How Retinoids Gave Me Panic Attacks And Depression

This post is in a completely different style/language than other posts I've done. 

As a blogger, what do you do after a breakup?

Write about why it happened, of course!

Contents:

  1. My Experience With Isotretinoin
  2. Adding In Pregnenolone
  3. Someone Else's Experience
  4. When I Finally Did Some Research
  5. How It Affects The Central Nervous System
  6. Genetics Of PTSD From Retinoic Acid
  7. Other Effects From Isotretinoin
  8. What's Next?

My Experience With Isotretinoin

 
 

I was originally given isotretinoin (13-cis retinoic acid, RA) for a problem I was having with my skin.

Historically, isotretinoin has been used to treat (antibiotic resistant) acne, so if depression is caused by self-image, it may actually help, but neither were my case.

I was developing excess dryness on my face from sun exposure and was worried about problems with skin aging at the time.

I was also having trouble with my vision.

I had only studied retinoic acid's effect on skin and vision, but had not thoroughly studied it's effects on the brain and body.

I just knew it could help with vision (possibly), since carotene converts into the active form of vitamin A (retinol) and that RA increases collagen production in the skin (so hoping to look younger, see better, and have my skin problem would go away).

Well, I got my script (from a doctor) for isotretinoin (different than tretinoin, but both are derived from retinoids and can act on the same receptors) and applied it after I took my nightly shower before bed. R R

I felt fine the next day and continued taking it nightly.

I started noticing a few days later that I was experiencing increased anxiety in the morning with my tea.

I shrugged it off as just being a caffeine-like side effect.

Adding In Pregnenolone

The next day, I decided to experiment with pregnenolone (the neurosteroid) at 20 mg.

I took it right in the morning and I noticed that I became relaxed/kind of sleepy from it.

Later that afternoon, I ended up having my first anxiety attack, which I have not had in years.

I decided it was the pregnenolone causing it because of the possible/contradictory inhibition of GABA receptors.

It was confusing, because first of all, pregnenelone turns into whatever hormone you need, it upregulates GABA receptors (usually), and the whole anxiety fiasco happened more eight hours after taking it.

Anyway, I noticed I had increased persistent anxiety that wouldn't go away and I was really curious as to what was going on.

I thought had messed up some steroid hormone did my brain or body (probably not though).

Back to the isotretinoin.

I ended up only taking the isotretinoin for ~1.5 weeks because I assumed there may have been something I was taking may have contributed to anxiety.

Also, neither my vision nor my skin had gotten better.

I had about 3/4 of the bottle left.

Someone Else's Experience

A week before really looking into retinoic acid's mechanism (below) a girl I was seeing was having troubles with wrinkles on her face, so I suggested she can have my bottle of isotretinoin, as I, of course, wasn't using it.

I guessed that it would be safe and wasn't too sure if it had given me anxiety since I had really attributed the earlier panic attack to the pregnenelone.

I also had not known about the other symptoms or genetic predispositions that were attributed to using isotretinoin.

She used it and about 6 days later (similar to how long it took me), she was having overly-depressive symptoms (which was common from her past history), anxiety, and PTSD-like flashbacks.

Psychologically, I guess she may have thought she was doing something wrong in our relationship so she cut it off with me (which I found to be odd since it was totally out of the blue).

Even later she had psychotic and bipolar-like symptoms. 

When I Finally Did Some Research

I finally (after doing a lot of research) learned about retinoic acid's (RA) effect on the central nervous system.

Isotretinoin is the only non-psychotropic drug in the FDA's top 10 list of drugs associated with depression. R

It has been very controversial as a drug and has a black box warning on it since 2005 warning about specifically depression and suicide. R

I didn't realize this because the prescription I was given came in a bottle that had no box or any labels on it.

On top of that, I was taking a supplement (she wasn't) that includes high amounts of beta-carotene (and other carotenoids).

I was taking it because I thought that would help my eyesight and act as an antioxidant from my large amounts of sun exposure.

Well, the body naturally takes beta-carotene and makes it into vitamin A.

And, as per my own genetics, I recycle retinol really well, as well as I convert beta-carotene into retinol very well, so it makes sense that I could have symptoms of hypervitaminosis A.

So let's first go over RA's (and hypervitaminosis A) symptoms/contradictions on psychiatric disperses.

RA may cause:

  • Aggression R
  • Anxiety (can be severe anxiety like panic attacks or social anxiety as well) R
  • Bipolar Disorder R
  • Blurred Vision R
  • Cognitive Disturbances R
  • Decreased Sociability R
  • Depression R R R R R R R R R R
  • Headaches (as well as increased cranial pressure) R R R
  • Irritability R
  • Mania R
  • Muscular Incoordination R
  • Nausea R
  • Obsessive Compulsive Disorder (OCD) R
  • Overly Alert R
  • Psychosis R
  • Post-Traumatic Stress Disorder (PTSD) R
  • Schizophrenia R
  • Suicide R R
  • Vomiting R

How It Affects The Central Nervous System

 
 

Now let's go over RA in a little more in depth (more in follow up post).

Vitamin A

Vitamin A performs a large number of functions in many systems among them the central nervous system (CNS).

The majority of these functions are performed by RA, the most active form of vitamin A, which binds to retinoic receptors to control gene expression in the brain.

Effects On Development

When RA is given to a pregnant mother it can cause problems with the infant such as:

  • Exencephaly R
  • Hydrocephalus R
  • Prosencephaly R

Effects On The Adult Brain

RA also influences the adult brain.

It can cause depression by acting on the striatum, hippocampus, frontal cortex and hypothalamus. R

It can also cause a dysregulation of neurotransmitters in striatum and hippocampus (in particular the dopaminergic system) and an inhibition of hippocampal neurogenesis (I've used NSI-189 to try to counteract this, after the fact). R

It has shown to induce a significant reduction in activity of the orbitofrontal cortex (a brain region associated with depression). R

RA may also lead to an increase in orbitofrontal functioning via their effects on the hippocampus, a brain area that modulates dopaminergic function in the orbitofrontal cortex. R R R

RA can change the way the hypothalamus creates and uses corticotropin releasing hormone (CRH), a stress regulator hormone. R

Genetics Of PTSD From Retinoic Acid

In terms of gene activity, RA regulates dopamine receptors (specifically DRD1 and DRD2) as well as serotogenic and glutaminergic receptors.

  • Binds to DRD1 and DRD2 (decreasing their activity) R R R R
  • Increases Expression of 5HT1A (causing less serotonin) R

ROR-alpha

Also some people with mutations in the rora gene have significantly increased chances of developing PTSD (with or without RA exposure)

  • rs893290 (worse outcome if you had previous history of physical abuse) R
  • rs8042149 - CC allele worst chance of PTSD, followed by AC, then AA R R
  • rs893260 R 
  • rs17303244 R
  • rs11071587 R
  • rs341401 R
  • rs11071588 R
  • rs16942660 R

Other Effects From Isotretinoin

Isotretinoin can stop bones from fully developing or cause them to continually overgrow. R R R

They can cause problems with saliva production (dry mouth) as well as cause dry eyes and decreased night vision. R R R R R 

These effects may be permanent. 

Isotretinoin can also cause dry skin (against what I was hoping for) and more fragile skin. R

One way it may do this is by indirectly decreasing the skin's microbial diversity. R

It can cause myalgia (muscular pain) and arthralgia (joint pain). R

It also can cause non-specific gastrointestinal symptoms including diarrhea, abdominal pain, IBD (like ulcerative colitis), IBS. R R

What's Next?

I'll be (and hopefully my friend) will discontinue taking isotretion. 

Studies have shown in 67% of patients that didn't have psychiatric problems before use of isotretion, their usual depression effects went away after stopping using it after a few months. R

Also, I will have a follow up post on the mechanism of retinol, retinoic acid, and their receptors RXR, ROR, etc.

As for the breakup thing, I'm practicing Ho'oponopono: put your hands on your heart and repeat "I Love You, I'm Sorry, Please Forgive Me, Thank You". R

It seems to work very well. 😊