Pasquale Valerio
WRT 204
Professor Ligi
Paper #3
Research
May 3, 2016: 2024 – Do my homework – Help write my assignment online
Psychopharmacology:
An Approach to using Schedule I Psychoactive Drugs
in
Medicine with Neurological Applications
Abstract:
Since the establishment of the Food
and Drug Administration (FDA) in 1930, the pharmaceutical and medical
industries have faced many challenges regarding drug production and marketing.
Every new drug undergoes rigorous research and clinical studies before being sent
to the FDA for approval. The process on average can take a minimum of 12 years for
a drug to be marketed which is always followed by post marketing surveillance.The
Drug Enforcement Administration (DEA) is responsible for the scheduling of
drugs that have medicinal properties but also carry a potential for abuse. Schedule
I drugs are considered to have no accepted medical use, and have a high
potential for abuse in the United States. There has been a breakthrough in
research that has provided conclusive evidence that suggest the medical use of
current Schedule I Psychoactive drugs such as3,4-Methylenedioxymethamphetamine(MDMA)andLysergic acid diethylamide (LSD)
for treating various psychiatric disorders. These disorders range from severe
anxiety disorders to Posttraumatic Stress Disorder (PTSD). Currently prescribed
psychoactive drugs work by influencing chemicals in the brain such as dopamine,
norepinephrine and serotonin, the chemicals responsible for mood, behavior,
cognitionand perception. Classes of these drugs include but are not limited toamphetamines,
anxiolytics, and antidepressants. While these medications provide relief to
patients, there are instances where the use of Schedule I Drugs such as MDMA
and LSD can provide therapeutic relief when used alongside current accepted
medications and/or therapy.
The Neuron:
A nerve cell, also known as a neuron is the
basic functioning unit of the central nervous system (CNS). Neurons communicate
between each other by releasing a neurotransmitter. Charles Sherrington was a
British Physiologist that âcoinedâ the word synapse when he was referring to
junction between neurons. He originated it from the Greek word synapto which means âto claspâ (Meyer,Quenzer,78). The only magnification technology
available to him at the time were simple compound light microscopes. As technology progressed, scientists were
able to develop and use the electron microscope. This allowed us to see that
the process occurs unidirectional, beginning at the presynaptic cell and ending
at the postsynaptic cell. Theytransmit their signals via a synaptic cleft. The
brain is composed of three different types of synapses connections. The most
common one is the axodendritic synapse which is the communication between the
terminal end (Axon) extending from the neuron of the presynaptic cell to meet
the dendrite of the postsynaptic cell (Refer to Figure 2 in Appendix for SEM
photo) (Meyer, Quenzer, 78). The dendrite
is similar to an axon, but the dendrite receives singles while the axon sends
them; this pathway does not apply in all cases.
Axiomatic synapses function by making a connection between a nerve
terminal and nerve cell body while axoaxonic synapses function by allowing one
axon synapsing on the terminal end of another axon. This synapse allows for the
presynaptic neuron to alter the release of neurotransmitters from the
postsynaptic neuron. This phenomenon is known as presynaptic inhibition (Meyer,
Quenzer, 78). There are instances where the alternation is
done to increase the release of neurotransmitters. This is known as presynaptic
facilitation.
Stimulation in neurons can occur by
a physical, chemical, or electrical stimulus which will either inhibit or excite
the neuron. In electrical simulation, the cell will undergo a spike in
electrical charge which is measured in millivolts (mV) causing an increase in
membrane potential known as depolarization. This is followed by repolarization and
hyperpolarization, until the cell returns to its resting potential. Each time
the cell depolarizes this process occurs and it only takes an average of 5ms per
cell. Excitotoxicity can occuras a result of a pre-existing condition or pro-longed
exposure to drugs and lead to excessive cell stimulation and deterioration over
time.
Neurotransmitters:
The four types of neurotransmitters primarily
associated with medications and illness are dopamine (DA), norepinephrine (NE),
serotonin (5-HT) and acetylcholine (ACh).Catecholamines are a type of monoamine
that consist of an amine (NH2) and catechol (1-2dihydroxybenzene)
functional group. The starting material to make catecholamines is an amino acid
known as tyrosine. (Refer to Figure 1 in appendix for synthesis diagram). To synthesize
the final product, tyrosine enters into a multi-step biological pathway which
alters it to become dopamine, norepinephrine, or adrenaline. After the
synthesis is complete, Catecholamines are transported and stored in synaptic
vessels which protect the neurotransmitter from degradation.This is an area of
study by pharmaceuticals companies to explore molecules that can stimulate the
release of neurotransmitters. Neurotransmitters will not be released by the nervous
system unless it is signaled to, so having medications that can signal the
release can treat people who may not be able to do it naturally.A Romanian
scientist named Lazăr Edeleanu first synthesized
amphetamine (1-phenylpropan-2-amine)in 1887(Meyer, Quenzer, 363).It was
not until 1929 when a California Biochemist ejected himself with 50mg of amphetamine
and took notes on its physiological and physical effects. It only took a couple
years for students to discoverthe drugâs potential as a study aid. Amphetamines
work by stimulating the brain to release thedopamine inside the synaptic vessel.This
is responsible for the intense euphoria you fell when you first start taking
the drug. Over-time you will become immune to the euphoric affects, but the
stimulant aspect will be there still. Doctors will usually start you at the
lowest dose (5-10mg) per day and check up on you monthly. The problem here is
that this can lead to addiction because these drugs are stimulating the release
of dopamine which is responsible for your brainâs reward system.
Acetylcholine (ACh) was discovered
by a German scientist named Otto Loewi. His discovery helped advance techniques
in medical therapy which led him to winning the Noble Prize in Physiology of Medicine
in 1936. Similar to the monoamines, acetylcholine is synthesized from a biosynthetic
pathway from choline and Acetyl CoA but this process is done in one step which
involves choline acetyltransferase as catalyst. Acetylcholinesterase is an
enzyme that is responsible for the breakdown of ACh to keep the levels at a
balance. ACh is needed to sustain life
in the human body, but if something goes wrong with the pathway it can be life
devastating. ACh may only be synthesized
by only a small number of neurons in the brain, it plays an important role in
behavioral functions.
Functional Chemistry:
The
understanding of the chemistry behind medications is vital to understanding their
physiological effects in any given organism. Heroin and morphine are great
examples to use to explain this because of their structure similarity. The only
distinguishing difference between morphine and heroin is that the two hydroxyl
(OH-) groups in morphine are replaced by two acetyl groups (CH3CO~R)
in heroin. The R is referring to the âRâ group which includes the rest of the
chemical structure. (Refer to Figure 3 In appendix for structures). This is why heroin is also knows as
diacetylmorphine. This change enhances heroinâs lipid solubility and as a
result, it absorbs faster and has a more rapid onset of action and thus results
in extreme euphoric effects. Most drugs that are related to neurological
effects are often designed to have an affinity for certain blood/brain barrier
systems. Once the heroin is in the brain, the acetyl groups mentioned earlier
will be enzymatically altered to the (OH-) groups and morphine will
be present. This âtrapsâ the morphine in the brain and results in slow
metabolism of the drug. Structural difference within molecules of close
resemblance often have same mechanisms of action, but may be used for different
parts of the body. A study conducted by the Shanghai Key Laboratory of New Drug
Design concluded that the physicochemical and drug-like properties are
influencedmostly by aromaticity, functional group presence and heavy atom
proportions(Fei, et al. 15). The heavy atom proportion was calculated by the
number of non-hydrocarbon atoms/number of non-hydrogen atoms which translate to
the number of non-carbon atoms divided by all elements in structure besides
hydrogen. They deemed this value their R value. This study proved that drugs
classes such as CNS drugs, or Antibiotics share similar structures.
MDMA/Amphetamine:
MDMA and amphetamine are also
related functionally and structurally.The notable difference between MDMA and amphetamine is the presence
of the methylenedioxy group attached to the aromatic ring. (Refer to Figure 4
in Appendix)Amphetamine
and its stereoisomers are the main active component in Adderall, a commonly
prescribed drugs for Attention Deficit Hyperactivity Disorder (ADHD) and
Narcolepsy. Adderall works by altering neurological function. For simplicity,
imagineyou are at a dance and the men (dopamine) and the women (receptor) are
on different sides of the dance floor. Adderall will push the boys the floor
and keep them there so all the girls can hang out with them all night long and
have a crazy party. Your brains reward center is responding to the Adderall and
as a result you are not going to look at other places to receive stimulation;
you just focus on what is important. MDMA is similar, but it works on your
serotonin and norepinephrine levels while also having moderate hallucinogenic
qualities.
PTSD Clinical Trial:
PTSD
is a psychological disorder that can be developed in an individual after a
traumatic incident such as war, or another life threating event. According to
PTSD United, roughly 44.7 million Americans are affected by PTSD. This
statistic is derived from the 70% of Americans that have experience a traumatic
experience in their lives. That value is 223.4 million people which is a lot
more than 44.7 million, but the number should be <1%. Martha Stout, a
clinical psychologist and author explains sanity in one of her publications, When I woke up Tuesday Morning it was Friday
(Stout, 383).This relates to the deterioration of cognitive and rational
function in the brain associated with PTSD patients. While one may not label
PTSD patients as insane, people suffering from the condition may feel as though
they are. TheMultidisciplinary Association for Psychedelic Studies
sponsored a Phase II clinical trial starting in 2004 to determine the safety
and efficacy of MDMA assisted psychotherapy in chronic PTSD patients (Mithoefer,
NCT00090064).The
pharmacological effects of MDMA include serotonin release, 5HT2 receptor
stimulation, and increase in levels of the neurohormones oxytocin, prolactin
and cortisol (Mithoefer, et al. 441).Mithoefer sites Rauch as sayingthe
neurocircuitry modelfor PTSD suggests a drop in fear conditioning by the
amygdala and the ventral/medial prefrontal cortex (vmPFC) (Mithoefer, et al.
441). Rauch supported this model with findingsof reduced hippocampal activity and volume,
increased activity in the amygdala and decreased activation of the medial
prefrontal cortex in people with PTSD. MDMA may be able to be used to reverse
the neurological abnormalities associated with PTSD. The study was designed so
that MDMA and a placebo were administered in a double blind fashion; neither
the patient nor administrator knew what was in the vial(Mithoefer,
et al. 441). This was Stage
I. Patients were asked to abstain from psychotropic medications during the
study except for emergency medications such as benzodiazepines(Mithoefer,
et al. 441). After the
study concluded that safety and efficacy were accounted for the administration
of MDMA/Placebo was increased to lengthen the window for therapeutic effects(Mithoefer,
et al. 441). Several
neurocognitive and physiological assessments were conducted during dosing for
safety reasons. Stage II of the study was nearly identical to stage I with
terms of appointments, but subjects were aware to what they were receiving.The
study found that in Stage I, 10/12 people in the MDMA group no longer met
DSM-IV diagnostic criteria for PTSD compared to 2 of the placebo group(Mithoefer,
et al. 448). Stage 2
presented with 100% supportive results, and all three of the subjects that
previously reported before the trail that they could not work as a result of
their PTSD returned to work(Mithoefer, et al. 448). This study concluded with significant
improvements using MDMA assisted psychotherapy compared to that of the placebo
with regard to symptoms. Neuropsychological testing showed no serious adverse
mental effects; physical effects were also negative(Mithoefer,
et al. 449). Although this
study concluded with promising results for the use of MDMA for assisted use
with psychotherapy in PTSD patients; more research and trials will need to be
conducted in order to approach the FDA and DEA.
Future Research:
There are other notable compounds
that can also be taken into medical consideration based off research. A notable
one is the synthetically made compound LSD. It is derived from ergot, which is
a substance produced by s parasitic fungus. Lysergic Acid Diethylamide was
first synthesized in 1938 by Albert Hoffman. His research led him to discover
LSD by combining Lysergic Acid, with other chemical compounds. He wassearching
for compounds with analeptic qualities that can be usedfor
new respiratory stimulants (Meyer, Quenzer, 433). The drug did not have any
promising effects and that resulted in him dropping the idea. It was not until
five years later when he revisited the research that he accidently ingested
small amounts of LSD in his laboratory and documented the effects. It was then
marketed in 1947 as Delysid for treating neurotic patients (Meyer, Quenzer, 433).
The drug was banned in the United Stated in 1967. Hoffman died in 2008 - Affordable Custom Essay Writing Service | Write My Essay from Pro Writers at the
age of 102. It was not until recently that we were able to observe the brain on
LSD.A recent news article published by Science Daily showed the fMRI andMEG
scans of a human brain under the influence of LSD (Refer to Figure 5 in
Appendix). The study group consisted of 20 healthy volunteers. Under normal
neurological conditions, the visual cortex processes information sent from our
eyes, however; when the volunteers took LSD, many brain areas contributed
(London, 2). Our brains as infants are free and unconstrained which contributed
to our hyper-emotion and imaginative nature (London, 2). Dr. Carhart Harris
explained this as our current brain which had become constrained and
compartmentalized while becoming an adult is transformed back to infancy stage
on LSD (London, 2). âThe Beckley/Imperial Research Program hope these
collective findings may pave the way for these compounds being used to treat
psychiatric disordersâ (London, 3).
The
research is mostly done in Nations other than the United States. We need to revisit
the law and take close consideration into researching these compounds for medicaluse.
We have expanded our knowledge since the laws have been made, medicine has
developed and changed. If we have the potential to restore people lives and
heal them, we should not be relying on theresearch of foreign programs and
agencies to educate us on how to do it. We need to educate ourselves.
Appendix:
Figure 1:
-taken from.zone/">http://bigtone.zone/.
Requested permission to use.
Figure 2:
Taken from http://blog.nervousencounter.com/?p=215
Figure
3:
– taken from http://icanhasscience.com/fun-stuff/chemistry-of-morphine-heroin-and-lemon-poppy-seed-cake/
*does not
include wedged Hydrogen chiral center on heroin figure
Figure 4:
-taken from.caymanchem.com/article/2196″>https://www.caymanchem.com/article/2196
Figure
5:
-Image from Imperial College London
Help write my assignment – Bibliography :
Fei,
Mao, et al. “Chemical Structure-Related Drug-Like Criteria Of Global
Approved Drugs.” Molecules 21.1 (2016: 2024 – Do my homework – Help write my assignment online):
1-18. Academic Search Complete. Web. 2 May 2016: 2024 – Do my homework – Help write my assignment online.
Imperial College London. “Brain on LSD
revealed: First scans show how the drug affects the brain.” ScienceDaily.
ScienceDaily, 11 April 2016: 2024 – Do my homework – Help write my assignment online.
Meyer,
Jerrold S., and Linda F. Quenzer. Psychopharmacology: Drugs, The Brain,
And Behavior (2Nd Ed.). Sunderland, MA, US: Sinauer Associates,
2013. PsycINFO. Web. 2 May 2016: 2024 – Do my homework – Help write my assignment online.
Mithoefer,
Michael, MD. “A Test of MDMA-Assisted Psychotherapy in People With
Posttraumatic Stress Disorder.” Home. Multidisciplinary Association
for Psychedelic Studies, Sept. 2010 – Essay Writing Service: Write My Essay by Top-Notch Writer. Web. 03 May 2016: 2024 – Do my homework – Help write my assignment online.
Mithoefer,
Peter, et al. “A Randomized, Controlled Pilot Study Of Mdma
(±3,4-Methylenedioxymethamphetamine)-Assisted Psychotherapy For Treatment Of
Resistant, Chronic Post-Traumatic Stress Disorder (PTSD).”Journal Of
Psychopharmacology 27.1 (2013): 40-52. PsycINFO. Web. 2 May 2016: 2024 – Do my homework – Help write my assignment online.
Stout,
Martha. âWhen I Woke Up Tuesday Morning, It Was Friday.â The New Humanities
Reader 2nd Ed. Ed. Richard E. Miller and Kurt Spellmeyer. New York: Houghton,
2006 – Write a paper; Professional research paper writing service – Best essay writers. 578-599. Print.
