3 replies to this topic

[stolpioni]

I have low dopamine due to SSRI's that I used for about a year, and now SAM-e that I've taken for another year.

This has caused high prolactin and hypothyrodism (which does not cure even when medicated).

 

So, I am pretty certain the culprit is low dopamine.

 

Now I want a safe, effective way to keep my dopamine levels high on a long term (life) basis.

 

I just started with L-Tyrosine, which I think is great...is this a safe alternative?

How about Mucuna Pruriens (root powder), NALT and DLPA?

 

My thinking now was to mix all of these...L-Tyrosine 3-4 times a week, Mucuna twice,

NALT/DLPA once or twice etc.

 

Also, will SAM-e be enough to keep the serotonin up? I know you should supplement with L-Tryptophan or

5-HTP to not lower the serotonin levels too much.

[Strelok]

I'm no expert, but here's my opinion.

 

I don't think it would be necessary to take L-Tyrosine and DLPA along with NALT.  I've used NALT by itself with good effect, and find it to be a better bang-for-the-buck than either L-Tyrosine or DLPA.  I don't have much experience with Mucuna, but I would be cautious about taking the same day as NALT.  I suggest experimenting with mucuna, and carefully titrating up to an effective dose.  The big thing with mucuna is whether or not it's an extract, and what its l-dopa content is.  It's the l-dopa that will pack an acute punch.

 

I don't know whether or not SAM-e will be enough to keep your serotonin levels up.  It really comes down to each inidividual's biochemistry, and it's just guesswork and speculation at this point..  The big concern here is avoiding too much serotonin, which I imagine would be possible with SAM-e combined with too much 5-HTP.  If you wanted to add something to SAM-e, I'd stick with L-Tryptophan to be on the safe side. 

 

Finally, I would recommend researching Mr. Happy's stack to upregulate dopamine receptors:  http://www.longecity...l=+uridine +dha

 

[Doc Psychoillogical]

I've been looking at dopamine metabolism a bit and wanted to share some of my understanding.  I've bolded everything you can get readily as a supplement.

 

There's a nice diagram over at wikipedia that details the whole process of dopamine metabolism:

http://en.wikipedia....ical_mechanisms

 

• L-Phenylalanine - Essential amino acid present in many foods such as eggs, cheese, etc.

Gets converted into PEA and Tyrosine.  PEA is the body's natural amphetamine that is quickly degraded by MAO-B and ALDH.

 

• D-Phenylalanine - Synthetic D-isomer form of Phenylalanine

 Only gets converted into PEA 

 

• Tyrosine - Found in many foods

 Gets converted into L-Dopa via Tyrosine Hydroxylase, the primary rate limiting enzyme in catecholamine metabolism.  

 

 Tyrosine Hydroxylase gets upregulated by nicotine and CREB activation (theoretically CILTEP)

 

• L-Dopa - Intermediate Product, given as a drug to treat Parkinsons.  Also in Mucuna Pruriens.

 Vitamin B6 as P5P is a cofactor in the conversion of L-Dopa to Dopamine

 

• Dopamine - Highly psychoactive compound associated largely with motivation

 Gets converted to norepinephrine. A cofactor in this conversion is Vitamin C.

 

PDE 4 and others inhibition:

• 2x450 mg Now Artichoke Extract. Other artichoke extract brands have been reported to work too.

cAMP Increase:

• 4mg of Forskolin from uncapping and weighing out the correct proportion of Better Body Sports 95% pure C-Bolic capsules. Other forskolin supplements have been reported to work too. To get the right amount of Forskolin from a C-Bolic capsule containing 25mg of forskolin you want to multiply the weight of the emptied out material by 4/25 to get 4mg of forskolin assuming it's evenly mixed.

Dopamine Metabolism Support (Important for avoiding fatigue due to increased dopamine metabolism!):

• 500mg Phenylalanine (Lower doses work better for some)
• B-Vitamin Complex
• 200mg Caffeine (Optional)

For mitigating forskolin's effects on Acetylcholinesterase:

• 800mg ALCAR (Generally 200mg of ALCAR for every 1mg of forskolin)

An earlier recommendation before we started adding ALCAR to counteract forskolin's effects was to take the following in the afternoon:

• 350mg Jarrow N-Acetyl L-Tyrosine (Possibly no longer necessary)

I don't take this now that I've added ALCAR to the stack.

I have been taking the artichoke extract variant of this stack almost every day since late 2011 with only positive effects. There have been several attempts to replace Artichoke extract with other PDE4 inhibitors (Quercetin and/or Hesperidin) by myself and other forum users but they have not been tolerable for most people who have tried them. 

These are some of the effects myself and others have reported:

• Improved mood and motivation
• Increased ability to study and retain information
• Improved long-term memory

Some people have reported nothing from taking the stack. Some users have reported tiredness after taking the stack for a while. With the later addition of dopamine metabolism supporting supplements and a forskolin dose of less than 5mg this has been less of an issue. Some users have reported diminished working memory while taking the stack, especially when taking higher does of forskolin or when taking the stack with Quercetin, which is not recommended.

Standard Disclaimer: This is a research thread. The evidence for this stack is largely theoretical and anecdotal. Proceed at your own risk, preferably after reading the whole thread. Please check with your doctor before starting a new supplement regime, especially if you have any health conditions.

Please feel free to add your comments and questions to the thread. The stack is still in active development, as you will see if you visit the later portions of the thread. The thread is a great read and contains lots of interesting scientific and anecdotal information so enjoy it. Thanks!

--- Update 4/09/2013 ---

I have been experimenting with Zembrin as a replacement for Artichoke extract. Zembrin is an extract of the plant Sceletium Tortuosum (a.k.a Kanna). Sceletium Tortuosum grows natively in South Africa and has been used in traditional medicine there for centuries. One of its components, mesembrenone, is a potent and relatively selective PDE4 inhibitor. I have only been using this stack for about a week, but so far results are good. My initial post on the thread about Zembrin is here. I have also made several follow-up posts about my experience. Artichoke Extract is a lot cheaper than Zembrin so it may be a better option for people on a budget. Myself and other users have reported good results with various other Kanna preparations which are also cheaper than Zembrin, so that may be another option. Please note that Zembrin and Kanna affect serotonin via an SSRI like effect and thus should probably not be taken by people who are currently taking SSRIs or other serotonin affecting drugs.

--- Update 6/13/2013 ---


Lately, there has been some exploration on the thread of various additions to the stack.

'Racetams that I and other forum users have anecdotally found to stack well with CILTEP: Piracetam, Phenylpiracetam.

'Racetams that forum users have anecdotally found do not stack well with CILTEP: Aniracetam

'Racetams that have provided mixed results for I and other forum users and should probably be avoided with CILTEP: Sunifiram.

Myself and other forum users have had anecdotally positive effects from adding : p5p and NADH.

Remember: Regardless of all these new developments, the basic artichoke stack still works just fine!


--- Update 6/21/2013 ---

Please note that I used Zembrin as a replacement for artichoke extract in the stack. I had some side effects when I took both together.

-- Update 6/27/2013 ---

I'm providing occasional updates and stack news at @ciltep on Twitter.

-- Update 9/10/2013 ---

Added ALCAR recommendation to the stack. Post #1 Post #2

-- Update 10/02/2013 --
I was interviewed on the smartdrugsmarts.com podcast

http://smartdrugsmar...m-potentiation/

with me is Roy Krebs of http://www.naturalstacks.com . Besides talking about the history and the mechanism of action of the stack and how awesome Longecity is we announced that we're going to be coming out this month with the first ever CILTEP all-in-one supplement!!

I've posted some comments and errata over here.

-- Update 11/24/2013 --

With regards to cycling, I take the stack every day. Some people take the weekends off or only take CILTEP when they need it. When taking days off I usually supplement with N-Acetyl-L-Tyrosine or L-Phenylalanine to avoid feeling less energetic than I would like.

If you read the thread, there are a few reports of the stack reversing tolerance to stimulants and/or increasing their effects. I would avoid taking CILTEP and stimulants like nicotine together. I haven't had any issues with reasonable amounts of caffeine though.

-- Update 03/12/2014--

There has been some discussion of various possible additions to the stack along with some experiments with D1/D2 affecting herbals. Results have been mixed.

Some have suggested that proper zinc and magnesium intake is required for optimal stack performance. 

[sativa]

Regarding cofactors needed to make dopamine, manganese is also required.

Won't longterm SSRI use result in the brain down regulating your serotonin receptors to maintain homeostasis (balance) due to the artificially elevated serotonin levels?

Some relevant quotes I found:

How might SSRIs cause depletions in tryptophan and serotonin?

SSRI drugs block the serotonin transporter (SERT) in the postsynaptic neuron, which in turn increases serotonin concentrations within the synaptic space. Greater serotonin concentrations accumulate not only in the synaptic space, but in the cytosol and periphery. When this happens, some of the serotonin receptors, such as the 5HT1A in the presynaptic neurons, get overwhelmed and start to down-regulate (inactivate)15. Under normal conditions the 5HT1A receptors would act to inhibit the presynaptic firing of serotonin, preventing the over-release of serotonin. Over time, SSRI treatment causes the 5HT1A receptors to become down-regulated, which causes those receptors to become uninhibited. Uninhibited 5HT1A receptors will increase pre-synaptic neuronal firing, releasing more serotonin into the synaptic space.

The lag time for efficacious SSRI treatment of 2-6 weeks has been attributed to this mechanism of 5HT1A receptor down-regulation. In other words, SSRIs typically do not provide a benefit until the pre-synaptic neurons get uninhibited, which takes a few weeks.

Treatment with SSRIs results in higher turnover rates of serotonin, as measured by urinary 5-hydroxyindoleacetate (5HIAA, a metabolite of serotonin that can be found in the urine). If SSRIs increase our body’s utilization of serotonin, it may start to deplete its precursor tryptophan. If chronic SSRI therapy depletes tryptophan to the degree that serotonin levels start to decline, relapse becomes likely, at least theoretically. As mentioned earlier, long term studies have shown that relapse rates occur in up to 75% of patients using SSRIs after 3 years of treatment. When relapse occurs, the dose of the SSRI is often increased, switched to a different one, or combined with another type of antidepressant.

http://www.siliconva...ng-Term-Therapy

Quote from a forum:

Yes, downregulation of 5HT receptor sites is the PURPOSE of SSRIs. It's often called 'receptor dieback.' You are right that this ultimately causes the opposite of the desired effect stated by the advertising campaigns (low serotonin=depression; SSRIs end depression by increasing serotonin).

The brain adjusts to the excess of serotonin caused by the reuptake inhibitor by shrinking/killing off the serotonin producing pumps and receptors. Its a vicious cycle that makes its users become physically dependent on the SSRI to maintain serotonin levels. Many researchers think the effectiveness of SSRIs is due to this receptor dieback! SSRIs, which are only 34% effective to begin with, lose their effectiveness with time as the body habituates to their effects. They are really terrible drugs for your body even though they can help people.

You can read more on this in The Anti-Depressant Fact Book and Prozac Backlash, both of which were written by highly respected and experienced psychiatrists

So, it seems in the short-term, effects might be positive but as time goes on, sides effects will undoubtedly become apparent.

Perhaps this alteration in the serotonin system causes some sort of a "rebound" effect on the dopamine system?

Edited by sativa, 24 April 2016 - 02:28 PM.