Carisoprodol is a muscle relaxant whose pharmacology and history is heavily connected to meprobamate,
a drug it's metabolized to.
Recreational use has existed for decades since it provides effects reminiscent of benzodiazepines
and ethanol.
Concerns about its abuse potential have grown over time, especially since the 2000s.
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using the link below.
The positive effects include sedation, relaxation, euphoria, increased sociability, disinhibition,
and anxiety reduction.
Among the potential negative effects are dizziness, drowsiness, headache, impaired coordination,
and slurred speech.
In medical settings it is used as a centrally-acting muscle relaxant for acute musculoskeletal
conditions like back pain.
When it's prescribed, the drug is usually combined with rest, physical therapy, and
other common treatments.
It does appear to reduce discomfort, but it's only recommended for a few weeks.
Pain relief and potentiation of other pain relievers does exist, according to some research.
Carisoprodol can be combined with NSAIDs, which might be more effective than using either
on their own.
Although you do run into a greater incidence of adverse central nervous system effects
than when an NSAID is used by itself.
It's not recommended as a first-line treatment, though doctors have long prescribed it more
often than they likely should.
The primary negatives in medical settings are psychomotor impairment and drowsiness.
You typically need to increase the dose a bit beyond the average medical dose to receive
effects like euphoria and disinhibition.
While you're likely to receive relaxation with under 600 mg, using higher doses in the
strong range may provide a sort of hypomanic state.
Which is characterized by disinhibition, euphoria, cheerfulness, and greater socialization.
The physical euphoria is one of the most notable recreational effects and is frequently stronger
than benzodiazepines.
It most often occurs with strong doses and cognitive euphoria can also be present.
Some of the relaxing, impairing, euphoric, and anxiolytic effects are comparable to alcohol.
The pleasant effects don't exist for everyone.
Some people actually find it mainly makes them depressed, somewhat dysphoric, and sedated.
Combining it with other drugs, particularly opioids, ethanol, and benzodiazepines, is
pretty common.
Doing so can lead to synergistic recreational effects in terms of relaxation and euphoria,
but it's also much riskier.
The drug usually works for 4 to 6 hours in medical settings and has an onset of about
30 minutes.
For the recreational effects, the onset range is 15 to 45 minutes and the drug lasts for
2 to 5 hours.
Carisoprodol is N-isopropyl meprobamate.
It differs from meprobamate in that it has an isopropyl addition.
Both are carbamate derivatives and Carisoprodol metabolizes into meprobamate.
The drug is sold as a racemic mixture.
Most of the attention regarding its pharmacology has historically been placed on its metabolism
to meprobamate, yet it is active on its own.
We've known since the drug was created that it has different properties.
And more recent evidence shows that while the prodrug factor is important, it's not
the only thing that matters.
Since it's a centrally acting muscle relaxer, it doesn't directly impact peripheral nerve
conduction or neuromuscular junction transmission.
This differs from a substance like Tubocurarine, for example.
Carisoprodol primarily operates through GABA receptors.
It's historically been compared to barbiturates in this regard, but it seems to differ from
both benzodiazepines and barbiturates.
We still don't fully understand what it's doing.
The drug appears to operate at one binding site as a positive allosteric modulator and
at another site as a direct activator or agonist.
Modu lation of GABA's activity and direct activation are seen at certain GABAa receptor
types, such as alpha-1 beta-2 gamma-2, which is the primary configuration in the brain.
Modulation occurs at other configurations, such as those with a beta-1 subunit, but the
efficacy is greater at beta-2.
Unlike with benzodiazepines, the efficacy remains when you take away the gamma subunit.
The level of direct activation at various configurations differs from the modulation.
Direct agonism is actually greater at B1-containing receptors, whereas B2 sees greater positive
modulation.
The ability for Carisoprodol to directly activate receptors contributes to it being more concerning
than benzodiazepines in overdose.
In fact, there appears to be a correlation between the potentially fatal concentration
and the concentration required for widespread direct activation.
A few other mechanisms might be contributing to the drug's action, such as serotonergic,
NMDA antagonist, and adenosine reuptake inhibition activity.
Metabolism to meprobamate does have an impact, even moreso with chronic use.
Meprobamate has its own GABAergic effects.
The drug is sold as 250 and 350 mg tablets.
A common medical dose is 350 mg taken 3 to 4 times per day.
In other settings, a light dose is 100 to 350 mg, a common dose is 350 to 700 mg, and
a strong dose is over 700 mg.
Many people do take significantly more, but doing so raises the risk of more concerning
negative effects.
Carisoprodol was created in 1956 by Frank Berger of Wallace Laboratories.
Berger was also part of the team that synthesized meprobamate, which quickly became a popular
drug for anxiety and other psychiatric conditions after launching in the mid-1950s.
Many drugs similar to meprobamate were being synthesized and tested, which led to Carisoprodol.
By 1959 the drug was on the market for back pain and muscle spasms.
It was described as having properties similar to meprobamate and mephenesin.
Studies around 1960 found it didn't produce much sedation in animals at low doses despite
causing clear EEG changes.
It was also found to be a pain reliever in some cases.
Early reports suggested there was no real abuse potential or physical dependence, but
it's abuse potential was known by 1978.
Concerns about its abuse potential grew in the 1990s due to an increasing number of case
reports detailing its recreational use and dependence potential.
At this time a lot of the concern was based around it being a prodrug for meprobamate,
which was known to have abuse potential.
However, a study in the 1990s found just a small percentage of physicians even knew it
was metabolized to the drug and they believed it had a lower abuse risk.
The DEA recommended scheduling it in 1996, but the FDA didn't agree due to a lack of
evidence.
In 1998, it was ranked 18th for drugs involved in emergency department visits in the US.
Between the 90s and 2000s, more claims appeared of it being taken to alter the effects of
opioids and sometimes benzodiazepines and ethanol.
Emergency department visits increased from 6,569 in 1994 to 19,513 in 2005.
Around the same time, individual states began scheduling it.
Online sellers contributed to greater non-medical use in the 2000s.
By the 2010s, some countries had moved away from using it, such as Sweden.
They either got rid of its use or restricted it to fewer patients.
It became a Schedule 4 drug in the US in 2012 following an apparent rise in misuse and adverse
events.
A post in the Federal Register justified the move with the following points:
"Carisoprodol possesses sedative properties that may underlie its therapeutic usefulness
and potential for abuse."
"In vitro studies demonstrated that carisoprodol possesses barbiturate-like effects."
The "discriminative stimulus effects are similar to other Schedule 4 drugs such as barbital,
meprobamate, and chlordiazepoxide"
And
"The record demonstrates that excessive carisoprodol use creates toxicity and withdrawal symptoms
similar to other Schedule 4 drugs."
It's a Schedule 4 drug in the US.
Elsewhere, it often isn't specifically controlled, but prescriptions may be less common.
Reports of over-the-counter status and unscheduled prescription status exist in a number of countries.
Carisoprodol has fairly moderate negatives at common doses, such as drowsiness and impaired
coordination.
In an overdose, it's capable of producing amnesia, coma, respiratory depression, and
death.
There are some reports of agitation, seizures, movement disorders, and muscular rigidity.
Most of the overdoses primarily involve CNS depression, which can be deadly, especially
when other depressants are involved.
When it's the only drug involved, around 12 grams is believed to be the point where an
overdose could be life-threatening.
The problem with giving a dose like that is there are individual differences which may
lead to a lower dose causing serious problems.
You shouldn't be using an amount anywhere near 12 grams.
The life-threatening dose is lower when other depressants are involved, so its worth avoiding
drugs like opioids, alcohol, and benzodiazepines.
Withdrawal does exist when the drug is taken for an extended period of time.
As with similar GABAergic substances, it can lead to seizures, delirium, and death.
The withdrawal often causes anxiety, insomnia, tremor, and tachycardia.
There's a pretty high incidence of hallucinations, mainly visual and auditory.
Those hallucinations can be very realistic and part of a general delirious state.
A typical progression of severe withdrawal is to have insomnia on the first night after
cessation, followed by psychosis and hallucinations at 36 to 48 hours.
The problems peak about 3 to 5 days after cessation.