Mechanism of Drug Addiction in the Brain
Addiction is a neurological disorder that affects the reward system in the brain. In a healthy person, the reward system reinforces important behaviors that are essential for survival, such as eating, drinking, sex, and social interaction. For example, the reward system ensures that you reach for food when you are hungry because you know that after eating, you will feel good. In other words, it makes the activity of eating pleasurable and memorable, so you would want to do it again and again whenever you feel hungry. Drugs of abuse hijack this system, turning the person’s natural needs into drug needs. The brain consists of billions of neurons, or nerve cells, which communicate via chemical messages, or neurotransmitters. When a neuron is sufficiently stimulated, an electrical impulse called an action potential is generated and travels down the axon to the nerve terminal. Here, it triggers the release of a neurotransmitter into the synaptic cleft – a space between neurons. The neurotransmitter then binds to a receptor on a neighboring neuron, generating a signal in it, thereby transmitting the information to that neuron. The major reward pathways involve transmission of the neurotransmitter dopamine from the ventral tegmental area – the VTA – of the midbrain to the limbic system and the frontal cortex. Engaging in enjoyable activities generates action potentials in dopamine-producing neurons of the VTA. This causes dopamine release from the neurons into the synaptic space. Dopamine then binds to and stimulates dopamine receptors on the receiving neuron. This stimulation by dopamine is believed to produce pleasurable feelings or rewarding effects. Dopamine molecules are then removed from the synaptic space and transported back into the transmitting neuron by a special protein called dopamine-transporter.
Most drugs of abuse increase the level of dopamine in the reward pathway. Some drugs, such as alcohol, heroin, and nicotine, indirectly excite the dopamine-producing neurons in the VTA so that they generate more action potentials. Cocaine acts at the nerve terminal. It binds to dopamine-transporter and blocks the reuptake of dopamine. Methamphetamine – a psychostimulant – acts similarly to cocaine in blocking dopamine removal. In addition, it can enter the neuron into the dopamine-containing vesicles where it triggers dopamine release even in the absence of action potentials.
Different drugs act in different ways, but the common outcome is that dopamine builds up in the synapse to a much greater amount than normal. This causes a continuous stimulation, maybe over-stimulation, of receiving neurons and is responsible for the prolonged and intense euphoria experienced by drug users. Repeated exposure to dopamine surges caused by drugs eventually de-sensitizes the reward system. The system is no longer responsive to everyday stimuli; the only thing that is rewarding is the drug. That is how drugs change a person’s life priorities. After some time, even the drug loses its ability to reward, and higher doses are required to achieve the rewarding effect. This ultimately leads to drug overdose.
How drug use affects the brain
Alcohol and benzodiazepines relax the brain’s signals and slow down the body. Opioids help relieve pain, but they also slow breathing to dangerous levels. Cocaine and methamphetamines can increase heart rate and blood pressure, putting dangerous amounts of stress on the body. Ecstasy stimulates the brain and alters memory and perception of reality. Marijuana can affect memory and learning. LSD causes people to disconnect from reality (often called a trip). Long-term use of any of these drugs can damage the brain, leading to addiction and withdrawal symptoms.
Some signs that drugs are affecting your central nervous system include:
Memory problems, difficulty learning, coordination problems, and mood changes. Medically supervised addiction treatment can not only help you stop using drugs, but it can also reduce the risk of damage to your brain and nervous system. Treatment programs can help you start a drug-free life.
How Medications Get Absorbed By Your Body
Medication absorption is the movement of a drug from its site of administration into the blood. Oral drugs enter the stomach where they either dissolve and pass through the cell membranes of epithelial cells lining the stomach or travel undissolved through the stomach to the small intestine, which is the most common site of absorption. Here, drugs dissolve and pass through the intestinal wall. Oral drugs then travel through the portal venous system to the liver, where they undergo the first pass effect. During this process, the liver metabolizes some of the drug, either inactivating it or excreting it into bile for elimination from the body. The remaining amount of active drug leaves the liver and reaches general circulation and target organs. If a drug is administered via intravenous injection, it passes directly into the bloodstream, thus bypassing absorption in the GI tract. If administered through intramuscular or subcutaneous injection, the drug enters either muscle or subcutaneous tissue, where it passes through gaps between cells into capillary walls and then into general circulation or target organs, also bypassing absorption in the GI tract. Bioavailability is the net amount of a dose of a drug that is actually absorbed into the bloodstream. The bioavailability of oral drugs is less than 100% because of the first pass effect of the liver. In contrast, the bioavailability of IV drugs is 100% because they are not exposed to the first pass effect of the liver. Different drug formulations alter bioavailability, because they are not absorbed at the same rate or to the same extent. For example, tablets dissolve at varying rates. Enteric coated drugs dissolve in the small intestine, not the stomach. Because gastric emptying time differs between individuals, absorption times also vary. Sustained release formulas contain tiny spheres that dissolve at different rates, resulting in a steady drug release throughout the day, but also resulting in variable absorption. Some factors affecting drug absorption are the rate of dissolution. Drugs that dissolve faster are absorbed faster. Surface area, since the lining of the small intestine has more surface area than the lining of the stomach, most drugs are absorbed faster in the small intestine. Blood flow, the greater the concentration gradient between the drug-filled stomach and the rapidly flowing drug-free blood, the faster the absorption. Lipid solubility, highly lipid soluble drugs pass through the phospholipids in the cell membrane more easily than drugs of low lipid solubility. And PH partitioning, absorption is faster when the difference between the PH at the site of administration and the PH of the plasma attracts more drug molecules to ionize in the plasma.
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