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 aiming for Double Wood, Jarrow, Nutricost, Nootropics Depot, and NOW Foods as vendors of choice for the supplements below. They all have a proven track record of providing the highest-quality research-backed ingredients with analytical testing. For a while now, these brands have 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 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 is typically supplemented as uridine monophosphate.
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.
Inositol is a natural B-vitamin (B8) involved in communication between neurotransmitters. 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 Jarrow 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.
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 a 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.
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.
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)102. 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.
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.
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.
- 1.Treadway MT, Buckholtz JW, Cowan RL, et al. Dopaminergic Mechanisms of Individual Differences in Human Effort-Based Decision-Making. Journal of Neuroscience. Published online May 2, 2012:6170-6176. doi:10.1523/jneurosci.6459-11.2012
- 2.Barron AB, Søvik E, Cornish JL. The Roles of Dopamine and Related Compounds in Reward-Seeking Behavior Across Animal Phyla. Front Behav Neurosci. Published online 2010. doi:10.3389/fnbeh.2010.00163
- 3.Arias-Carrión O, Stamelou M, Murillo-Rodríguez E, Menéndez-González M, Pöppel E. Dopaminergic reward system: a short integrative review. Int Arch Med. 2010;3:24. doi:10.1186/1755-7682-3-24
- 4.Blum K, Chen A, Braverman E, et al. Attention-deficit-hyperactivity disorder and reward deficiency syndrome. Neuropsychiatr Dis Treat. 2008;4(5):893-918. doi:10.2147/ndt.s2627
- 5.Adinoff B. Neurobiologic processes in drug reward and addiction. Harv Rev Psychiatry. 2004;12(6):305-320. doi:10.1080/10673220490910844
- 6.Blum K, Noble E, Sheridan P, et al. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA. 1990;263(15):2055-2060. https://www.ncbi.nlm.nih.gov/pubmed/1969501
- 7.Blue K, Cull J, Braverman E, Comings D. Reward Deficiency Syndrome. American Scientist. 1996;84(2):132-145.
- 8.Blum K, Chen A, Giordano J, et al. The addictive brain: all roads lead to dopamine. J Psychoactive Drugs. 2012;44(2):134-143. doi:10.1080/02791072.2012.685407
- 9.Kenny PJ. Common cellular and molecular mechanisms in obesity and drug addiction. Nat Rev Neurosci. Published online October 20, 2011:638-651. doi:10.1038/nrn3105
- 10.Lenoir M, Serre F, Cantin L, Ahmed S. Intense sweetness surpasses cocaine reward. PLoS One. 2007;2(8):e698. doi:10.1371/journal.pone.0000698
- 11.Johnson P, Kenny P. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010;13(5):635-641. doi:10.1038/nn.2519
- 12.Di S, Patrono E, Patella L, Puglisi-Allegra S, Ventura R. Animal models of compulsive eating behavior. Nutrients. 2014;6(10):4591-4609. doi:10.3390/nu6104591
- 13.Volkow N, Wang G, Fowler J, Tomasi D, Telang F, Baler R. Addiction: decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain’s control circuit. Bioessays. 2010;32(9):748-755. doi:10.1002/bies.201000042
- 14.Lin L, Sidani J, Shensa A, et al. ASSOCIATION BETWEEN SOCIAL MEDIA USE AND DEPRESSION AMONG U.S. YOUNG ADULTS. Depress Anxiety. 2016;33(4):323-331. doi:10.1002/da.22466
- 15.Woods H, Scott H. #Sleepyteens: Social media use in adolescence is associated with poor sleep quality, anxiety, depression and low self-esteem. J Adolesc. 2016;51:41-49. doi:10.1016/j.adolescence.2016.05.008
- 16.Ra C, Cho J, Stone M, et al. Association of Digital Media Use With Subsequent Symptoms of Attention-Deficit/Hyperactivity Disorder Among Adolescents. JAMA. 2018;320(3):255-263. doi:10.1001/jama.2018.8931
- 17.Hoge E, Bickham D, Cantor J. Digital Media, Anxiety, and Depression in Children. Pediatrics. 2017;140(Suppl 2):S76-S80. doi:10.1542/peds.2016-1758G
- 18.Richards D, Caldwell P, Go H. Impact of social media on the health of children and young people. J Paediatr Child Health. 2015;51(12):1152-1157. doi:10.1111/jpc.13023
- 19.Shensa A, Sidani J, Dew M, Escobar-Viera C, Primack B. Social Media Use and Depression and Anxiety Symptoms: A Cluster Analysis. Am J Health Behav. 2018;42(2):116-128. doi:10.5993/AJHB.42.2.11
- 20.Schou A, Billieux J, Griffiths M, et al. The relationship between addictive use of social media and video games and symptoms of psychiatric disorders: A large-scale cross-sectional study. Psychol Addict Behav. 2016;30(2):252-262. doi:10.1037/adb0000160
- 21.Vannucci A, Flannery K, Ohannessian C. Social media use and anxiety in emerging adults. J Affect Disord. 2017;207:163-166. doi:10.1016/j.jad.2016.08.040
- 22.Wang L, Pooler AM, Albrecht MA, Wurtman RJ. Dietary Uridine-5’-Monophosphate Supplementation Increases Potassium-Evoked Dopamine Release and Promotes Neurite Outgrowth in Aged Rats. JMN. Published online 2005:137-146. doi:10.1385/jmn:27:1:137
- 23.AGNATI L, FUXE K, RUGGERI M, et al. Effects of chronic treatment with uridine on striatal dopamine release and dopamine related behaviours in the absence or the presence of chronic treatment with haloperidol. Neurochemistry International. Published online 1989:107-113. doi:10.1016/0197-0186(89)90082-x
- 24.Myers CS, Napolitano M, Fisher H, Wagner GC. Uridine and Stimulant-Induced Motor Activity. Experimental Biology and Medicine. Published online October 1, 1993:49-53. doi:10.3181/00379727-204-43633
- 25.Myers CS, Fisher H, Wagner GC. Uridine reduces rotation induced by l-Dopa and methamphetamine in 6-OHDA-treated rats. Pharmacology Biochemistry and Behavior. Published online December 1995:749-753. doi:10.1016/0091-3057(95)00169-w
- 26.Pateraki I, Andersen-Ranberg J, Jensen N, et al. Total biosynthesis of the cyclic AMP booster forskolin from Coleus forskohlii. Elife. 2017;6. doi:10.7554/eLife.23001
- 27.Wanderoy MH, Westlind-Danielsson A. Cellular and Molecular Neurobiology. Published online 1997:547-555. doi:10.1023/a:1026367023458
- 28.Johansson MH, Westlind-Danielsson A. Forskolin-induced up-regulation and functional supersensitivity of dopamine D2long receptors expressed by Ltk− cells. European Journal of Pharmacology: Molecular Pharmacology. Published online October 1994:149-155. doi:10.1016/0922-4106(94)90081-7
- 29.Wanderoy MH, Westlind-Danielsson A, Ahlenius S. Dopamine D2 receptor upregulation in rat neostriatum following in vivo infusion of forskolin. NeuroReport. Published online September 1997:2971-2976. doi:10.1097/00001756-199709080-00033
- 30.Trovero F, Gobbi M, Weil-Fuggaza J, Besson M-J, Brochet D, Pirot S. Evidence for a modulatory effect of sulbutiamine on glutamatergic and dopaminergic cortical transmissions in the rat brain. Neuroscience Letters. Published online September 2000:49-53. doi:10.1016/s0304-3940(00)01420-8
- 31.Ollat H, Laurent B, Bakchine S, Michel B-F, Touchon J, Dubois B. Effets de l’association de la Sulbutiamine à un inhibiteur de l’acétylcholinestérase dans les formes légères à modérées de la maladie d’Alzheimer. L’Encéphale. Published online April 2007:211-215. doi:10.1016/s0013-7006(07)91552-3
- 32.YAJIMA S, LEE S-H, MINOWA T, MOURADIAN MM. Sp Family Transcription Factors Regulate Expression of Rat D2Dopamine Receptor Gene. DNA and Cell Biology. Published online May 1998:471-479. doi:10.1089/dna.1998.17.471
- 33.Rahman S, Neuman RS. Myo-inositol reduces serotonin (5-HT2) receptor induced homologous and heterologous desensitization. Brain Research. Published online December 1993:349-351. doi:10.1016/0006-8993(93)91557-9
- 34.Harvey BH, Scheepers A, Brand L, Stein DJ. Chronic inositol increases striatal D2 receptors but does not modify dexamphetamine-induced motor behavior. Pharmacology Biochemistry and Behavior. Published online February 2001:245-253. doi:10.1016/s0091-3057(00)00459-7
- 35.Unfer V, Facchinetti F, Orrù B, Giordani B, Nestler J. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. Endocr Connect. 2017;6(8):647-658. doi:10.1530/EC-17-0243
- 36.Giménez R, Raïch J, Aguilar J. Changes in brain striatum dopamine and acetylcholine receptors induced by chronic CDP-choline treatment of aging mice. Br J Pharmacol. 1991;104(3):575-578. doi:10.1111/j.1476-5381.1991.tb12471.x
- 37.Singh S, Mishra A, Mishra SK, Shukla S. ALCAR promote adult hippocampal neurogenesis by regulating cell-survival and cell death-related signals in rat model of Parkinson’s disease like-phenotypes. Neurochemistry International. Published online September 2017:388-396. doi:10.1016/j.neuint.2017.05.017
- 38.Barnes C, Markowska A, Ingram D, et al. Acetyl-1-carnitine. 2: Effects on learning and memory performance of aged rats in simple and complex mazes. Neurobiol Aging. 1990;11(5):499-506. doi:10.1016/0197-4580(90)90110-l
- 39.Singh M, Miura P, Renden R. Age-related defects in short-term plasticity are reversed by acetyl-L-carnitine at the mouse calyx of Held. Neurobiol Aging. 2018;67:108-119. doi:10.1016/j.neurobiolaging.2018.03.015
- 40.Sershen H, Harsing L, Banay-Schwartz M, Hashim A, Ramacci M, Lajtha A. Effect of acetyl-L-carnitine on the dopaminergic system in aging brain. J Neurosci Res. 1991;30(3):555-559. doi:10.1002/jnr.490300313
- 41.Bossoni G, Carpi C. Effect of acetyl-L-carnitine on conditioned reflex learning rate and retention in laboratory animals. Drugs Exp Clin Res. 1986;12(11):911-916. https://www.ncbi.nlm.nih.gov/pubmed/3816508
- 42.Tolu P. Effects of Long-term Acetyl-L-carnitine Administration in Rats I. Increased Dopamine Output in Mesocorticolimbic Areas and Protection toward Acute Stress Exposure. Neuropsychopharmacology. Published online September 2002:410-420. doi:10.1016/s0893-133x(02)00306-8
- 43.Ando S, Tadenuma T, Tanaka Y, et al. Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats. J Neurosci Res. 2001;66(2):266-271. doi:10.1002/jnr.1220
- 44.Ferreira G, McKenna M. L-Carnitine and Acetyl-L-carnitine Roles and Neuroprotection in Developing Brain. Neurochem Res. 2017;42(6):1661-1675. doi:10.1007/s11064-017-2288-7
- 45.Ghirardi O, Milano S, Ramacci M, Angelucci L. Long-term acetyl-L-carnitine preserves spatial learning in the senescent rat. Prog Neuropsychopharmacol Biol Psychiatry. 1989;13(1-2):237-245. doi:10.1016/0278-5846(89)90021-3
- 46.Goo M, Choi S, Kim S, Ahn B. Protective effects of acetyl-L-carnitine on neurodegenarative changes in chronic cerebral ischemia models and learning-memory impairment in aged rats. Arch Pharm Res. 2012;35(1):145-154. doi:10.1007/s12272-012-0116-9
- 47.Taglialatela G, Caprioli A, Giuliani A, Ghirardi O. Spatial memory and NGF levels in aged rats: natural variability and effects of acetyl-L-carnitine treatment. Exp Gerontol. 1996;31(5):577-587. doi:10.1016/0531-5565(96)00052-6
- 48.Valerio C, Clementi G, Spadaro F, et al. The effects of acetyl-l-carnitine on experimental models of learning and memory deficits in the old rat. Funct Neurol. 1989;4(4):387-390. https://www.ncbi.nlm.nih.gov/pubmed/2620857
- 49.Lino A, Boccia M, Rusconi A, Bellomonte L, Cocuroccia B. [Psycho-functional changes in attention and learning under the action of L-acetylcarnitine in 17 young subjects. A pilot study of its use in mental deterioration]. Clin Ter. 1992;140(6):569-573. https://www.ncbi.nlm.nih.gov/pubmed/1638856
- 50.Singh S, Mishra A, Srivastava N, Shukla R, Shukla S. Acetyl-L-Carnitine via Upegulating Dopamine D1 Receptor and Attenuating Microglial Activation Prevents Neuronal Loss and Improves Memory Functions in Parkinsonian Rats. Mol Neurobiol. 2018;55(1):583-602. doi:10.1007/s12035-016-0293-5
- 51.Nasca C, Xenos D, Barone Y, et al. L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. Proc Natl Acad Sci U S A. 2013;110(12):4804-4809. doi:10.1073/pnas.1216100110
- 52.Chiechio S, Canonico P, Grilli M. l-Acetylcarnitine: A Mechanistically Distinctive and Potentially Rapid-Acting Antidepressant Drug. Int J Mol Sci. 2017;19(1). doi:10.3390/ijms19010011
- 53.Nishizawa K, Torii K, Kawasaki A, et al. Antidepressant-Like Effect of Cordyceps sinensis in the Mouse Tail Suspension Test. Biol Pharm Bull. Published online 2007:1758-1762. doi:10.1248/bpb.30.1758
- 54.Tianzhu Z, Shihai Y, Juan D. Antidepressant-like effects of cordycepin in a mice model of chronic unpredictable mild stress. Evid Based Complement Alternat Med. 2014;2014:438506. doi:10.1155/2014/438506
- 55.Wang J, Liu Y, Li L, et al. Dopamine and serotonin contribute to Paecilomyces hepiali against chronic unpredictable mild stress induced depressive behavior in Sprague Dawley rats. Molecular Medicine Reports. Published online August 16, 2017:5675-5682. doi:10.3892/mmr.2017.7261
- 56.Guo J, Li C, Wang J, Liu Y, Zhang J. Vanadium-EnrichedCordyceps sinensis,a Contemporary Treatment Approach to Both Diabetes and Depression in Rats. Evidence-Based Complementary and Alternative Medicine. Published online 2011:1-6. doi:10.1093/ecam/neq058
- 57.Young S. Biologic effects of mindfulness meditation: growing insights into neurobiologic aspects of the prevention of depression. J Psychiatry Neurosci. 2011;36(2):75-77. doi:10.1503/jpn.110010
- 58.Kruis A, Slagter HA, Bachhuber DRW, Davidson RJ, Lutz A. Effects of meditation practice on spontaneous eyeblink rate. Psychophysiol. Published online February 12, 2016:749-758. doi:10.1111/psyp.12619
- 59.Kjaer TW, Bertelsen C, Piccini P, Brooks D, Alving J, Lou HC. Increased dopamine tone during meditation-induced change of consciousness. Cognitive Brain Research. Published online April 2002:255-259. doi:10.1016/s0926-6410(01)00106-9
- 60.Jung Y-H, Kang D-H, Byun MS, et al. Influence of brain-derived neurotrophic factor and catecholO-methyl transferase polymorphisms on effects of meditation on plasma catecholamines and stress. Stress. Published online July 26, 2011:97-104. doi:10.3109/10253890.2011.592880
- 61.Korponay C, Dentico D, Kral TRA, et al. The Effect of Mindfulness Meditation on Impulsivity and its Neurobiological Correlates in Healthy Adults. Sci Rep. Published online August 19, 2019. doi:10.1038/s41598-019-47662-y
- 62.Krishnakumar D, Hamblin M, Lakshmanan S. Meditation and Yoga can Modulate Brain Mechanisms that affect Behavior and Anxiety-A Modern Scientific Perspective. Anc Sci. 2015;2(1):13-19. doi:10.14259/as.v2i1.171
- 63.Lin T, Kuo Y. Exercise benefits brain function: the monoamine connection. Brain Sci. 2013;3(1):39-53. doi:10.3390/brainsci3010039
- 64.Feng Y-S, Yang S-D, Tan Z-X, et al. The benefits and mechanisms of exercise training for Parkinson’s disease. Life Sciences. Published online March 2020:117345. doi:10.1016/j.lfs.2020.117345
- 65.Rosa HZ, Barcelos RCS, Segat HJ, et al. Physical exercise modifies behavioral and molecular parameters related to opioid addiction regardless of training time. European Neuropsychopharmacology. Published online March 2020:25-35. doi:10.1016/j.euroneuro.2019.12.111
- 66.Kruk J, Kotarska K, Aboul-Enein BH. Physical exercise and catecholamines response: benefits and health risk: possible mechanisms. Free Radical Research. Published online February 18, 2020:1-21. doi:10.1080/10715762.2020.1726343
- 67.Flack KD, Ufholz K, Johnson L, Roemmich JN. Increasing the Reinforcing Value of Exercise in Overweight Adults. Front Behav Neurosci. Published online December 3, 2019. doi:10.3389/fnbeh.2019.00265
- 68.Meeusen R, Van Cutsem J, Roelands B. Endurance exercise‐induced and mental fatigue and the brain. Exp Physiol. Published online March 16, 2020. doi:10.1113/ep088186
- 69.Robertson CL, Ishibashi K, Chudzynski J, et al. Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment. Neuropsychopharmacol. Published online October 27, 2015:1629-1636. doi:10.1038/npp.2015.331
- 70.Jun Zhang, Rui Xue, Yun-Feng Li, You-Zhi Zhang, Hong-Wen Wei. Anxiolytic-like effects of treadmill exercise on an animal model of post-traumatic stress disorder and its mechanism. J Sports Med Phys Fitness. Published online January 2020. doi:10.23736/S0022-4707.20.10120-8
- 71.Cawley E, Park S, aan het, et al. Dopamine and light: dissecting effects on mood and motivational states in women with subsyndromal seasonal affective disorder. J Psychiatry Neurosci. 2013;38(6):388-397. doi:10.1503/jpn.120181
- 72.Tsai H-Y, Chen KC, Yang YK, et al. Sunshine-exposure variation of human striatal dopamine D2/D3 receptor availability in healthy volunteers. Progress in Neuro-Psychopharmacology and Biological Psychiatry. Published online January 2011:107-110. doi:10.1016/j.pnpbp.2010.09.014
- 73.Bedrosian T, Nelson R. Timing of light exposure affects mood and brain circuits. Transl Psychiatry. 2017;7(1):e1017. doi:10.1038/tp.2016.262
- 74.Castañeda T, de P, Prieto D, Mora F. Circadian rhythms of dopamine, glutamate and GABA in the striatum and nucleus accumbens of the awake rat: modulation by light. J Pineal Res. 2004;36(3):177-185. doi:10.1046/j.1600-079x.2003.00114.x
- 75.Parry B, Maurer E. Light treatment of mood disorders. Dialogues Clin Neurosci. 2003;5(4):353-365. https://www.ncbi.nlm.nih.gov/pubmed/22033495
- 76.Blum K, Febo M, Thanos P, Baron D, Fratantonio J, Gold M. Clinically Combating Reward Deficiency Syndrome (RDS) with Dopamine Agonist Therapy as a Paradigm Shift: Dopamine for Dinner? Mol Neurobiol. 2015;52(3):1862-1869. doi:10.1007/s12035-015-9110-9
- 77.Wurtman R. Synapse formation in the brain can be enhanced by co-administering three specific nutrients. Eur J Pharmacol. 2017;817:20-21. doi:10.1016/j.ejphar.2017.09.038
- 78.Martins J. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr. 2009;28(5):525-542. doi:10.1080/07315724.2009.10719785
- 79.Ajith T. A Recent Update on the Effects of Omega-3 Fatty Acids in Alzheimer’s Disease. Curr Clin Pharmacol. 2018;13(4):252-260. doi:10.2174/1574884713666180807145648
- 80.Lauritzen L, Brambilla P, Mazzocchi A, Harsløf L, Ciappolino V, Agostoni C. DHA Effects in Brain Development and Function. Nutrients. 2016;8(1). doi:10.3390/nu8010006
- 81.Hopperton K, Trépanier M, James N, Chouinard-Watkins R, Bazinet R. Fish oil feeding attenuates neuroinflammatory gene expression without concomitant changes in brain eicosanoids and docosanoids in a mouse model of Alzheimer’s disease. Brain Behav Immun. 2018;69:74-90. doi:10.1016/j.bbi.2017.11.002
- 82.Perez-Pardo P, Dodiya H, Broersen L, et al. Gut-brain and brain-gut axis in Parkinson’s disease models: Effects of a uridine and fish oil diet. Nutr Neurosci. 2018;21(6):391-402. doi:10.1080/1028415X.2017.1294555
- 83.Ghasemi F, Wang F, Sinclair A, Elliott G, Turchini G. How does high DHA fish oil affect health? A systematic review of evidence. Crit Rev Food Sci Nutr. 2019;59(11):1684-1727. doi:10.1080/10408398.2018.1425978
- 84.Al-Ghannami S, Al-Adawi S, Ghebremeskel K, et al. Randomized open-label trial of docosahexaenoic acid-enriched fish oil and fish meal on cognitive and behavioral functioning in Omani children. Nutrition. 2019;57:167-172. doi:10.1016/j.nut.2018.04.008
- 85.Valentini K, Pickens C, Wiesinger J, Fenton J. The effect of fish oil supplementation on brain DHA and EPA content and fatty acid profile in mice. Int J Food Sci Nutr. 2018;69(6):705-717. doi:10.1080/09637486.2017.1413640
- 86.Gray K, Sonne S, McClure E, et al. A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults. Drug Alcohol Depend. 2017;177:249-257. doi:10.1016/j.drugalcdep.2017.04.020
- 87.Lochner C, Roos A, Stein D. Excoriation (skin-picking) disorder: a systematic review of treatment options. Neuropsychiatr Dis Treat. 2017;13:1867-1872. doi:10.2147/NDT.S121138
- 88.Morley K, Baillie A, Van D, et al. N-acetyl cysteine in the treatment of alcohol use disorder in patients with liver disease: Rationale for further research. Expert Opin Investig Drugs. 2018;27(8):667-675. doi:10.1080/13543784.2018.1501471
- 89.França K, Lotti T. N-acetyl cysteine in the treatment of trichotillomania. Dermatol Ther. 2017;30(3). doi:10.1111/dth.12446
- 90.Grant J, Kim S, Odlaug B. N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol Psychiatry. 2007;62(6):652-657. doi:10.1016/j.biopsych.2006.11.021
- 91.Nocito E, Andrade R, Ruffo C, Siciliano S, da S, Fidalgo T. N-acetylcysteine for treating cocaine addiction – A systematic review. Psychiatry Res. 2017;251:197-203. doi:10.1016/j.psychres.2017.02.024
- 92.Duailibi M, Cordeiro Q, Brietzke E, et al. N-acetylcysteine in the treatment of craving in substance use disorders: Systematic review and meta-analysis. Am J Addict. 2017;26(7):660-666. doi:10.1111/ajad.12620
- 93.Taylor M, Bhagwandas K. N-acetylcysteine in trichotillomania: a panacea for compulsive skin disorders? Br J Dermatol. 2014;171(5):1253-1255. doi:10.1111/bjd.13080
- 94.Nielsen S, Gowing L, Sabioni P, Le F. Pharmacotherapies for cannabis dependence. Cochrane Database Syst Rev. 2019;1:CD008940. doi:10.1002/14651858.CD008940.pub3
- 95.Asevedo E, Mendes A, Berk M, Brietzke E. Systematic review of N-acetylcysteine in the treatment of addictions. Braz J Psychiatry. 2014;36(2):168-175. doi:10.1590/1516-4446-2013-1244
- 96.Gipson C. Treating Addiction: Unraveling the Relationship Between N-acetylcysteine, Glial Glutamate Transport, and Behavior. Biol Psychiatry. 2016;80(3):e11-2. doi:10.1016/j.biopsych.2016.05.007
- 97.Barroso L, Sternberg F, Souza M, Nunes G. Trichotillomania: a good response to treatment with N-acetylcysteine. An Bras Dermatol. 2017;92(4):537-539. doi:10.1590/abd1806-4841.20175435
- 98.McClure E, Gipson C, Malcolm R, Kalivas P, Gray K. Potential role of N-acetylcysteine in the management of substance use disorders. CNS Drugs. 2014;28(2):95-106. doi:10.1007/s40263-014-0142-x
- 99.Gray K, Watson N, Carpenter M, Larowe S. N-acetylcysteine (NAC) in young marijuana users: an open-label pilot study. Am J Addict. 2010;19(2):187-189. doi:10.1111/j.1521-0391.2009.00027.x
- 100.Knackstedt L, LaRowe S, Mardikian P, et al. The role of cystine-glutamate exchange in nicotine dependence in rats and humans. Biol Psychiatry. 2009;65(10):841-845. doi:10.1016/j.biopsych.2008.10.040
- 101.Amen S, Piacentine L, Ahmad M, et al. Repeated N-acetyl cysteine reduces cocaine seeking in rodents and craving in cocaine-dependent humans. Neuropsychopharmacology. 2011;36(4):871-878. doi:10.1038/npp.2010.226
- 102.Fernandes B, Dean O, Dodd S, Malhi G, Berk M. N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis. J Clin Psychiatry. 2016;77(4):e457-66. doi:10.4088/JCP.15r09984
- 103.Taksande B, Khade S, Aglawe M, Gujar S, Chopde C, Kotagale N. Agmatine Inhibits Behavioral Sensitization to Ethanol Through Imidazoline Receptors. Alcohol Clin Exp Res. 2019;43(4):747-757. doi:10.1111/acer.13972
- 104.Wang X, Zhao T, Su R, Wu N, Li J. Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats. Neurosci Bull. 2016;32(6):523-530. doi:10.1007/s12264-016-0031-z
- 105.Sameer S, Chakraborty S, Ugale R. Agmatine attenuates acquisition but not the expression of ethanol conditioned place preference in mice: a role for imidazoline receptors. Behav Pharmacol. 2013;24(2):87-94. doi:10.1097/FBP.0b013e32835efc46
- 106.Thorn D, Li J, Qiu Y, Li J. Agmatine attenuates the discriminative stimulus and hyperthermic effects of methamphetamine in male rats. Behav Pharmacol. 2016;27(6):542-548. doi:10.1097/FBP.0000000000000244
- 107.Ozden O, Kayir H, Ozturk Y, Uzbay T. Agmatine blocks ethanol-induced locomotor hyperactivity in male mice. Eur J Pharmacol. 2011;659(1):26-29. doi:10.1016/j.ejphar.2011.03.010
- 108.Taksande B, Nambiar S, Patil S, Umekar M, Aglawe M, Kotagale N. Agmatine reverses ethanol consumption in rats: Evidences for an interaction with imidazoline receptors. Pharmacol Biochem Behav. 2019;186:172779. doi:10.1016/j.pbb.2019.172779
- 109.Zaniewska M, McCreary A, Sezer G, Przegaliński E, Filip M. Effects of agmatine on nicotine-evoked behavioral responses in rats. Pharmacol Rep. 2008;60(5):645-654. https://www.ncbi.nlm.nih.gov/pubmed/19066410
- 110.Morgan A, Campbell U, Fons R, Carroll M. Effects of agmatine on the escalation of intravenous cocaine and fentanyl self-administration in rats. Pharmacol Biochem Behav. 2002;72(4):873-880. doi:10.1016/s0091-3057(02)00774-8
- 111.Li F, Wu N, Su R, et al. Imidazoline receptor antisera-selected/Nischarin regulates the effect of agmatine on the development of morphine dependence. Addict Biol. 2012;17(2):392-408. doi:10.1111/j.1369-1600.2011.00373.x
- 112.Kotagale N, Taksande B, Gahane A, Ugale R, Chopde C. Repeated agmatine treatment attenuates nicotine sensitization in mice: modulation by alpha2-adrenoceptors. Behav Brain Res. 2010;213(2):161-174. doi:10.1016/j.bbr.2010.04.049
- 113.Freitas A, Egea J, Buendia I, et al. Agmatine, by Improving Neuroplasticity Markers and Inducing Nrf2, Prevents Corticosterone-Induced Depressive-Like Behavior in Mice. Mol Neurobiol. 2016;53(5):3030-3045. doi:10.1007/s12035-015-9182-6
- 114.Piletz J, Aricioglu F, Cheng J, et al. Agmatine: clinical applications after 100 years in translation. Drug Discov Today. 2013;18(17-18):880-893. doi:10.1016/j.drudis.2013.05.017
- 115.Li Y, Gong Z, Cao J, Wang H, Luo Z, Li J. Antidepressant-like effect of agmatine and its possible mechanism. Eur J Pharmacol. 2003;469(1-3):81-88. doi:10.1016/s0014-2999(03)01735-7
- 116.Halaris A, Piletz J. Relevance of imidazoline receptors and agmatine to psychiatry: a decade of progress. Ann N Y Acad Sci. 2003;1009:1-20. doi:10.1196/annals.1304.001
- 117.Uzbay T. The pharmacological importance of agmatine in the brain. Neurosci Biobehav Rev. 2012;36(1):502-519. doi:10.1016/j.neubiorev.2011.08.006
- 118.Blum K, Modestino E, Gondré-Lewis M, et al. “Dopamine homeostasis” requires balanced polypharmacy: Issue with destructive, powerful dopamine agents to combat America’s drug epidemic. J Syst Integr Neurosci. 2017;3(6). doi:10.15761/JSIN.1000183
- 119.Davis L, Michaelides M, Cheskin L, et al. Bromocriptine administration reduces hyperphagia and adiposity and differentially affects dopamine D2 receptor and transporter binding in leptin-receptor-deficient Zucker rats and rats with diet-induced obesity. Neuroendocrinology. 2009;89(2):152-162. doi:10.1159/000170586
- 120.Hernández V, Luquín S, Jáuregui-Huerta F, et al. Dopamine receptor dysregulation in hippocampus of aged rats underlies chronic pulsatile L-Dopa treatment induced cognitive and emotional alterations. Neuropharmacology. 2014;82:88-100. doi:10.1016/j.neuropharm.2013.11.013
- 121.Gantz S, Levitt E, Llamosas N, Neve K, Williams J. Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA. Cell Rep. 2015;12(6):944-954. doi:10.1016/j.celrep.2015.07.005
- 122.Nisoli E, Memo M, Missale C, Carruba M, Spano P. Repeated administration of lisuride down-regulates dopamine D-2 receptor function in mesostriatal and in mesolimbocortical rat brain regions. Eur J Pharmacol. 1990;176(1):85-90. doi:10.1016/0014-2999(90)90135-s
- 123.Carey R, Pinheiro-Carrera M, Dai H, Tomaz C, Huston J. L-DOPA and psychosis: evidence for L-DOPA-induced increases in prefrontal cortex dopamine and in serum corticosterone. Biol Psychiatry. 1995;38(10):669-676. doi:10.1016/0006-3223(94)00378-5
- 124.Pulikkalpura H, Kurup R, Mathew P, Baby S. Levodopa in Mucuna pruriens and its degradation. Sci Rep. 2015;5:11078. doi:10.1038/srep11078
- 125.Infante M, Perez A, Simao M, et al. Outbreak of acute toxic psychosis attributed to Mucuna pruriens. Lancet. 1990;336(8723):1129. doi:10.1016/0140-6736(90)92603-f
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