How drugs alter our brain: Effects on brain chemistry

Don’t worry; this is not another “Don’t do drugs. Drugs are bad.” kind of an article; this is just me writing about how I am utterly mind-blown by the effect drugs and alcohol have on our brain chemistry… I’m not very fun at parties. 

What are drugs?

Drugs are substances (not including food and water) that physiologically or psychologically alter bodily functions upon consumption. Drugs can be legal (typically alcohol, caffeine, tobacco, prescription medication) or illegal (typically cocaine, heroin, cannabis, ecstasy).

Not all types of drugs affect the body in the same way; some act as stimulants (cocaine, Adderall, meth), or depressants (alcohol, opioids), or both (nicotine). Some drugs called hallucinogens (LSD, psilocybin found in mushrooms) alter perception dramatically.

What are neurotransmitters?

Neurotransmitters are chemical messengers that relay signals between neurons (or other brain cells) in the brain. Of all the neurochemicals present in the brain, some are called neurotransmitters because they facilitate signal transmission between neurons. Communication occurs in the narrow gap between the presynaptic and postsynaptic neurons, called the synaptic cleft. There are more than 60 neurotransmitters in the human body. Psychiatric medicine usually alters neurotransmitter behavior (like SSRIs for depression).

Neurotransmitters can have an excitatory, inhibitory, or modulatory influence on a neuron. That means it can promote neural activity (excitatory), demote neural activity (inhibitory), or change the type of neural activity (modulatory).

Excitatory neurotransmitters such as Acetylcholine, Norepinephrine, Epinephrine (aka adrenaline), and Dopamine increase the action potential (electrical spike) of the receptor.

Inhibitory neurotransmitters such as GABA, Serotonin, & Dopamine restrict the action potential of the receptor.

Dopamine is a special neurotransmitter as it has both inhibitory and excitatory effects on the receptor. Because, a neurotransmitter’s effect depends on the receptor it binds to.

What are hormones?

Hormones are chemical messengers that are secreted directly into the blood from the endocrine gland. The blood carries them to tissues and organs in the body and can affect mood, metabolism, growth, sexual function, reproduction. 

Oxytocin, melatonin, estrogen, progesterone are some examples of hormones.

Neurotransmitters and hormones may sound similar but are not. 

Difference between Neurotransmitters and Hormones

Neurotransmitters	Hormones
Produced by nervous system	Produced by endocrine system
Communicate signal across synaptic cleft	Relays signals through blood
Signal transmission is faster (within milliseconds)	Signal transmission is slower (minutes to days)
Classified as excitatory or inhibitory	Classified as amino acid based or steroids

Common drugs people consume

Cocaine, aka snow, coke, or nose candy, is a highly addictive stimulant. It creates a euphoric feeling upon consumption along with extreme sensitivity to sensory inputs, alertness, attentiveness, and irritability. It is easy to develop a tolerance for cocaine. After repetitive use, it may take higher and more frequent dosages to create an effect equal to the first time it is consumed.

Alcohol is categorized as a depressant, i.e., it impairs and slows down cognitive functions resulting in slurred speech, disturbed perceptions, and lowers inhibitions (remember all the bad decisions you’ve made under its influence?). Because alcohol impairs the cognitive functions, you may not fully experience the pain caused by an injury when under the influence. You may feel the pain once the alcohol wears off.

Benzodiazepines come under the depressant class of drugs as they decrease (or depress) the level of activity in the central nervous system and slow down the relay of messages between the brain and the body. Psychiatrists typically prescribe these to help induce sleep, relieve stress, reduce anxiety, and treat epilepsy.

Nicotine is found in tobacco and other nightshade plants like peppers (did not see that coming); it has a sedative and a stimulant effect on the body. Exposure to nicotine makes an individual experience a “kick,” partly because nicotine stimulates the adrenal glands, resulting in a release of adrenaline – a hormone that stimulates the body. This stimulation leads to an instant release of glucose and an increase in heart rate, breathing activity, and blood pressure. Nicotine, like heroin and cocaine, also causes dopamine release in the pleasure or motivation areas of the brain.

Opiates or opioids are drugs used to treat pain as they are depressants. Human bodies have opiate receptors for the natural opioids (endogenous opioids – neurotransmitters such as endorphins) our body produces for pain management or stress resilience. The natural opiates are usually made from opium poppy plants. Synthetic opioids are man-made versions of natural opiates. Synthetic opioids bind themselves to the opiate receptors imitating the effects of the endogenous opioids by blocking the perception of pain and causing feelings of euphoria by influencing Dopamine-based neural circuits. 

The consumer of this substance may find himself craving the feeling of pleasure as soon as it’s gone, causing them to want to consume more, and making them dependent on the substance.

A recent study by Stoeber et. al^[1]. suggests that synthetic drugs were activated in the Golgi Apparatus, a location where endogenous opioids cannot reach. According to the researchers, synthetic opioids travel directly to the Golgi apparatus without binding to receptors, reaching their target in only 20 seconds instead of 1 minute; the faster the drug takes effect, the higher its addictive potential.

Commonly affected Neurotransmitters

Dopamine

Dopamine is not only a neurotransmitter but also a hormone; its function depends on the type of dopamine receptor it binds to, which are mostly found in the central nervous system. The Dopamine in the synaptic cleft undergoes reuptake by the dopamine active transporter (DAT).

There are 5 types of dopamine receptors, and each has different functions and locations^[2]. The commonly attributed Dopamine = reward sensation comes from the D1 and D2 receptor’s role^[3] in natural and synthetic reward-associated behavior.

Dopamine receptor type	Location	Function
D1	Caudate putamen, nucleus accumbus, substantia nigra pars reticulata, olfactory bulb	Learning and memory, reward behavior, locomotion, attention, impulse control, regulation of renal function
D2	Striatum, VTA, olfactory bulb, cerebral cortex	locomotion, attention, sleep, memory, learning, reproductive behavior, reward behavior
D3	Striatum, islands of Calleja, cortex	Locomotion, cognition, impulse control, attention, sleep, regulation of food intake
D4	Medulla, amgdala, midbrain and frontal cortex;	Cognition, impulse control, attention, sleep, reproductive behavior
D5	Cortex, substantia nigra, hypothalamus	Cognition, attention, decision making, motor learning, renin secretion

Serotonin

Serotonin is a neurotransmitter known for stabilizing mood, regulating emotions, sleep, appetite, and digestion. The serotonin transporter regulates serotonin levels; it terminates the effects of serotonin by removing it from the synaptic cleft and reusing it in the presynaptic terminal

GABA

Gamma aminobutyric acid (GABA) is an inhibitory neurotransmitter that blocks impulses between nerve cells in the brain^[4] and decreases activity in the nervous system. Low levels of GABA may be linked to anxiety, epilepsy, or chronic pain.

The effect of drugs on brain chemistry

In this section, we’ll look at the specific effects of drugs on dopamine, serotonin, and GABA which translate into larger experiences.

Cocaine’s effect on brain chemistry

Cocaine can be snorted, smoked, or injected into the body; it rapidly enters the bloodstream and penetrates the brain. It achieves its main psychological effect (aka the high) by creating a build-up of Dopamine by attaching itself to the dopamine transporter and blocking the normal recycling process. This results in a build-up of Dopamine in the synapse, which contributes to the drug’s pleasurable effects.

Cocaine exhibits a high affinity for the serotonin transporter^[5] and increases serotonin reuptake, contributing to mood changes. 

Dopamine may be responsible for the locomotor activating and euphoric effects of cocaine (upper), while serotonin may be involved in the deterioration of mood during cocaine withdrawal (downer).

Alcohol’s effect on brain chemistry

Like a drug, alcohol affects the central nervous system (CNS) and various neurological pathways^[6], causing significant brain changes. 

Ethanol (a form of alcohol consumed in beverages) is classified as a depressant; at a lower concentration, it lowers inhibitions and allows individuals to relax and improve mood. However, it also can affect the hippocampus (responsible for memory regulation) and compromises memory formation. Higher concentrations of alcohol in the blood may also temporarily impair coordination and judgment.

Alcohol increases GABA activity in the brain in two ways: 

1. it can alter the presynaptic neuron (where GABA is released) and increases the release, or
2. it can alter the GABA receptor activity in the postsynaptic neuron (where GABA is received). 

The central nucleus of the amygdala^[7] (responsible for emotions and emotional behavior) is especially sensitive to the initial effects of alcohol withdrawal on GABA levels. It may play an important role in treating alcohol use disorders.

Alcohol is associated with various neurotransmitter systems in the brain’s reward and stress circuits that compound alcohol’s effects. Not only consumption but also the anticipation of accessing of alcohol produces Dopamine. Alcohol withdrawal decreases dopamine function, contributing to withdrawal symptoms and possible relapse.

Nicotine’s effect on brain chemistry

Tobacco smoking results in the release of a rush of neurotransmitters, especially serotonin. It may lead to adaptations in the serotonin transporter, responsible for removing serotonin in the synapse and regulating serotonin levels. One study by Staley et al.^[8] (2001) has examined possible differences in serotonin transporter availability between smokers and nonsmokers. It provided some evidence that smoking may regulate the serotonin transporter in men, but additional studies are needed to confirm these findings. 

The D1 receptor is vital in tobacco smoking^[9] due to its involvement in the mesolimbic reward pathway and because it has been implicated in cognition. The cognitive impairments and deficits that some smokers report during withdrawal make this an important area of research. However, not many studies have evaluated differences in D1 receptor availability between smokers and nonsmokers. Tobacco smokers had significantly lower D1 receptor availability compared to nonsmokers.

These findings are important because the serotonin system is responsible for mood regulation and a poor mood during tobacco smoking withdrawal. It is a primary reason many tobacco smokers cannot successfully quit smoking.

Opiate’s effect on brain chemistry

When heroin, oxycodone, or any other opiate^[10] travels through the bloodstream to the brain, the chemicals attach to opioid receptors. When these chemicals interact with the receptor, the same biochemical brain process of reward gets triggered as the feelings of pleasure that arise from activities like eating and sex.

Opioids are prescribed for pain relief, but when they activate such reward processes in the absence of substantial pain, they may motivate repeated use of the opioid, just for pleasure.

Opioids activate the mesolimbic (midbrain) reward system. It generates signals in a brain region (ventral tegmental area) that results in the release of Dopamine in another region called the nucleus accumbens. The release of Dopamine into the nucleus accumbens causes feelings of pleasure. Other brain areas create a lasting memory that associates these pleasurable feelings with the environment or circumstances they occur in; these memories often lead to cravings of the drug when the person encounters a similar environment/circumstance. This craving may be so intense that it pushes the person to seek more of these drugs despite obstacles.

People take opioids repeatedly in the early stages of abuse because opioids stimulate the brain’s reward system. However, in the later stages, the obsession with using opioids extends beyond a simple drive for pleasure. This increased obsession is related to tolerance and dependence.

Case: Neil is prescribed a strong pain-killer (oxycodone) for his severe back pain. It relieves the pain, and with some physiotherapy, the pain is gone. Neil continues to take these prescribed medications because even if there is no pain, it makes him feel good. He soon craves for the “good feeling” and finds that the prescription pill is the easiest and most effective way of achieving that feeling. The repeated use of the drug increases his tolerance for it as it takes him thrice the original amount to achieve that pleasurable feeling, and creates a dependence as he cannot get through the day without them.

Primary Reference:

Cosgrove, K. P. (2009). Imaging Receptor Changes in Human Drug Abusers. Behavioral Neuroscience of Drug Addiction Current Topics in Behavioral Neurosciences, 199-217. doi:10.1007/7854_2009_24

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