What do psychedelics do to the brain, and how does change in brain

activity influenced by psychoactive drugs affect the ability for people’s

Quincy Buickerood
Senior Project Advisor: Steve Smith

ABSTRACT
Mental illness and addiction are common problems that many people experience.
Methods of treatment are not adequate to solve the problem that is afflicting the world. In this
paper, I explore the use of psychedelic drugs as a treatment for mental illnesses and addiction.
The recerash has been conducted on thousands of people since the middle of the 20th century.
The research shows that psychoactive drugs like LSD, psilocybin and DMT help treat mental
illness and addiction. The psychedelic drugs temporarily change the way the brain interacts with
itself and sensory inputs, to help the user understand what is important and put things into
perspective. This temporary change helps people end their addictions and stop suffering from
their mental illnesses. These findings have the potential to change the way we treat mental
sinesses, they need to be further researched and eventually become a part of modern medicine.

12th Grade Humanities

An estimated 34.2 million adults in the United States of America smoke cigarettes,

(Center for Disease Control) 17.3 million adults in the United States of America have had at least

one major depressive episode, (National Institute of Mental Health) and 19.7 million adults

battled a substance use disorder (Thomas). Current methods of treating addiction and depression

are inadequate.

Psychedelics can minimize addiction, depression, and other mental illnesses.

Psychedelics are psychoactive drugs that change the way the brain interacts with itself and

processes sensory information. When psychedelics are consumed, they interact with the brain by

altering the receptors and change the connections within the brain. All psychedelics interact with

the brain differently, some create more visually and auditory stimulation and others create more

internal stimulation, even if the method of reaction is different within the brain all psychedelics

have the power to heal in different ways. Psychedelics have been used as a medicine in different

cultures around the world for centuries. From the use of soma in the Sanskrit text to the Native

Americans’ use of peyote. Psychedelic drugs have a rich history of healing, although they are

commonly thought of as a party drug or a drug used by counter-culture hippies they can be used

to cure sicknesses of the mind.

Psychedelics create a spiritual experience that shows the user the importance of

something they hold close to their heart, this experience is enhanced and more effective for

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healing when guided by someone that has experience instructing people with a psychedelic trip.

It can also show the user something they dislike about themselves or something in their life. The

psychoactive drugs give the user the ability to look at themselves from a different angle and

become separate from the negative part of them or of their life, this new perspective often gives

the user the ability to cut away the bad and extinguish it. Lifelong smokers are often able to quit

smoking permanently immediately after an experience with a psychedelic drug. They sometimes

describe themself seeing the smoking part of their body as a small and nasty creature that they’re

disgusted by. Similar to antidepressant drugs, psychedelics alter the way the brain works by

putting things into a realistic perspective leading to a chemical equilibrium in the brain. When

the brain is not in an equilibrium the brain's owner is usually depressed or manic due to an

imbalance of chemicals in the brain. Psychedelics are an effective method of treating depression,

addiction, and other mental conditions, because they change the conductivity between the parts

of the brain to induce spiritual experiences that positively impact mental health.

Part II:Historical Context and Background Information

The modern exploration of psychedelic drugs accidentally started in 1943 Dr. Albert

Hoffman, a Swiss chemist synthesized lysergic acid diethylamide (LSD) from a fungus that

grows on rye. In 1943 on April 16th Hoffman accidentally orally ingested a small amount of the

synthesized lysergic acid diethylamide; sending him on the first-ever acid trip. He experienced

dream-like hallucinations portrayed in wild colors with unnatural movement and perceptions. A

few days later on April 19th, Hoffman intentionally ingested over ten times the amount of LSD

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with a dosage of 250 micrograms. He recorded in his journal 40 minutes after his ingestion

“beginning dizziness, feeling of anxiety, visual distortions, symptoms of paralysis, desire to

laugh” (​Calderon​) With his lab assistant’s help, he rode his bike home from his lab experiencing

fantastic visions and explosions of colors. Enthusiasts of the drug remember Hoffman and his

historic discovery, Bicycle Day is celebrated on April 19th, (​Calderon​).

“By the mid-1960s, over 40,000 patients had taken LSD, and psychedelic researchers

had published over 1,000 scientific papers, many books, as well as held several international

conferences” (Bakalar and Grinspoon 22). Ps​ychedelics, mainly LSD, were taking the United

States by storm. It was easy for medical professionals to get their hands on the drug and research

was being done by many people including the United States government. Humphrey Osmond

was an English psychiatrist that moved to Saskatchewan Canada to conduct LSD research.

Humphrey Osmond and Abram Hoffer, a Canadian biochemist, conducted research on

alcoholics; giving them a very high dose of LSD created an overwhelming experience helping to

cure 66% of the patients with alcoholism after 3 years, in comparison to 18% for the control

subjects (Dyck 384). This was one of the first times that psychedelics were used as a medicine

for the treatment of addiction; the results showed significant promise. This study inspired Bill

Wilson, (one of the founders of Alcoholics Anonymous) who wanted psychedelics to be used in

the 12 step program to treat alcoholism, as it created a similar reaction to a spiritual experience

he had which he thought was vital to cure alcoholism. (​Roger​) Hoffer continued to publish

studies related to curing alcoholism with LSD.

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 Alcoholism was not the only disease being experimented on, “In 1954… Sandison

published a paper with his colleagues Spencer and Whitelaw describing LSD-assisted

psychotherapy on 36 patients in which the treatment was overwhelmingly positive and without

adverse effects” (​Sessa​). Spencer, Whitelaw, and Sandison claimed they were able to pull

unconscious thoughts to the forefront of patients' minds. They were able to help patients that had

been unresponsive to other forms of treatment. Follow-ups two years later reported that, of

ninety-four patients over 60% had recovered or improved even though they had failed to respond

to conventional therapy previously (Snader and Whitelaw 335).

In 1962 the most famous psychedelic study was conducted. On April 20th, Walter

Pahnke conducted a double-blind study at a Good Friday service at Harvard. Ten people were

given an active placebo while ten others were given a 30mg dose of psilocybin. After the two

and a half-hour service the participants were interviewed and tested on three different tests to

determine if they had a mystical experience. A majority of the patients that received psilocybin

were scored to have a mystical experience when compared to the control group which had almost

none (​Britannica​).

Psychedelics have been used for centuries to cure medical abnormalities and to induce

spiritual experiences. Ancient cultures to modern day cultures from around the world have made

psychedelics an integral part of their lives. Due to their unimaginable effects and rampit

popularity, they were almost the wonder drug of the 20th century. People were optimistic about

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the potential of the mysterious group of drugs; for addiction and medical illnesses these drugs

showed great potential. With all of the promise and potential the drugs unlocked, it is easy to

wonder why they are not something used more commonly in today's society.

LSD was outlawed in the United States of America in 1968, (History LSD) LSD went

from a drug being used by the ​Central Intelligence Agency​, to being outlawed less than a decade

later (History MK-Ultra). The downfall of psychedelics is a tragedy that consists of people

saying the wrong thing at the wrong time and a tremendous amount of bad luck. When the

studies on clinical value were reproduced it became apparent that the early studies were

sometimes overstated. Researchers that were fans of the drugs were not able to recreate the

results that the pioneering studies had reported. The original studies were often criticized for

being short term and seldom had follow-ups conducted and the often small sample size was poor

for studies. Many argued that the drugs were only temporary fixes for problems and the positive

effects caused by the drugs and the treatment didn't last very long.

The results were sometimes unrepeatable and on occasion had negative outcomes. A trial

was done to reproduce the trial done in Saskatchewan. The recreating of the trial was small, and

focused solely around the use of LSD. The participants were blindfolded and restrained to ensure

the results were only from the use of the LSD, and not due to other factors. The study was unable

to reproduce the original results that were found, suggesting that the original results were skewed

to show what the recerasches wanted to be shown (Smart, et al. 469-481).

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 Arnold Ludwig, a psychiatrist performed a study in the late 1960’s lasting 4 years with a

group of 176 participants. They used four different types of therapy and found that the LSD had

no change in the end result of the study (Ludwig et al. 570). The researchers determined that the

LSD only affected the motivation in the recipients but had almost no difference in one year

follow up.

Many of the studies were also missing comprehensive control groups that accounted for

how people were likely to act like in the same situation without the psychedelic present in their

system. Many studies like the one performed by Kurland et al. had two groups: a high dosage

group with 400mg and a low dosage group with 50mg which isn't a control group just a different

test ( Ludwig et al. 570). A better research design would have been to exchange the 50mg dose

that the control group took for an active placebo. An active placebo is something that is taken by

the control group in an experiment to give the illusion of the thing that is being tested, so in

psychedelics it is usually a substance that is taken orally that makes the mouth tingle.

Even more troubling than being ineffective, psychedelic drugs can sometimes induce

permanent psychosis in people, this is often only true for people that have mental illness running

in their family. Very aarely, people either attempt suicide or commit suicide. A study found that

4 out of every 2500 people that take LSD atempt to commit suicide and that 1 out of thoes 4

people commit suicide (Cohen 30-40).

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 Society’s disenchantment with psychedelics was not only based on the poorly designed

studies, over reported results, and potential for death or serious mental illness. An arguably more

serious PR problem arose with the counterculture movement. Prominent figures such as Timothy

Leary, the well known Harvard professor and face of the psychedelic movement, said things that

threatened the government. He famously said “turn on, tune in, drop out” as a recommendation

to America's youth.

Dated and goofy, as those words sound to our ears, there was a moment when they were

treated as a credible threat to the social order. An invitation to America's children not

only to take mind-altering drugs but to regret the path laid out to them by their parents

and their government. Including the pathing taking young men to Vietnam (Michael

Pollan 4:30:17-4:30:29).

With the political movement around the counterculture, the words of Timothy Leary were

over-exaggerated and seen as a threat.

The actions of Timothy Leary were more than just words and struck at the status quo, he

was promoting psychedelics to students,

By 1962 various faculty members and administrators at Harvard were concerned about

the safety of Leary and Alpert’s research subjects, and critiqued the rigor of their

unorthodox methodology (in particular, the researchers conducted their investigations

when they, too, were under the influence of psilocybin). Leary and Alpert’s colleagues

challenged the scientific merit of their research, as well as the seemingly cavalier attitude

with which it was carried out (e.g. poorly controlled conditions, non-random selection of

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 subjects). Editorials printed in the Harvard Crimson accused Alpert and Leary of not

merely researching psychotropic drugs but actively promoting their recreational use

(Harvard ​Timothy Leary​).

Timothy Leary’s actions were detrimental to the psychedelic movement; and harmful to himself

as well. As a teacher with powerful influence on the next leaders and scholars of the day it was

frightening for the government to see him pushing psychedelics in such a strong way, this made

the government have a fear of psychedelics because of the way he endorsed them. Harvard could

not have someone on their staff that was so conshervishal so he was fired from Harvard in 1963.

During their time at Harvard, Richard Alpert and Timothy Leary administered

psychedelics with poor methods and under imperfect conditions. Students were not selected

randomly and sometimes put in serious danger, even if the poor conditions were due to

negligence they were still dangerous. The professors also let students indirectly get their hands

on many different kinds of psychedelics which would otherwise be illegal (​Weil​).

The fall of psychedelics in the 1960s was due to a multitude of factors: bad studies, poor

decisions, and a dangerous drug that was not fully respected or understood. “Congress passed the

Drug Abuse Control Amendments of 1965, and the law was signed by President Johnson”

(RAAB).

Even with the fall of psychedelics and the poor light they have in the eyes of many

people they are still seen by some as the future of medicine. Despite the potential danger and

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illegality of psychedelics, in many places around the world they continue to be seen as an

important part of medicine and even a way to understand the brain and its high-functioning,

complex functions (Randerson). Many scientists want to continue to research psychedelics for

the potential role they could play in treating addiction and mental illness. Professionals are

willing to risk their carriers, jump through bureaucratic hoops, and maneuver government

regulations to further research psychedelics (Halpern). For many scientists, the risk of

researching psychedelics is not outweighed by the potential reward (Bakalar and Grinspoon).

The rate at which new information and studies around psychedelics are being published is

increasing but still slow.

Part III: Research and Analysis

The new studies that are being conducted from the mid-1990s to the present are

promising. With results showing that psychedelics can cure addiction and mental illness, but do

not show the very high numbers that were gathered in the pioneering days of psychedelic

research. Psilocybin was used in the early 2000s to help reduce symptoms of obsessive

compulsions disorder. A double-blind study was performed on people that had responded poorly

or not at all to antidepressants. 71% of the patients reported feeling better only one day after the

treatment, 35% felt better a week later compared to no improvement when given the placebo

(Berman et al.).

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 Psychedelic studies used on people that are not sick also show a majority of people being

happier after and feeling more satisfied in life; overwhelmingly 79% of the recipients had an

increased sense of well being. It is a necessity to pursue the scientific study of psychedelics with

all of the benefits they have to sick people and even to healthy people. Although there are

potential negative side effects, there are for every drug and most of the time psychedelic drugs

are safer for the user than other drugs (​Griffiths et al.​).

Psychedelics are a medical wonder that have the potential to help hundreds of millions of

people world wide, mitigate, and even cure addiction, depression, and other mental illnesses. The

list of side effects on popular antidepressants like fluoxetine are very long with the possibility of

serious mental and physical problems (​Drugs Fluoxetine​). Drugs like LSD, psilocybin, and other

psychedelics also have negative side effects but are seen as a much more dangerous path to

curing mental illness even if they are just as effective; unfortunately this is simply a result of the

drugs negative connotation and stigma it has been given.

Depression is caused by many small different things in the brain, “Decreased

hippocampal volumes have been noted in subjects with depression” (​Pandya et al.​) “Decreased

amygdala core volume has been reported in depression” (​Pandya et al.​). The brain's chemical

levels are unbalanced and the neurotransmitters are not firing and transmitting in the way they

are expected to for the brain to function correctly.

Neurotransmitters are chemicals that relay messages from neuron to neuron. An

antidepressant medication tends to increase the concentration of these substances in the

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 spaces between neurons (the synapses). In many cases, this shift appears to give the

system enough of a nudge so that the brain can do its job better. (​Harvard Health

Publishing​).

So if this is what antidepressants do and psychedelics can help cure and mitigate depression what

do they do to the brain?

Psychedelics change the way the brain perceives sensory information and signals from

other parts of the brain. A study where patients were administered a dose of LSD and then their

brain was scanned in an fMRI found that,

The contrast drug vs. placebo… resulted in increased effective connectivity from the

thalamus to the VS[​visual cortex​] and the PCC[​posterior cingulate cortex​] to the VS.

Furthermore, decreases in effective connectivity were found: from the thalamus to the

Temp[​temporal lobe​], the VS to thalamus, the VS to PCC, and the VS to Temp (​Preller et

al.​).

The change in the brain with LSD has something to do with the spiritual like experience that

people are having when taking the drugs. Another study done with LSD of 15 people shows a

significant change in brain activity during the administration of the LSD. “Principal findings

include increased visual cortex CBF, RSFC, and decreased alpha power, predicting the

magnitude of visual hallucinations” (​Carhart-Harris et al.​). LSD has a strong effect over the brain

changing moods and other brain functions,

LSD produced robust psychological effects; including heightened mood but also high

scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait

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 openness were observed 2 weeks after LSD (and not placebo) and there were no changes

in delusional thinking (​Kaelen et al.​).

LSD affects different receptors like the dopamine receptor, adrenergic receptor and the

glutamine receptor. The serotonin receptors are hit by the LSD at a different rate than normal,

forcing the receptor to form a cap around the LSD compound. When the LSD is stuck in the

receptor it continues to fire creating hallucinations. The brain deals with this by sucking the

receptor into the cell to degrade the LSD, this can take over 12 hours to dissipate which is why

trips sometimes last for long periods of time (AsapSCIENCE ​Your Brain on LSD and Acid

00:00:53).

When the brain is on LSD it changes a significant amount,

decreased flow in the default node network, correlation to strong changes in cortex

characterized as ego-dissolution, described as a feeling where boundary that separates

you from the rest of the world dissolves. Many people report this feeling brings a

reconnection with themselves, others and the natural world” (AsapSCIENCE ​Your Brain

on LSD and Acid​ 00:01:32).

Psilocybin, the active ingredient in magic mushrooms, has a similar effect on people to

LSD and is often grouped together under the banner of psychedelics. When magic mushrooms

are consumed the body of the recipient breaks the psilocybin into psilocin which then goes to the

brain. In the brain, “It prevents the reuptake of the nero-transmitter serotonin, increasing its

activity. On top of this psilocin actually has a similar chemical structure to serotonin meaning it

can also bind to and stimulate receptors in the brain” (AsapSCIENCE ​Your Brain On Shrooms

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00:00:22). Unnatural levels of stimulation in the brain make it seem like there is something going

on that isn't real. This creates unnatural auditory and visual stimulations along with spiritual

feelings, often creating reflecting about one's life.

DMT or dimethyltryptamine is found in ayahuasca and in toad venom. DMT is most

often used to heal instead of having a wild visual experience like most users of psilocybin and

LSD are looking for. When people use DMT they tend to feel more comfortable with themself

and what they are thinking.

The default mode network is distinct in the brain that if overactive is associated with

depression, anxiety and social phobia, and fMRI scans show that ayahuasca causes a

significant decrease in activity within the default mode network. This is usually linked

with a meditative state and explains why some ayahuasca drinkers feel at peace with

themselves and find a renewed sense of purpose (​AsapSCIENCE ​Your Brain On Ayahuasca:

The Hallucinogenic Drug 0

All psychedelic drugs change the mind in some way; each has its own slightly different

mechanism for activation of stimulation of the brain that is still being explored and discovered

by scientists.

Part IV: Discussions and Conclusions

With millions of people suffering from depression, addiction, and other mental illnesses it

is imperative to find a way that is better than current methods to cure these illnesses. Each person

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is different and what works for one may not work for another, but often when mainstream

methods don't work it is impossible not to turn to alternatives. Addicts and people suffering from

a mental illness don't necessarily need to turn immediately to psychedelics nor should they but it

needs to be an option for people who want it.

With an increase in the legal availability of psychedelics and the appropriate

administration of the drugs in a safe place done by professionals the number of people suffering

from an addiction and the number of people with a mental illness would surely go down. This, in

turn, decreases the number of people committing suicide and dying in addiction-related accidents

benefitting society in a multitude of ways.

The research around psychedelics shows a promising collection of drugs with the

potential to make many people's lives better. Although some research has been done we still

don't have a very clear understanding of the exact effects that psychedelics have on each user.

Each different drug in the broad category of psychedelics has its own different quirk and unique

ability. A drug that is so unique and used in legal medicine needs to have years of testing done

on it to be made safe for the users and to become FDA approved. With most other drugs

something like set and setting is not very important but when a drug interacts with the innermost

part of someone's mind it needs to be understood at a deeper level. Every part of the drug's

effects on the human brain needs to be understood and not just the drug's effects, but what the

impact of external factors are when someone is under the drug's influence.

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 Psychedelics may become an integral part of medicine in the future. The potential of the

drugs' power to bring realizations to people in need is one of the most positive effects a drug

could have on someone with an addiction and/or mental health issue.

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 Work Cited

https://docs.google.com/document/d/1jOAs_KH4ICEgHjE-L-zTu3Hs4EX2Kdnnb9dIDV

oTdZw/edit?usp=sharing

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