Answer by Alex K. Chen:

This is seriously hard to say, and depends a lot on how much you consume, what you use it for, and your basic genetic makeup.… has some interesting information regarding tolerance/addiction. Tolerance/addiction can happen over time, but it is reversible (however, it could be unpleasant). There may be drugs in the future that may help with the unpleasantness of caffeine withdrawal (it’s possible that bupropion and modafinil could work – as both of them are often used to alleviate withdrawal symptoms from other addictive drugs)

As one starts to regularly take in caffeine, the body and mind build up a tolerance to it, so getting the same kind of boost as one’s first-ever sip takes more caffeine—this, researchers can agree on. Exactly how that tolerance develops is not so clear. Many studies have suggested that, just as with any drug addiction, the brain strives to return to its normal function while under “attack” from caffeine by up-regulating, or creating more adenosine receptors. But regular caffeine use has also been shown to decrease receptors for norepinephrine, a hormone akin to adrenaline, along with serotonin, a mood enhancer. At the same time, your body can see a 65 percent increase in receptors for GABA, a compound that does many things, including regulate muscle tone and neuron firing. Some studies have also seen changes in different adenosine receptors when caffeine becomes a regular thing.

As for effects independent of tolerance/addiction, their effects on the brain seem to mostly lie on the “good” side (although this isn’t necessarily true for the heart – caffeine can increase the risk of heart attacks in populations already vulnerable to heart disease). See… for an article published by a top neuroscience journal.

There is suggestive evidence that caffeine could prevent Parkinson’s Disease (see…).

Scientists working with a mouse model of Parkinson’s disease have found that caffeine prevents the loss of the neurotransmitter dopamine, which is depleted in the neurodegenerative illness. If the new findings are any indication of caffeine’s effects in humans, a coffee a day may help keep Parkinson’s away. The results of this study will be published in the May 15 issue of the journal Neurology.

Specifically, the new research, conducted by Michael Schwarzchild of Massachusetts General Hospital and his colleagues, links caffeine’s protective effects to the so-called A2A receptor. The dopamine neurons that degenerate in Parkinson’s target neighboring neural cells that sport this receptor. But caffeine apparently antagonizes the A2A receptor, rendering it inactive and thereby halting the progressive destruction that characterizes the disease. Indeed, those mice in Schwarzchild’s study that were pretreated with caffeine retained near-normal dopamine levels when exposed to a chemical known to induce Parkinson’s-like symptoms by decreasing brain dopamine.

And Alzheimer’s too (see…)

“Epidemiological studies first revealed an inverse association between the chronic consumption of caffeine and the incidence of Parkinson’s disease,” according to Mendonça and Cunha. “This was paralleled by animal studies of Parkinson’s disease showing that caffeine prevented motor deficits as well as neurodegeneration “Later a few epidemiological studies showed that the consumption of moderate amounts of caffeine was inversely associated with the cognitive decline associated with aging as well as the incidence of Alzheimer’s disease. Again, this was paralleled by animal studies showing that chronic caffeine administration prevented memory deterioration and neurodegeneration in animal models of aging and of Alzheimer’s disease.
Key findings presented in “Therapeutic Opportunities for Caffeine in Alzheimer’s Disease and Other Neurodegenerative Diseases”

Some of its findings:

  • Multiple beneficial effects of caffeine to normalize brain function and prevent its degeneration
  • Caffeine’s neuroprotective profile and its ability to reduce amyloid-beta production
  • Caffeine as a candidate disease-modifying agent for Alzheimer’s disease
  • Positive impact of caffeine on cognition and memory performance
  • Identification of adenosine A2A receptors as the main target for neuroprotection afforded by caffeine consumption
  • Confirmation of data through valuable meta-analyses presented
  • Epidemiological studies corroborated by meta-analysis suggesting that caffeine may be protective against Parkinson’s disease
  • Several methodological issues must be solved before advancing to decisive clinical trials

Is it credible? I would think so. One of the top aging researchers in the nation, Matt Kaeberlein, did tell me that caffeine extends the lifespan of C. elegans by 33% (by what mechanism – it’s unclear – it could be phosphodiesterase inhibition or mTOR inhibition). Caffeine also increases lifespan in yeast – see…

Here’s a literature review of caffeine’s effects (…, published in 2006 – before caffeine was found to be neuroprotective in Alzheimer’s too):

The results of epidemiological research suggest that coffee consumption may help prevent several chronic diseases, including type 2 diabetes mellitus, Parkinson’s disease and liver disease (cirrhosis and hepatocellular carcinoma). Most prospective cohort studies have not found coffee consumption to be associated with significantly increased cardiovascular disease risk. However, coffee consumption is associated with increases in several cardiovascular disease risk factors, including blood pressure and plasma homocysteine. At present, there is little evidence that coffee consumption increases the risk of cancer. For adults consuming moderate amounts of coffee (3–4 cups/d providing 300–400 mg/d of caffeine), there is little evidence of health risks and some evidence of health benefits. However, some groups, including people with hypertension, children, adolescents, and the elderly, may be more vulnerable to the adverse effects of caffeine. In addition, currently available evidence suggests that it may be prudent for pregnant women to limit coffee consumption to 3 cups/d providing no more than 300 mg/d of caffeine to exclude any increased probability of spontaneous abortion or impaired fetal growth.

One thing for sure though: We definitely do need more research to see if neuroprotection is affected by tolerance

Are there any permanent effects of caffeine intake on brain structure or function?