Oxycodone is a semi-synthetic opioid which
has been used since the early 1900s.
It is one of the most common opioids in medical
settings and is widely taken for recreational
reasons as well.
Since the introduction of OxyContin, a controlled
release form of the drug, its use has increased.
The positive effects include euphoria, pain
relief, mood lift, music enhancement, relaxation,
sedation, and anxiety reduction.
Among the negative effects are drowsiness,
nausea, vomiting, constipation, cognitive
impairment, dizziness, and respiratory depression.
Variation exists in a notable way with the
Some people receive a lot of euphoria, while
others do not.
When the euphoria exists, it can be similar
to what’s provided by morphine and heroin.
And the drug is capable of causing a “nod,”
which is a heavily sedated, often euphoric
state, sometimes accompanied by waking dreams.
It tends to be less sedating than other opioids
and it can either facilitate sleep or cause
In medical settings, the most common negatives
are nausea, drowsiness, and constipation.
All of those can decline over long periods,
though constipation persists more than the
Combining oral oxycodone with oral naloxone
may reduce the constipation.
There are many applications for Oxycodone
that have been realized and it is commonly
prescribed for acute post-operative pain,
chronic cancer pain, and, more controversially,
chronic noncancer pain.
It is effective, to varying amounts, in most
cases of pain.
One of the least controversial uses for it,
is in acute pain.
Prescribing it for long periods of time in
cancer patients is also not terribly controversial
and its efficacy is pretty similar to morphine.
In other chronic cases, there are patients
who receive benefit for years and dose increases
are minimal after the first 3 months.
Yet, there is ultimately a lack of evidence
for its long-term efficacy and it isn’t risk-free,
so there’s usually an emphasis on trying alternative
Others cases where it may have some application
include visceral and neuropathic pain.
Oxycodone compares favorably to morphine in
They offer a similar level of pain relief,
while Oxycodone causes fewer hallucinations,
may be less likely to cause drowsiness, and
often causes less itching due to lower histamine
Overall, they have very similar effects in
The drug works in 10 to 30 minutes and lasts
for 4 to 6 hours when an instant release product
With a controlled release product, the onset
is around 30 minutes and the effects may last
up to 12 hours.
Many people find it only lasts for 6 to 10
Intranasally, the onset is 1 to 5 minutes
and the duration is 3 to 5 hours.
Oxycodone is a semi-synthetic opioid synthesized
from thebaine, which occurs naturally in Papaver
Like morphine, codeine, and hydrocodone…oxycodone
is in the phenanthrene class of opioids.
It appears to exert much of its activity through
the mu-opioid receptor, though actions at
delta and kappa have not been entirely ruled
Some limited research shows kappa-opioid receptors
may be contributing to some kinds of pain
It was even suggested at one point that oxycodone
primarily operated through kappa receptors,
but that doesn’t seem accurate.
A significant level of dopamine release is
also triggered in the nucleus accumbens and
perhaps to a greater degree than morphine.
The differences between Oxycodone and Morphine
in this area haven’t been fully explored.
Compared to morphine, Oxycodone has a lower
affinity at the mu-opioid receptor, but this
is counteracted by greater availability in
On the pharmacokinetic side, it is primarily
metabolized to noroxycodone, but a smaller
portion also becomes oxymorphone.
Oxymorphone and another metabolite, noroxymorphone,
have been put forth as possible contributers
to oxycodone’s effect.
With the available research, Oxycodone itself
seems to be most important, with its metabolites
playing little to no role.
Oxycodone is available from 5 to 30 mg and
controlled release products range from 10
to 80 mg.
In medical settings, a common dosing regimen
is 5 to 10 mg every 6 hours.
In non-medical settings, a light instant release
dose is 2.5 to 10 mg, a common dose is 10
to 25 mg, and a strong dose is 25 to 30 mg.
For controlled release, a light dose is 10
to 20 mg, a common dose is 20 to 40 mg, and
a strong dose is over 40 mg.
Intranasally, a light dose is 2.5 to 5 mg,
a common dose is 5 to 15 mg, and a strong
dose is 15 to 25 mg.
Researchers at the University of Frankfurt
in Germany synthesized Oxycodone from thebaine
During the same year, tests were conducted
in animals to investigate its efficacy as
a pain reliever.
Between those tests and some trials in humans,
it was found Oxycodone could offer a slightly
greater level of pain relief than morphine,
had a longer duration of action, and produced
less nausea, drowsiness, and depression of
the circulatory and respiratory systems.
Clinical use in Germany began between 1917
It was introduced by Merck under the name
Eukodal and was mainly used for acute pain.
Within a few years, reports had already appeared
describing the drug’s euphoric and recreational
Dr. Hans Kreitmair, one of the top pharmacologists
at Merck, began studying a combination of
scopolamine, oxycodone, and ephedrine in the
That combination reportedly produced intense
and long-lasting sedation and pain relief,
while not affecting vital signs.
Clinical trials of the combo, called SEE,
SEE entered the German market in 1928.
SEE was popular in Germany and Central Europe
during the 1930s, but its greatest use came
during World War 2.
Prior to the War, surgeons were using it for
sedation, pain relief, and amnesia.
Some of the most influential research into
SEE was conducted by Dr. Martin Kirshner,
who ended up promoting SEE.
Around 1938, Wehrmacht, the German Armed Forces,
adopted the combination, referring to it as
The drug was used during minor and major procedures
to provide pain relief.
Merck sold 2 million ampules of SEE to German
Armed Forces during the course of the War.
Some surgeons in Germany weren’t fans of the
drug and suggested it’d be better for morphine
and methamphetamine to be used instead.
Concerns about SEE led one part of the Army
to abandon it, and by 1945, the German forces
were using it far less.
Most of the decline came from production and
distribution problems caused by Allied bombings.
After the War came to an end, the product,
then known as Scophedal, was still used to
a limited degree by surgeons in Germany, Austria,
Switzerland, and Scandinavia.
Production ended in 1987.
Oxycodone entered the US market in the late
1930s, but it took over a decade for use to
The first widely used product, known as Percodan,
was introduced by Endo Pharmaceutical in 1950.
It contained oxycodone and aspirin.
While concerns about the over-use of Oxycodone
are usually connected to the 2000s, a similar
situation developed in the 1950s and 1960s.
Percodan’s manufacturer was accused of downplaying
the harms, doctors were accused of over-prescribing,
and some people felt Oxycodone was ruining
This situation was obvious in California.
Percodan initially carried a relatively severe
warning, which stated:
“The habit-forming potentialities of Percodan
approach those of morphine more closely than
those of codeine.
The same care should therefore be exercised
when using Percodan as when morphine is prescribed.”
That warning was eventually dropped and simply
replaced with, “may be habit-forming.”
At the same time, the US production of Oxycodone
jumped from 9 kilograms around 1950 to 569
kilograms in 1960.
Campaigners appeared in order to fight the
drug and they had four main arguments:
Oxycodone is being prescribed too much and
for too many conditions.
People with no history of addiction or crime
are becoming addicted and committing crime.
“Thousands of tablets are being diverted into
illegal channels” and “California is faced
for the first time in its history with the
problem of underworld sources actively seeking
an otherwise licit narcotic as a substitute
Other ingredients in Percodan, such as Aspirin,
could have their own negative effects when
used at high doses.
Chief of California’s Bureau of Narcotic Enforcement,
John Storer, said:
“People are eating Percodan as though it were
popcorn, with extremely telling effects.”
One of the proposed reasons for California’s
allegedly out-of-control Oxycodone use was
“California has an undue share of unstable
personalities who welcome bizarre methods
of escaping reality”
Forged prescriptions were found to be very
common around Los Angeles and San Francisco.
The drug’s widespread use in California continued
through the 1960s.
It was also popular in other countries, both
in medical and non-medical settings.
In 1954, an estimated 11.5% of narcotic misuse
in France was attached to Oxycodone.
One source wrote:
“This substance, which began to be used in
France only a few years ago, has proved to
be particularly dangerous with regard to drug
It seems to act more like heroin than like
And in the 1960s, it became the top injectable
opioid for operative pain in Finland.
The modern history of Oxycodone in the US
begins in the 1980s.
New oxycodone products entered the market
around this time and its use for severe pain
increased due to the availability of oxycodone-only
Prior to the 1990s, the overall use of Oxycodone
was still relatively low and abuse didn’t
receive much attention.
Codeine and Pethidine were more significant
members of the market.
The use of oxycodone increased significantly
following OxyContin’s release in 1996.
Between 1996 and 2005, production, prescribing,
and non-medical use all increased.
Part of Oxycodone’s rise among recreational
users in the early 2000s was tied to the easy
extraction of the drug from Oxycontin.
Marketing by Purdue, the maker of Oxycontin,
helped increase prescriptions for chronic
cancer pain and for non-malignant pain.
In some cases, the drug’s efficacy was overstated
and the harms may have been minimized.
Even now, people tend to believe prescription
opioids are safer than they actually are.
Deaths attributed to Oxycodone increased from
14 in 1998 to 1,007 in 2006.
In 2007, Purdue pled guilty to providing misleading
information about OxyContin to regulators
The settlement cost the company hundreds of
millions of dollars, though Purdue has made
billions from the drug.
An attempt to reduce non-medical use came
in 2010, when the FDA approved OxyNeo, a reformulated
OxyContin that was harder to tamper with for
OxyNeo fully replaced the old version by late
While this appears to have decreased the non-medical
use of controlled release Oxycodone, many
people simply moved to instant release oxycodone,
other prescription opioids, and black market
Since the 2010s, there has been a push in
multiple countries to change prescribing practices.
Many people in the medical establishment believe
limited supplies should be provided in acute
cases, with patients receiving enough Oxycodone
for days rather than weeks.
And in chronic cases, they believe other drugs
and non-drug therapies should be promoted
with the goal of reserving Oxycodone for cancer
pain, severe pain, and treatment-resistant
Currently, the controlled release version
is widely used for chronic pain and the instant
release version is taken for acute and breakthrough
Oxycodone is Schedule 2 in the US.
It is usually controlled elsewhere.
The negative effects of Oxycodone at common
doses are moderate, but overdoses can be severely
Drowsiness, nausea, and constipation are the
kind of negatives seen with common medical
When an overdose occurs, significant respiratory
depression, consciousness impairment, coma,
and bradycardia or tachycardia can occur.
Respiratory depression can lead to death.
Death is possible without any combinations,
but using other CNS depressants greatly increases
the chance of harm.
When respiratory depression occurs, mechanical
ventilation could be necessary, though the
standard response to an overdose is naloxone.
More naloxone may be required for overdoses
involving controlled release oxycodone.
Two problems associated with long-term use
are depression and cognitive impairment, the
latter of which seems to be correlated with
Using an amount in the hundreds of milligrams
carries the risk of some form of impairment.
Another issue with long-term use is hyperalgesia,
which is effectively a lowering of the pain
threshold that allows previously unproblematic
stimuli to become painful.
The actual prevalence of this problem is unknown,
but it’s clearly the case that very high doses
for months or years carries the risk of making
someone’s problem worse.
Tolerance to the recreational effects usually
develops within a few weeks and it may occur
sooner, with the onset varying by user.
Using the drug for a long period of time will
result in physical dependence, including the
existence of withdrawal, which includes nausea,
insomnia, sweating, anxiety, restlessness,
muscle aches, diarrhea, and tachycardia.
As was previously mentioned, the acute risks
of oxycodone are significantly increased when
combined with depressants like benzodiazepines,
other opioids, and alcohol.
If you have any questions, feel free to leave
them in the comments section.
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