As a class project, a group of students wrote a skit based on the premise that, in the future, caffeine would be proscribed as an illegal drug. They envisioned that caffeine users would go to extreme lengths to get their “fix.” While this scenario is laughable science fiction, could it portend less dramatic changes in our country’s notion of caffeine-related safety? A comparison between two stimulants, cocaine and caffeine, might make you think differently about that question.

Recall that the reward pathway, in which dopamine is a primary neurotransmitter, is essential to our ability to feel good about survival activities but is also activated by things that do not promote and can potentially hinder our survival (Cunningham et al., 2012). Whether gambling, gaming, or using drugs of abuse, activation of the reward pathway can result in addiction. There are a number of ways to increase the amount of dopamine in the synapse. Figure 1 depicts a neuron that projects to the nucleus accumbens. Upon stimulation of this neuron, dopamine will be released (red circles, panel A). Some substances, such as caffeine, will elevate dopamine release (panel B). Other substances block the recycling of dopamine back into the presynaptic neuron. This is the primary mechanism of cocaine’s euphoria-inducing power (panel C).

Figure 1.

Dopaminergic neurons stimulate the reward pathway. The reward pathway is made up of many neurons (A). Their axon bulb contains vesicles full of dopamine neurotransmitter (red circles). These are released into the synapse when the neuron is stimulated. Thrifty neurons will recycle neurotransmitter so that the presynaptic neuron can release it later (“waterwheel” icon). Some drugs of abuse elevate the dopamine levels in the synapse by increasing dopamine release (B). Other drugs block the recycling of dopamine into the presynaptic neuron (C).

Figure 1.

Dopaminergic neurons stimulate the reward pathway. The reward pathway is made up of many neurons (A). Their axon bulb contains vesicles full of dopamine neurotransmitter (red circles). These are released into the synapse when the neuron is stimulated. Thrifty neurons will recycle neurotransmitter so that the presynaptic neuron can release it later (“waterwheel” icon). Some drugs of abuse elevate the dopamine levels in the synapse by increasing dopamine release (B). Other drugs block the recycling of dopamine into the presynaptic neuron (C).

In the Andes, coca leaf (Erythroxylum coca) tea has been used medicinally and socially for thousands of years (DEAmuseum, 2013). It aids digestion, suppresses appetite, and increases the energy levels of those working long hours at high altitudes (DEAmuseum, 2013). Cocaine use in the Andes does not result in abuse, overdose, or addiction. This is partly due to natives of Peru using extremely low concentrations of cocaine (0.1–1.2%; Erowid, 2013). Additionally, because these teas are administered orally, cocaine stimulates the reward pathway only to a small extent.

By contrast, extracted cocaine is much more pure (80–97%) and is usually absorbed through the nasal mucosal membranes or lung endothelium (Erowid, 2013). Purified, non-oral cocaine results in dramatic euphoria. It can also lead to major physiological changes in circulatory function, sometimes resulting in cardiac arrest and death (NIDA, 2010). Purified, smoked cocaine is approximately 3.5× more addictive than insufflated (snorted) cocaine, which is more addictive than its orally administered counterpart (O’Brien & Anthony, 2005). Thus, concentration and means of intake cause very different scenarios in cocaine use and addiction.

Coffee (Coffea arabica and others) is also a social beverage. Mild mood elevation is typical among coffee consumers. Caffeine is also extracted and concentrated as a byproduct of making decaffeinated coffee. It is used in the manufacture of sodas, headache medications, and energy drinks. As with cocaine, extraction of the chemical compound from the plant can result in elevation of dosage. Energy drinks deliver up to 2–25 times the concentration of caffeine in coffee. With these increases in dosage, we are beginning to see increases in caffeine-related health problems. Between 2004 and 2012, the consumption of high-caffeine energy supplements has been implicated in at least 18 deaths (FDA, 2012). Lesser health impacts have also been reported (FDA, 2012).

Although it is too early to know whether an elevation of caffeine addiction results from consumption of these high concentrations, two differences between the stories of caffeine and cocaine assuage concern about high-concentration caffeine addiction. One difference is that high concentrations of caffeine do not typically result in euphoria – rather, they result in jittery, anxiety-like sensations. Additionally, purified caffeine is still used orally. Oral administration of any drug reduces the euphoria and risk of addiction. Even for addicts, caffeine has much less impact than cocaine. Caffeine users rarely become societal menaces, nor do they suffer a loss of productivity: most will say that they lose productivity without their “drug.” But will access to higher and higher concentrations of caffeine result in elevated addiction and enough unexpected self-harm that regulators will be itching to limit our access? The future is here: two senators are urging the FDA to investigate these energy drinks more carefully (Blumenthal, 2012).

In our next article, we will focus on depressants, specifically opiates. Join us as we further explore the reward pathway, drug delivery and access, and drug addiction.

Acknowledgments

This project was funded by the National Institute on Drug Abuse, National Institutes of Health, under award no. R25DA028796. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

References

References
Cunningham, S.L., Buckland, H.T. & Martin-Morris, L. (2012). What is the link between eating, reproducing, & addiction? American Biology Teacher, 74, 590–591.
DEAmuseum. (2013). The origins of coca. [Online.] Available at http://www.deamuseum.org/ccp/coca/history.html.
Erowid. (2013). Erowid: documenting the complex relationship between humans & psychoactives. [Online.] Available at http://www.erowid.org/.
FDA. (2012). Energy “drinks” and supplements: investigations of adverse event reports. [Online.] Available at http://www.fda.gov/Food/NewsEvents/ucm328536.htm.
NIDA. (2010). DrugFacts: Cocaine: what adverse effects does cocaine have on health? http://www.drugabuse.gov/publications/drugfacts/cocaine.
O’Brien, M.S. & Anthony, J.C. (2005). Risk of becoming cocaine dependent: epidemiological estimates for the United States, 2000–2001. Neuropsychopharmacology, 30, 1006–1018.