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How to Repair Dopamine Receptors Naturally – 10 Ways to Upregulate

Last Updated: August 6, 2020

nature trail

When people reference “boosting dopamine,” what they usually mean is actually repairing or upregulating the receptors involved in the dopamine reward pathway or “pleasure pathway.” Here we examine various practices and supplements to repair dopamine receptors naturally.

Disclosure:  Some of the links on this page are referral links. At no additional cost to you, if you choose to make a purchase after clicking through those links, I will receive a small commission. This allows me to continue producing high-quality, ad-free content on this site and pays for the occasional cup of coffee. I have first-hand experience with every product or service I recommend, and I recommend them because I genuinely believe they are useful, not because of the commission I get if you decide to purchase through my links. Read more here.

In a hurry? Here’s the list:

1. Uridine
2. Forksolin
3. Sulbutiamine
4. Inositol
5. CDP-Choline
6. ALCAR
7. Cordyceps
8. Meditation
9. Exercise
10. Sunlight


Contents

  • Introduction – The Neuroscience of Addiction and Dopamine
  • Supplements to Repair Dopamine Receptors
    • Uridine
    • Forskolin
    • Sulbutiamine
    • Inositol
    • CDP-Choline (Citicoline)
    • ALCAR (Acetyl-L-Carnitine)
    • Cordyceps
  • Meditation
  • Exercise
  • Sunlight
  • Bonus Tips – Alleviating Symptoms, Curbing Cravings, and Feeling Better
    • Fish Oil
    • Tyrosine
    • NAC (N-Acetyl-Cysteine)
    • Agmatine
    • A Note on Mucuna Pruriens (L-DOPA)
    • Exercise, Meditation, Sunlight

Introduction – The Neuroscience of Addiction and Dopamine

Dopamine is referred to as the “molecule of addiction.” Dopamine’s evolutionary purpose is to motivate you to do things that increase your chance of survival and passing on your genes; it drives you to pursue potential rewards. Research has shown that highly-motivated people have higher dopamine levels, and that low levels of dopamine are associated with a lack of motivation and anhedonia​1–3​. This topic is obviously closely related to motivation; I recently wrote a post on the best nootropics for motivation.

As an admittedly overly-simplistic, reductionistic explanation of an extremely complex process, dopamine-spiking activities – gambling, porn, junk food, etc. – actually lead to the desensitization and downregulation (decrease in sensitivity and number) of dopamine receptors, especially those that keep dopamine levels elevated persistently, such as cocaine use. Continuing on that extreme example, this is why in the case of regular drug use (even caffeine), increasingly higher dosages are needed to achieve the same effect. Receptors become sensitized to that stimulus and you build up a tolerance. Furthermore, we know that low dopamine levels are associated with these addictive behaviors, essentially chasing the dopamine “high.”​3,4​ If you’re reading this post, you’re probably someone who has perhaps previously engaged in those types of behaviors that have beaten down your dopamine receptors over time.

Some people are also simply born with fewer dopamine D2 receptors. In 1990, Blum et al noted a genetic connection between a specific allele of the dopamine D2 receptor gene (DRD2) and the susceptibility to develop alcoholism​5​. Building on that research, they found that people with this specific gene polymorphism were more likely to have dysfunction of the mesolimbic reward system, yielding a hypodopaminergic state that makes them predisposed to addiction, compulsivity, and impulsivity of behavior. This condition became known as “Reward Deficiency Syndrome” or RDS​6​. Later research discovered that carriers of this gene have on average 30-40% fewer dopamine D2 receptors, and that these carriers make up approximately 1/3 of the US population​7​.

The addiction model appears to be the same for the aforementioned activities as it is for drug use. That is, behavioral addictions share many of the same mechanisms and alterations in brain chemistry as chemical addictions​8​. Rats prefer sugar to cocaine​9​. Overeating to obesity leads to the same changes in the brain as drug addiction. When rats are given unlimited access to food, they indulge to obesity​10​. The dopaminergic system is more powerful than the opioid system; the want and desire for pleasure can be more powerful than the pleasure received. This is a subtle but important distinction. Continually engaging in these addictive behaviors also hardens their “cues” and cravings, and partially scrambles the prefrontal cortex, leading to impaired impulse control. This makes it “easier” to return to that junk food, video game, etc. over and over again in the future​3,4,11,12​.

I would argue that modern society lends itself to more of these dopamine spiking activities, with some of them being specifically designed to be addictive – junk food, social media, video games, binging TV shows, high-speed internet usage, etc., so much so that we see supernormal responses to some of these things by the dopaminergic and opioid systems​2,3,10,11​. A massive amount of research in recent years suggests that these things are directly contributing to the significant increases in diagnoses of anxiety, depression, ADD, and ADHD across all age groups​13–20​. The evolution of our monkey brains simply can’t keep up with the advancement of technology.

Thankfully, the growth in the understanding of these neuroscientific concepts has led to people consciously choosing to avoid doing these activities so often and seeking ways to mitigate the aforementioned effects in order to repair or “fix” their dopamine receptors that have been abused over time. We’ve seen the emergence of groups like “NoFap,” in which millions of “fapstronauts” across the globe are swearing off the dopamine-spiking activities of porn, masturbation, and/or orgasm (PMO) for a period of time. There are also specific support groups on Reddit dedicated to helping people quit their addictions to video games, gambling, smoking, and more. People are returning to nature and partaking in “dopamine fasts” where they abstain from the use of technology like cell phones and television, and even food, for 24 hours at a time. Others are deleting their profiles on Facebook, Twitter, Instagram, Snapchat, etc., and quitting social media altogether, citing its harmful effects on mental health and society​13–20​.

In this post we’ll examine methods, practices, and supplements to repair dopamine receptors naturally and help fix the mesolimbic pleasure pathway, or at the very least help accelerate that process. Note, however, that there’s no magic bullet; the most important part of the healing process is still simply avoiding the addictive behavior or dopamine-spiking activity.

Whenever possible, I’m suggesting Nootropics Depot (10% off with email signup) as the vendor of choice for the supplements below. They’re basically the gold standard in the supplement industry. They have a proven track record of providing the highest-quality research-backed ingredients with verifiable third-party analytical testing. They also just happen to have great customer service and fast shipping. For a while now, they’ve been the antidote to the issues that have plagued the supplement industry and given it a bad reputation – label inaccuracy, questionable purity and safety, and lack of efficacy. In short, make sure you’re buying from a trusted seller and make sure you know what you’re getting.

Supplements to Repair Dopamine Receptors

Let’s explore supplements with clinical evidence of helping to repair and upregulate dopamine receptors.

Uridine

Uridine is found naturally in the body and, oddly enough, in beer. Uridine has evidence of modulating dopamine levels via upregulation of striatal D-2 receptors. It has been shown to alleviate symptoms of depression and bipolar disorder and promote a greater sense of well-being. Anecdotal evidence exists of uridine supplementation helping overcome addictions like smoking. It is often supplemented as part of the famous “Mr. Happy Stack” – uridine, DHA/EPA (fish oil), and choline – for synaptogenesis​21–24​.

Uridine can be supplemented via triacetyluridine or uridine monophosphate. Triacetyluridine is the more bioavailable form and thus requires a lower dose than uridine monophosphate. You can find triacetyluridine capsules from Nootropics Depot here.

Buy Triacetyluridine from Nootropics Depot

Forskolin

Forskolin is the primary bioactive ingredient in the herb Coleus forskohlii. It’s popular for its potential fat burning effect, for which more research is needed. Research suggests that forskolin may be able to potently upregulate dopamine receptors via increasing cAMP levels​25–28​. You can find forskolin from Nutricost on Amazon here.

Buy Forskolin on Amazon

Sulbutiamine

Sulbutiamine is made up of two thiamine molecules and a sulfur group. Sulbutiamine is basically a more bioavailable form of thiamine. Research suggests that sulbutiamine modulates the dopaminergic, cholinergic, and gluatmatergic transmission systems and upregulates both D1 and D2 dopamine receptors​29–31​​.

Anecdotal evidence abounds for sulbutiamine being anti-fatigue and augmenting attention, cognition, energy, and learning. You can buy Sulbutiamine capsules from Nootropics Depot here.

Buy Sulbutiamine from Nootropics Depot

Inositol

Inositol is a natural B-vitamin (B8) involved in communication between neurotransmitters. Inositol is often used in high doses alongside medications to alleviate symptoms of depression, OCD, panic attacks, and anxiety. Inositol has evidence of upregulating both serotonin and dopamine receptors​32,33​. Find inositol on Amazon here. Note that you may want to get a powdered form and mix it in a drink due to the high dosages used. Safe usage for antidepressant effects has seen doses from 6g all the way up to 18g daily. Inositol is often paired with choline, which is covered below.

Shop Inositol on Amazon

CDP-Choline (Citicoline)

Choline is found naturally in the body. It is the precursor to acetylcholine, and is necessary for proper brain function. It is often supplemented to prevent memory impairment associated with aging.

Mice treated with CDP-choline at 100mg/kg daily over 7 months displayed an 11% increase in D2 dopamine receptor density. Those treated with 500mg/kg daily saw an 18% increase in D2 receptors​34​.

You can find CDP-Choline (also called citicoline) from Nootropics Depot here. Note that for some people like myself, choline supplementation may cause tension headaches. Egg yolks are high in choline if you’d rather go that route.

Buy CDP-Choline at Nootropics Depot

ALCAR (Acetyl-L-Carnitine)

ALCAR (Acetyl-L-Carnitine) is simply a more neuro-active, acetylated version of the amino acid Carnitine. While usually used as a pre-workout supplement, ALCAR has plenty of evidence showing its neuroprotective, neuromodulatory, and neurogenerative effects, as well as its ameliorative effects on memory and learning in cases of cognitive impairment, brain injury, or cognitive decline due to aging​35–47​. While most of the things on this list primarily act on the D2 dopamine receptor, ALCAR actually upregulates D1 receptors and does not affect D2​48​. It also seems to exert antidepressant effects via modulation of glutamate receptors​49,50​. You can buy ALCAR capsules from Nootropics Depot here.

Buy ALCAR at Nootropics Depot

Cordyceps

Similarly, the Cordyceps mushroom has evidence showing it exerts antidepressant, anti-fatigue effects via upregulation of D2 dopamine receptors and enhancing the expression of the rate-limiting enzyme tyrosine-hydroxylase that converts L-tyrosine to L-DOPA (which is then converted to dopamine)​51–54​.

If you want to use a multi-mushroom blend, get Thrive 6 from Freshcap Mushrooms. I reviewed it here. If you just want Cordyceps, you can get capsules from Nootropics Depot here.

Buy Cordyceps at Nootropics Depot

Meditation

At this point this post might start sounding “woo woo” since we’re talking about simple things you can do every day, but don’t worry, we’re still seeing what the scientific research has to say. Meditation is one example where Western medicine is starting to clinically verify the claims of long-standing beliefs or practices of Eastern medicine.

While no studies currently show specific influence of meditation on dopamine receptors, a handful of studies do show a reliable increase in striatal dopamine release, increasing levels of circulating dopamine. Meditation may not provide a lasting effect on receptors per se, but it gets an honorable mention here because it may offer at least a temporary relief for symptoms of low dopamine levels like anhedonia, lack of motivation, low energy, etc​55–59​. Clearly more research is needed in this area, as practicing meditation has grown in popularity in recent years. The aforementioned effects also seem to apply to yoga​60​.

Exercise

Clinical evidence abounds for the myriad of health benefits from exercise. Similar to meditation, exercise seems to modulate the dopaminergic system and increase levels of dopamine, norepinephrine, and serotonin, but may not specifically upregulate the receptors thereof​61​. These effects seem to be especially pronounced in cases of drug withdrawal and addicition recovery, which is directly related to the topics discussed here. As such, exercise should still have appreciable ameliorative effects for those suffering from low dopamine levels, as well as in cases of Parkinson’s disease, of which a main characteristic is impaired dopamine function​62–68​.

Sunlight

Similarly, sunshine exposure seems to increase dopamine synthesis, providing ameliorative therapeutic benefits for those who suffer from seasonal affective disorder (SAD) and depression. Sunshine exposure appears to modulate and enhance the dopaminergic system as a whole and was shown to increase striatal D2 and D3 dopamine receptor availability​69–71​. These effects may be secondary to blue light simply regulating circadian rhythms, but it also appears that neurotransmitters themselves also follow a circadian rhythm independent of light​72​. It’s unclear if artificial blue light devices exert these same effects on the dopaminergic system, though they do seem to have positive effects on the serotonergic system​73​.

Bonus Tips – Alleviating Symptoms, Curbing Cravings, and Feeling Better

Again, abstinence from the dopamine-spiking behavior is the most important part of the healing process. In the beginning stages of that abstinence, symptoms of low dopamine availability will be their strongest – depressed mood, anhedonia, apathy, etc. Many refer to this as a “flatline” period. While it may seem counterintuitive, I would argue it may be prudent to mildly boost dopamine during this time period.

People experiencing the symptoms of an impaired dopaminergic system – and a debilitated brain as a whole – are more likely to return to the addictive behavior. Essentially, if you feel good, you’re more likely to stay the course in your abstinence. Recent research from Blum et al seems to agree, suggesting that at least temporary alleviation of symptoms should improve quality of life and decrease the likelihood of relapse. In their words: “we argue that a more prudent paradigm shift should be biphasic—short-term blockade and long-term upregulation, enhancing functional connectivity of brain reward circuits.”​74​ Recall that Blum et al originally discovered the genetic connection to decreased dopamine receptors in the early 1990’s and coined the term “Reward Deficiency Syndrome” (RDS).

So how do we do that? By laying foundational support for the dopaminergic system and the neuroplasticity-inducing processes that are slowly repairing the pathways of the addicted brain during abstinence, and by doing what we can to avoid cravings.

Fish Oil

Recall the aforementioned “Mr. Happy Stack” – DHA/EPA (fish oil or an equivalent), uridine, and choline – has evidence of promoting neurogenesis and synaptogenesis – the formation of new neurons and new synapses between neurons​75​. Fish oil – specifically EPA – also seems to have ameliorative effects on symptoms of depression, among its myriad other health benefits​76–83​. Vegetarians and vegans may prefer algae-derived DHA and EPA; just know I have no experience with that variation, and the research has used fish oil.

NOW Foods has one of the most cost-efficient fish oil supplements out there, and it’s enteric coated so no fish burps. You can find it on Amazon here.

Buy Fish Oil on Amazon

Tyrosine

L-Tyrosine is the amino acid precursor for the neurotransmitters dopamine, epinephrine, and norepinephrine. Think of as the raw material used to “manufacture” dopamine. Essentially, no tyrosine stores = no dopamine. L-Tyrosine converts to L-DOPA via the enzyme tyrosine-hydroxylase. Recall that Cordyceps mushroom enhances the expression of that enzyme. People who supplement with L-Tyrosine report better focus and energy levels.

If you’re eating a high-protein diet, you may be have enough already, as tyrosine is found in high concentrations in meat, bananas, dairy, eggs, nuts, and seeds. But this makes it arguably more important for vegetarians and vegans to supplement.

You can find L-Tyrosine from Nootropics Depot here.

Buy L-Tyrosine at Nootropics Depot

NAC (N-Acetyl-Cysteine)

NAC is simply the prodrug of L-Cysteine, an amino acid. NAC is a potent antioxidant, and is responsible for increasing glutathione in the body.

NAC may be the most important tool in the arsenal here in terms of reducing cravings. It has tons of clinical evidence demonstrating its efficacy in decreasing cravings, compulsivity, and addictive behavior related to trichotillomania (hair pulling), excoriation (skin picking), smoking, gambling, cocaine, marijuana, and more, via modulating glutamate​84–98​. Mechanistically, it’s believed that NAC may actually alter “drug-induced plasticity that underlies drug-seeking behavior.”​99​

It also happens to have the added benefits of being hepatoprotective (attenuates damage to the liver) and having ameliorative effects on symptoms of depression​100​. Anecdotal evidence abounds of people seeing success with NAC for curbing cravings of many kinds.

The clinically effective dosage seems to be 1200-2400mg daily. You can buy NAC from Nootropics Depot here.

Buy NAC at Nootropics Depot

Agmatine

Similar to NAC, Agmatine, a natural byproduct of the amino acid arginine, has shown promise in reducing addictive consumption of alcohol, nicotine, methamphetamine, and opioids, via its modulation of imidazoline receptors​101–110​. Agmatine also seems to possess antineurodegenerative and antidepressant properties​111–115​.

You can find Agmatine Sulfate capsules at Nootropics Depot here.

Buy Agmatine at Nootropics Depot

A Note on Mucuna Pruriens (L-DOPA)

Many people wanting to “boost dopamine” simply turn to its direct precursor, L-DOPA, via an extract called Mucuna pruriens, also known as velvet bean. Supplements are usually standardized for their L-DOPA content. Mucuna pruriens does seem to reliably increase dopamine, but there’s the problem. It’s bypassing the rate-limiting step (tyrosine > L-DOPA via tyrosine hydroxylase) and directly increasing dopamine, thereby downregulating dopamine receptors and depleting serotonin in the process over the long term​116–120​, which are the precise problems we’re trying to fix. L-DOPA from Mucuna pruriens will almost certainly exert feel-good effects temporarily, but you’d be doing yourself a disservice.

Arguably more importantly, L-DOPA and Mucuna pruriens have been linked to mania, dyskinesia, psychosis, homicidal thoughts, and a range of other nasty side effects​121–123​. Avoid it. It’s not the harmless “dopamine bean” as which it’s marketed.

Exercise, Meditation, Sunlight

Again, while exercise, meditation, and sunlight may not specifically upregulate dopamine receptors, they do seem to reliably boost dopamine levels, alleviate symptoms of depression, and lower cortisol, among other health benefits.

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Medical Disclaimer:  While I love diving into and extracting useful information from clinical research related to health, fitness, supplements, and more, I am in no way a medical expert. The content on this website is for informational purposes only; it is not professional medical advice, nor is it a substitute for professional medical advice. None of the statements on this website have been evaluated by the FDA. Products mentioned are not intended to diagnose, treat, cure, or prevent any disease. Read my lengthier medical disclaimer here.

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About John Williamson

Analytical and entrepreneurial-minded data nerd, digital marketing expert, usability enthusiast, armchair research scientist, health/nutrition/supplement aficionado, Boglehead, and Oxford comma advocate. I lead the Paid Search marketing efforts at Gild Group. I'm not a big fan of social media, but you can find me on LinkedIn and Reddit.

Reader Interactions

Comments

  1. Bob says

    August 6, 2020 at 1:18 pm

    Hey John thanks for the article. Should i take all the 10 supplements you listed above together ? if not which ones should i choose to take together for the best effect ?

    Reply
    • Bob says

      August 6, 2020 at 1:18 pm

      7 supplements i meant

      Reply
    • John Williamson says

      August 6, 2020 at 11:33 pm

      Hey Bob, glad you found it useful and thanks for your comment.

      Hard for me to say that you should definitely do or not do something, especially since most of these things exert effects via different mechanisms. Really comes down to how much you want to spend and what specific effects you may or may not be looking for, e.g. NAC to help curb cravings and urges.

      Some of these are synergistic for neurogenesis like the famous “Mr. Happy Stack” I mentioned – uridine, choline, and fish oil. You’ll also likely find that some of these supplements are more expensive than others, so that may influence your decision on which ones to get. You could simply eat eggs instead of buying choline. Sorry, I know that’s pretty vague but I hope it offers at least a little help.

      Reply
  2. Dhruvit says

    July 18, 2020 at 8:20 am

    Hi again, can you create one post on how to restore Glutamate Receptors.

    Reply
  3. Witt says

    May 29, 2020 at 2:07 pm

    thanks so much man. I’m 22 days clean after pretty heavy Adderall use for 2 years. Gonna refer to this post a lot in the upcoming months.

    Reply
  4. Dhruvit says

    May 28, 2020 at 8:36 am

    hi, i think you forgot one in the list
    i. e Fasting (Food Restriction increases d2 dopamine receptors) and its the best by my experience.

    Reply
  5. Dhruvit says

    May 27, 2020 at 2:01 pm

    can you also write a post on Chronic Stress Recovery

    Reply
  6. Dhruvit says

    May 25, 2020 at 6:50 am

    can you tell which one of them is the most effective. and can you also tell how much effective than others?

    Reply
  7. Talin says

    May 16, 2020 at 11:35 am

    Hey John. I wanted to sincerely thankyou for this blog. I was wondering if you utilize any supplements or take anything to increase brain functioning, neural plasticity, and verbal fluency? Seriously this post alone made me feel hope that I haven’t felt in a while. So thankyou.

    Reply
    • John Williamson says

      May 16, 2020 at 12:23 pm

      You’re welcome! Glad you enjoyed it and got something out of it. Regarding cognition, I use most of the things on this list: https://www.theoptimizingblog.com/nootropics-for-studying-focus-memory/

      Reply
  8. Dhruvit says

    May 16, 2020 at 9:55 am

    i have researched for something like this for while but post on how to increase dopamine receptors only how to increase dopamine. man…. you are god
    and thank you so much for making this post.

    Reply
    • John Williamson says

      May 16, 2020 at 12:22 pm

      Thanks for the kind words!

      Reply

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