Opioid withdrawal

Opioid withdrawal is a set of symptoms (a syndrome) arising from the sudden withdrawal or reduction of
opioids where previous usage has been heavy and prolonged.[1][2] Signs and symptoms of withdrawal can
include drug craving, anxiety, restless legs, nausea, vomiting, diarrhea, sweating, and an increased heart
rate. Opioid use triggers a rapid adaptation in cellular signalling pathways that means, when rapidly
withdrawn, there can be adverse physiological effects. All opioids, both recreational drugs and medications,
when reduced or stopped, can lead to opioid withdrawal symptoms. When withdrawal symptoms are due to
recreational opioid use, the term opioid use disorder is used, whereas when due to prescribed medications,
the term prescription opioid use disorder is used.[3] Opioid withdrawal can be helped by the use of opioid
replacement therapy, and symptoms may be relieved by the use of medications including lofexidine and
clonidine.[4]

Contents
Signs and symptoms
Pathophysiology
Diagnosis
Treatment and management
Acute withdrawal
alpha 2 adrenergic agonists
Withdrawal in opioid use disorder
Dangerous or ineffective treatments
Neonatal opioid withdrawal
See also
References

Signs and symptoms

Withdrawal from any opioid produces similar signs and symptoms. However, the severity and duration of
withdrawal depend on the type and dose of opioid taken and the duration and frequency of use.[5]

The symptoms of opioid withdrawal may develop within minutes or up to several days following reduction
or stopping.[1] Symptoms can include: extreme anxiety, nausea or vomiting, muscle aches, a runny nose,
sneezing, diarrhea, sweating and fever.[1] Males may also experience spontaneous ejaculations whilst
awake.[1]

Pathophysiology
Repeated dosages of opioids can quickly lead to tolerance and physical dependence. This is due to the
marked decrease in opioid receptor sensitivity caused by long-term receptor stimulation triggering receptor
desensitisation (in this case receptor internalisation).[2] Tolerance causes a decrease in opioid sensitivity,
impairing the efficacy of endogenous (our own body's) opioid molecules that function in multiple brain
regions. Opioids partially signal through the decrease in cellular cAMP. Cells with decreased cAMP adapt
to regulate cAMP and increase production. In the tolerant brain the sudden withdrawal of opioids coupled
with the reduced sensitivity to inhibitory signals from the endogenous opioid systems can cause abnormally
high levels of cAMP that may be responsible for withdrawal behaviours.[5] Similar changes may also be
responsible for the peripheral gastrointestinal effects such as diarrhea, as there is a reversal of the effect on
gastrointestinal motility.[6]

Due to the difference in lipophilicity and mode of release between opioid analgesics, the severity, and
duration of withdrawal symptoms may differ.

The followings are the general descriptions of duration of opioid withdrawal symptoms:[7]

High intake for a long duration (> 6 Months) is associated with a more severe level of
withdrawal symptoms.
Short-acting or slow-release opioids result in more rapid onset and shorter duration of
withdrawal symptoms.
Longer-acting opioids result in slower onset but longer duration of withdrawal symptoms.

Diagnosis
The diagnosis of opioid withdrawal requires recent use or exposure to opioids and symptoms consistent
with the disorder.[8] The severity of symptoms can be assessed by validated withdrawal scales, such as the
Clinical Opiate Withdrawal Scale (COWS).[9]

Treatment and management

Treatment for opioid withdrawal is based on underlying diagnostic features. A person with an acute opioid
withdrawal but no underlying opioid use disorder can be managed by slowly reducing opioids and
treatments aimed at the symptoms.[2]

Acute withdrawal

alpha 2 adrenergic agonists

A major feature of opioid withdrawal is exacerbated noradrenaline release in the locus coeruleus. Alpha 2
adrenergic agonists can be used to manage the symptoms of acute withdrawal. Lofexidine and clonidine are
also used for this purpose; both are considered to be equally effective, though clonidine has more side
effects than lofexidine.[10]

Withdrawal in opioid use disorder

The treatment of withdrawal in people with opioid use disorder also relies on symptomatic management
and tapering with medications that replace typical opioids, including buprenorphine and methadone. The
principle of managing the syndrome is to allow the concentration of drugs in blood to fall to near zero and
reverse physiological adaptation. This allows the body to adapt to the absence of drugs to reduce the
withdrawal symptoms. The most commonly used strategy is to offer opioid drug users long-acting opioid
drugs and slowly taper the dose of the drug. Methadone and buprenorphine are often used in treating opioid
withdrawal syndrome.[11]

Dangerous or ineffective treatments

The cost and expense of opioid replacement treatments have led to

some people trying treatments with limited evidence. At high
doses, loperamide has been reported by some drug users to
alleviate opioid withdrawal syndrome.[12] The doses reported in
the literature are associated with a strong risk of damage to the
heart.[13]
Buprenorphine patches can deliver
Neonatal opioid withdrawal the opioid drug via A transdermal
route, with long-lasting effects.

Many thousands of newborns each year are affected by being

exposed to opioids during their prenatal development.[14] Maternal
use of opioids has become prolific. The use of opioids during pregnancy creates a dependency in the
newborn who experiences withdrawal symptoms shown in clinical signs of opioid withdrawal. These signs
are grouped as the neonatal opioid withdrawal syndrome, also known as the neonatal abstinence
syndrome.[14] The central nervous system (CNS), and the autonomic nervous system (ANS) are affected.

Common signs associated with the CNS are high-pitched crying, reduced sleep, tremors, seizures,
gastrointestinal dysfunction, and vomiting. Common ANS-associated signs include sweating, hyperthermia,
yawning and sneezing, faster breathing rate, and nasal congestion.[14]

See also
Neonatal withdrawal
Opioid-induced hyperalgesia
Psychiatric diagnosis

References Suboxone tablet (Buprenorphine)

delivers the opioid drug through a
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