In 2018, Yale School of Medicine conducted two studies that centers around using nicotine patches for autistic people displaying aggression. The very patches that help grown adults quit smoking to overcome a nicotine addiction to reduce their risk of lung cancer and heart disease.
There are some parents who heard rumors that nicotine could be used to “treat their children’s aggression, even though there is insufficient evidence to support” this claim. The Yale School of medicine is “rewriting nicotine’s unfavorable reputation. This rumor could cause these parents to run to the store and buy their kids nicotine patches to use and experiment on their kids.
“Although [transdermal nicotine] is FDA approved to treat smoking sensation in adults, we ethically can’t conduct a clinical trial on a number of patients without getting approval from Yale’s institutional Review Board.”
Autism Speaks not only awarded Yale Medical School a grant, they partnered with them for these studies.
What is Nicotine?
Nicotine is the addictive drug in tobacco products. Cigarettes, cigars, smokeless tobacco and most e-cigarettes all contain nicotine. People who use tobacco become addicted soon after they start. They have a very hard time stopping. It is just as addictive as heroine and cocaine. Some people are unable to stop.
Nicotine in Youth and Young Adults
Nicotine has negative effects on the developing brain and changes its chemistry. Human brain development continues until the age of 25. Nicotine use during childhood, adolescence and young adulthood is associated with :
- Memory
- Attention
- Learning
Nicotine causes changes in the brain that make it more vulnerable to chronic use of addictive drugs. In high doses, nicotine is considered a poison. Children have been harmed and died from drinking e-cigarette liquid.
Nicotine Replacement Therapies
It seems to be counter productive but nicotine replacement therapies, such as nicotine patches, helps smokers quit. They provide a lower level of nicotine that can help reduce withdrawal symptoms while the person transitions to a tobacco free life. It is not recommended for people who have never smoked or used any type of tobacco product.
How the Studies were Funded
Autism Speaks claim they changed and do not want to find a cure and advocate for autistic people. Yale University received a grant for $185,000 from Autism Speaks to conduct these studies. Autism Speaks did not consider the risks of giving people who have never smoked nicotine patches.
Autism Speaks says:
“Aggression is highly comorbid with autism spectrum disorder (ASD) and is a strong predictor of negative outcomes for patients and families. Current pharmacological options for aggression are of limited efficacy for many and can result in further morbidity. Better understanding of the neurobiology underlying aggression in ASD and novel pharmacological treatment strategies rationally derived from these mechanisms are required to solve this critical problem. Genetic, neuropathological, and animal model studies have found abnormalities of the nicotinic acetylcholine receptor (nAChR) system in brains of people with ASD, and nAChRs influence the properties of essentially all major neurotransmitter systems. The nAChR agonist nicotine reduces aggression in multiple animal models, and our preliminary data suggests its effect is via activation of the α7 receptor. CHRNA7, the gene for α7, is deleted in 15q13.3 microdeletion syndrome, which phenotypically can include ASD and aggression. This project thus hypothesizes that modulation of nAChR signaling might be a novel treatment strategy for aggression in ASD. This hypothesis will be tested by 1) identifying the neurocircuitry and pharmacology underlying nicotine’s anti-aggressive effect in mouse models of aggression and ASD, and 2) determining the efficacy of transdermal nicotine for aggression in ASD in a pilot clinical trial.”
[Personal note: Treating autistic people with dignity and not trying to change them will cause less aggression. Behavior is communication. ]
The Studies:
Reduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in Hospitalized Adolescent with Autism Spectrum Disorder
In this study, only one participant was used in this study. They conducted this study based on a given mechanism of action independent of the current dopamine receptor drugs currently prescribed for aggression. Based on this, they tested to see if nicotine, delivered through a patch on the skin, may safely reduce irritability and aggression in autistic people with incomplete symptom response when other treatments are inaffective.
They conduct this study despite warnings on the effects of what nicotine can do to a developing brain.
JC was admitted to the study hospital for “severe and worsening behavioral problems, including self directed aggression.” This child is a non speaking autistic adolescent. The parents and staff tried medication and it did not work, behavior interventions (who wants to be its ABA?).
Informed consent was given by the parent for this trial. A copy of the informed consent packet was not available. A 21 mg nicotine patch was placed on the child’s skin on an as needed basis, at the hospital’s discretion for agitation, irritability or aggression. Instead of tending to his needs, they applied the nicotine patch to solve their problems.
There were no smoking in the household. This child has never been exposed to nicotine before. The child weighed 320 lbs and the dose was reported as effective. They would have used a lower dose if they did not observe the child.
The first application was done during a incident of agitation. The child did not escalate further after the application.
The next day when the child became agitated, a patch was not applied and “physical restraint was required.”
After this protocol, the child required no further emergency medication administration.
Yes it worked but should have have done it? What will be the lasting effects of the nicotine on this child?
This Study when applied to Ethical Principles when Involving Developmentally Disabled People in Research
People who are developmentally disabled are uniquely vulnerable populations. They experience greater burden from mental health issues because they received poorer quality of care than their typical peers. Because of this, a code of ethics is necessary. The different principles of ethics and they relate to this study will be explained.
Principle of Validity
The researchers are more likely to understand the nature and purpose of the study better than participants. Because of this, the researchers are responsible for being aware of the requirement of validity. The aims of the study should be the understanding and treatment of a condition.
Experimenting with a non controlled drug on an autistic child will not allow the researchers to understand autism better
Principle of Distributive Justice
The principle of distributive justice considers fair, equitable and appropriate division of risk as well as benefits generated by a given study.
When there is a risk to a developing brain when exposed to nicotine is not a fair division of risk and benefits. The effects of this drug on young developing brains will not be seen right away.
Principle of Beneficence and Nonmaleficence
It is important to balance the competing claims of potential benefits and risks assumed by each participant. The four categories of research on children relating to risks and benefits according to the National Institute of Health Inclusion of Children as participants:
- not greater than minimal risk/direct benefit
- not greater than minimal risk/no direct benefit
- greater than minimal risk/direct benefit
- greater than minimal risk/no direct benefit
All of these combinations are permitted but the strength of the argument justifying each category must be stronger when the risks to the participants reach greater than minimal levels and when the prospects of direct therapeutic benefits decrease.
According to this principle, the argument for altering brain chemistry is not discussed when conducting this study. Complete disregard of the risk on the developing brain. The dose of nicotine is the same as an adult who is trying to quite smoking when the child in question has never been exposed to nicotine before.
Principle of Autonomy
The principle of autonomy is the informed consent, protection of privacy, and confidentiality. The regulatory procedure allows participants or legal representatives to express free will with respect to various angles of research. This includes risks and benefits.
According to this principle, autonomy was not met. The possibility of how the developing brain will be altered due to nicotine being exposed to a developing brain.
An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder
According to Yale School of Medicine, “several studies suggest a potential role for transdermal nicotine in reducing symptoms of aggression in neuropsychiatric disorders, including schizophrenia and severe dementia . . . Further study of the potential role of nicotinic agents (nicotine) in treating irritability and aggression in individuals with ASD is thus strongly supported by the significance of. the clinical problem.”
This was an exploratory 3 week, randomized, placebo controlled crossover study. The participants were randomized to receive one week of 7mg daily transdermal nicotine (TN) or a placebo. This was followed by a washout period where all subjects would receive a week of a placebo and then followed with 1 week of 7mg or a placebo. Whoever received the placebo during the first week did not receive in the third week and visa versa.
The informed consent packet even says,“Discontinuation of the nicotine patch after use for 7 days may result in symptoms of nicotine withdrawal, which include headache, stomach upset, nausea, anxiety, and irritability. Previous studies in adult non-smokers have shown this risk to be extremely rare, even after periods much longer than 7 days. However, nicotine patch has not been studied systematically in adult individuals with ASD. If you experience such symptoms, please contact the study staff. – Nicotine is the addictive component in tobacco products such as cigarettes, and the addictive potential of nicotine is believed to be related to how quickly it is absorbed into the body. The nicotine patch delivers nicotine slowly into the body. Although unlikely, there is the potential you may become addicted to nicotine through use of the nicotine patch.”
The is the only study of this kind that has been published.
The participants were English Speaking male or female participants who were 18-60 years old with prior diagnosis of autism using the DSM 4 or 5. They must have a history of displaying aggression, irritability, agitation as reported by a parent or caregiver.
They needed to have a baseline score in the Aberrant Behavior Checklist (ABC)- Irritability subscale of 16 or greater. Each participant needed to be living with a caregiver who was able to complete written behavior scales at all three visits, rate participant behaviors in the designated time frame. No independent autistics were allowed to participate`.
All participants were required to be on a stable medication regimen with no changes within the past 14 days. They must have a BMI 17.1-45.
Anyone with prior or current use of tobacco products were excluded from the study. Anyone with a previous allergy to nicotine patches were also excluded.
This study included 8 participants. There were 7 males and 1 female. One was in a residential facility and the other 7 were at home. After completing the trial, one had to be excluded because they did not qualify due to age. Another participant completed all study visits but upon completion it was found that their caregiver did not fill out the behavior assessment correctly.
The participants were :
- 28 year old male
- 20 year old male
- 23 year old male
- 22 year old male
- 24 year old male
- 24 year old male
- 27 year old female
- 24 year old male
Its quite evident that they had trouble conducting this study. They planned on enrolling 16 participants but it did not work out.
One subject reported skin irritation from the patch. One caregiver reported one day of nightmares and GI symptoms.
The baseline was improved during the TN compared to the placebo. There were not enough participants in this study to determine a viable result.
This Study when applied to Ethical Principles when Involving Developmentally Disabled People in Research
People who are developmentally disabled are uniquely vulnerable populations. They experience greater burden from mental health issues because they received poorer quality of care than their typical peers. Because of this, a code of ethics is necessary. The different principles of ethics and they relate to this study will be explained.
Principle of Validity
The researchers are more likely to understand the nature and purpose of the study better than participants. Because of this, the researchers are responsible for being aware of the requirement of validity. The aims of the study should be the understanding and treatment of a condition.
There was not enough particpants in this study to produce a viable result
Principle of Distributive Justice
The principle of distributive justice considers fair, equitable and appropriate division of risk as well as benefits generated by a given study.
When there is a risk to a developing brain when exposed to nicotine is not a fair division of risk and benefits. The effects of this drug on young developing brains will not be seen right away. Most of the participants were under 25.
Principle of Beneficence and Nonmaleficence
It is important to balance the competing claims of potential benefits and risks assumed by each participant. The four categories of research on children relating to risks and benefits according to the National Institute of Health Inclusion of Children as participants:
- not greater than minimal risk/direct benefit
- not greater than minimal risk/no direct benefit
- greater than minimal risk/direct benefit
- greater than minimal risk/no direct benefit
All of these combinations are permitted but the strength of the argument justifying each category must be stronger when the risks to the participants reach greater than minimal levels and when the prospects of direct therapeutic benefits decrease.
It is not known how nicotine patches affect people who have never smoked or used tobacco products, especially with still developing brains. It would have been more ethical if people who were past the age of brain development.
Principle of Autonomy
The principle of autonomy is the informed consent, protection of privacy, and confidentiality. The regulatory procedure allows participants or legal representatives to express free will with respect to various angles of research. This includes risks and benefits.
According to this principle, autonomy was not met. The possibility of how the developing brain will be altered due to nicotine being exposed to a developing brain. Other causes of the aggression and irritability were not explored. That would have been more effective.
Sources:
Fierce Autie 