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 recreational effects.
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
insomnia.
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
others.
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 treatments.
Others cases where it may have some application include visceral and neuropathic pain.
Oxycodone compares favorably to morphine in some ways.
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
release.
Overall, they have very similar effects in overdose.
The drug works in 10 to 30 minutes and lasts for 4 to 6 hours when an instant release product
is used
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 hours.
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
somniferum.
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 out.
Some limited research shows kappa-opioid receptors may be contributing to some kinds of pain
relief.
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 the brain.
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
in 1916.
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 and 1919.
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
effects.
Dr. Hans Kreitmair, one of the top pharmacologists at Merck, began studying a combination of
scopolamine, oxycodone, and ephedrine in the mid-1920s.
That combination reportedly produced intense and long-lasting sedation and pain relief,
while not affecting vital signs.
Clinical trials of the combo, called SEE, soon started.
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
"Kirschner's injection."
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
really increase.
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 lives.
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:
1.
Oxycodone is being prescribed too much and for too many conditions.
2.
People with no history of addiction or crime are becoming addicted and committing crime.
3.
"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 for heroin.
And
1.
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
that:
"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 addiction.
It seems to act more like heroin than like morphine."
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 products.
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
and prescribers.
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 recreational purposes.
OxyNeo fully replaced the old version by late 2011.
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
heroin.
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
pain.
Currently, the controlled release version is widely used for chronic pain and the instant
release version is taken for acute and breakthrough pain.
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
dangerous.
Drowsiness, nausea, and constipation are the kind of negatives seen with common medical
doses.
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 dose.
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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