Nutritionally reviewed by Diana Lee, RD.
When people reference “boosting dopamine,” what they should 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.
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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, ADHD, and anhedonia1–4. 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.”3,5 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 alcoholism6. 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 RDS7. 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 population8.
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 addictions9. Rats prefer sugar to cocaine10. 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 obesity11. 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 future3,5,12,13.
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 systems2,3,11,12. 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 groups14–21. 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 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, in an attempt to reset dopamine levels. Others are deleting their profiles on Facebook, Twitter, Instagram, Snapchat, etc., and quitting social media altogether, citing its harmful effects on mental health and society14–21.
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 in-house and 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 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, which are known to affect mental health. 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 synaptogenesis22–25.
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.
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 levels26–29. You can find forskolin from Nutricost on Amazon here.
Sulbutiamine is made up of two thiamine (vitamin B1) molecules and a sulfur group. Sulbutiamine is basically a more bioavailable form of thiamine; it also crosses the blood brain barrier easier than thiamine. Research suggests that sulbutiamine modulates the dopaminergic, cholinergic, and gluatmatergic transmission systems and upregulates both D1 and D2 dopamine receptors30–32.
Anecdotal evidence abounds for sulbutiamine being anti-fatigue and augmenting attention, cognition, energy, and learning. You can buy Sulbutiamine capsules from Nootropics Depot here.
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 receptors33,34. 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. Women with PCOS specifically should choose an inositol supplement that contains myo-inositol35.
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 receptors36.
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.
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 neuroregenerative effects, as well as its ameliorative effects on memory and learning in cases of cognitive impairment, brain injury, or cognitive decline due to aging37–49. While most of the things on this list primarily act on the D2 dopamine receptor, ALCAR actually upregulates D1 receptors and does not affect D250. It also seems to exert antidepressant effects via modulation of glutamate receptors51,52. You can buy ALCAR capsules from Nootropics Depot here.
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)53–56.
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, etc57–61. 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 yoga62.
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 thereof63. These effects seem to be especially pronounced in cases of drug withdrawal and addiction 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 the loss of dopamine-producing cells64–70.
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 availability71–73. These effects may be secondary to blue light regulating circadian rhythms, but it also appears that neurotransmitters themselves also follow a circadian rhythm independent of light in the nucleus accumbens, a primary region of the reward circuit74. 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 system75.
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.”76 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.
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 neurons77. Fish oil – specifically EPA – also seems to have ameliorative effects on symptoms of depression, among its myriad other health benefits78–85. 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.
L-Tyrosine is the amino acid precursor for the neurotransmitters dopamine, epinephrine, and norepinephrine. Think of it 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 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.
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 glutamate86–100. Mechanistically, it’s believed that NAC may actually alter “drug-induced plasticity that underlies drug-seeking behavior.”101
It also happens to have the added benefits of being hepatoprotective (attenuates damage to the liver) and having ameliorative effects on symptoms of depression102. 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.
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 receptors103–112. Agmatine also seems to possess antineurodegenerative and antidepressant properties113–117.
You can find Agmatine Sulfate capsules at Nootropics Depot here.
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 term118–122, 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 effects123–125. 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. A whole-food-based diet would also pair well with these efforts.
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