone (DHDOC) and allotetrahydrodeoxycorticosterone (THDOC), a GABAa receptor-modulating neurosteroid with anticonvulsant properties.1
As you’re aware, finasteride (propecia/proscar) blocks 5-reductase.
So, apparently, finasteride by decreasing DHDOC and THDOC levels inhibits the effect of GABA. What does this mean to you? GABA is the most prevalent inhibitory neurotransmitter in the CNS (Central Nervous System ie. your brain). It is somewhat counter intuitive to think that inhibiting the effect of GABA (which is itself an inhibitory neurotransmitter) could have a negative impact on mental function… but the following good analogy has been made…
“It’s like New York City or Boston during a blackout,” Leventhal said, describing what would happen if neurons weren’t restricted to specific responses. “With all the gating mechanisms like the stoplights out, you’d think traffic would move faster. But it doesn’t.” 6
What do scientists believe GABA’s function impacts on- There are 3 GABA receptors A, B, and C… GABA A has anxiolytic functions (ie. anti anxiety… FYI valium acts by stimulating GABA receptors)… GABA B affects memory and mood,… GABA C- unknown… Other higher brain functions (eg. visual recognition, understanding language, memory, mental decline in the elderly, and possibly learning) are linked to GABA but I’m still researching- and unsure if they’re linked to A or B… This is pertinent because thus far the studies i’ve reveiwed have focused on the relation between GABA A and finasteride… it isn’t a far jump to think that these same neurosteroids finasteride impacts on would also affect GABA B but I haven’t been able to determine that as of yet… I will update you when I learn more.
The following are excerpts from different articles:
a)Higher brain functions, such as visual recognition or understanding language, require the processing of information in the brain but decline as people get older. This decline appears to be due to a reduction in a neurotransmitter called GABA, say researchers.
Macaque monkeys, with an age equivalent to 90-years in humans, were not as sharp as their younger counterparts in visual tests despite having perfect eyesight. But when they were given drugs to increase levels of GABA in the brain they improved vastly, say the team.
Delivering GABA calms the neurons down and they become more selective, says neuroscientist Audie Leventhal, at the University of Utah School of Medicine, who led the study. “They look the same as they did 20 years ago,” he says.
Importantly, this suggests that mental decline could be easily treated, says Leventhal. “The fact is all the cells are still there and functioning, it’s a transmitter problem - it’s treatable,” he told New Scientist.2
b)Neurosteroids (ie. DHDOC and THDOC) also are capable of interacting directly with GABAa receptors, albeit at high concentration. Of clinical significance, neurosteroids have been demonstrated to have anxiolytic (anti anxiety), hypnotic, anesthetic, and anticonvulsant effects,and have been implicated as having a role in memory enhancement, behavioral actions, and neuroprotection…
In an elegantly designed set of experiments, Reddy and Rogawski showed that the stress-induced neurosteroid DOC is capable of positively modulating GABAAreceptors through its metabolites DHDOC and THDOC.3
c)pharmacological modulation of GABAa-receptor efficacy with exogenous agents (e.g., benzodiazepines and -carbolines) is known to occur through allosteric mechanisms that modulate the effectiveness (positive and negative) of GABA at this receptor. The most potent endogenous modulators are 5 alpha-reduced steroids. Production of these steroids was attenuated in adult rats with systemic injection of Finasteride, a competitive substrate for 5-reductase.4
GABA == ?-aminobutyric acid (Neuroscience, p110)
Identified in the 1950s. (Neuroscience, p111)
It is a neurotransmitter: it is released from presynaptic terminal buttons into the synaptic cleft in response to action potentials. (Neuroscience, p111)
GABA is the most prevalent inhibitory neurotransmitter in the CNS. (Neuroscience, p110) Although in the spinal cord about half of inhibitory neurons use glycine instead. (Neuroscience, p112)
Curtis & Watkins (1959) showed that GABA had an inhibitory effect on neurons: it inhibits the ability of neurons to fire action potentials (Neuroscience, p119)
Altered GABA function or degeneration of GABAergic neurons leads to many disorders: (MNP, p154-155)
Enhancement of GABAergic function is a highly effective method for treating some types of anxiety and epilepsy. (MNP, p155) 5
e)Biological Explanation of Anxiety
Inactivity of GABA neurotransmitter:
Normal person: There is a dangerous or anxiety-provoking stimulus à neurons fire impulses that increase excitability and anxiety à excited neurons send messages to other neurons through feedback loop to release GABA neurotransmitter à GABA neurotransmitter is released and binds to receptors of the excited neurons à GABA is an inhibitory neurotransmitter that inhibits the excitability of the neurons à anxiety is reduced
Person with anxiety: There are problems with the feedback loop or amount of GABA released à not enough GABA binds to the receptors of the excited neurons à excited neurons continue firing à person remains in prolonged state of anxiety.7
a)Is the GABA B receptor modulated by the neurosteroids that finasteride impacts on or just GABA A?