Drugs of abuse, such as cocaine, methamphetamine (METH), morphine, heroin, nicotine, and alcohol, have been discovered to promote BBB dysfunction through changing TJ formation and protein expression (Hawkins and Davis, 2005; Abbott et al., 2006). Additional mechanisms that may contribute to BBB disruption include increased production of reactive oxygen species, activation of matrix metalloproteinases, and changes in the activity of transporters involved in drug clearance from the brain.
The ability of drugs to penetrate the BBB is a key factor in determining their potential for causing neurological damage. The brain capillary wall serves as a barrier between the bloodstream and the cerebral spinal fluid (CSF) that surrounds it. This barrier prevents large molecules from entering the brain while allowing small nutrients and other substances into the brain. However, this barrier can be breached by certain drugs or chemicals which allows them to enter the brain.
Some drugs known to breach the BBB include: nicotine, caffeine, amphetamines including METH, barbiturates, phencyclidine (PCP), and ketamine. These compounds are able to do so by interacting with receptors located on the surface of endothelial cells that make up the BBB. This interaction causes them to become more permeable which allows other substances to pass through them which would not normally do so.
The BBB's General Properties Large molecules cannot readily flow across the BBB. Low lipid (fat) soluble molecules are not absorbed by the brain. However, lipid-soluble compounds, such as barbituate medicines, enter the brain quickly. Molecules with a strong electrical charge are slowed down. This is why neuroleptics (medications used to treat schizophrenia), which are large, negatively charged molecules, can reach the brain quickly.
How does the body get rid of chemical toxins? Through the liver and kidneys. The lungs also play a role in removing chemicals from the body through exhalation. But they are not able to expel all substances including drugs taken by mouth or injected into the body. The brain and spinal cord are protected from these toxic substances by the BBB. Even though the brain itself has no direct connection to the lymph system, many organs produce cells called lymphocytes that help fight off infections. These immune cells use certain chemicals to find their way to specific tissues where they attack invaders such as bacteria or viruses.
What happens if the BBB is broken? That would allow any type of molecule to cross into the brain. Such a breach could happen with an autoimmune disease like multiple sclerosis or gliadel wafers in someone who has undergone chemotherapy. Other ways this can happen is with trauma to the head or using very large doses of antibiotics.
The type of medication utilized determines the effect on the brain. According to the National Institute on Drug Abuse, marijuana, heroin, and opiate-like compounds can function as neurotransmitters, which neurons send to one another to conduct impulses and messages. These substances are called illicit drugs because they are banned by most countries for medical and recreational use.
When an individual uses a drug over a period of time, their body becomes tolerant to it. This means that they need to use the substance at higher doses to receive the same effect. Eventually, even these high doses may not be enough to produce a desired response. At this point, the person is said to be using the drug habitually or regularly.
Drug addiction affects the brain's ability to function properly. It changes the structure of certain areas of the brain that control emotions, motivation, memory, and cognition. These changes lead to behaviors associated with addiction. For example, when a person uses heroin once or twice a week, it can change the structure of parts of the brain that control movement, coordination, and judgment. However many people who use heroin regularly develop problems with anxiety, depression, or paranoia. This indicates that the drug has affected the brain's capacity to regulate emotion.
After years of using drugs, some individuals experience irreversible damage to the brain tissue that results in cognitive deficits.
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The blood-brain barrier (BBB) blocks most medications from entering the brain. Certain small-molecule medicines with a molecular weight of 400 Da and 8 hydrogen bonds may traverse the BBB via lipid-mediated free diffusion. Large proteins, such as exogenous antibodies or fragments thereof, or endogenous proteins greater than 60 kDa in size, cannot cross the intact BBB by simple diffusion. They must use transport systems located on capillary endothelial cells to enter the brain.
Drugs that can cross the blood-brain barrier include: anticonvulsants, antipsychotics, antidepressants, anxiolytics, sedatives, and pain relievers. Drugs that do not cross the blood-brain barrier include: beta blockers, calcium channel blockers, angiotensins, and antihypertensives.
In general, drugs that can pass through the blood-brain barrier are more likely to be effective against neurodegenerative diseases like Alzheimer's disease or Parkinson's disease. These diseases affect the brain and mind and often lead to severe cognitive impairment or dementia. Patients with these disorders usually require many drugs to control their symptoms. Each drug used alone is rarely enough to cure the disease, but combinations of therapies often work better.
There are two main classes of drugs that can pass through the blood-brain barrier: amino acids and peptides and small molecules.
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