Dopamine is incredibly necessary for (a good) life.
Dopamine reduces appetite (the dopamine system is hyposensitive in obesity (R)), promotes activity/movement, exploration, euphoria (low dopamine causes anhedonia), creativity, focus, learning, memory, motivation and so much more.
Dopamine is often mistaken for being responsible for addition, but it’s actually low dopamine that leads to addiction. With low dopamine, you constantly want to get a spike of dopamine just to feel normal again. With normal dopamine you don’t desire activities that spike dopamine and are much less likely to become addicted.
However everyday activities, such as social media, TV, games, etc., can over time have an adverse effect on your dopamine levels, especially if you start to neglect the basics of increasing dopamine.
Similarly to testosterone, which binds to the androgen receptors, the dopamine receptors need to be sensitive for you to enjoy the full effects of dopamine. If dopamine receptor expression/density is low then the effect of dopamine will be reduced; hyposensitive, as seen in obesity and other disorders.
Let’s dive into a few supplements that can increase dopamine receptors.
Uridine is also used in the less energy-consuming salvage pathway that creates precursors (phosphomonoesters (PME)) to phosphatidylcholine (PC) and phosphatidylethanolamine (PE) (R). The precursor (PME) to PC and PE is reduced in bipolar and other mental disorders (R).
Cytidine supplementation [which can convert to uridine] was associated with an earlier improvement in depressive symptoms (weeks 1–4; p=0.02, 0.001, 0.002, and 0.004, respectively) and also produced a greater reduction in cerebral glutamate/glutamine levels in patients with bipolar depression (weeks 2, 4, and 12; p=0.004, 0.004, and 0.02, respectively). Cytidine-related glutamate/glutamine decrements correlated with a reduction in depressive symptoms.Reference
CDP-choline/citicoline (cytidine-5′-diphosphate choline) is converted to both choline and cytidine upon ingestion, the latter of which converts into uridine in the body.
Phosphatidylcholine synthesis is controlled by cellular levels of its precursor, cytidine-5′-diphosphate choline (CDP-choline) and PC is required for cellular growth and repair.
The effects might be replicated by eating eggs with brewers yeast or uridine supplementation.
Intriguing data, showing that on a molar mass basis citicoline is significantly less toxic than choline, are also analyzed. It is hypothesized that, compared to choline moiety in other dietary sources such as phosphatidylcholine, choline in citicoline is less prone to conversion to trimethylamine (TMA) and its putative atherogenic N-oxide (TMAO). Epidemiological studies have suggested that choline supplementation may improve cognitive performance, and for this application citicoline may be safer and more efficacious.Reference
250mg to 500mg appear to be all that’s need for cognitive benefits, however, doses can go up to 1-2g daily for Alzheimers or appetite control.
Myo-inositol is a sugar alcohol that’s naturally made (from glucose) and found in the body, especially the brain. It mediates cell signal transduction (e.g. horizontal gene transfer) in response to a variety of hormones, neurotransmitters and growth factors. It also acts as an osmolyte and participates in cellular hydration.
It’s found in high concentrations in citrus fruit and whole grains.
Standard doses include 2-4g daily (your kidney creates about 2g daily), but doses of 18g (6g x3 daily) for OCD has been used with success.
Sulbutiamine is a thiamine derivative developed in Japan in the mid-60’s as a beriberi treatment drug and it’s also used in France for tiredness and fatigue.
Sulbutiamine results from the fusion of two thiamine molecules linked by a disulfide bridge. It’s lipophilic (fat-loving) so it’s quickly and easily absorbed in the body.
Although sulbutiamine is about 10 times more effective at increasing intracellular thiamine concentrations than regular thiamine, the increases in intracellular ThDP (thiamine diphosphate) and ThTP (thiamine triphosphate) concentrations were barely significant after 4 h, suggesting a tight regulation of ThDP synthesis (R). The ultimate goal is to boost thiamine diphosphate/thiamine pyrophosphate which is the cofactor for the B1 dependent enzymes. As a side note, thiamine requires magnesium to be converted to its active form, thiamine pyrophosphate.
As an example, after administering this molecule [sulbutiamine] to rats for 5 days, there was a significant increase in the density of dopamine D1 receptor binding sites in prefrontal and anterior cingulate cortex (+26% and +34%, respectively), as well as a significant decrease in the density of kainate binding in the cingulate cortex, the nucleus accumbens (−36% and −28%, respectively), striatum, and hippocampus.Reference
The human equivalent dose is 1.8mg/kg to increase dopamine receptors. Doses of 400-600mg has been used without ill effects (R).
Sulbutiamine only seem superior to regular thiamine HCL because it replenishes intracellular thiamine pyrophosphate faster than regular B1, but if you take high doses of thiamine HCL, the effect should be the same as sulbutiamine over time (given that you have enough magnesium and there isn’t anything wrong with your B1 transporters).
Forskolin is found in Coleus forskohlii plant and could help with fat loss and has been shown to increase free testosterone. It can also potentially increase dopamine release (R), dopamine D2 receptor expression (R), and act as a D1 agonist (R).
Phenylpiracetam is a phenylated analog of the piracetam and it was developed in 1983 as a medication for Soviet cosmonauts to treat the prolonged stresses of working in space.
It has anti-amnesic, antidepressant, anticonvulsant, anti-anxiety, anti-inflammatory and memory enhancement effects and it’s also neuroprotective.
- Decreases the number of nicotinic acetylcholine and NMDA receptors, which can help against anxiety and depression
- Increases the dopamine D1, D2 and D3 receptors
- Increases GABA-A receptors (R)
- Inhibits dopamine uptake (and perhaps noradrenaline as well) (R)
- Binds to α4β2 nicotinic acetylcholine receptors (R)
Soyuz, a Russian cosmonaut, reported that during his 197 days in the space station “the drug [phenylpiracetam] acts as the equalizer of the whole organism, ‘combs’ it(sic причесывает), completely excluding impulsiveness and irritability inevitable in the stressful conditions of space flight.” (R)
A good dose is 100-200mg x2-3 daily 2-3 times per week.
Tianeptine is an atypical antidepressant that has serotonin reuptake promoting properties instead of inhibitory properties like most anti-depressants.
Tianeptine doesn’t appear to act on any receptor (except the μ-opioid receptor), but it does increase dopamine release and enhances the functional responsiveness of dopamine D2 and D3 receptors (R).
It’s anti-serotonergic and pro-dopamine (and opioid) effects make it great against depression, anxiety, asthma, vascular constriction, hypersensitivity to pain, etc.
Although most studies use doses of 12mg x3 daily, but a good starting dose would be around 10mg to gauge how you respond to this substance.
Tianeptine is a potent serotonin reuptake enhancer, which reduces the harmful effects of free serotonin, such as vasoconstriction, vascular leakage, asthma, inflammation, etc. Instead of using tianeptine to bind up free serotonin, rather reduce the production of serotonin in the gut, by solving gut issues.
The Protocol that Smashes Serotonin and Endotoxin and causes Dopamine to Skyrocket!!
This dopaminergic diet is the best thing ever in a highly serotonergic Western environment.
#8 Lavender EO
Lavender increases dopamine D3 (R), which has anti-depressant properties. However, lavender is also estrogenic, so it’s a no-no for me.
Caffeine (at doses of 300mg daily) upregulates the expression of the dopamine D2 and D3 receptors, which has anti-depressant and pro-alertness effects (R).
This interesting study found that an adenosine A2A receptor antagonist (e.g. caffeine), combined with niacin and curcumin (against brain inflammation) can be very helpful against Parkinson’s (this combination has only been studied in mice) (R).
#10 Increase testosterone
Testosterone increases the synthesis of dopamine, increases dopamine sensitivity and reduces dopamine uptake, thus enhancing its actions (R, R, R). Testosterone promotes physical activity via boosting dopamine.
- Maximize testosterone: a 26 quick tip guide
- The complete guide to maximizing your testosterone
- The high testosterone personality
An-jun-ning, a commercial traditional Chinese medicine formula used for the treatment of opioid addiction, that can restore dopamine, dopamine receptor D2 and tyrosine hydroxylase (the enzyme that converts tyrosine to L-dopa) back to normal levels in cocaine-addicted animals (R). It’s speculated that the Corydalis yanhusuo, of which tetrahydropalmatine is the primary active component, is the specific herb/ingredient with the dopamine restoring properties (R).
Sunshine exposure modulates and enhances the dopaminergic system as a whole and can increase striatal D2 and D3 dopamine receptor availability (R).
Getting out in the morning is one of the best things you can do to boost your dopamine and set your mood for the day.
#13 Acetyl-L-carnitine (ALCAR)
ALCAR has been shown to increase the dopamine D1 receptors (R). I wouldn’t use ALCAR since it can lower thyroid hormones, so rather eat red meat and consume the precursors and cofactors to ALCAR, such as lysine, vitamin C, iron, vitamin B6, NAD (from vitamin B3) and zinc so that your body can create it as it needs it.
#14 Boost BDNF
Brain-derived neurotrophic factor (BDNF) has been shown to increase/normalize dopamine receptor D3 expression (R). D1 activation by dopamine can help to increase the expression of BDNF, so boosting dopamine can be highly beneficial in of itself.
- Maximize dopamine and live life on cloud nine with laser focus, drive, ambition, euphoria & great energy
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Other BDNF promotors include 7,8-dihydroxyflavone, lion’s mane mushroom, forskolin and histone deacetylase inhibitors (HDAC), such as valproic acid and niacinamide.
As always, thanks so much for reading my article. Let me know in the comments below if you have any questions. And if you found this article to be insightful and helpful please like and share so this information can help others as well.
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