C a r d i o p u l m o n a r y I m a g i n g C l i n i c a l Pe r s p e c t i ve

Berkowitz et al.
Pulmonary Effects of Synthetic Marijuana

Cardiopulmonary Imaging
Clinical Perspective
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Pulmonary Effects of Synthetic

Marijuana: Chest Radiography and
CT Findings
Eugene A. Berkowitz1 OBJECTIVE. The purpose of this article is to present the first chest radiographic and CT
Travis S. Henry 1 descriptions of organizing pneumonia in response to smoking synthetic marijuana.
Srihari Veeraraghavan2 CONCLUSION. Chest radiographs showed a diffuse miliary-micronodular pattern.
Gerald W. Staton, Jr. 2 Chest CT images showed diffuse centrilobular nodules and tree-in-bud pattern and a histo-
Anthony A. Gal 3 pathologic pattern of organizing pneumonia with or without patchy acute alveolar damage.
This distinct imaging pattern should alert radiologists to include synthetic marijuana abuse
Berkowitz EA, Henry TS, Veeraraghavan S, in the differential diagnosis.
Staton GW Jr, Gal AA

Keywords: miliary-micronodular pattern, organizing
pneumonia, synthetic cannabinoids, synthetic marijuana,
tree-in-bud pattern
DOI:10.2214/AJR.14.13138
Received May 1, 2014; accepted after revision
October 7, 2014.
1
Department of Radiology and Imaging Sciences,
Cardiothoracic Division, Emory University School
ofMedicine, 1365 Clifton Rd NE, AT 508, Atlanta, GA
30322. Address correspondence to E. A. Berkowitz
(eberkow@emory.edu).
2
Department of Medicine, Division of Pulmonary, Allergy,
and Critical Care Medicine, Emory University School
ofMedicine, Atlanta, GA.
3
Department of Pathology and Laboratory Medicine,
Emory University School of Medicine, Atlanta, GA.
AJR 2015; 204:750757
0361803X/15/2044750
American Roentgen Ray Society
S
ynthetically produced cannabi-
noids are novel dangerous psycho-
active chemical concoctions
sprayed onto dried herbs and
plants that can be smoked to mimic the ap-
pearance and effects of cannabis. Usage is pre-
dominantly by teenagers and young adults.
Synthetic cannabinoid receptor agonists pro-
duce effects similar to the natural variety but
have a different chemical structure from delta-
9-tetrahydrocannabinol (THC), the main can-
nabinoid found in natural marijuana. Synthetic
cannabinoids are schedule I drugs, the most
restrictive category under the Controlled Sub-
stances Act, but are readily available across
the United States, and their use has been dra-
matically increasing [13], with a concomitant
increase in reports to poison control centers [4,
5] and emergency department visits [6].
Synthetic marijuana ranges from four to
660 times more potent than THC, depending
of the specific compound [7], and can cause
mood elevation, relaxation, panic or anxi-
ety, suicidal ideation and harmful thoughts,
altered perception, acute psychosis, hallu-
cinations, paranoia, agitation and violent
behavior, or the inability to move despite
being conscious [7, 8]. Tachycardia, hyper-
tension, arrhythmias, myocardial ischemia,
muscle spasms, seizures, tremors, and nau-
sea or vomiting have been reported as well
as withdrawal and addiction in regular users
[912]. To date, pulmonary involvement has
not been described to this extent, although
anecdotal reports suggest that severe po-
tentially life-threatening pulmonary conse-
quences can occur with smoking synthetic
marijuana [1315]. Because the chemicals
sprayed onto the dried herbs and plants may
vary between the several brands, the adverse
reactions may be protean. In this article, we
describe the chest radiographic and CT find-
ings with histopathologic findings of orga-
nizing pneumonia as a result of smoking
synthetic marijuana.
Materials and Methods
The institutional review board granted a waiver
for this retrospective review of case series. We re-
viewed the electronic medical records of four pa-
tients who presented with similar clinical, radi-
ologic, and histopathologic findings. CT studies
were performed using two scanners: BrightSpeed
(GE Healthcare) with the following parameters:
reconstruction thickness, 1.25 0.6 mm; pitch,
1.375:1; rotation time, 0.5 second; table speed,
27.5 mm/rotation; 120 kVp; 380 mA; 190 mAs;
and reconstruction kernel-chest and LightSpeed
(GE Healthcare) with the following parameters:
reconstruction thickness, 1.25 0.6 mm; pitch,
0.938:1; rotation time, 0.6 second; table speed,
18.75 mm/rotation; 120 kVp; minimum 50 to
maximum 350 mA with body mass index (BMI)
less than 30 or minimum 100 to maximum 440
mA with BMI 30 or greater; and reconstruction
kernel-chest. Table 1 summarizes the patient de-
mographics, clinical data, imaging findings, and
histopathologic diagnoses.
Results
Four men ranging from 18 to 24 years old
initially presented with pulmonary symp-

750 AJR:204, April 2015

 Pulmonary Effects of Synthetic Marijuana

TABLE 1: Patient Summary Data

Patient No.
Characteristic 1 2 3 4
Age (y) 20 24 21 18
Sex Male Male Male Male
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Synthetic marijuana Yes Yes Unknown type of marijuana Unknown type of marijuana
Symptoms Dyspnea, hypoxemia, Tachypnea, dyspnea, cough, Dyspnea, cough Cough, shortness of breath
chest pain tachycardia
Pulse oximetry (room air) (%) 79 80 82 84
WBC Elevated (transferred on Elevated (transferred on Elevated (transferred on Normal
steroids) steroids) steroids)
Infectious causea Negative Negative Negative Negative
Chest radiography Diffuse miliary-micronodular Diffuse miliary-micronodular Diffuse miliary-micronodular Diffuse miliary-micronodular
pattern and patchy foci of pattern pattern and patchy foci pattern
lower lobe atelectasis- pattern of lower lobe
consolidation atelectasis-consolidation
CT Diffuse centrilobular nodules Diffuse centrilobular nodules Diffuse centrilobular nodules Diffuse centrilobular nodules
and tree-in-bud pattern and tree-in-bud pattern and tree-in-bud pattern and tree-in-bud pattern
Specimens RUL, RLL Declined RUL, RML, RLL RUL, RML, RLL
Pathology report Organizing pneumonia NA Organizing pneumonia, patchy Organizing pneumonia
alveolar damage with
eosinophilia
NoteRUL = right upper lobe, RLL = right lower lobe, RML = right middle lobe, NA = not applicable.
aHIV-1, HIV-2, viral-fungal panels, Mycobacterium, sputum-blood cultures, bronchoscopy with bronchoalveolar lavage cultures all negative for infectious cause.

TABLE 2: Patient Outcomes

Patient No.
Characteristic 1 2 3 4
Clinical Chronic dyspnea, cough Chronic dyspnea, cough Death due to respiratory Mild residual symptoms,
failure improved pulmonary
function tests, and exercise
intolerance
Pulmonary function testing Moderate to severe airways Severe airflow limitation with NA Moderate air flow limitation;
obstruction air trapping, moderate mild decreased diffusion
reduced diffusion capacity capacity
Follow-up CT Bronchiolitis obliterans None available NA Bronchiolitis obliterans
NoteNA = not applicable.

toms, an abnormal physical lung exami-
nation, and decreased pulse oximetry lev-
els on room air, ranging from 79% to 84%
(Table 1). Initial chest radiography showed
diffuse miliary-micronodular patterns in all
four patients (Figs. 1A, 1B, 2A, 2B, 3A, 3B,
4A, and 4B). Chest CT displayed in lung
windows showed diffuse tiny centrilobular
nodules and tree-in-bud pattern in all four
patients (Figs. 1C, 1D, 2C, 2D, 3C, 3D, 4C,
and 4D). Extensive clinical and laboratory
workup did not show an infectious source
in any of the four patients (Table 1). Vid-
eo-assisted thoracoscopic surgical biopsy
of three of the four patients (patient 2 de-
clined) showed organizing pneumonia with
plugs of loose organizing granulation tissue
or intraalveolar fibrin in the distal bronchi-
oles, scattered eosinophilia (with or without
giant cells), and patchy bronchiolocentric
fibrosis with or without small patchy foci of
acute lung injury (Figs. 1E1G, 3E, 3F, 4E,
4F, and Table 1).
Patient 3 died of respiratory failure dur-
ing the initial hospital admission. Three pa-
tients were seen on follow-up in the pulmo-
nary clinic: patient 1 had moderate to severe
air flow limitations and a bronchiolitis ob-
literans pattern on CT, patient 2 had severe
airflow limitation and air trapping on pul-
monary function testing with functional lim-
itation, and patient 4 had mild obstruction
with air trapping and a bronchiolitis obliter-
ans pattern on CT (Table 2).
Discussion
This article is the first case series in the lit-
erature showing the bronchopulmonary ef-
fects of smoking synthetic marijuana, result-
ing in a distinct MDCT imaging pattern of
diffuse centrilobular nodules and tree-in-bud
pattern in response to airways-centered in-
jury of organizing pneumonia with or with-
out patchy foci of acute lung injury. When
burned and inhaled, the cocktail of chemical
gases may cause damage to the bronchiolar
endothelium, leading to acute respiratory dis-
tress that may progress to respiratory failure.
These four patients had strikingly similar
clinical, radiologic, and histopathologic find-
ings. These findings have not been previous-
ly described with the inhalation of natural

AJR:204, April 2015 751


marijuana despite its extensive use. One case
report from a toxicology journal described
similar radiographic and CT findings with-
out a histopathologic diagnosis [14]. All four
patients had similar CT patterns of diffuse
centrilobular nodules and tree-in-bud pattern
throughout the lungs. The tree-in-bud pattern
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is caused by dilated bronchioles filled with
mucus, pus, intraluminal granulation tissue,
cells, or blood. The differential diagnosis
for diffuse centrilobular nodules and tree-
in-bud pattern includes infectious bronchi-
olitis (Mycobacterium including tuberculo-
sis, fungi, mycoplasma-bacteria, and virus),
congenital airways diseases (cystic fibrosis,
dyskinetic cilia syndrome, bronchiectasis),
aspiration or toxic inhalation connective tis-
sue disorders (follicular bronchiolitis associ-
ated with Sjgren syndrome and rheumatoid
arthritis), idiopathic (obliterative bronchiol-
itis, panbronchiolitis), immunologic (aller-
gic bronchopulmonary aspergillosis, immu-
nodeficiency disorders), neoplastic disease
(adenocarcinoma, chronic lymphoid leuke-
mia, primary pulmonary lymphoma), and
microangiopathic tumor emboli (rare non-
airway-related tree-in-bud pattern) [16, 17].
The histopathologic finding of organizing
pneumonia in patients who presented with
diffuse centrilobular nodules and tree-in-
bud pattern on chest CT has been described
in only two other cases without a cause [18,
19]. We were able to confirm the use of syn-
thetic marijuana before the development of
symptoms in two of the patients (patients 1
and 2); patients 3 and 4 did smoke marijuana
before the onset of symptoms but were un-
sure if they had smoked synthetic marijuana,
natural marijuana, or a combination of both.
On the basis of the rare identical presentation
in a short time period when synthetic mari-
juana was freely available (3 of the 4 patients
presented within few months of each other),
we believe that the use of synthetic marijua-
na likely played a causative role in their pul-
monary disease.
A series of case reports, including in the
lay press [20], highlights the widespread use
and the severity of the health effects with
synthetic marijuana use [2126]. Several
deaths and serious illnesses have been re-
ported, including a teenager who developed
respiratory failure and needed lung trans-
plantation after smoking synthetic marijua-
na [27]. With the use of varied chemicals in
these concoctions, it is not surprising to see
multiorgan involvement in case reports of
acute kidney injury [28, 29] and myocardial
752 AJR:204, April 2015
Berkowitz et al.
infarction [30]. Normal urine tests for mari-
juana metabolites will be negative if the pa-
tient has smoked synthetic marijuana alone;
commercial testing for oral fluid, blood, and
urine to detect up to 22 synthetic cannabi-
noid compounds (blood and oral fluid) and
metabolites (urine) are available [31].
This article should alert radiologists and
treating physicians in the emergency depart-
ment or ICU of the chest radiographic and
CT manifestations of synthetic marijua-
na use. If the chest radiograph shows a dif-
fuse miliary-micronodular pattern or chest
CT image shows diffuse centrilobular nod-
ules and tree-in-bud pattern, the radiologist
should include synthetic marijuana use in the
differential diagnosis and question the pa-
tient or perform urine or blood testing to de-
tect synthetic marijuana metabolites.
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A B

C D
Fig. 1Patient 1: 20-year-old man who smoked synthetic marijuana and presented with progressive shortness of breath. Patient had diffuse centrilobular
nodules and tree-in-bud pattern on chest CT with histopathologic diagnosis of organizing pneumonia.
A and B, Chest radiograph (A) and magnified view (B) show diffuse miliary-micronodular pattern with patchy focal consolidation at lung bases. Patchy foci of
more discrete consolidation represented combination of atelectasis and acute lung injury.
C and D, Axial (C) and coronal (D) chest CT images in lung windows with maximum intensity projection show diffuse centrilobular nodules and tree-in-bud
pattern. Note sparing of periphery of parenchyma, differentiating these nodules from miliary-hematogenous or perilymphatic distribution.
(Fig. 1 continues on next page)

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 Berkowitz et al.
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E
Fig. 1 (continued)Patient 1: 20-year-old man who
smoked synthetic marijuana and presented with
progressive shortness of breath. Patient had diffuse
centrilobular nodules and tree-in-bud pattern on
chest CT with histopathologic diagnosis of organizing
pneumonia.
EG, Histopathology images of video-assisted
thoracoscopic surgery open lung biopsies show
organizing pneumonia with bronchiolocentric
distribution of patchy fibrosis with tufts of young,
basophilic collagen and inflammatory cells (arrow)
filling distal bronchioles and extending into adjacent
alveoli.

A B
Fig. 2Patient 2: 24-year-old man who smoked synthetic marijuana and presented with dry cough, progressive shortness
of breath, and wheezing. This patient had diffuse centrilobular nodules and tree-in-bud pattern on CT. A and B, Chest
radiograph (A) and magnified view (B) show diffuse miliary-micronodular pattern. Appearance is similar to that seen in
patient in Figure 1.
(Fig. 2 continues on next page)

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 Pulmonary Effects of Synthetic Marijuana
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C D
Fig. 2 (continued)Patient 2: 24-year-old man who smoked synthetic marijuana and presented with dry cough, progressive
shortness of breath, and wheezing. This patient had diffuse centrilobular nodules and tree-in-bud pattern on CT.
C and D, Axial (C) CT image using bone algorithm and coronal (D) chest CT image displayed in lung windows with maximum
intensity projection show diffuse centrilobular nodules and tree-in-bud pattern. Patient 2 declined video-assisted thoracoscopic
surgical open lung biopsy.

A B
Fig. 3Patient 3: 21-year-old man who smoked marijuana daily but did not recall if it was synthetic marijuana, natural marijuana,
or combination. Patient had progressive shortness of breath, cough, and hemoptysis.
A and B, Chest radiograph (A) and magnified view (B) show diffuse miliary-micronodular pattern.
(Fig. 3 continues on next page)

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 Berkowitz et al.
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C D
Fig. 3 (continued)Patient 3: 21-year-old man
who smoked marijuana daily but did not recall if
it was synthetic marijuana, natural marijuana, or
combination. Patient had progressive shortness of
breath, cough, and hemoptysis.
C and D, Axial (C) and coronal (D) chest CT images
in lung windows with maximum intensity projection
show diffuse centrilobular nodules and tree-in-bud
pattern. Patchy foci of more discrete consolidation
were thought to represent combination of atelectasis
and acute lung injury.
E and F, Video-assisted thoracoscopic surgical wedge
biopsy images show organizing pneumonia and patchy
foci of superimposed acute lung injury. There was
bronchiolocentric injury (arrow, E) and component
of diffuse alveolar damage with intraalveolar fibrin,
inflammation, pneumocyte hyperplasia, and foci of
increased tissue eosinophilia (F).

E F

A B
Fig. 4Patient 4: 18-year-old man who presented with chest pain, shortness of breath, cough, and wheezing after heavy marijuana
use of unknown type or combination.
A and B, Chest radiograph (A) and magnified view (B) show faint diffuse miliary-micronodular pattern.
(Fig. 4 continues on next page)

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C D
Fig. 4 (continued)Patient 4: 18-year-old man who
presented with chest pain, shortness of breath,
cough, and wheezing after heavy marijuana use of
unknown type or combination.
C and D, Axial (C) and coronal (D) chest CT images
in lung windows with maximum intensity projection
show subtle diffuse centrilobular nodules and tree-
in-bud pattern.
E and F, Video-assisted thoracoscopic surgical
wedge biopsy (E) shows multifocal organizing
pneumonia involving many bronchioles (arrows). At
higher magnification (F), young basophilic collagen
and inflammatory cells are present in bronchiolar
lumen (arrow).

E F

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