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Chapter 36
Cocaine-Induced Headache
UtkuTopbaş andAynurÖzge
36.1 Introduction
Headache attributed to a substance or its withdrawal is a distinct diagnostic category
in the International Classication of Headache Disorders, third edition (ICHD-3),
encompassing headaches triggered by the use or cessation of various pharmacological and non-pharmacological agents [1]. Among these, cocaine-induced headache
represents a relatively rare but clinically relevant condition, mainly due to the growing global use of cocaine and its neurovascular complications [2].
Cocaine acts as a powerful sympathomimetic agent by inhibiting the reuptake of
dopamine, norepinephrine, and serotonin, leading to heightened adrenergic activity
and resultant vasoconstriction, blood pressure elevation, and neuronal excitability,
all of which are implicated in the pathogenesis of acute headache [2, 3]. While some
users report cocaine as a headache reliever—particularly in the context of cluster
headache management via intranasal administration—others develop new-onset or
worsening headaches shortly after use [4]. These headaches are typically bilateral,
throbbing in nature, and of moderate severity, developing within an hour of cocaine
use and resolving within 72h, as dened by the ICHD-3 criteria [1].
Chronic cocaine use has also been associated with more serious complications,
such as reversible cerebral vasoconstriction syndrome (RCVS), intracerebral hemorrhage, arterial dissection, and structural white matter changes observable via neuroimaging [5–8]. These ndings underscore the complexity and potential severity of
U. Topbaş
Toros State Hospital, Mersin, Turkey
A. Özge (
Mersin State Hospital, Mersin, Turkey
Switzerland AG 2026
D. Uludüz et al. (eds.), Rare Causes of Headache Disorders, Headache,
https://doi.org/10.1007/978-3-032-10242-3_36
*)
341© The Author(s), under exclusive license to Springer Nature
342
U. Topbaş and A. Özge
cocaine’s impact on the central nervous system. Cocaine’s role in triggering seizures and psychiatric agitation further complicates its clinical presentation [2, 9].
Despite its inclusion in formal headache classications, cocaine-induced headache remains underrecognized in clinical settings due to factors such as patient
reluctance to disclose substance use and overlapping symptoms with other neurological or psychiatric conditions [10]. Moreover, regional variations in cocaine
purity and use patterns may inuence its clinical effects and reporting [11].
Considering these challenges, a high index of suspicion and careful history-taking
are essential when evaluating patients presenting with acute headache in emergency
or critical care settings.
This chapter presents a detailed case illustrating the complex interplay between
acute headache, seizure activity, and underlying vascular pathology in the context of
recent crack cocaine use, offering an opportunity to review diagnostic and therapeutic approaches for this uncommon but essential headache subtype.
36.2 Pathophysiology
Cocaine, chemically known as benzoylmethylecgonine, is an ester alkaloid derived
from the leaves of the coca plant. Due to its ester structure and high bioavailability,
cocaine can easily cross cell membranes and quickly produce systemic and neurological effects. It can be administered to the body through various routes: intranasal
(snorting), inhalation (crack), oral consumption, and intravenous (IV) injection [12].
Cocaine causes signicant vasoconstriction in the central nervous system and
inhibits the reuptake of the neurotransmitters dopamine and noradrenaline in presynaptic neurons. This leads to an excessive accumulation of dopamine and noradrenaline in the synaptic cleft, which further intensies the vasoconstriction.
Additionally, cocaine stimulates the release of noradrenaline and adrenaline from
the adrenal medulla, which enhances systemic vasoconstriction. The increased levels of dopamine in the mesolimbic pathway and the nucleus accumbens are responsible for pleasurable and addictive effects. The metabolites of cocaine, namely
benzoylecgonine and ecgonine, also lead to vasoconstriction. Since these metabolites have longer half-lives, the secondary effects of vasoconstriction continue even
after the initial effects of cocaine have faded [2].
So far, three different types of headache associated with cocaine use have been
described. Type 1 usually occurs after intravenous or inhaler use. Immediately after
ingestion, a bilateral throbbing headache of moderate intensity occurs which may
last up to three days. This pain may be accompanied by focal neurologic ndings.
Severe vasoconstriction occurs immediately after cocaine ingestion. This leads to
transient ischemia caused by the increase in noradrenaline in the presynaptic cleft,
which results in pain. Additionally, cocaine enhances calcium-mediated contractility in vascular smooth muscle cells, thereby deactivating the compensatory vasomotor mechanisms. As a result of prolonged vasoconstriction, complications such as
36 Cocaine-Induced Headache
343
stroke, subarachnoid hemorrhage, and RCVS can be seen after this type of headache
[2, 13].
Type 2 headache usually occurs in individuals who engage in binge intranasal
usage of cocaine. The headache disappears temporarily after intranasal intake and
intensies after 45–90minutes. After each intranasal intake, the headache is alleviated and becomes more severe with the next intranasal intake. Intranasal use of
cocaine in patients with cluster-type headache may be due to the acute anesthetic
effect of cocaine in the sphenopalatine ganglion. The reduction in headache is
explained by an increase in presynaptic serotonin in the acute use of cocaine.
Increased levels of serotonin can improve pain by activating the 5-HT1B and
5-HT1D receptors in the trigeminal ganglia, similar to the action of triptans.
However, with prolonged cocaine use, there is a secondary depletion of presynaptic
serotonin, which can lead to an exacerbation of pain [2, 13, 14].
Type 3 headache is a type of headache related to cocaine withdrawal rather than
cocaine use. Chronic use of cocaine causes upregulation of postsynaptic dopaminergic, serotoninergic, and noradrenergic receptors. Therefore, these neurotransmitters
are depleted in the presynaptic cleft faster than usual. Headaches begin 2–4weeks
after cocaine withdrawal and can persist for up to 9months. This type of headache
is included in the ICHD-3 headache attributed to withdrawal from chronic use of
other substance [1, 2, 13].
36.3 Case Presentation
A 29-year-old male named Mehmet was brought to the emergency unit by his wife.
She reported that her husband had been behaving strangely, yelling at her for no
apparent reason and continuously pacing around the house. He was experiencing a
bilateral throbbing headache on his temporoparietal region rated as 6 out of 10in
severity, accompanied by nausea. However, he did not have photophobia, phonophobia, or osmophobia. Mehmet appeared agitated, mildly confused, and disoriented regarding time. His pupils were mid-dilated bilaterally, and his skin was dry.
Both the Brudzinski and Kernig signs were negative, and he exhibited no neck stiffness. The fundoscopic examination showed no signs of papilledema. At the time of
admission, his blood pressure was recorded as 150/87mm Hg, and his body temperature was 37°C. Blood tests indicated that his creatinine kinase levels were
moderately elevated, three times higher than the standard upper limit. Both he and
his wife denied using any substances. However, his medical records indicated that
he was currently on probation for illicit drug use. Twelve months ago, he had a seizure after using drugs and was discharged with levetiracetam. He refused to take
any medications as advised by the doctors. After one hour, his headache worsened
without changing in characteristics. We administered 1000 mg of intravenous
paracetamol for his headache and performed a computed tomography (CT) scan.
The CT revealed a space-occupying mass lesion in the left temporal lobe, with no
hemorrhages detected. Upon returning to the CT room and then to the emergency
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U. Topbaş and A. Özge
room, the patient experienced generalized tonic–clonic seizures that lasted for one
minute. We administered IV diazepam to treat the seizures, but he did not respond
to verbal stimuli for one hour following the rst seizure. He then had a second seizure episode, leading us to conrm status epilepticus. We treated him with 15mg/
kg of IV phenytoin over 45minutes and subsequently transferred him to the intensive care unit (ICU). We collected a urine sample to send to a toxicology laboratory
for substance use screening. A lumbar puncture could not be performed due to the
presence of a temporal mass lesion. Instead, we conducted an urgent magnetic resonance imaging (MRI) with contrast and MRA to rule out the possibility of subarachnoid hemorrhage. The MRI revealed a lesion in the left temporal lobe that resembled
a vascular abnormality (see Fig.36.1). The MRA showed no signs of an aneurysm
or arterial rupture; it only revealed vascular and microvascular tangles in the left
temporal lobe, with no extravascular contrast enhancement, consistent with arteriovenous malformation (AVM; see Fig.36.2).
In the ICU, his mental status returned to baseline after 12hours. He was awake
but extremely agitated, attacking everyone around him and yelling. He even began
to harm himself by hitting the medical staff. We consulted the psychiatry department, and they advised starting treatment with 5mg of haloperidol and 5mg of
biperiden administered intramuscularly. We initiated the treatment, and he soon fell
asleep again.
After another 10hours, he woke up and complained of a headache and nausea.
He nally admitted that he had smoked two crack cocaine cigarettes two hours
before arriving at the emergency unit. His headache remained the same as it had
been at the beginning: a bilateral, throbbing pain in the temporal regions. The pain
was moderately severe, so we treated him with IV dexketoprofen. By the next day,
his headache had entirely resolved. A urine sample revealed the presence of cocaine
metabolites. He refused further treatment and wanted to go home. We informed him
Fig. 36.1 MRI with non-contrast revealed left temporal T1 and T2 hypointensities (red arrows)
resembling berry-like vascular structures. MRI Magnetic resonance imaging
36 Cocaine-Induced Headache
Fig. 36.2 MRA shows intravascular contrast enhancements and microvascular tangles on the left
MCA.Findings consistent with left temporal lobe arteriovenous malformation. MCA Middle cerebral artery, MRA Magnetic resonance angiography
345
of the risks associated with refusing tests and treatment. After he had signed the
necessary forms, we discharged him with a prescription for valproic acid, 500mg to
be taken twice daily.
36.4 Clinical Presentation (Table36.1)
Cocaine-induced headache remains a diagnostically challenging entity due to its
variable clinical manifestations and frequent overlap with other neurological or psychiatric conditions. According to the ICHD-3 criteria, such headaches typically
present within one hour of cocaine administration and resolve spontaneously within
72hours [1]. However, real-life clinical presentations, such as the case described
here, often deviate from textbook denitions, involving more complex symptomatology and overlapping syndromes.
Cocaine exerts its effects primarily through the inhibition of monoamine reuptake, resulting in intense sympathomimetic stimulation. This neurochemical surge
may contribute to vasoconstriction, hypertension, and increased excitatory neurotransmission, mechanisms implicated in the pathogenesis of cocaine-related headache [2]. Furthermore, cocaine use has been associated with serious cerebrovascular
complications, including reversible cerebral vasoconstriction syndrome (RCVS),
arterial dissections, and intracranial hemorrhages, particularly in chronic or highdose users [3–5].
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U. Topbaş and A. Özge
Table 36.1
8.1.5 Cocaine-induced headache
Description:
Headache developing within 1hour of, and caused by, administration of cocaine by any route. It
resolves spontaneously within 72hours
Diagnostic criteria:
A.Any headache fullling criterion C
B.Any route has administered cocaine
C.Evidence of causation demonstrated by all of the following:
1. Headache has developed within 1hour of cocaine administration
2. Headache has resolved within 72hours after cocaine administration
3. Headache has at least one of the following four characteristics:
(a) Bilateral
(b) Mild-to-moderate intensity
(c) Pulsating quality
(d) Aggravated by physical activity
D.Not better accounted for by another ICHD-3 diagnosis
Comment: The principal routes of cocaine administration are oral (“chewing”), intranasal
(“snorting”), intravenous (“mainlining”), and inhalation (smoking)
Diagnostic criteria of cocaine-induced headache according to the ICHD-3
36.5 Diagnostic Algorithm
Neuroimaging ndings in patients presenting with headaches and cocaine use vary
widely. In some cases, cocaine can unmask or exacerbate pre-existing vascular malformations, such as arteriovenous malformations (AVMs) or berry aneurysms, by
triggering acute hypertensive episodes [2]. Cocaine-induced cerebral vasculopathy
may be reversible, but the risk of permanent structural damage, particularly in the
white matter, has been demonstrated using diffusion tensor imaging techniques [6].
36.6 Treatment
Interestingly, cocaine is paradoxically used in some clinical contexts as an abortive
agent for cluster headaches due to its local vasoconstrictive and anesthetic effects
when applied intranasally [7]. However, such off-label applications are not without
risk and may lead to cranial nerve complications or dependency [7, 8].
Seizure activity, often observed in patients with acute cocaine toxicity, may be
the result of direct cortical excitability or secondary to vascular insults [2]. The
presence of psychiatric agitation or psychosis, as seen in the described patient, also
aligns with the known neurobehavioral sequelae of cocaine use, further complicating the diagnostic picture [2, 9].
From a public health perspective, rising trends in cocaine purity and regional
variability in its street formulations must be considered as they can inuence both
36 Cocaine-Induced Headache
347
the potency and the pattern of adverse effects [10]. Despite the clinical relevance,
cocaine-induced headache is likely underdiagnosed, partly due to patient hesitancy
to report substance use and the lack of awareness among healthcare providers [2].
Psychosocial interventions and pharmacologic strategies remain central to addressing cocaine addiction, yet effective management of headache in this population
remains an area requiring further study [11, 15].
36.7 Conclusion
• Cocaine-induced headache is a recognized secondary headache disorder under
ICHD-3, yet remains underdiagnosed due to patient non-disclosure and clinical
overlap with other neuropsychiatric conditions.
• Cocaine’s neurovascular effects, including vasoconstriction, excitotoxicity, and
hypertension, are central to headache pathophysiology and may precipitate life-
threatening complications such as RCVS, intracerebral hemorrhage, or arterial
dissections.
• Neuroimaging plays a crucial role in excluding structural lesions and vascular
abnormalities in patients presenting with headaches and a history of cocaine use.
• Cocaine use may unmask latent cerebrovascular pathologies, such as arteriove-
nous malformations, which can exacerbate clinical presentation and complicate
management.
• While intranasal cocaine has historically been used in procedures and cluster
headache management, this practice carries risks, including cranial nerve
involvement and dependency.
• Seizure activity and psychiatric agitation are common comorbidities, underscor-
ing the need for a multidisciplinary approach involving neurology, emergency
medicine, and psychiatry.
• Epidemiological studies are needed to determine the true prevalence and patterns
of cocaine-induced headaches in different populations, especially in emergency
settings.
• Further research into biomarkers and neuroimaging correlates may help differen-
tiate cocaine-induced headaches from other secondary headaches and identify
high-risk patients early.
• The development of specic clinical protocols for headache evaluation in indi-
viduals with known or suspected substance use could improve detection and
reduce complications.
• There is a need for prospective studies evaluating the effectiveness of different
acute and preventive headache treatments in the context of active or past
cocaine use.
• As substance abuse trends evolve, longitudinal studies assessing the impact of
changing cocaine purity and formulations on neurological outcomes, including
headache, are warranted.
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U. Topbaş and A. Özge
• Finally, integration of addiction services with headache and emergency care may
offer a more holistic treatment model, improving long-term outcomes for patients
with substance-induced neurological symptoms.
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Part VII
Headache Attributed to Disorder of
Homoeostasis