Things w/ clinical evidence of upregulating dopamine receptors, curbing cravings

One of the most common questions is ?How can I speed up the reboot process?? Other common questions reference ?boosting dopamine.? We?re actually more concerned with upregulating dopamine receptors over the long term during the reboot process, specifically D2 receptors, that have been beaten down over the years. The following things have clinical evidence of doing just that.

Obligatory preface and disclaimers:
  • First, the most important piece of the healing process is obviously still abstaining from the addictive behavior itself.
  • Secondly, this is admittedly a simplistic, reductionistic view of the healing process and of the dopaminergic system itself. I acknowledge that dopamine, while it does seem to be the primary aspect of the neurobiological processes involved, is only one aspect. There are obviously more complex mechanisms at play with different neurotransmitters, regions, and pathways in the brain.
  • Similarly, these things - and simply upregulating dopamine receptors - may not necessarily speed up the recovery process as a whole and may not make things like PIED go away faster, though they should help alleviate symptoms, help you feel better during your reboot, and at least speed up the repair of the dopamine receptors per se.
  • I?m not a medical doctor. This is not professional medical advice and should not be substituted for professional medical advice. Ask a doc before combining these with any prescription drugs you?re on, as they may be contraindicated, especially dopamine agonists and NDRI?s like Levodopa, Adderall, Ritalin, etc.
  • Everything here is backed by scientific research. There?s a link to 116 research studies at the end.
  • Common tips and techniques that have been covered ad nauseam like socializing, finding new hobbies, browser blockers, etc. aren?t covered here. Obviously you should try to employ those as well.

Assumptions, most of which are the foundational neuroscientific understanding from YBOP:
  • We know that spiking dopamine - both acutely and chronically - from things like porn, gambling, junk food, etc. leads to the desensitization and downregulation (decrease in sensitivity and number) of dopamine receptors, especially in the context of extreme, artificial stimuli, and especially with things that persistently increase dopamine levels, like cocaine and multi-tabbed porn browsing sessions.
  • We know that low dopamine is associated with low energy levels, lack of focus and motivation, poor learning and memory, symptoms of depression, apathy, anhedonia, and reward-seeking behavior.
  • We know that the addiction model appears to be largely the same for behaviorial addictions as it is for chemical addictions, and share many of the same neurobiological mechanisms and alterations in the brain.
  • Recent developments in neuroscience seem to agree that the dopaminergic system is involved in the want or desire of the pleasure/high, not necessarily in the pleasure itself, which is delivered via the opioid system, among other things. Interestingly, that desire can be chemically stronger than the pleasure received, thus the addiction.

So here?s the list:
  • Uridine - found naturally in human breast milk and oddly, in beer. Lots of anecdotal evidence for uridine helping people quit smoking. I prefer triacetyluridine, which is more bioavailable than uridine monophosphate. Main component of the famous ?Mr. Happy Stack.?
  • Forskolin - usually supplemented for its potential fat burning effect. Make sure you're getting a standardized extract.
  • Sulbutiamine - two thiamine molecules and a sulfur group. Modulates the dopaminergic, cholinergic, and gluatmatergic transmission systems.
  • Inositol - natural B vitamin (B8). Involved in communication between neurotransmitters. Often used in high doses alongside medications to alleviate symptoms of depression, OCD, panic attacks, and anxiety.
  • CDP-Choline - Found naturally in the body. Precursor to acetylcholine, and is necessary for proper brain function. It is often supplemented to prevent memory impairment associated with aging.
  • ALCAR (Acetyl-L-Carnitine) - 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.
  • Cordyceps - It?s a mushroom. It exerts antidepressant and 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. Aim for a whole fruiting body extract from a reputable source like Real Mushrooms, Freshcap, or Nootropics Depot.
  • Meditation - While no studies currently show specific influence 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. (think ?flatline?).
  • Exercise - Similar to meditation, exercise seems to modulate the dopaminergic system and increase levels of dopamine, norepinephrine, and serotonin, among its myriad other health benefits.
  • 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. 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??. 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.

Alleviating symptoms, decreasing urges, and feeling better

Broadly speaking, things that increase dopamine (agonists) generally downregulate/decrease receptors. Things that decrease dopamine (antagonists) generally upregulate/increase dopamine receptors. The brain tries to achieve homeostatic balance.

It may sound counterintuitive, but I would argue it may be prudent to actually mildly boost dopamine during the initial stages of the reboot process, and especially during the famous ?flatline.? People experiencing the aforementioned symptoms of low dopamine levels are more likely to re-engage in the addictive behavior. On the flip side, if you feel good, you are more likely to stay the course in your abstinence/recovery. Moreover, ?normal? levels of circulating dopamine should translate into less reward-seeking behavior.

Recent research from 2015 seems to agree. From Kenneth Blum et al, the addiction expert researchers who originally discovered the genetic connection to decreased dopamine receptors in the early 1990?s and coined the term ?Reward Deficiency Syndrome? (RDS): ?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.?

So how can 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 urges.
  • Fish oil - supports brain health and may have ameliorative effects on symptoms of depression. As part of the famous ?Mr. Happy Stack? (DHA/EPA, uridine, and choline), it has evidence of promoting the actual growth of neurons and synapses between neurons.
  • L-Tyrosine - the amino acid precursor to dopamine and catecholamines. Essentially, no tyrosine = no dopamine. Tyrosine converts to L-DOPA which converts to dopamine. I would not recommend supplementing L-DOPA (typically from mucuna pruriens) directly; you?d be bypassing the rate-limiting step and increasing dopamine indiscriminately, thereby downregulating dopamine receptors and depleting serotonin in the process over the long term, which works precisely against what we?re trying to achieve during the healing process. L-DOPA supplementation is also associated with mania, dyskinesia, psychosis, homicidal thoughts, and a range of other nasty side effects. If you?re eating a high-protein diet, you may be have enough tyrosine already, as tyrosine is found in high concentrations in meat, dairy, beans, nuts, and seeds. But this makes it arguably more important for vegetarians and vegans to supplement.
  • 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 urges and cravings. It has tons of clinical evidence demonstrating its efficacy in decreasing cravings and addictive behavior related to trichotillomania (hair pulling), excoriation (skin picking), smoking, gambling, cocaine, marijuana, and more, via modulating glutamate?. Mechanistically, it?s believed that NAC may actually alter ?drug-induced plasticity that underlies drug-seeking behavior.? ? It also happens to have the added benefits of being hepatoprotective (attenuates damage to the liver) and having ameliorative effects on symptoms of depression?. 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. Personally, 1800mg daily allows me to completely avoid biting my fingernails.
  • 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?. Agmatine also seems to possess antineurodegenerative and antidepressant properties.?
  • Exercise, Meditation, Sunlight - Again, these things seem to reliably boost dopamine levels, alleviate symptoms of depression, and lower cortisol, among their myriad other health benefits. Wear sunscreen.

Links to 116 research studies at the bottom of this page (my blog post).

TL;DR: Addictive behaviors like porn, gambling, drug use, etc. downregulate dopamine receptors over time. 7 dietary supplements have clinical evidence of upregulating dopamine receptors, and several supplements and activities can boost circulating dopamine levels. These things may not expedite the healing process as a whole, but should at least help alleviate withdrawal symptoms, get you feeling better faster, and help repair dopamine receptors. The most important piece of the healing process is obviously still abstaining from the addictive behavior itself.

Stay safe out there!


Active Member
Thank you for this well-researched post mate. I've been supplementing fish oil and exercising and meditating for a while, but still felt like something was missing.

Have been taking 500 mg of l-tyrosine for the past couple of days and feel a massive difference in my drive to simply get shit done. Will keep taking it to see if the effects persist. NAC looks promising and I think I've seen it around in stores here, will try it out.

Thanks again.