Drug Addiction Mechanisms in the Brain

Brain’s limbic system is the target site of action of cocaine. This area of the brain is involved in pleasure and motivation. Cocaine causes the dopamine build-up in the synapses by creating a feeling of being “high”. Cocaine induces action by binding to the dopamine transporter, which transports excess dopamine back to the presynaptic neuron. The nucleus accumbens (NAc) of the limbic system is the primary target of cocaine action. Cocaine also alters gene expression in the limbic system by altering dopamine transporters or dopamine receptors. Cocaine causes auditory hallucinations, restlessness, paranoia, and psychosis. This chapter reviews the impact of cocaine on the brain. 

As per the Drug Enforcement Administration (DEA) and the Controlled Substances Act (CSA) reports, heroin is a Schedule I drug. Heroin causes addiction to the brain like any other addictive substance. Heroin addiction has both long-term and short-term effects on the body. The brain has natural opioid receptors. Heroin is a synthetic opioid. When taken regularly, the brain stops making its own natural opioids. This affects the pain/reward system and causes withdrawal symptoms in patients. Heroin addiction damages the brain's reward system and breathing. Less breathing causes less oxygen supply to the brain. There are reports that state that dementia-like situation is created in the brain due to heroin abuse. Heroin lipophilicity allows the entry of it into the Blood Brain Barrier. μ-opioid receptors (MOR), causing the addictive effects of the heroin in the brain. Dementia symptoms, memory issues, and mental health changes like depression or anxiety are the symptoms that are caused by heroin abuse. Both individual and environmental factors influence a person's ability to abuse heroinanopioid which provides intense feelings of pleasure. 

3,4-methylenedioxy-methamphetamine (MDMA) is a synthetic drug very similar to hallucinogens and stimulants. This drug is also called ecstasy or molly. It produces feelings of pleasure, warmth, distorted sensory time and perception. MDMA increases the activity of serotonin, dopamine and norepinephrine in the brain. It causes various health effects such as nausea, sweating, chills, muscle cramping, etc. The effect of this drug can be seen in 3 to 5 hours in the body. A spike in body temperature can be seen in MDMA users that can be fatal as it affects the liver, kidney, and heart leading to death. Addiction to MDMA is not yet proven, however, withdrawal symptoms such as fatigue and depression are noted. MDMA is usually taken via the mouth or snorting in the form of tablets or capsules. This drug is also taken or abused along with other drugs such as LSD, alcohol, and marijuana. MDMA is a scheduled drug with no proven medical use. MDMA causes a surge of serotonin, dopamine, and norepinephrine in the brain to regulate mood, learning, memory, stress, anxiety, etc. This chapter discusses the effects of MDMA on the human brain.

LSD is a potent hallucinogen. It was first synthesised in 1938. It is marketed under numerous names. Ergot, a fungus that develops on rye and grains, is used to make LSD. The effect of LSD is mind-altering, pleasurable, and stimulating. Sometimes, exposure to this drug causes so-called unpleasant experiences, such as “bad trips”. It is classified as a Class 1 drug (highly abused) by the Drug Enforcement Agency. Paranoia or psychosis can occur as a negative sequence of taking LSD. Changes in perception, sense of time and space, and mood are reported due to the use of LSD. This medication can be taken orally or through the tongue using tablets, droplets, or blotter paper. LSD is marketed in the streets as blotter paper, thin squares of gelatin, tablet form, liquid sugar cubes, and pure liquid form. Since this is a mindaltering drug, it causes changes in serotonin levels in the brain. LSD affects one's ability to make rational decisions. Speaking with a healthcare professional, talk therapy, and additional medical therapy are options since there is no medication to treat LSD.

Methamphetamine (METH) is a highly addictive stimulant that affects the central nervous system. It is a widely abused psychostimulant. Monoaminergic neurotransmitter terminals are affected by METH intake. METH structure is very similar to amphetamine, a drug used to treat attention-deficit hyperactivity disorder (ADHD). METH is taken in various modes, such as smoking, swallowing, snorting, injecting powder, etc. Dopamine levels, serotonin levels, and norepinephrine levels are increased due to METH uptake, leading to extremely strong euphoric effects. This dopamine surge causes the brain to repeatedly take the drug and is responsible for addiction. As a short-term effect, METH causes increased wakefulness and physical activity, decreased appetite, faster breathing, rapid and/or irregular heartbeat, increased blood pressure, and body temperature. METH overdose causes hyperthermia and convolution, which can lead to death if not treated. METH also causes irreversible brain damage. Amphetamine psychosis, dementia-like symptoms, increased anti-social behaviour, and increased susceptibility to neurodegenerative diseases are the long-term neurological effects of METH use.

Morphine is a Schedule II drug and it is used in pain treatment. Like other opioid drugs, it also has addictive properties. The other street names of Morphine include M, Miss Emma, Monkey, Roxanol, and White Stuff. There are natural alkaloids come from the resin of opium poppy, Papaver somniferum. Morphine is attached to the receptors in the brain and spinal cord to block pain signals. Morphine impacts the level of dopamine and serotonin by acting in the brain's reward system. Breathing and heart rate are also modified due to morphine which has both short-term and long-term effects. Morphine can last up to 4 to 6 hours in blood. It also acts on the dendrites and spines in order to change the plasticity of the neurons. Endogenous and exogenous opiates target the same tissues and cells.

Ketamine is a dissociative anaesthetic drug that functions as a blocker of NMDA receptors. Moreover, it causes a neurostimulatory effect and is also used as a sedative. Ketamine has many names, such as Special K, Green K, Super K, Super Acid, Jet, and Cat Valium. Ketamine is used as a recreational drug in clubs, also known as a “club drug”. As a recreational drug, it causes the patient to experience delirium and an altered state of consciousness. Patients with cardiovascular disabilities can also be given ketamine as a sedative. Ketamine can be taken in various methods, such as orally, rectally, intranasally, IV, IM, or intrathecally. Ketamine abuse can lead to secondary renal damage and upper gastrointestinal symptoms. 

Fentanyl is an opioid usually used in general anaesthesia, due to which it is also called an analgesic drug. These drugs can relieve the pain within the body by blocking the neurotransmitters or chemicals that cause pain in the body. Opioids can work in both the ascending pathways of the brain as well as the descending pathways of the brain for pain modulation. Fentanyl is more potent than morphine and herion. Fentanyl is also given as transdermal patches or lozenges in the treatment of pain management. Fentanyl is also sold illegally and can cause of death too when abused. Because of its strong property to be addicted, fentanyl also is mixed with the heroine. Moreover, fentanyl has its own effects during withdrawal, which causes behaviour changes. Fentanyl can bind to μ-opioid receptors (MORs) to exert its effects. In addition, fentanyl abuse is becoming more common globally. Fentanyl causes the brain to suffocate by decreasing the oxygen supply, causing hypoxia and hyperglycemia as well. Fentanyl abuse can cause serious cognitive issues, leading to severe structural damage manifested as hormonal and neuronal disturbances. By suppressing the two brainstem areas, opioids cause disturbances to breathing. 

Alcohol affects brain activity in various ways. It has both short-term and long-term effects. It causes slurred speech, short-term memory dysfunctions hallucinations, etc. by timing the activity of neuronal cells. Moreover, it causes teratogenic effects in the fetus ifthe mother is consuming alcohol during pregnancy. Alcohol can damage the brain cells, cause a lowering of serotonin levels, and higher GABA levels, cease new brain cells to be formed, and cause damage to the blood vessels and nerve cells in the brain. In addition, alcohol abuse causes WernickeKorsakoff’s syndrome, which is due to the lack of vitamin B1 in drinkers. Also, alcohol abuse causes Wernicke’s encephalopathy which is characterised by muscle problems, being confused, etc. Memory loss and less coordination are the long-term effects of alcohol abuse. All regions of the brain, such as the cerebellum, limbic system, and cerebral cortex, can be affected by alcohol abuse. The cerebellum is responsible for the movement of the body, and alcohol disrupts this balance causing emotional and memory issues. Alcohol consumption on a regular basis leads to reduced brain size or a rapid aging process. Alcohol disorder is listed as one of the most prevalent mental health problems in the world.

Nicotine is present in the tobacco products. Once smoked, nicotine immediately reaches the brain and binds with nicotinic receptors causing damage to the brain cells. The adolescent brain is especially very sensitive to products such as e-cigarettes, nicotine, and tobacco. Chronic nicotine exposure causes permanent brain damage and cognitive decline. Interestingly there are reports on the use of nicotine and its effects on the epigenetic changes in the brain. These kinds of changes may prepare the brain for further abuse of various illegal drugs. As a result of chronic nicotine exposure brain infarcts, white matter hyperintensities, brain atrophy, and dementia are also known to occur. Neurodevelopment in children is potentially harmed due to exposure to nicotine and nicotinic products. This is due to the inflammation, atherosclerosis, and oxidative stress to the neuronal cells. Pregnant mothers and people who are at risk of developing neurodegenerative disease need to be forbidden from using nicotine. Nicotine can be dangerous when taken with alcohol as it can lead to depression and neurocognitive decline. This chapter addresses the effects of nicotine on the adolescent and adult brain.