Which Drugs Kill Brain Cells?

Impact of Drugs on Brain Cells

The impact of drugs on brain cells is a topic of critical importance in understanding how substance misuse can lead to serious health consequences. The brain is made up of numerous cells, known as neurons, which communicate with each other through neurotransmitters. Drugs can interfere with this complex system, leading to detrimental effects on an individual's brain health and overall well-being.

Drugs Mimicking Neurotransmitters

Substances like marijuana and heroin can activate neurons by imitating the chemical structure of natural neurotransmitters in the body. This mimicry can lead to abnormal messages being transmitted through the brain's network, disrupting normal neuronal communication. This disruption can alter important brain areas necessary for life-sustaining functions, affecting basic functions essential to life, like heart rate, breathing, and sleeping.

Disruption of Neuronal Communication

Other drugs, such as amphetamine or cocaine, can cause neurons to release abnormally large amounts of natural neurotransmitters. Furthermore, these drugs can prevent the normal recycling of these brain chemicals by interfering with transporters, leading to a disruption in the normal communication between neurons. Over time, continuous use of these substances can cause changes in the brain that lead to addiction — a compulsive drug use despite harmful consequences.

In understanding the question of 'which drugs kill brain cells?', it is crucial to comprehend how these substances interact with the brain's intricate network of neurons. These interactions showcase how drugs can interfere with the brain's normal functioning, leading to potential damage and long-term health problems.

Neural Effects of Specific Drugs

Understanding the neural effects of specific drugs can help underscore the gravity of their potential for causing brain cell damage. This section will focus on the effects of opioids on brain functions, the relationship between dopamine surges and addiction, and how drugs can diminish the ability to derive pleasure naturally.

Opioids and Brain Functions

Opioids, a category of drugs that includes powerful prescription painkillers and illicit substances like heroin, have a profound impact on brain functions. They work by attaching to opioid receptors in the brain, blocking the perception of pain. However, their misuse can lead to significant health risks. An opioid overdose can trigger severe respiratory depression, potentially leading to hypoxia-related brain injury, which may result in long-term consequences. Individuals who abuse opioids are particularly at risk of overdose, especially when using potent synthetic opioids like fentanyl.

Dopamine Surges and Addiction

Many drugs, including amphetamines and cocaine, can cause neurons to release abnormally large amounts of natural neurotransmitters, disrupting normal communication between neurons in the brain. Furthermore, these drugs can cause much larger surges of dopamine, reinforcing the connection between drug consumption, pleasure, and cues associated with drug use. This can lead to craving and addiction, even years after abstinence [1].

Diminished Pleasure from Drugs

The misuse of drugs can have a significant impact on the brain's reward circuit. Over time, drug misuse can reduce the brain's production of neurotransmitters or the number of receptors that receive signals. This can diminish the ability to experience pleasure from natural rewards and lead to an increase in drug consumption to attain a familiar high. This cycle can perpetuate drug use and make cessation more difficult, leading to long-term damage to the brain's ability to derive pleasure naturally.

Understanding these neural effects is crucial to comprehending the full scope of how drugs can damage brain cells. The detrimental changes caused by these substances underline the importance of prevention and effective substance abuse treatment.

Drug Misuse and Neurotransmitters

Substance misuse has a profound impact on the brain's neurotransmitters, leading to changes that may contribute to addiction and other adverse effects. Understanding these changes is vital when discussing which drugs kill brain cells and can influence brain health.

Reduced Neurotransmitter Production

Certain drugs, such as marijuana and heroin, mimic the structure of natural neurotransmitters in the body, activating neurons and leading to abnormal messages being sent through the brain's network [1]. Other drugs like amphetamine or cocaine cause neurons to release abnormally large amounts of these neurotransmitters, disrupting normal communication between neurons.

As a response to the influx of external substances, the brain may adjust by producing fewer neurotransmitters in the reward circuit, or by reducing the number of receptors that can receive signals. This results in the person's reduced ability to experience pleasure from naturally rewarding activities, an effect known as anhedonia.

Decreased Receptor Sensitivity

Alongside reduced neurotransmitter production, chronic drug use can also lead to decreased receptor sensitivity. This means that the receptors become less responsive to neurotransmitters, which can further impair normal brain function and contribute to feelings of flatness, lack of motivation, lifelessness, or depression [1]. As a result, the individual may become unable to enjoy things that were previously pleasurable, leading to a vicious cycle of increased drug use.

Tolerance and Increased Consumption

The brain's adjustments to drug misuse aren't limited to changes in neurotransmitter production and receptor sensitivity. When exposed to drugs consistently, the brain develops tolerance. This means that the person requires higher doses of the drug to achieve the same effect. Over time, this can lead to increased consumption, which further compounds the negative effects on brain health.

Drugs can also cause much larger surges of dopamine, reinforcing the connection between drug consumption, pleasure, and cues associated with drug use. This can lead to cravings and addiction even after years of abstinence.

In summary, drug misuse can lead to significant changes in the brain's neurotransmitter production and receptor sensitivity, potentially causing long-term damage. By understanding these effects, individuals can make informed decisions about substance use and its potential impact on their brain health.

Drugs and Brain Cell Damage

Many drugs have potential to cause harm to brain cells, or neurons. Some of these are therapeutic drugs, used to treat various health conditions, but their adverse effects can result in neuronal damage. In this section, we will explore two such examples: CAR T Cell Therapy and antibiotics.

Neurotoxicity of CAR T Cell Therapy

CAR T cell therapy is a promising medical treatment used to fight various forms of cancer. However, a major concern with this therapy, especially when delivered to the brain, is neurotoxicity. Neurotoxicity can disrupt or even kill neurons, leading to potential neurological complications.

In a clinical trial conducted by Penn Medicine, all six patients treated with CAR T cell therapy exhibited substantial but manageable neurotoxicity. This emphasizes the need for careful monitoring and management of side effects when using CAR T cell therapy, especially in treatments involving the brain.

Antibiotic-Induced Neurological Effects

Antibiotics are common drugs used to fight bacterial infections. However, they can also lead to neurotoxic side effects. These effects can present in various ways and are particularly prevalent in patients with pre-existing central nervous system disease, renal insufficiency, and advanced age. Treatment for these side effects often involves discontinuing the offending antibiotic, using antiepileptic drugs for seizures, and hemodialysis in certain cases [3].

Different types of antibiotics have been associated with specific neurotoxic effects. These include:

• Aminoglycosides: Known to cause ototoxicity, peripheral neuropathy, encephalopathy, and neuromuscular blockade. In the case of gentamicin, peripheral neuropathy and encephalopathy have been reported.
• Cephalosporins: Associated with neurotoxicity ranging from encephalopathy to non-convulsive status epilepticus. This is particularly true in the setting of renal impairment [5].
• Penicillins: Known to cause a wide spectrum of neurotoxic manifestations including encephalopathy, behavioral changes, myoclonus, seizures, as well as non-convulsive status epilepticus (NCSE). Ampicillin has been associated with neurotoxicity in very low birth weight neonates.

In conclusion, while certain medical treatments and antibiotics can be beneficial, they can also potentially harm brain cells. It is essential to be aware of the possible side effects, especially for individuals at higher risk, and to take necessary precautions to minimize potential damage to brain cells.

Specific Drugs and Brain Health

Understanding the effects of specific substances on brain health is vital when discussing drugs that may result in brain cell damage. In this section, we will focus on the effects of alcohol on brain development, and how certain pediatric medicines can lead to neuroapoptosis, or programmed cell death in the brain.

Alcohol Effects on Brain Development

Alcohol is widely recognized as a substance that can have detrimental impacts on brain health. Specifically, exposure to alcohol during early embryogenesis, equivalent to the 4th week of gestation in humans, can cause excessive death of cell populations essential for normal development of the face and brain. This cell death can lead to craniofacial malformations and structural brain anomalies, as seen in Fetal Alcohol Spectrum Disorder (FASD). Thus, alcohol is a key substance to consider when discussing which drugs kill brain cells.

Pediatric Medicine and Neuroapoptosis

In the realm of pediatric and obstetric medicine, many drugs, including general anesthetics (GAs) and anti-epileptics (AEDs), mimic the effects of alcohol in triggering widespread apoptotic death of neurons and oligodendroglia (OLs) in the third trimester-equivalent animal brain. This can result in neurodevelopmental disability syndromes similar to FASD.

These drugs, when administered during a period equivalent to the human third trimester of gestation, cause apoptotic death of neurons and OLs in the developing brain. This results in brain changes, regional reductions in brain mass, and long-term neurobehavioral disturbances [7].

A growing body of evidence suggests that several classes of drugs frequently used in pediatric and obstetric medicine, including GAs and AEDs, and substances abused by pregnant women, including alcohol and barbiturates, trigger neuroapoptosis throughout the developing brain of various animal species, including non-human primates.

Exposure of the developing human brain to GAs in early infancy, or to alcohol or AEDs in late gestation, can cause FASD-like neurodevelopmental disability syndromes. This is realized by triggering apoptotic death and deletion of neurons and OLs from the developing brain.

Understanding the role of these specific drugs in brain health, particularly in relation to brain cell death, underlines the importance of cautious and informed use of these substances. The potential for significant and long-lasting damage to brain cells highlights the need for ongoing research in this area.

Innovative Drug Therapies

Even though certain substances can be harmful to brain cells, it's important to highlight that not all drugs are detrimental. In fact, some drugs, especially those developed for medical purposes, can be beneficial for brain health. These innovative therapies are designed to target and treat specific conditions, such as brain tumors. Let's explore two of these promising therapies: a customized drug for glioblastoma and a dual-target cell therapy for brain tumors.

Customized Drug for Glioblastoma

Glioblastoma (GBM) is the most common and aggressive type of cancerous brain tumor in adults. Despite decades of research, no known cure exists for this condition, leading to a median survival rate of less than one year for recurrent GBM.

However, researchers have recently developed a new type of drug, similar in structure to TMZ, designed to selectively kill glioblastoma cells that lack MGMT while sparing normal cells. This drug causes a type of DNA damage that can be quickly repaired by MGMT in normal cells but leads to cell death in cancer cells that lack MGMT.

The experimental compound KL-50, derived from this new drug, has shown promising results in early studies. KL-50 selectively killed human glioblastoma cells that lacked MGMT, regardless of the functionality of the mismatch repair pathway. Moreover, KL-50 was not toxic to normal human cells. Further studies on mice indicated that KL-50 effectively suppressed tumor growth without displaying any toxicity to normal cells, making it a potential contender for clinical trials in humans.

Dual-Target Cell Therapy for Brain Tumors

Another promising therapy involves the use of CAR T cell therapy, a type of treatment that relies on engineered immune cells to fight tumors. However, a major concern with this therapy, particularly when delivered to the brain, is neurotoxicity, which can disrupt or kill brain cells.

To address this challenge, researchers from the Perelman School of Medicine at the University of Pennsylvania and Penn Medicine's Abramson Cancer Center have conducted a Phase I clinical trial that administers CAR T cell therapy with two targets (epidermal growth factor receptor and interleukin-13 receptor alpha 2) to patients with recurrent glioblastoma. This dual-target approach is designed to bypass the tumor's defenses and effectively kill it.

In this trial, MRI scans conducted 24 to 48 hours after the administration of the dual-target CAR T cells revealed reduced tumor sizes in all six patients. These reductions have been sustained for several months in a subset of patients, indicating a positive outcome for the treatment.

These innovative therapies demonstrate the potential of drugs to be beneficial for brain health, particularly in the context of treating brain tumors. While much research is still needed, these early results provide hope for future advancements in the field.

References

[1]: https://nida.nih.gov/publications/drugs-brains-behavior-science-addiction/drugs-brain

‍[2]: https://lagunatreatment.com/co-occurring-disorder/prolonged-abuse/

‍[3]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175508/#Sec6title

‍[4]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175508/#Sec7title

‍[5]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175508/#Sec8title

‍[6]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175508/#Sec9title

‍[7]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938204/

‍[9]: https://www.nih.gov/news-events/nih-research-matters/customized-drug-kill-brain-cancer-cells