Coffee, Depression, Alcoholism and Drug Abuse – A Mini-review

Research Article

Austin J Pharmacol Ther. 2014;2(1): 1007.

Coffee, Depression, Alcoholism and Drug Abuse – A Mini–review

Roseane Maria Maia Santos1* , Tracy Hunter 2, Darcy Roberto Andrade Lima 3

1Department of Pharmaceutical Sciences, South University School of Pharmacy, USA

2Department of Pharmacy Wingate University School of Pharmacy

3Department of Instituto de Neurologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

*Corresponding author: : Roseane Maria Maia Santos, Department of Pharmaceutical Sciences, South University School of Pharmacy709 Mall Boulevard, Savannah, GA 31419, USA

Received: January 02, 2014; Accepted: January 20, 2014; Published: January 23, 2014


Coffee is a natural productthat when roasted and breweddelivers thousands of pharmacologically active compounds.Recent studies have revealed that 3 to 4 cups of coffee a day as pleasurable, low cost and convenient way to prevent diverse health problems. Depression, acommon mood disorder, is a risk factor for alcoholism and substance abuse. In the last decade, epidemiological studiesilluminating preventative effects of coffee have shown an inverse relationship of consumption with the risk of developing diseases affecting the central nervous system. The caffeine in coffee is widely studied and often assumed to be the key pharmacologically active ingredient if not the singular active agent. However other pharmacologically active constituents, primarily chlorogenic acids and related quinides, are demonstrating health benefits. These abundant components are capable of promoting ‘in vivo’ inhibition of morphineinducedanti– nociceptive behavior in mice in the same order of magnitude as that reported for naloxone. This review explores the interplay among coffee, depression, alcohol and drug consumption.It explores the preventative effects of coffee and proposes a mechanistic theory to explain the action of coffee constituents on mood disorders such as depression and their consequences as alcoholism and drug abuse.


Coffee is one of the most–consumed beverages in the world. Numerous studies have examined its health properties and whether the overall effects are positive or negative has been widely debated. This review focuses on a narrow range of effects, the interplay among coffee, depression, alcohol and drug consumption. Its purpose is to present coffee as more than just caffeine by presenting research on other pharmacologically active compounds.

Coffee and Depression

Depression, a common mood disorder, is the second leading cause of disability in the US and throughout the world. Genetic and environmental factors [1], such as alteration in serotonin transporter (5–HT T) and adverse life events increase the risk of a major depression episode [2]. When left untreated, depressed individuals are at risk of developing a host of medical illnesses ranging from cardiovascular diseases, obesity, diabetes and thyroid disease [3]. Depressed individuals and those with anxiety disorders are more likely to abuse alcohol and drugs.

Stress is a pervasive factor in everyday life and appears to play a major role in the pathophysiology of psychiatric disorders, particularly depression [4,5]. History indicates that mankind seeks substances to induce pleasurable sensations and escape from discomfort related to perceived stress. Drugs of abuse, the legal ones or ‘social drugs’ (tobacco and alcohol) as well as the illegal ones (cocaine, amphetamines and opiates), are typically used for the euphoric sensation or to reduce stress, depression and anxiety [5,6].

Drug abuse and misuse costs our economy and society greatly as measured in increased health care costs, crime and lost productivity. In 2010 it was estimated that 22.6 million or 8.9% of Americans over the age of 12 were current or former illicit drug users. Around 10 million individual 12 to 20 years of age admitted to being alcohol drinkers, of these, 6.5 million were binge drinkers and 2 million heavy drinkers. Besides the social costs, each year, drug abuse and drug addiction cost employers over 122 billion dollar in lost productivity time and another 15 billion dollars in health insurance costs. These are some of the conclusions that the U.S. Department of Health and Human Services (DHHS), Substance Abuse and Mental Health Services Administration (SAMHSA), Center for Behavioral Health Statistics and Quality published in their 2010 National Survey on Drug Use and Health [7].

The SAMHSA published its plan of action for the period of 2011–2014 [8] and its first priority is the prevention of substance of abuse and mental illness. According to this report, the annual total estimated cost of substance of abuse in US is around $ 510 billion and by 2020, behavioral health disorders will surpass all physical diseases as a major cause of disability worldwide [9].

Recent studies have revealed that 3 to 4 cups of coffee a day to be a pleasurable, low cost and convenient way to prevent various health problems [10–16]. The beneficial effects of coffee, as well as some harmful ones, are commonly attributed to coffee’s caffeine content [17–23]. For example, caffeine acts primarily as central nervous system stimulant, improving psychomotor performance, increasing vigilance and reducing fatigue [11];conversely other negative effects on cardiovascular system have been reported [22,24–26]. However, coffee is more thancaffeine. Quinides are found in amounts twice that of caffeine.These substances, formed during the roasting process by dehydration of polyphenols known as chlorogenic acids (CGA’s) have been the object of animal studies and in vitro studies. These substances are thought to be responsible for the antidepressant effect of the decaffeinated coffee as discussed in the following sections [27– 33].

Coffee and Depression: Experimental Studies

The discovery of opiate receptor–active peptide fragments (exorphins) identified in casein and gluten hydrolysates, and morphine in bovine and human milk led Boublik et al. 1983 [34,35] to screen for similar peptides or alkaloids in other foods. Using rat brain homogenate assay to detect opiate receptor activity they tested instant coffee powders from various manufacturers. They reported that approximately one–fifth of the concentration of a specific quinide contained in a cup of coffee displaced 50% of the binding of the opiate antagonist naloxone. However, at this time, the molecular identity producing this effect could not be determined but was suggested to be of an isomer of feruloylquinide, one of the various quinides originating from chlorogenic acids.

Takeda H et al. 2003 [36] examined the antidepressive and/or anxiolytic effect of caffeic acid, the main component of chlorogenic acids (CGA’s) [Figure 1] present in roasted coffee, in two different types of stress models in mice. In both models they concluded that caffeic acid acted through indirect modulation of the alpha–1A adrenoreceptor system.


De Paulis T et al. 2002 [37] studied dicinnamoylquinides, another group of compounds derived from CGA’s present in roasted coffee. Interestingly, their results showed that these quinides not only bind to the human adenosine transporter, but inhibit the re–uptake of adenosine with potency approximately three times higher than the antagonic effect of caffeine at the human adenosine alpha–2A receptor. This suggests that dicinnamoylquinides present in the coffee could have the potential to raise extracellular levels of adenosine, thereby counteracting the stimulant effect of caffeine.

Later, de Paulis T. in 2004 [38] demonstrated that roasted coffee contains compounds that are pharmacologically active on the human opioid receptor system and identified their structures. The compounds identified, cinnamoyl–1,5–quinides, bind to µ opioid receptors and dose–dependently reverse the anti–nociceptive effects of morphine. This study provides experimental data that confirms the hypothesis from Flores et al (2000) [1,5] that a daily moderate intake of coffee may act as a prophylactic agent by blocking µ opioid receptors. Blocking these receptors decrease the craving for self–reward that could be involved in depression, alcoholism and substance of abuse.

It is commonly understood that the way drugs cause pleasure or reward is by mimicking neurotransmitters that activate the brain reward system — the mesolimbic system [3]. The limbic system is involved with emotion, learning and memory. Positive experiences and the use of alcohol and drugs (cocaine, amphetamines, and nicotine) may lead to rewarding feelings and conditioned behavior by means of reinforcing learning and memory mechanisms. The neuronal circuit implicated in reinforcing behavior that leads to drug addiction appears to be the dopaminergic mesolimbic system [Figure 2] composed of cell bodies in the ventral tegmental area (VTA) with projections to the nucleus accumbens (Nac) through the medial forebrain bundle (MFB). In the VTA, beta–endorphin neurons via μ receptors block the inhibitory action of GABA neurons, increasing the release of dopamine in Nac. This effect is counteracted by dynorphin activation of κ receptors, so that basal dopamine release is determined by the balance between those two opposing opioid systems.