The Use of Psychedelics as Treatment for Addiction

Neurophysiology of Addiction

The reasons why one person will become an addict while another person will not are still widely unknown. Genetic factors have an influence on whether or not someone will develop an addiction. Most of the genes that increase the likelihood of addiction have not been identified; researchers hypothesize there are possibly hundreds of genes that affect this. Environmental factors are just as important as genetic in determining whether or not someone will develop an addiction. Exposure to the drug of abuse, psychological distress, childhood abuse, and the use of gateway drugs all affect the chances of a person developing an addiction. 

A build-up of ΔFosB is demonstrated in the brains of virtually all persons suffering from addiction. ΔFosB is an unusually stable product of the FosB gene. After repeating drug exposure, ΔFosB becomes the most prevalent protein of the FosB family. ΔFosB suppresses dynorphin which contributes to the increase of the rewarding effects of drugs.

 

Psychedelic Therapy for Subjects with Addiction

Psychedelic drugs were widely used in the 1960s because of the euphoric experience users reported. Clinic research with psychedelics was put on hold after Presiden Nixon declared a war on drugs. Since then, a fear, aversion, and stigma has surrounded the use of psychedelics. Although these drugs are some of the safest drugs when used in their classical form, more research must be conducted to understand their benefits to humanity. The following video provides a short history of psychedelics, current therapeutic treatments, and future directions for research: This Will Change Your Mind About Psychedelic Drugs.

 

What is a “microdose”?

Microdosing is the practice of repeatedly taking small doses of a drug not to get high, but maintain better homeostasis. The typical size dose depends on a variety of factors: amount of food consumed, body weight, and type of drug. The general rule for a microdose is 5-10% of a normal dose. A microdose is typically taken twice a week during a time of the day outside of work/school hours. The benefits of microdosing are most prevalent when not mixing other drugs or alcohol with it. The user should be in a comfortable setting when taking a microdose. Figure 1 shows an overview of common benefits and drawback of microdosing psychedelics. 

How and why people 'microdose' tiny hits of psychedelic drugs | CBC News

Figure 1: This image depicts various symptoms experienced by those utilizing the practice of microdosing. There are both benefits and drawbacks that must be considered before taking a substance of any type.

Experimental Evidence of the Benefits of Psychedelics on Addiction

In 2014, researchers conducted an experiment to determine if psychedelics can help those addicted to tobacco with quitting smoking. The participants were all aware they were receiving the drug (psilocybin) and not a placebo.  The first round of psilocybin was a “typical” dose, not a microdose. After receiving the drug, the participant laid on a couch wearing sunglasses and listening to music. Researchers were present during the entirety of the patients trip, but did not talk to them or guide them along their spiritual experience. This first round of drug was administered on the participant’s target quit date for smoking. A microdose was then administered two weeks later. 

During the following year, participants had multiple check ins with the researchers to track smoking habits. 80% of participants abstained from cigarettes for at least one week, 67% were still clean one year later, and 60% had not smoked for over 16 months. Researchers are not sure of the exact neurphysiological mechanisms by which psychedelics work, but they hypothesize that the feeling of mystical significance participants experience aids with success in quitting. 

Another experiment was conducted on ten voluntary participants diagnosed with alcohol dependence. They received orally administered psyilcybin in two supervised sessions with the researchers. Participants did not abstain from alcohol use during the first four weeks of experimentation (they had not yet received any psilocybin). After receiving psyilocybin, abstinence from alcohol greatly increased when statistically analyzed (p < 0.05).  These effects were long lastly without the need to readminister psilocybin. Participants reported decreases in their craving levels and increase in their self-confidence to maintain abstinence. Abstience was maintained for 90% of participants six months after psylocibin administration.

 

Alcohol Addiction & Sleep

Alcohol is a depressant to the Central Nervous System that causes the brain to slow down. However, that doesn’t mean that it helps your brain get a good night’s rest. It is a common perception that alcohol will help you fall asleep and keep you asleep due to its sedative effects that can help you relax and cause drowsiness. The excuse of “better sleep” is one reason alcohol is such a common addiction. (1)

Normal Stages of Sleep:

  1. NREM:
    • the transition between wakefulness and sleep
    • Body shuts down
    • Heartbeat, breathing, and eye movement will slow down
    • Muscles relax
    • Brain activity decreases
    • “light sleep stage”
  2. NREM:
    • Heartbeat and breathing continues to slow down into deeper sleep
    • Body temperature decreases
    • Eyes will become still
    • Longest sleep stage
  3. NREM:
    • Heartbeat, breathing rates, and brain activity reach the lowest levels
    • Eye movements cease and the muscles are relaxed
    • Slow-wave sleep
  4. REM:
    • After 90 minutes of falling asleep
    • Active eye movements
    • Breathing rate and heartbeat are faster
    • Dreaming occurs
    • Memory consolidation

(2)

Alcohol reduces the duration of the REM stage and causes sleep disruptions. REM sleep is important as it maintains mental and brain health, the most restorative stage, processing of the day’s events, and the cleaning of neuro-toxins. This is helpful to reduce the chances of developing Alzheimer’s and Parkinson’s. Once the individual has consumed the alcohol it is absorbed into the bloodstream from the stomach and small intestine. The enzyme in the liver will then metabolize the alcohol which causes an increase in waking up, trips to the bathroom, and poor quality of sleep. The increase of sleep disruptions will result in a feeling of tiredness the next day. In order to fall asleep, the individual may fall into a vicious cycle of drinking to get “a good night’s sleep”, fall asleep faster, building a tolerance, soon developing an addiction, and destroying the individual’s circadian rhythm. It is suggested to not drink 4 hours before bed in order to avoid sleep disturbances caused by metabolizing. (3) (4)

A Deep Dive Into Brainwaves: Brainwave Frequencies Explained (5)

An increase of alpha and delta brain waves is found during sleep after consuming alcohol. The increased activity of these two waves is correlated to the feeling of fatigue, depression, and cause of sleep disorders. Delta activity helps with memory processing and consolidation from the day’s events. Delta waves are the slowest waves and are most commonly found in babies, children, brain injuries, individuals with learning disabilities, and severe ADHD (6),  Normal alpha activity occurs during rest not sleep. They help with creativity, lower feelings of anxiety and depression, increases pain tolerance, and boosts stress resilience. (7)

Below is a diagram showing the difference of the Theta and Delta brain waves in the frontal and parietal lobes of individuals who were exposed and not exposed to alcohol before sleeping. Theta waves are normally seen during meditation, prayer, and sharp focus with the benefits of increased creativity, daydreaming, and storing memories, sensations, and emotions. (8)

 

Delta and theta power during slow wave sleep in the frontal and... | Download Scientific Diagram

(9)

Interestlingy, it is found that the elder population are more prone to have alcohol relate sleep disorder due to higher levels of alcohol found in their blood and brain compared to younger adults when consuming the same amount of alcohol content. (1)

 


Resources:

  1. https://www.webmd.com/sleep-disorders/drug-alcohol-related
  2. https://www.sleepfoundation.org/nutrition/alcohol-and-sleep
  3. https://desertcoverecovery.com/blog/alcohols-impact-on-sleep/
  4. https://clearliferecovery.com/rehab-blog/alcohol-rehab-costa-mesa-california-explores-the-impact-of-alcohol-on-sleep/
  5. https://choosemuse.com/blog/a-deep-dive-into-brainwaves-brainwave-frequencies-explained-2/
  6. https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/brain-waves
  7. https://daveasprey.com/alpha-brain-waves-lower-stress/
  8. https://nhahealth.com/brainwaves-the-language/
  9. https://www.researchgate.net/figure/Delta-and-theta-power-during-slow-wave-sleep-in-the-frontal-and-parietal-cortex-after_fig1_324041698

Addiction and Adolescents

What is addiction?

Addiction is characterized by an uncontrollable urge to engage in behaviors that are pleasure to someone, but can have extremely negative neurological impacts. In this blog, the focus will be on addiction to substance addiction, such as cocaine and opioids. Drug addictions are dangerous because illicit drugs create neurological changes that extend far beyond the high.

Neurological changes in addiction

The main pathway of addiction that leads to repetitive and overwhelming behaviors to seek out drugs is influenced by the mesolimbic dopamine system, responsible for releasing dopamine from the ventral tegmental area (VTA) to the nucleus accumbens and other structures of the brain responsible for creating memories. Memory forming structures include the nucleus accumbens, hippocampus, amygdala, and prefrontal cortex, all of which aid in synaptic plasticity.

Synaptic plasticity is a neuron’s ability to strengthen or weaken the communication between neurons, which allows for the brain to learn and store memories. With drug exposure, the neurons learn and form memories through synaptic plasticity. When there is prolonged drug exposure, positive and negative behavior reinforcements are responsible for how drug-related behaviors begin.

Factors that reinforce behavior:

            CREB

Negative behavior reinforcement is modulated by a transcription factor, CREB. CREB decreases pleasure from taking drugs and contributes to uncomfortable physical and emotional symptoms when the drug level decreases, contributing to tolerance and dependence with every drug exposure in the VTA and nucleus accumbens.

DeltaFosB

Positive behavior reinforcement is modulated by a transcription factor DeltaFosB. DeltaFosB is upregulated with drug exposure in the nucleus accumbens, and helps to form new synapses on dendrites to influence learned behaviors and memories related to drugs. Positive reinforcement from DeltaFosB increases the reward and pleasure sensation from taking drugs, which is seen in most, if not all, addictive drugs.

           BDNF

With opioids and even marijuana, the act of taking these drugs can decrease BDNF produced in dopamine neurons. Reduced BDNF synthesis can decrease the activation of a tyrosine kinase receptor, which then reduces the activation of IRS-2, Akt, and mTor. The downregulation of this causes neurons in the VTA to lose volume. The loss of neuronal volume can increase an addict’s neuronal excitability and decrease dopamine release on the nucleus accumbens, which can increase the symptoms of tolerance and dependence seen with CREB. Stimulants, such as cocaine, increase BDNF signaling in the nucleus accumbens to strengthen the behavior to administer drugs, which is similar to DeltaFosB.

Who is at risk for addiction?

Genetics, environmental factors, and previous drug (nicotine, marijuana, cocaine, meth, etc.) exposure all pose potential risks for developing an addiction. Being surrounded by friends or in an environment with drugs can influence someone’s decision to try various substances. Adolescents who have had drug exposures can be at an increased risk compared to adults.

Youth drug exposure:

In adolescence (13 years-20 years), the brain has an increased capacity to learn and form memories compared to adults. With the increased capacity for synaptic plasticity of adolescents, exposure to gateway drugs or street drugs can create an increased ability to learn and store memories associated with that drug compared to adults. Also, as the brain is still undergoing development, adolescents experience a heightened sense of reward from dopamine compared to adults because DeltaFosB is more readily expressed in adolescents than adults. Also, adolescent brains do not experience as much negative reinforcement as adults do. Then, the prefrontal cortex, controls impulse, does not fully develop until the mid-twenties.

These factors of decreased negative reinforcement, increased positive reinforcement, and an immature prefrontal cortex means that taking drugs is more pleasureful and thinking about the full impact of taking drugs is decreased. On top of the pleasure, the synapses from learning and memory formation from taking the drugs are more extensive than adults due to increased DeltaFosB synthesis, making addiction in adolescence hard to treat. Additionally, some brain structures decrease in size, such as the amygdala and pars opercularis, which also control impulse, as seen in Figure 1.

Brain Structures and Drug Use:

Figure 1: Brain structure changes during adolescent drug use

 

Adolescents who already use gateway drugs have an amplified DeltaFosB accumulation when using other drugs, such as cocaine, to increase the pleasure of the high compared to an adolescent just using a hard drug as cocaine and even compared to adults.

Summation:

Addiction is tough to cope with for the individual, as well as the family and friends of that individual. Addiction treatment is more than just telling someone not taking the drug, but rather a neurological disease that needs more research to be done on effective treatment options. In general, drug education needs to be more extensive on why adolescents should not consume drugs.

Sources:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2274940/
  2. https://europepmc.org/article/med/19547960
  3. https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1491&context=etd
  4. https://www.routledge.com/rsc/downloads/9781138919105_chapter_2.pdf
  5. https://europepmc.org/article/med/19547960
  6. https://www.drugabuse.gov/news-events/nida-notes/2019/04/research-links-adolescent-substance-use-to-adult-brain-volumes
  7. https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1491&context=etd

Addiction is a disease

What is addiction?

Addiction is the compulsive seeking of an addictive substance or act despite horrible consequences. In addiction there is a loss of control, the individual can no longer determine their actions. The addiction I will be focusing on is drug addiction. Drugs have the ability to change the brain in a way that drives uncontrollable behaviors to seek out drugs and continue their consumption.

Figure 1: https://www.drugabuse.gov/drug-topics/trends-statistics/overdose-death-rates

Since 2000, there have been over 700,000 deaths due to drug overdose in the US. 11.7% of Americans aged 12+ have used illegal drugs within the past 30 days. 165 million Americans aged 12+ currently abuse drugs, including alcohol, tobacco, and illegal drugs. Over 70,000 drug overdose deaths occur in the US annually. The number of overdose deaths increases at an annual rate of 4.0%. Figure 1, shows how many overdose deaths have occurred pere year since 1999.

9.5 million adults over the age of 18 have both a substance abuse disorder and a mental illness. There are more frightening statistics like these that could take up the rest of this post, but I think I have made my point. Drugs are scary and they cause disaster. 1

Drugs and your brain

Figure 2: https://youtu.be/f7E0mTJQ2KM

The circuit of the brain that receives the most attention in addiction is called the Mesolimbic Dopamine Pathway (ML-DA). In figure 2, you can see where in the brain this pathway is by the purple area between the two structures. This path is also known as the reward system. The start of the path is in the ventral tegmental area (VTA) a group of neurons located in the midbrain. 65% of these neurons are dopaminergic, meaning they produce the neurotransmitter dopamine. Dopamine is our feel-good neurotransmitter, it doesn’t cause pleasure itself, but it induces other things to produce those feelings. When the VTA is activated by a stimulus it sends dopamine to the nucleus accumbens (NAc).

What kind of stimulus can activate the VTA?

There are three main stimuli that stimulate the VTA: a reward, anticipation of a reward, and a stressor. The type of stimuli will determine the kind of signal VTA neurons send and thus how much dopamine is produced. If the stimulus is a drug of abuse, the signal will send a lot of dopamine to the NAc.

Figure 3: Artstract by Alison Amundson

The NAc is a region in the basal forebrain, and it is best known for its role in reward, cognition, reinforcement, and motivational salience. When this structure is stimulated by the dopamine from the VTA, it encodes a value to the stimulus. Researchers believe that the NAc is involved in stimulating actions to pursue rewards and inhibiting actions not helpful in obtaining a reward. The transitions between the two types of firing patterns form the VTA are thought to change concentrations of DA at the terminal and ultimately help encode the salience of stimuli, promote seeking of reward, and tune reward predication error for cue-associated behaviors.

There are some general assumptions provided for what dopamine does in this system. Dopamine is released in response to positive rewarding stimuli, but also in aversive stimuli & stress AND in the anticipation of a potential reward. This response to DA, is one of the reasons for the affective neuroethological perspective that views the ML-DA system in terms of its ability to activate an instinctual emotional appetitive state (seeking) evolved to induce organisms to search for all varieties of life-supporting stimuli and to avoid harms. This view is that the reward system not only aims to seek out rewards but also to avoid non-rewarding stimuli. Therefore, this could relate to the withdrawal factor of addiction. Symptoms of withdrawal are uncomfortable; thus, the reward system could stimulate the addict to seek out a reward (drugs). The memory of the NAc is that this drug has value, and this mechanism could potentially encode a value for a drug that is the same as food and water (actual life-sustaining substances).

Addiction is not a choice

After reading this information on how drugs change brain chemistry, you should understand that addiction is not a choice. Drugs create a hold on an individual that they cannot shake. Their brain has turned on them to need this drug for survival. Therefore, drug addiction is not easy to overcome. Drug addicts require our empathy for the disease state they are in. It takes tremendous strength to quit drugs of abuse, you can’t just stop taking drugs. Drugs are scary and they cause disaster.

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898681/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125054/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920543/

A foreign perspective on Schizophrenia

I think it’s one thing to be health condition but, it’s another to be able to get the help that you need. I grew up in an area that used to see mental illness as evil spirits, bad karma, family misfortunes. This not only caused stigmatization and discrimination against mental health patients but it also prevented the patients of the disease to be able to get the adequate help that they need.

In other words, Schizophrenic patients are prone to human rights violations in society and even in mental health facilities (WHO,2019).

Mental illnesses that attack the central nervous system such as Schizophrenia are mostly genetic and/or can be triggered by environmental stressors such as drug abuse, domestic abuse, other neurological illness, etc.

Schizophrenia is a psychosis largely characterized by cognitive, emotional, physical distortions. The actual cause of it is not fully known but hypotheses have been made of the possible reason behind the gradual deterioration and based on the symptoms. There are cognitive, positive, and negative symptoms. Positive include delusions, negative include lack of emotional expression, and cognitive symptoms include the inability to make decisions (PsychCentral, 2021).

 

Considering that a large probability of proneness to schizophrenia is linked to genetic and early development, it is important to understand the role of the Wnt signaling pathway in this cascade

The Wnt signaling pathway

It is involved in cell maintenance and renewal. Basically, Wnt ligands bind their receptor complex which causes the recruitment of APC to the membrane, facilitating the dissociation of the destruction complex. This results in decreased phosphorylation of β-catenin. When the destruction complex is dissociated, β-catenin is then able to get into the nucleus and influence the targeted genes.

 

In a study on the “Convergent functional genomics of schizphrenia“, the targeted genes, in this case, researched in different groups included African Americans and European Americans, and were graded and ranked out of 5points as seen in the illustration below

The top genes targeted include DISC 1 (protects synaptic plasticity), and decreased expression of MBP ( involved in protein formation for myelin formation). Both these genes for example allow responsiveness to stimuli and learning which is seen to be hindered in schizophrenic patients.

 

The question at this point is how can we better deal with it, in terms of prevention, treatment and awareness. Given that it can be heredited, to what extent to we start treating it? Do we wait for symptoms to show once the disease has progressed? Can technology and gene therapy be the future for mitigating schizophrenia gene vulnerability? And how can Schizophrenic patients get affordable help regardless of their economic standpoints?

 

These are the big questions to think about in my opinion in order to progress more in the treatment of schizophrenia for long-term.

References:

  1. John M. Grohol, Psy.D. “Schizophrenia Symptoms: Negative, Positive, and More.” Psych Central, Psych Central, 4 Feb. 2021, https://psychcentral.com/schizophrenia/schizophrenia-symptoms?utm_account=&utm_medium=cpc&utm_semcampaign=&utm_adgroup=&utm_match=b&utm_query=&utm_term=&utm_content=540967374863&utm_source=google&marinid=s&gclid=CjwKCAjwhuCKBhADEiwA1HegOXz527pV8bxnc59QXv7zMOppnMTflRYTKeTiTg13jh_FpCC06OhxQRoCS3UQAvD_BwE.
  2. “Schizophrenia.” World Health Organization, World Health Organization, https://www.who.int/news-room/fact-sheets/detail/schizophrenia.
  3. Ayalew, M, et al. “Convergent Functional Genomics of Schizophrenia: From Comprehensive Understanding to Genetic Risk Prediction.” Nature News, Nature Publishing Group, 15 May 2012, https://www.nature.com/articles/mp201237.

How to Humanize Mental Illness

Mental illness is a rising phenomenon in our society, and it is something that as a society we have failed to appropriately address. People with mental illnesses are often shunned or downright discriminated against for something that no one can control. Hopefully this post will shed some light on the concept of mental illness and what can be done to help rather than hinder the efforts to help people with mental illnesses.

 

What is a Mentally Ill Person? And Can They Control It?

Mental illness is often considered an attention seeking tool or lumped in with general psychosis, but neither could be farther from the truth. Mentally ill people have a chemical or genetic dysfunction that is causing either direct damage or indirect changes to the way the brain functions. For example, schizophrenia is based on a pathway called the Wnt pathway, when any one part of that pathway goes wrong the chances of developing schizophrenia skyrocket. Schizophrenia can also be caused by a number of genetic issues, but the moral of the story is that mental illnesses like schizophrenia are caused by major impacts to the brain and are under no control of individuals. More on schizophrenia and Wnt signaling

 

What Are Symptoms of Mental Illnesses?

The most important thing to know about mental illness symptoms is that no two people present their symptoms in the same way. Sometimes the symptoms are not visible to outside view, which further complicates the matter. Using schizophrenia as an example, there are symptoms that are described as both positive and negative. Positive symptoms are symptoms specific to schizophrenia, which is primarily described by hallucinations and delusions that feel completely real to the person. On the other hand, negative symptoms could be cause by a variety of things: these symptoms include lack of emotion, lack of joy, speech issues, and lack of initiative. Figure 1 below visualizes the important distinction between these symptoms. Not only are these symptoms challenging to see and diagnose, they also are very individual based on the type of hallucinations and type of negative symptoms experienced. More on schizophrenia symptoms

Figure 1: The Positive and Negative Symptoms of Schizophrenia: A Common Mental Illness. Taken from above source

 

What Are We Doing, and What Can We Do?

Mental illnesses are challenging to treat due to their direct impact on the brain and the stigma that comes with being mentally ill. There are a fair amount of medicines that focus on management of symptoms, such as anti psychotics and lithium, but in addition to symptoms and varying effectiveness these treatments don’t do much to actually manage schizophrenia in a patient. When the illness becomes too overwhelming or the behaviors become out of control, hospitalization may be necessary, but for the majority of other people impacted by mental illness they live in the same world as neurotypical people. The best way to “treat” schizophrenia and other mental illnesses is to interact with these people with empathy and grace. People may seem weird or even dangerous to you, but it’s entirely possible they just have a different brain chemistry than you. The more society begins to understand and welcome these people, the better off they will be and the better science can begin to understand these people. As the Platinum Rule says; treat others the way they want to be treated

Figure 2: The Platinum Rule. https://cawood.com/blog/platinum-rule/

Back to the Future… Please…

Figure 1; Picture Provided by Me

Alright, before you go any further in this blog post please just know that the information provided might make for an uncomfortable read. Now that you’ve been warned…. let’s begin. We’ve talked for a while now about schizophrenia and the underlying mechanisms that are related with the disease. In our conversations we’ve mentioned the side effects of antipsychotics; weight gain, dry mouth, constipation, hormonal imbalances, muscle twitches, etc. But it is important to look at the past and see where we have come as a scientific community. Treatments for schizophrenia have not always been so mild, if you can even consider the above side effects as being mild. Although I am a huge fan of imagery for learning I will not be including any images of many of the procedures that are listed. Reading about some of these things is distressing enough, seeing them seems unnecessary.

So, we are all probably aware that we require insulin to stay alive. As a reminder insulin acts on a tyrosine kinase receptor. Although we require insulin, more importantly we require regulated levels of insulin. If we receive excessive levels there is a potential that we could go into a coma. Medical professionals in the past thought that these comas had the potential to “jolt” someone out of their current mental illness. So, over the course of several weeks they would directly inject enough insulin to put someone into a coma, then after several hours they would administer glucose to bring their patients out of their induced state. Over the course of treatment, insulin levels would be increased until the staff felt that the treatment had reached its maximum “helpfulness.” What could go wrong when you induce 30-50 comas in the span of a month or two? Well of course the answer is a lot, some of the side effects included obesity, brain damage, and death, none of which sound overly pleasant to me. Sadly, even with extensive use of this treatment there was never any proof that inducing comas was an effective treatment method, yet the technique was used for quite a long time (JSTOR DAILY).

Wow, such a pleasant start to this blog post, let’s get into a slightly less appalling technique… the use of trephining, leucotomies, and lobotomies. Of course today we look at these techniques and consider them to be rather barbaric, although they did have the potential to erase behaviors attributed to schizophrenia. Trephining we are probably pretty familiar with, the surgery essentially boiled down to drilling a hole into someone’s head in order to “let out the demons!!!” I mean come on, of course that’s what drilling a massive hole into someone’s skull would do for them, there couldn’t possibly be any negative side effects. Below you can see the results of these surgeries, many of which people surprisingly survived (Faria, M., 2013). Sadly though there weren’t any improvements for the most part because demons are not known to actually reside in the skull. If there was improvement it was because the technique happened to damage brain tissue that coincidentally stopped the target behavior. Although it was never stated that these surgeries were done to schizophrenics one can assume that they were likely the victims of these procedures. “Madness” and “demons” are similar to voices and other positive symptoms of schizophrenia, there wasn’t a real definition for the disease until the end of the 19th century.

Figure 2 

Figure 3

Leucotomies and lobotomies are very similar, just with a small difference between the two. Leucotomies focused on destroying the underlying white matter in the brain, while lobotomies were more focused on the prefrontal cortex and destroying the exterior grey matter (Faria, M., 2013). Look below for a visual representation of the separation between grey and white matter within the brain.

Figure 4

Although there is technically a distinction, lobotomies are usually thought of as the accumulation of both procedures. Interestingly enough leucotomies seem to have come before the lobotomy. Both leucotomies and lobotomies were performed initially using direct injections of alcohol into the target region in order to destroy brain matter. However, surgeons preferred to use a modified ice pick later on in the development of the surgery in order to directly damage the target region. It is actually super interesting to note that these doctors did actually have a method to their own madness. They would move their technique either posterior or anterior based on the illness that they were trying to treat. In some ways this does make sense, different regions of the brain are responsible for different behaviors. These surgeries did impact patients with schizophrenia, surgeons often noted that their patients had a much more flat personality, and that they did not have as many schizophrenia related symptoms (Faria, M., 2013). They would also note that after surgery these patients were easier to manage, leading one to ask the question, “were these surgeries out of necessity or because they were convenient for the facility.” These procedures essentially turned people into vegetables and assumed that these states were better than schizophrenia, a bold take. Just because something technically alleviates a problem does not mean that the end result is better.

Ok, now that we have discussed things that really don’t work at all, let’s talk about something that is still used today and quite useful. Electroshock therapy (ECT) is used to induce a seizure, which has been shown to relieve symptoms of mental illness. I don’t know exactly how, perhaps you could blog about it? ECT has serious benefits and is actually known to improve the lives of those that fail to respond to other treatments. The older equipment that was used is shown below.

Figure 5

Sadly however, ECT has a disturbing past. The technique was used to often as a punishment rather than a treatment, staff would administer ECT in order to control difficult patients and to maintain order in the hospital. Additionally, ECT did not use modern techniques in the past that make it safer today Although the following resources were technically available, for some reason those that conducted ECT procedures elected not to use any of them. There was no use of muscle relaxants to alleviate physical damage from the seizure itself, and no anesthesia was used to stop the pain from the actual shock. If that doesn’t sound pleasant enough, ECT was used for all of the wrong reasons in order to “cure” things that weren’t actually mental illnesses. A prime example of this would be the use of ECT to “treat” homosexuality (Sadowsky, J., 2017). 

Okay so it is hard to sit here in my comfy chair and write about the things that were being done to those in the past. However, context is an important part of any intellectual conversation and I think it is important to include some now that we have concluded our conversation. The doctors and medical professionals of the time were in a real pickle, the mental hospitals were overflowing and they needed ways to help the patients who were otherwise never going to leave the systems that were in place to try and help them. Psychiatric medicine is not like it is today, there were so many people who were hospitalized for things that we can treat easily in modern times through the use of over the counter medications. Although it seems barbaric to us now, and frankly it was considered barbaric even in the past, the surgeons were trying to help even though they probably did more harm than good. Remember though that the individuals of the past did not know what we do now, we have the luxury of sitting here knowing as much as we do, only because of their trials and tribulations. The patients of the past suffered so that we can better treat those in society today.

The (unproven, deadly) common cure for … – JSTOR DAILY. (n.d.). Retrieved October 6, 2021, from https://daily.jstor.org/the-unproven-deadly-common-cure-for-schizophrenia/. 

Faria, M. A. (2013, April 5). Violence, mental illness, and the brain – A brief history of psychosurgery: Part 1 – from trephination to lobotomy. Surgical neurology international. Retrieved October 6, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640229/. 

Phutane, V. H., Thirthalli, J., Kesavan, M., Kumar, N. C., & Gangadhar, B. N. (2011, April). Why do we prescribe ECT to schizophrenia patients? Indian journal of psychiatry. Retrieved October 6, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136018/. 

Sadowsky, J. (2017, January 13). Electroconvulsive therapy: A history of controversy, but also of help. Scientific American. Retrieved October 6, 2021, from https://www.scientificamerican.com/article/electroconvulsive-therapy-a-history-of-controversy-but-also-of-help/. 

Treatment of schizophrenia. Treatment of Schizophrenia – an overview | ScienceDirect Topics. (n.d.). Retrieved October 6, 2021, from https://www.sciencedirect.com/topics/medicine-and-dentistry/treatment-of-schizophrenia. 

 

The Drug Paradox

The Power of a Pill

Treating individuals with addiction is not as easy as telling someone to simply “stop taking a drug.” There are many reasons this claim is problematic, but some of which include the fact that drugs, especially drugs of abuse, change the neurochemistry of one’s brain, making the desire and craving for a drug not simply the result of lack of willpower. In fact, the behaviors an individual feels from withdrawal from a drug are directly the result of this change in brain chemistry. The behaviors are biological. Drugs have the power to change the wiring/ circuitry of the brain, and they also alter synaptic plasticity. This can make one wonder, is this change permanent? Can it be undone? Are there treatment options to overcome addiction?

Dual Deficit Model

Specifically, drugs such as cocaine and methamphetamines produce a “rush” or “high” that is scientifically mediated by an increase in extracellular DA levels in mesolimbic brain areas.

We know that chronic use of these abused stimulants will cause a shift in neurochemistry, including changes in circuitry and synaptic plasticity. Research has shown that withdrawal from chronic cocaine and alcohol abuse is likely the result of the lack of DA and 5-HT function. The negative withdrawal states experienced by many users is likely the result of long-term changes in both the structure and function of the brain. Researchers propose a dual deficit model of stimulant addiction in which drug-induced DA and 5-HT dysfunction results in withdrawal symptoms, drug craving, and relapse.

Figure One: Dual Deficit Model

Figure One shows the dual deficit model and how decreased synaptic DA in stimulant withdrawal causes “Parkinson-like symptoms” whereas decreased 5-HT creates depressed moods, OCD-like symptoms, and lack of impulse control.

Hope with PAL-287

The goal is that individuals with deficits in DA and 5-HT functioning may be able to utilize medication that corrects the abnormalities in this functioning. Researchers hoped to identify and characterize a nonamphetamine transporter substrate that would release DA and 5-HT, without affecting NE, however, this was unsuccessful as it was impossible to remove NE and DA releasing properties. However, researchers found a lead on PAL-287, a nonamphetamine monoamine releaser which has mixed DA/5-HT releasing qualities. This is hopeful, as other drugs typically use either DA or 5-HT properties, not a combination of the two. Administration of PAL-287 to rats increased the extracellular DA and 5-HT, with large impacts on 5-HT compared to DA.

The results with PAL-287 show that nonamphetamine substrate at DAT and SERT will release DA and 5-HT from neurons. It will also be minimally reinforcing, and also suppress the ongoing cocaine self-administration. In addition, repeated high-dose administration to rats of PAL-87 fails to affect brain tissue 5-HT levels, unlike others (MDMA) which cause significant 5-HT deficiencies. Moreover, PAL-287 does not support self-administration behavior, which is key finding. And most importantly, chronic administration of the drug diminishes cocaine self-administration in monkeys, providing a promising outlook for it’s impact on humans.

      Overall, PAL-287 has many desirable qualities, including:

  • minimal locomotor activation
  • lack of long-term 5-HT neurotoxicity
  • weak reinforcing effects

Abstract by T. Zetocha

While there is still more research to be done, these findings make the treatment for addiction hopeful.

https://psycnet.apa.org/fulltext/2008-17521-003.pdf?auth_token=c33ed3a8e66ca61048165ad594a6e75060e9ed5c

Understanding Schizophrenia to Gain Empathy

Schizophrenia

Schizophrenia is a chronic disorder affecting how a person thinks, feels, and behaves. Around 1% of the United States population is diagnosed with schizophrenia. Now, 1% may not seem like a lot, however, it is about 3.3 million people. 3.3 million people just like you suffer from delusions, hallucinations, disorganized speech, mood disturbances, disorganized motor behaviors, and

Figure 1: This image represents the age range and gender of patients admitted to the ER for schizophrenia related reasons. Presented by the CDC.

disturbances of volition. At that is just in the U.S.! It is estimated by the World Health Organization that 20 million people worldwide are diagnosed with schizophrenia.

During 2009-2011, an estimated 382,000 ER visits in the US related to schizophrenia. Of those visits 32.7% had to be admitted to the hospital. Schizophrenia diagnoses occupy 20-40% of psychiatric hospital beds. Figure 1, shows the age ranges of these patients and the differences in gender.

Figure 2: https://www.verywellmind.com/what-are-the-symptoms-of-schizophrenia-2953120

Individuals with schizophrenia have a set of positive and negative symptoms. Positive symptoms are distortions of a person’s thinking. Negative symptoms make feeling and expressing emotions for the person a challenge. In figure 2, the distinction between positive and negative symptoms is depicted.

 

It is incredibly important for research on schizophrenia to continue. As of now the cause of schizophrenia is still quite wonky.

Changes in the brain

 

Through brain imaging, researchers have found that schizophrenia in the brain can look like: a reduction of gray and white-matter, temporal lobe volume reductions, anomalies of the superior temporal gyrus, enlargement of the

Figure 3: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181763/

ventricles, and reduced connection between temporal and frontal lobe white matter. In figure 3, you can see the changes in the brain of 34-year-old female patient with schizophrenia. These images clearly show a reduction in white matter and enlargement of the ventricles over the course of several years.

 

 

An emerging view is that schizophrenia is a developmental disease caused by changes in the structure and functioning of important brain systems involved in working memory, declarative memory, language processing, etc. These changes appear to be influenced by genetic and environmental risk factors present during development prenatal, childhood, and adolescence.

Molecular changes in the brain 

There is evidence accumulating on the Wnt signaling pathway and its role in schizophrenia. This pathway may lead to answers on how to best treat symptoms of schizophrenia and possible causes of these symptoms.

Figure 4: http://www.wormbook.org/chapters/www_wntsignaling/wntsignaling.html

Schizophrenics have an overactive dopamine system in their brain. When dopamine binds to its D2 receptors it inhibits the enzyme known as Akt, which decreases inhibitory phosphorylation of GSK3-beta. In a pathway known as Wnt, if GSK3-beta cannot be inhibited it will remain in a “destruction complex”, that is responsible for breaking down beta-catenin. Beta-catenin is the molecule that binds to a set of transcription factors to tell them to start transcribing a certain gene. If the destruction complex destroys beta-catenin, then we cannot express genes that are important for neural development and neural system functioning.  Figure 4, represents the wnt signaling pathway. On the left, there is no Wnt signal attached to the receptor, leading to the degradation of beta-catenin. On the right, there is a Wnt signal on the receptor, so beta-catenin can initiate gene transcription.

This is what we see in schizophrenia. The brain is not reading important genes, so abnormal development and functioning occurs, which can lead to the disease state of schizophrenia.

Substance Abuse Disorder 

47% of patients with schizophrenia have serious problems with drug or alcohol abuse during their lifetime. The following are estimated percentages of drug abuse for people diagnosed with schizophrenia:

  • 60-90% cigarette smoking
  • 21-86% alcohol
  • 17-83% cannabis
  • 15-50% cocaine

The common theory behind why those with schizophrenia have substance abuse disorders is it helps lessen pain, symptoms of the disease, and adverse side effects of medications. A biologically based theory is that schizophrenia and substance use disorders may share a common pathophysiology in overlapping neural circuits, thus may relate to dysfunction of the brain reward circuit in patients.

Final word 

I bring up the prevalence of substance abuse disorder with schizophrenia to push empathy on to you for those with schizophrenia. These patients have chemical and structural changes occurring inside their brain. They have no control over this. Something occured in their development, at what point we don’t know, but something happened that caused this disease. A disease that is so painful, many turn to self-medication with drugs to survive. The stereotype of people with schizophrenia is that they are crazy. But, these people are people. Life for them is not like it is for us, but it is not their fault. So, the best thing for us to do is to show the empathy. We can never understand what it’s like to have a brain like theirs, but we can give kindness, compassion, and empathy.

Resources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800495/

https://pubmed.ncbi.nlm.nih.gov/23379509/

https://www.cdc.gov/nchs/products/databriefs/db215.htm

Learning about Schizophrenia

There are many types of illnesses that a person can have with some of these being mental illnesses. One prominent mental illness the public should learn more about is Schizophrenia. The public should learn more about Schizophrenia because it is a very detrimental disease to not only the person who has it, but to the person’s family as well. 

According to a scientific study on Schizophrenia, schizophrenia is said to be a very common and chronic psychiatric disorder and is one of the leading causes of disabilities in the world [1]. As of right now, there is no known specific cause of Schizophrenia, but the symptoms can show in a period between late adolescence and early adulthood. According to the MayoClinic, symptoms such as delusions, hallucinations, disorganized speech, and abnormal motor behavior can cause problems in a person’s cognitive thinking, behavior, and emotions [2]. This shows that Schizophrenia, if left untreated, can affect a person’s way of life in an extremely detrimental way. 

While the exact cause of Schizophrenia remains unknown, a pathway that is linked to developing Schizophrenia involves the use of a Wnt receptor and GSK3. Wnt signal pathways lead to Dvl-mediated cellular increase causing activation of APC [1]. With this, APC can cause production of GSK-3β, which inhibits production of β-catenin [1]. It is the activity of GSK-3β that potentially causes schizophrenia to develop. These characteristics present can make the Wnt signaling a target of drug treatment. Since there is no cure for Schizophrenia, there are treatments. A common treatment for Schizophrenia is the use of Lithium, which is mainly used for Bipolar Disorder [1]. The way this treatment works is that lithium directly inhibits the GSK3β activity by acting as a competitive inhibitor with magnesium, leading to accumulation of β-catenin [1]. This can lead to a person with schizophrenia having their mood stabilized. The Wnt pathway and Lithium treatment is shown on the figure below. 

Along with factors that treat Schizophrenic patients, there are other factors that increase the risk of developing it. For example, infections with agents of influenza, rubella virus, herpes, and poliovirus have been known to increase the risk of developing schizophrenia [3]. This means that Schizophrenia may be linked to weak immune systems when the person is ill. These symptoms can also cause the person to not function normally like everyone else. For example, people with Schizophrenia may neglect personal hygiene, avoid eye contact, have a lack of motivation, depressed moods, and may appear to be emotionless [2]. Because of this, people with Schizophrenia would most likely need to be cared for and watched over if they have other disabilities. It was also discovered that infections of different viruses have not only affected the mother during pregnancies, but have also been known to increase the risk of the fetus developing schizophrenia in the future [3].

From the studies on Schizophrenia, it is clear that it is a very detrimental disease that can affect the person and those close to them. I believe that having the public be able to understand what this disease is can be very helpful. This is so they can have an understanding of what families can go through when one of their own is diagnosed with Schizophrenia. 

  1. https://pubmed.ncbi.nlm.nih.gov/23379509/ 
  2. https://www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-2035444
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037097/

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