Surgical considerations of
marijuana use in elective
Henry B. Huson
, Tamara Marryshow Granados
, Yvonne Rasko
Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA, USA
Department of Family Medicine, Brown University, Pawtucket, RI, USA
Division of Plastic Surgery, University of Maryland Medical Center, Baltimore, MD, USA
E-mail address: firstname.lastname@example.org (H.B. Huson).
Background: Marijuana consumption is estimated as upwards of 9.5% of the U.S.
adult population. Nevertheless, few trials exist on potential implications for surgical
outcomes amongst users.
Methods: A current literature review explored marijuana’seﬀects to answer: (I)
How is marijuana use screened for in clinical and pre-operative settings? (II)
What are potential surgical complications of marijuana use? (III) How should
surgeons handle patient marijuana use regarding elective surgery? (IV) Are
marijuana’seﬀects the same or diﬀerent from those of tobacco?
Results: In acute settings, marijuana’seﬀects peaked at approximately 1 hour post
initiation, lasting 2e4 hours. Marijuana increased cardiac workload, myocardial
infarctions and strokes in young, chronic users. Cannabis caused similar
pulmonary complications to those of a tobacco smoker. Marijuana caused airway
obstruction and increased anesthetic dosages needed to place laryngeal airways.
Use within 72 hours of general anesthesia was advised against. In vitro and
in vivo studies were contradictory regarding prothrombic or antithrombotic eﬀects.
Conclusions: Marijuana use is problematic to surgeons, left without evidence-
based approaches. In emergency settings, marijuana use may be unavoidable.
26 June 2018
5 September 2018
5 September 2018
Cite as: Henry B. Huson,
Tamara Marryshow Granados,
considerations of marijuana
use in elective procedures.
Heliyon 4 (2018) e00779.
2405-8440/Ó2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
However, further research would provide much needed information to guide
Keywords: Evidence-based medicine, Surgery, Health profession
Marijuana use dates back to 2727 BC to Chinese Emperor Shen Nung. After
spreading through the Greek and Roman empires and into the Islamic empire of
North Africa and the Middle East, it was brought to the Western hemisphere by
the Spanish . Originally lauded for its utility as ﬁber, it was not until its migration
into North America that it began to be used in a similar fashion as it is today. Used in
the form of hemp, it was seen throughout society as rope, clothing and even paper.
While marijuana has been used by Americans recreationally for years, it is a subject
that is becoming more commonplace in our modern society. According to the Na-
tional Institutes of Health, marijuana use in 2015e2016 rose from 4.1% to 9.5%
of the U.S. adult population . With more states eliminating the legal ramiﬁcations
of its use and a growing debate about its federal legality, this is a subject that
routinely makes local and national headlines. With a diverse array of commercial
products becoming available from chocolate squares to oral sprays, marijuana is
also no longer restricted to a rolled cigarette.
The medical community has also joined the debate. The most obvious correlation
between medicine and marijuana is medicinal marijuana. Marijuana’seﬀects have
been well documented, allowing the push for its use as medicine within multiple spe-
cialities. Proponents of its use point to its eﬀects on the endocannabinoid system.
Studies show that through its impact on diﬀerent pathways it may be used as an anal-
gesic, immunosuppressant, muscle relaxant, anti-inﬂammatory agent, appetite
modulator, antidepressant, antiemetic, bronchodilator, neuroleptic, antineoplastic
and antiallergen . Medical marijuana also diﬀers in chemical composition, con-
taining a higher tetrahydrocannabinol (THC) concentration and less cannabinol
than the recreational version. This is even before taking into consideration the
various extraneous agents that may be found within the available recreational
There is however, very little, if any research evaluating marijuana’s use in surgery.
This paucity of literature presents a problem. While many surgeons may ask about
recreation drug use including marijuana, many other drugs have established evi-
dence based outcomes that allow variation in surgical planning as needed. However,
when it comes to marijuana, surgeons are left to determine what to do with this in-
formation on their own.
2405-8440/Ó2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
Despite the multiple studies on the physiologic eﬀects of marijuana use, clinical
studies, if any, are not cited in the medical literature. This study reviews the literature
available on marijuana’seﬀects and discusses potential complications that may
result within the surgical setting. With a reported estimation of 10%e20% of patients
between the ages of 18 and 25 years regularly using marijuana , this review seeks
to become an initial step for further exploration of the subject and to reveal why there
is a need for more in-depth research.
2. Main text
2.1.1. Study collection
A search on the eﬀects of marijuana, marijuana and elective surgery, and marijuana’s
eﬀects on surgery was undertaken in PubMed, Medline, EMBASE, Google.com and
Scholar.google.com. Articles were reviewed using the keywords "marijuana,"
"elective surgery," "surgery," “anesthesia,”“complication,”“THC,”“tobacco”and
"cannabis." After removing duplicates, 263 studies resulted. After articles were
identiﬁed, attention was paid to study design, type, outcomes and publication. The
authors independently reviewed titles and abstracts to ascertain relevance to the
topic at hand. Authors also searched reference lists of included studies as well as
other narrative reviews.
2.1.2. Data consideration
Due to limited research and reviews on this subject, information was utilized from
articles on surgery in various ﬁelds, such as orthopedic, dental and bariatric with
anesthesia considerations and general topics related to marijuana also examined.
The following information was gathered: marijuana’s prevalence in the United
States, marijuana’seﬀects on the cardiovascular system and pulmonary system, po-
tential coagulopathies, marijuana’seﬀects in relation to anesthesiology, evidence
based screening methods for recreational drug use, potential surgical complications
that may result from marijuana use, and recommendations on marijuana use and
Information pulled from the literature was used to answer the following key ques-
tions: (I) How is marijuana use screened for in clinical and pre-operative settings?
(II) What are potential complications in the surgical setting of marijuana use? (III)
How should surgeons handle patient marijuana use regarding elective surgery?
(IV) Are marijuana’seﬀects the same or diﬀerent from those of tobacco?
2405-8440/Ó2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
2.2.1. Pharmocological eﬀects
When marijuana is smoked, THC and other cannabinoids are absorbed rapidly
through the lungs with eﬀects peaking in 15 minutes. These eﬀects can persist for
up to a dose-dependent 4 hours in the acute setting. When ingested orally however,
onset of eﬀects is slower (15 minutes versus 90 minutes) but has a longer duration of
action (4 hours versus 5e6 hours), due to continued absorption in the gut. This is
despite a lower bioavailability due to ﬁrst-pass metabolism by the liver which results
in a blood concentration 25% of what is obtained if smoked. The cognitive/psycho-
motor eﬀects can be present for up to 24 hours regardless of administration route .
Cannabinoids are highly lipid soluble. This leads to a slow release into the blood-
stream with a single dose not fully eliminated for up to 30 days .
The cardiovascular eﬀects of marijuana use range from benign to worrisome based
on the timeline of use and dosage. In a series single blind study comparing the eﬀects
of high and low doses of THC in healthy young men, tachycardia was induced
beginning within the time of inhalation, and persisting at least 90 minutes, with
the maximum heart rate reached at an average of 30 minutes. The study also found
a signiﬁcant elevation in systolic and diastolic blood pressures as well as the pres-
ence of premature ventricular contractions (PVCs) in subjects who received the
higher doses. These experiments showed a correlation between the dose and the ta-
chycardic and cardiovascular changes . In addition, Malit et al.’sstudy on the ef-
fects of intravenous THC found the majority of patients to exceed the 100 beats per
minute mark but also experience intermittent spikes in heart rate with a possible eti-
ology of psychological distress . Beaconsﬁeld et al. postulated a mechanism of
beta adrenergic stimulation for the tachycardia as he was able to block the tachy-
cardia with the use of propranolol .
Pharmacology lays credence to this. At lower or moderate doses, marijuana increases
sympathetic activity reducing parasympathetics and producing an elevation in heart
rate, cardiac output and blood pressure. However, the opposite is true as the dosage in-
creases. At high doses, the parasympathetic system takes over, leading to bradycardia
and hypotension with animal studies postulating that the sympathetic inhibition occurs
due to the bioactive constituent of cannabis’seﬀects on the CB1 receptors .
In addition to sinus tachycardia, marijuana use has been linked to multiple electro-
cardiogram (ECG) changes in various case reports. Daccarrett et al. found Brugada-
like changes in a 19 year old male with a known history of cannabis use and no
anatomical/functional abnormalities . A case was also reported in which
cannabis use was linked to the development of atrial ﬂutter and atrial ﬁbrillation
, while other studies have reported the presence of sinus bradycardia and AV
Marijuana use also has a role as a risk factor for myocardial infarction. Aronow et al.,
found that while comparing marijuana to placebo, cannabis causes an increase in car-
boxyhemoglobin, a resultant increase in myocardial oxygen demand, decrease in ox-
ygen supply as well as an induction of platelet aggregation . One case report
showed a 21 year old male who presented with a ST elevation myocardial infarction
due to plaque rupture as a complication of marijuana use . In Mittleman et al.’s
analysis of over 3,800 cases of myocardial infarction, 124 patients reported use
within the last year of which 37 reported use within 24 hours, with 9 reporting
use within an hour of the event. The study found a statistically signiﬁcant 4.8
fold increase in myocardial infarction within the ﬁrst hour of marijuana use
(P <.001). In fact, as THC content of marijuana increases, there are a growing num-
ber of clinical studies demonstrating the association between cannabis use and
adverse cardiovascular events. One such study followed 1913 adults prospectively
and demonstrated that in patients with prior myocardial infarction, marijuana use
up to once per week increased risk of death 2.5 fold while more frequent use yielded
a fourfold risk of dying .
Marijuana has also been reported as a risk factor for stroke. Over 80 cases have been
reported in which patients had strokes, with a higher prevalence of ischemic strokes,
that were associated with either a recent increase, in the days leading up to the event,
or chronic history of heavy marijuana use. They believed that the marked swings in
blood pressure or the reversible cerebral vasoconstriction that resulted from mari-
juana use were likely mechanisms of stroke but admitted that no ﬁrm conclusions
could be drawn without further studies . In addition, Lawson reported a similar
belief that drug induced vasospasm was a plausible explanation for TIAs, but also
with the caveat that due to the confounding medications/illicit substances being
used in his patient, no direct association could be determined .
Also of interest is marijuana use’seﬀect on other cardiovascular vessels. When
cohort studies were performed comparing marijuana users with resultant limb arter-
itis to patients suﬀering from thromboangiitis obliterans, marijuana associated arter-
itis occurred in younger, usually male patients with a unilateral, lower limb as the
common presentation .
The most common route of marijuana administration is inhalation via smoking. Due
to the unﬁltered nature of the marijuana cigarette compared to commercially avail-
able tobacco cigarettes, the amount of carcinogens and irritants, like tar, that enter
the upper airway is increased  with approximately a three-fold increase in tar
inhalation and one third more tar deposition in the respiratory tract . More spe-
ciﬁcally, the tar produced from cannabis smoke contains greater concentration of
benzanthracenes and benzopyrenes (each a carcinogen) than tobacco smoke .
In addition, as compared to smoking tobacco, there is a two-thirds greater puﬀvol-
ume, one-third greater depth of inhalation and a four-fold longer breath-holding
time, all of which are common practices to try to maximize THC absorption, which
is around 50% of cigarette content . These practices result in ﬁve times the
amount of carboxyhemoglobin levels as compared to the typical tobacco smoker
 despite the presence of similar quantities of carbon monoxide from the incom-
plete combustion of the organic compounds found within each product . In re-
porting his case, Schwartz theorized that high temperatures in which marijuana burns
compared to tobacco may increase the irritancy of marijuana to the mucous mem-
branes . While the higher temperature is a possibility, the evidence of mari-
juana’s irritancy is well documented. In a cohort study comprised of 40 healthy
patients, Roth et al. showed that cannabis smokers had signiﬁcantly increased visual
bronchitis index scores resulting from large airway epithelial damage, edema, and
erythema. On mucosal biopsy, goblet cell hyperplasia with subsequent increase in
secretions, loss of ciliated epithelium and squamous metaplasia were also present
in 97% of smokers. They concluded that marijuana use is associated with airway
inﬂammation that is similar to that of a tobacco smoker . A cross-sectional study
on over 6000 patients, from 1988 to 1994, found an increased incidence of chronic
bronchitis symptoms such as wheezing and productive cough occurring in patients
10 years younger, on average, than tobacco smokers . Case-control trials per-
formed found similar ﬁndings with regards to increases in wheezing, shortness of
breath, cough and phlegm as well as the similarities with tobacco use .
Bryson also concluded based on his review of the literature, that the pulmonary com-
plications in the chronic marijuana smoker are equivalent to those seen in the chronic
tobacco smoker , while Wu et al. estimated that 3e4 cannabis cigarettes daily
equates to about 20 tobacco cigarettes in terms of bronchial tissue damage .
Cannabis use has also been linked to a higher risk in cancers, possibly due to the
increased carcinogens entering the airway. Similar to tobacco use, marijuana use
plays a signiﬁcant role in the development of lung cancer. In a case control study
performed in New Zealand, young adults (under the age of 55) had an 8% increase
in lung cancer risk for each joint year of cannabis smoking after adjusting for the
cofounders, such as age, sex, ethnicity and family history . Berthiller et al.
pooled data from a multitude of institutions across multiple countries, comprising
of over 1200 patients, and reported an increased risk of lung cancer for every mari-
juana use . In addition, a 40 year cohort study (1969e2009) with about 48,000
patients reported an increased risk of lung cancer in young men (aged 18e20 years
old) who had smoked marijuana more than 50 times. This study was limited however
by the nature of patient self-reporting . Head and neck cancers have also been
theorized to be at a higher risk similar to that of tobacco smoking. However, a pooled
analysis performed by Berthiller et al. found that infrequent marijuana smoking did
not confer a greater risk after adjusting for cofounders. The authors did note that due
to the low prevalence of frequent smoking within the study population, that a moder-
ately increased risk could not be ruled out . In another population based case
control study, there was an increased incidence of head and neck cancers in patients
with a 30 joint-year history, yet the association did not exist when accounting for
tobacco smoking  suggesting the risk is greater with tobacco than marijuana.
2.2.2. Impact on anesthesia
Marijuana’s prevalence is evident amongst all patient populations. In a cross-
sectional study conducted by Mills et al., the rate of marijuana use via patient
self-reporting was found to be 14% amongst surgical patients in 2003. This led
the authors to conclude that questions about illicit drug use should be a routine
part of the preanesthetic assessment, especially in patients that the anesthesiologist
ﬁnds hard to settle, due to anxiety or other psychologic manifestations, because of
the potential anesthetic complications that may occur .
In a series of case reports, Guarisco presented three patients who suﬀered from sig-
niﬁcant respiratory distress due to isolated uvulitis, a disease of low incidence typi-
cally associated with infection or traumatic irritation from instruments used in the
airway. Investigating further, all three patients were found to have inhaled large
quantities of cannabis within six to twelve hours of the onset of symptoms leading
to the conclusion of a possible correlation with inhaled irritants such as cannabis.
Due to known cases of isolated uvulitis [35,36] and the possible link with marijuana,
the authors suggest that toxicology urine and blood studies for THC should be per-
formed in cases where marijuana use is suspected but not conﬁrmed by history tak-
ing . Multiple other cases have also been reported with similar ﬁndings. In a case
series by Sloan, three adolescents suﬀered acute uvular inﬂammation post the heavy
use of marijuana, having smoking at least three marijuana cigarettes, despite nega-
tive throat cultures . In 1971, a cohort study was performed in which a large
quantity of marijuana, over 100 grams, was smoked over several months. Of the
31 subjects, almost half suﬀered from recurrent rhinopharyngitis as well as devel-
oped acute uvular edema after the heavy marijuana inhalation which lasted approx-
imately 12e24 hours . These ﬁndings stress the importance in the maintenance
of the airway during anesthesia following acute marijuana use due to the potential
airway obstruction that may occur.
In fact, in presenting a case of uvular edema and airway obstruction with cannabis
inhalation 4 hours prior to surgery, Pertwee recommended that elective operations
should be avoided altogether if a patient was recently exposed to cannabis smoke
. This recommendation seems reasonable when taking into consideration the
life-threatening bronchospasm leading to asphyxia, brain damage or death resulting
from tracheal intubation in patients with obstructive airways . One proposed
course of action has been the therapeutic use of steroids. In Guarisco’s study, he
theorized that steroids should help inhaled irritant uvulitis . As steroids increase
endotracheal permeability, decrease mucosal edema and stabilize lysosomal
membranes, thus decreasing the inﬂammatory response, the theory has scientiﬁc ba-
sis. In a prospective, randomized, double-blind study, Silvanus et al. found that the
addition of methylprednisolone to salbutamol in patients with a partially reversible
airway obstruction helped in the diminution of the reﬂex bronchoconstriction that
can result from tracheal intubation . This led to Hawkins et al.’srecommenda-
tion that at the ﬁrst signs of airway obstruction, dexamethasone should be used as the
drug of choice, 1 mg/kg every 6e12 hours over the course of one to two days (Haw-
kins). This recommendation gained credence in the dramatic relief that dexametha-
sone provided in the post-traumatic cases [35,36]. However, Mallat et al. concluded
that although marijuana-induced uvular edema is a serious postoperative complica-
tion that has a potential for simple treatment, in the case of an elective surgical pro-
cedure with an acute history of cannabis exposure, surgery should be cancelled as
prophylactic treatment may not be eﬃcient . The complications of the airway
are not limited to intubation however. The inhalation of toxic chemicals as well as
smoke can cause laryngospasm by chemoreceptor stimulation. In addition, the inha-
lation of hot gasses can trigger laryngospasm via thermoreceptor stimulation, espe-
cially in the case of lowered sensory aﬀerent neuron threshold potentials such as in
light anesthesia. In line with this, White presented a case in which a known cannabis
smoker suﬀered severe laryngospasm following extubation .
As found within the reviews, multiple observations have been made showing cross-
tolerance between marijuana and barbiturates, opioids, prostaglandins, chlorproma-
zine and alcohol. In addition, animal studies have shown additive eﬀects amongst
them all except for alcohol [45,46]. These drug interactions have led to further
exploration of its reactions to other medication groups. As a result of fat sequestra-
tion and subsequent slow elimination from the tissues, cannabinoids may be present
to interact with multiple anesthetic agents. In Symons’s case report, the patient
required multiple boluses of propofol and two additional doses of midazolam to
achieve appropriate sedation . In a prospective, randomized, single-blind study
of 60 patients, chronic marijuana users required signiﬁcantly increased doses of pro-
pofol to facilitate successful insertion of the laryngeal mask and thus suggesting that
the increased doses, in chronic marijuana users, may be a requirement for appro-
priate loss of consciousness as well as jaw relaxation and airway reﬂex depression.
The authors theorized that the variations in the level of delta9-THC can explain var-
iations in propofol responses . In a review written in the American Association
of Nurse Anesthetists Journal, Dickerson reported the synergistic eﬀects of cannabis
to include: potentiation of nondepolarizing muscle relaxants, potentiation of norepi-
nephrine, the augmentation of any drug causing respiratory or cardiac depression, as
well as a more profound response to inhaled anesthetics sensitization of the myocar-
dium to catecholamines due to the increased level of epinephrine . On the subject
of muscle relaxants, THC depletes acetylcholine stores and exerts an anticholinergic
eﬀect and thus creates a potentiation of the nondepolarizing muscle relaxants .A
review by Hall et al. explored THC’s interaction with drugs aﬀecting heart rate and
arterial pressure and found that due to cannabis’s own cardiovascular eﬀects (as dis-
cussed previously), it may interact with medications such as beta-blockers, anticho-
linergics and cholinesterase inhibitors . Due to these potential autonomic
reactions, as well as theoretical psychiatric complications, such as withdrawal eﬀects
and their interference with anesthetic induction or postoperative recovery, there has
been a stress made to inquiring about drug history [52,53] or avoiding elective op-
erations altogether . Dickerson, in his review, recommended that, due to all po-
tential eﬀects and interactions, not only should an extensive history of drug use be
elicited at the time of the preoperative assessment, including the frequency of use
and time of last use, but that anesthesia should be avoided in any patient with
cannabis use within the past 72 hours . This gained further credibility in a ran-
domized, double-blind trial, in which an apparent drug interaction was observed in
the patient population who underwent general anesthesia within 72 hours of mari-
juana use leading to a sustained postoperative tachycardia, a ﬁnding potentially
due to an interaction between cannabinol metabolites and atropine administration
during anesthesia .
2.2.3. Peri-operative complications
One of the most researched and known risk factor for peri- or postoperative compli-
cations, increased hospitals costs and resource usage is smoking, speciﬁcally to-
bacco smoke. In fact, the rates of perioperative respiratory events, such as re-
intubation, hypoventilation, hypoxemia, laryngospasm, bronchospasm, and aspira-
tion, have a total incidence of 5.5% in smokers compared to 3.1% in nonsmokers,
making these events 70% more prevalent with smoking . In addition, in a ran-
domized controlled trial out of Denmark, orthopedic surgery patients who smoked
were compared to those who underwent cessation counseling and nicotine replace-
ment therapy. In the study, they found an overall complication rate of 18% compared
to the 52% found in the smoking group, including a cardiac event rate of 0%
compared to 10% . A similarly designed study found a signiﬁcant relative risk
reduction of 49% for not only systemic complications but that of wounds as well
. These call into question the role of marijuana on perioperative complications,
especially when taking into consideration that the pulmonary complications in the
chronic cannabis smoker are equivalents to that of a chronic tobacco smoker, prob-
ably due to the cannabis smoke products . One such pulmonary complication is
airway obstruction, extensively linked to marijuana use [35,36,37], in which
Warner et al. found that untreated, such as a lack of smoking cessation in the case
of marijuana, leaves patients at a high risk for perioperative complications .
When it comes to the case of cardiovascular maintenance in the perioperative period,
marijuana presents complications. As mentioned previously, cannabis use can create
a series of ECG changes that must be considered and monitored such as PVCs ,
atrial ﬁbrillation , AV block [12,13], or Brugada-like changes . As a worst
case scenario, cannabis use has been linked to plaque rupture and resultant myocar-
dial infarction . These are all causes for concern considering that Gregg et al.
reported, in conducting a series of 55 clinical trials in patients medicated with
THC, that peak heart rate increased by 24.1% in surgical patients compared to the
non-surgical. The authors concluded that THC may have a synergistic cardiovascu-
lar relationship with surgical stress . This tachycardia gave credence to Bryson’s
recommendation that ketamine, pancuronium, atropine and epinephrine, all drugs
known to aﬀect heart rate, should be avoided in patients with history of acute mari-
juana use , while the bradycardia and hypotension that results from high doses of
marijuana called into question the amount of atropine and vasopressors needed .
Despite the impetus behind these recommendations, 1 trial showed epinephrine to
have no synergistic eﬀect with marijuana when it comes to cardiovascular eﬀects
, showing more research is needed on the potential interactions of marijuana
and perioperative medications.
Field visualization plays a key role in any operation. Marijuana, however, may aﬀect
this. In a literature review published in Poland, Zakrzeska et al. explored how can-
nabinoids and their metabolites and their eﬀects on the receptors CB1, CB2, CBPT
and CBED as well as other systems may impact hemostasis. The authors concluded
that despite the studies that have shown contradictory eﬀects, based on the physi-
ology, it is reasonable to conclude that marijuana could have an anti-hemostatic ef-
fect . Multiple studies have backed up that conclusion. In 1979, Schaeﬀer et al.
reported that cannabis users had a diminished ability for platelet aggregation .
This led to further investigations and in 1989, Formukong et al. looked at cannabi-
noids’eﬀect on platelet aggregation. The authors found that in both rabbit and hu-
man platelet aggregation that was induced by adenosine diphosphate or epinephrine
was inhibited by cannabinoids in a dose-dependent manner and with cannabidiol
more potent than THC in this eﬀect . Then in 2007, an in vitro coagulation study
showed that marijuana and two of the major cannabinoids, including THC, had an
anticoagulant property and even more so, an antithrombotic eﬀect. In the in vivo
model testing clotting times of lean and obese rats, those treated with cannabis
had clotting times 1.5 to 2 times greater than the controls, thus supporting the results
of the in vitro study . In a follow-up study in 2014, the whole blood of donors
who had consumed cannabis had diminished platelet aggregation. The conclusion
was drawn that endocannabinoid receptor agonists reduce platelet activation as
well as aggregation, and as such might have potential in antithrombotic therapies
. This anticoagulatory eﬀect could counteract the surgeon’s attempts to create
hemostasis within the operative ﬁeld and thus limit visualization.
Yet Zakrzeska also concluded that marijuana use may put certain individuals at risk
for thromboembolism , a second issue of surgical concern. Even though an
intravenous injection of cannabis has been shown to cause a signiﬁcant drop in the
platelet count which seems in line with the belief of anticoagulation, it is the mari-
juana components that cause a release of ADP from erythrocyte, leading to platelet
aggregation. This aggregation is the reason behind the reduction in platelet count
. The theory of marijuana use leading to platelet aggregation leads toward sub-
stantiating the conclusion Desbois et al. made in regards to an increased predilection
for myocardial infarctions and arterial disease . Reports of cases similar lead to
Deusch et al.’s in vitro study. The cannabinoid receptors CB1 and CB2 were found
on the cell membrane of the human platelet via western blot. Delta-9-
tetrahydrocannabinol, which is the ingredient within cannabis responsible for the
psychological eﬀects, demonstrated the ability to signiﬁcantly increase the expres-
sion of glycoprotein IIb-IIIa as well as P-selectin thus increasing the activation of
the human platelet. This ﬁndings lead to the conclusion that THC, through its eﬀects
on the cannabinoid receptors on platelets, may create a prothrombotic setting favor-
ing the development of cardiovascular events .
As surgical technique and ﬁeld advance, more complicated and potentially painful
procedures are becoming more common practice. Surveying patients indicated
that over 80% experience postoperative pain that was rated as either moderate or se-
vere . This pain can set oﬀa series of physiologic changes that may harm various
systems ranging from cardiovascular to the central nervous system , and has
been shown to lengthen hospital stays and time to ﬁrst ambulation, impede postop-
erative nursing and physiotherapy, increase healthcare costs, and reduce the patient’s
satisfaction with the outcome . However, multiple reviews of the available liter-
ature have concluded that appropriate and adequate postoperative analgesia im-
proves recovery, including improving cardiac function and decreasing mortality
and morbidity related to pulmonary function, decreases thrombosis risk, diminishes
the possibility of chronic pain syndrome, and improves overall outcome . Mari-
juana plays a role now in medicine as an analgesic. Prescribed for a number of di-
agnoses, medical marijuana has been shown in over 18 randomized trials to be
both eﬀective and safe in the treatment of chronic pain, with the best evidence being
for neuropathic pain . Investigating the role marijuana plays as an analgesic,
Russo found that due to cannabis’s role in multiple pathways, safety, and potential
side eﬀects and beneﬁts shown in the clinical trials, marijuana may play a more
important role in pain management when combined with opioids . However,
the appropriate management of marijuana users with opioids postoperatively is
more complicated than these trials suggest. In chronic marijuana users, the periop-
erative narcotic requirements to gain appropriate analgesia were signiﬁcantly
increased. Yet despite this increase, patients were more likely to subjectively expe-
rience less pain than those of their non-marijuana using counterparts . Clinically,
this increase materialized in the form of a narcotic requirement twice that of the
average patient of the same height and weight each day over the course of two
postoperative days , demonstrating a potential interaction between marijuana
and opioids which must be taken into account when considering the potential post-
operative complications that may arise from the increased doses of opioids.
In a literature review published in the Journal of Obesity Surgery, Rummel et al.
posed the question of whether or not marijuana use should be a contraindication
to bariatric surgery. In their investigation, the authors determined that there was a
lack of a generalized screening protocol for marijuana use amongst providers and
thus there is no account of a known eﬀect on procedures due to confounders. Yet,
due to the many eﬀects marijuana has on the cardiovascular, pulmonary, immuno-
logic, and central nervous system, the conclusion was drawn that it is fair to hypoth-
esize that cannabis use has the potential to worsen adverse outcomes in the
postoperative period . These potential risks and lack of screening resulted in
the recommendation that practitioners of bariatric surgery should be devoted to as-
sessing controlled and problematic levels of preoperative substance use and take the
time to discuss the potential postoperative risks with patients . However, the
American Association of Clinical Endocrinologists, the Obesity Society, and the
American Society for Metabolic and Bariatric Surgery took the recommendations
one step further by stating that current drug use, including marijuana, should be
treated as exclusionary criterion in the case of bariatric surgery . These recom-
mendations for an elective procedure should potentially be considered in the case of
all elective surgical procedures.
After an extensive and comprehensive review of available literature, a fund of
knowledge was found to exist pertaining to the physiological eﬀects of marijuana
as well as the metabolites within, most notably THC and cannabinol. While this in-
formation has been present with 40 years of research, no investigation has taken
place pertaining to patients’marijuana use and surgical considerations, such as eﬀect
on wound healing, that the piecing together of this data warrants.
The documented evidence of marijuana’seﬀects is of great concern for surgery.
Whether it be the presentation of arrhythmias [10,11,12,13], myocardial infarction
[15,16], stroke , pulmonary obstruction [35,36,37] as well as anesthetic con-
cerns [47,48,50] and/or thromboembolus [19,64,65] or bleeding [59,60,61,62,
63], marijuana’s multi-system, multi-organ eﬀects are possible confounders to a va-
riety of medical outcomes, let alone surgical. With THC and cannabinoids being
shown to be present for up to 30 days within the fat , its potential to aﬀect the
entire operative course in either chronic or acute smokers must be evaluated.
One potential reason behind the lack of or limitation of clinical trials pertaining to
surgical outcomes, including wound cleaning, is due to the most commonly smoked
drug, tobacco. While this may change in time with marijuana use being legalized in
more states and the potential increase in patients admitting use, the available clinical
trials and cohort studies suﬀer from the current diﬃculties. As there is a relationship
between the smokers of tobacco and those of marijuana, it can also be diﬃcult to
separate out the eﬀects of one from the other. While the marijuana cigarette may
contain more carcinogens [20,22] and equate to more tobacco cigarettes in number
, the resultant airway inﬂammation is similar to that of tobacco , blurring the
causation line via pathologic examination. Additionally, few studies have elicited in-
formation on the frequency of use of both marijuana and tobacco products as well as
the diﬀerences in amount despite the repetition that exists in the recommendations
for marijuana screening. However, one particular cohort study of just over 1000 pa-
tients was able to separate out the individual acute eﬀects but also the synergistic
eﬀects of tobacco use and marijuana use on the lungs via the use of salbutamol
and incentive spirometry. This study, however, is limited due to relying on patient
self-reporting of lifetime marijuana use .
Another possible reason complicating the clinical data on marijuana is the presence
of contradictory reports and trials, most prevalent in the debate on coagulopathy [59,
As cannabis use becomes more prevalent within our society due to the legalization of
both medicinal and recreational cannabis across the country, the lack of data leaves
surgeons without much evidence-based approaches to marijuana management
within the surgical patient population, one in which marijuana users comprise
14% of as of 2003 . While a patient’s history of marijuana use may be unavoid-
able in the case of emergency surgery, further research is necessary to provide the
needed information to utilize in the time of elective surgical procedures.
Author contribution statement
All authors listed have signiﬁcantly contributed to the development and the writing
of this article.
This research did not receive any speciﬁc grant from funding agencies in the public,
commercial, or not-for-proﬁt sectors.
Competing interest statement
The authors declare no conﬂict of interest.
No additional information is available for this paper.
 Cannabis C, Poppy: Nature’s Addictive Plants. (n.d.). Retrieved September
07, 2016, from: https://www.deamuseum.org/ccp/cannabis/history.html.
 National Institutes of Health (NIH). Turning Discovery Into Health. (n.d.).
Retrieved September 07, 2016, from: https://www.nih.gov/.
 J. Michael Bostwick, Blurred boundaries: the therapeutics and politics of med-
ical marijuana, Mayo Clin. Proc. 87 (2) (2012) 172e186.
 British Medical Association, Therapeutic Uses of Cannabis, Harwood Aca-
demic Publishers, London, 1997.
 M.O. Maykut, Health consequences of acute and chronic marijuana use, Prog.
Neuro Psychopharmacol. Biol. Psychiatr. 9 (1985) 209e238.
 S. Johnson, E.F. Domino, Some cardiovascular eﬀects of marihuana smoking
in normal volunteers, Clin. Pharmacol. Ther. 12 (1971) 762e768.
 L.A. Malit, R.E. Johnstone, D.I. Bourke, R.A. Kulp, et al., Intravenous delta9-
Tetrahydrocannabinol: eﬀects of ventilatory control and cardiovascular dy-
namics, Anesthesiology (1975).
 P. Beaconsﬁeld, J. Ginsburg, R. Rainsbury, Marihuana smoking. Cardiovascu-
lar eﬀects in man and possible mechanisms, N. Engl. J. Med. 287 (1972)
 G. Kunos, Z. Jarai, S. Batkai, et al., Endocannabinoids as cardiovascular mod-
ulators, Chem. Phys. Lipids 108 (2000) 159e168.
 M. Daccarett, M. Freih, C. Machado, Acute cannabis intoxication mimicking
brugada-like ST segment abnormalities, Int. J. Cardiol. 119 (2) (2007)
 B.A. Fisher, A. Ghuran, V. Vadamalai, T.F. Antonios, Cardiovascular compli-
cations induced by cannabis smoking: a case report and review of the litera-
ture, Emerg. Med. J. 22 (2005) 679e680.
 D.A. Kosior, K.J. Filipiak, P. Stolarz, et al., Paroxysmal atrial ﬁbrillation
following marijuana intoxication: a two-case report of possible association,
Int. J. Cardiol. 78 (2001) 183e184.
 D. Akins, M.R. Awdeh, Marijuana and second-degree AV block, South. Med.
J. 74 (1981) 371e373.
 W.S. Aronow, J. Cassidy, Eﬀect of smoking marihuana and of a high-nicotine
cigarette on angina pectoris, Clin. Pharmacol. Ther. 17 (1975) 549e554.
 C.J. Hodcroft, M.C. Rossiter, A.N. Buch, Cannabis-associated myocardial
infarction in a young man with normal coronary arteries, J. Emerg. Med. 47
(3) (2014) 277e281.
 Pacher, et al., Cardiovascular eﬀects of marijuana and synthetic cannabinoids:
the good, the bad, and the ugly, Nat. Rev. Cardiol. (2018).
 Wolﬀ, Jouanjus, Strokes are possible complications of cannabinoids use, Ep-
ilepsy Behav. (2017).
 T.M. Lawson, A. Rees, Stroke and transient ischemic attacks in association
with substance abuse in a young man, Postgrad. Med. 72 (1996) 692e693.
 A.C. Desbois, P. Cacoub, Cannabis-associated arterial disease, Ann. Vasc.
Surg. 27 (7) (2013) 996e1005.
 D.P. Tashkin, A.H. Coulson, V.A. Clark, et al., Respiratory symptoms and
lung function in habitual, heavy smokers of marijuana alone, smokers of mari-
juana and tobacco, smokers of tobacco alone, and nonsmokers, Am. Rev. Re-
spir. Dis. 135 (1987) 209e216.
 T.C. Wu, D.P. Tashkin, B. Djahed, et al., Pulmonary hazards of smoking mari-
juana as compared with tobacco, N. Engl. J. Med. 318 (1988) 347e351.
 National Academy of Sciences, Marihuana and Health, National Academy of
Sciences, Washington, DC, 1982.
 M. Benson, A.M. Bentley, Lung disease induced by drug addiction, Thorax 50
 D. Hoﬀmann, K.D. Brunnemann, G.B. Gori, et al., On the carcinogenicity of
marijuana smoke, Recent Adv. Phytochem. 9 (1975) 63e81.
 R. Schwartz, Uvular edema and erythema (Letter), Pediatr. Infect. Dis. J. 3
 M.D. Roth, et al., Airway inﬂammation in young marijuana and tobacco
smokers, Am. J. Respir. Crit. Care Med. 157 (1998) 928e937.
 B.A. Moore, E.M. Augustson, R.P. Moser, A.J. Budney, Respiratory eﬀects of
marijuana and tobacco use in a U.S. sample, J. Gen. Intern. Med. 20 (2005)
 E.O. Bryson, E.A. Frost, The perioperative implications of tobacco, marijuana,
and other inhaled toxins, Int. Anesthesiol. Clin. 49 (1) (2011) 103e118.
 S. Aldington, et al., Cannabis use and risk of lung cancer: a case-control study,
Eur. Respir. J. 31 (2008) 280e286.
 J. Berthiller, K. Straif, M. Boniol, et al., Cannabis smoking and risk of lung
cancer in men: a pooled analysis of three studies in Maghreb, J. Thorac. Oncol.
3 (2008) 1398e1403.
 R.C. Callaghan, P. Allebeck, A. Sidorchuk, Marijuana use and risk of lung
cancer: a 40-year cohort study, Cancer Causes Control 24 (2013) 1811e1820.
 J. Berthiller, Y.C. Lee, P. Boﬀetta, et al., Marijuana smoking and the risk of
head and neck cancer: pooled analysis in the INHANCE consortium, Cancer
Epidemiol. Biomarkers Prev. 18 (2009) 1544e1551.
 M. Hashibe, H. Morgenstern, Y. Cui, et al., Marijuana use and the risk of lung
and upper aerodigestive tract cancers: results of a population-based case-con-
trol study, Cancer Epidemiol. Biomarkers Prev. 15 (2006) 1829e1834.
 P.M. Mills, N. Penfold, Cannabis abuse and anaesthesia, Anaesthesia 58
 R. Ravindran, S. Priddy, Uvular edema, a rare complication of endotracheal
intubation, Anesthesiology 48 (1978) 374.
 T.D. Seigne, A. Felske, P.A. DelGiudice, Uvular edema, Anesthesiology 49
 J.L. Guarisco, M.L. Cheney, F.E. LeJeune Jr., H.T. Reed, Isolated uvulitis sec-
ondary to marijuana use, Laryngoscope 98 (1988) 1309e1310.
 M.P. Sloan, On uvulitis from smoking marijuana (Letter), Pediatr. Notes 9
 F.S. Tennant Jr., M. Preble, T.J. Prendergast, P. Ventry, Medical manifesta-
tions associated with hashish, J. Am. Med. Assoc. 216 (1971) 1965e1969.
 R.G. Pertwee, Neuropharmacology and therapeutic potential of cannabinoids,
Addiction Biol. 5 (2000) 37e46.
 R.A. Caplan, K.L. Posner, R.J. Ward, F.W. Cheney, Adverse respiratory
events in anesthesia: a closed claims analysis, Anesthesiology 72 (1990)
 M.T. Silvanus, H. Groeben, J. Peters, Corticosteroids and inhaled salbutamol
in patients with reversible airway obstruction markedly decrease the incidence
of bronchospasm after tracheal intubation, Anesthesiology 100 (2004)
 A. Mallat, J. Roberson, J.G. Brock-Utne, Preoperative marijuana inhala-
tiondan airway concern, Can. J. Anaesth. 43 (1996) 691e693.
 S.M. White, Cannabis abuse and laryngospasm, Anaesthesia 57 (2002)
 G.G. Nahas, Toxicology and pharmacology, in: G.G. Nashas (Ed.), Marijuana
in Science and Medicine, Raven Press, New York, 1984, pp. 109e246.
 R.G. Pertwee, Tolerance to and dependence on psychotropic cannabinoids, in:
J.A. Pratt (Ed.), The Biological Basis of Drug Tolerance and Dependence, Ac-
ademic Press, New York, 1991, pp. 232e263.
 I.E. Symons, Cannabis smoking and anaesthesia, Anaesthesia 57 (2002)
 P. Flisberg, M.J. Paech, T. Shah, et al., Induction dose of propofol in patients
using cannabis, Eur. J. Anaesthesiol. 26 (2009) 192e195.
 S.J. Dickerson, Cannabis and its eﬀect on anesthesia, AANA J. 48 (1980)
 K. Karam, S. Abbasi, F.A. Khan, Anaesthetic consideration in a cannabis
addict, J. Coll. Phys. Surg. Pak. 25 (2015) S2eS3.
 W. Hall, N. Solowij, Adverse eﬀects of cannabis, Lancet 352 (1998)
 R.N. Kumar, W.A. Chambers, R.G. Pertwee, Pharmacological actions and
therapeutic uses of cannabis and cannabinoids, Anesthesia 56 (2001)
 C.H. Ashton, Adverse eﬀects of cannabis and cannaboids, Br. J. Anaesth. 83
 J.M. Gregg, B.L. Campbell, K.L. Levin, J. Ghia, R.A. Elliot, Cardiovascular
eﬀects of cannabinol during oral surgery, Anesth. Analg. 55 (1976) 203e213.
 B. Schwilk, U. Bothner, S. Schraag, M. Georgieﬀ, Peri-operative respiratory
events in smokers and non-smokers undergoing general anaesthesia, Acta
Anaesthesiol. Scand. 41 (1997) 348e355.
 A.M. Møller, N. Villebro, T. Pedersen, H. Tønnesen, Eﬀect of preoperative
smoking intervention on postoperative complications: a randomized clinical
trial, ACC Curr. J. Rev. 11 (2002) 13e14.
 D. Lindstr€
om, O. Sadr Azodi, A. Wladis, et al., Eﬀects of a perioperative
smoking cessation intervention on postoperative complications: a randomized
trial, Ann. Surg. 248 (2008) 739e745.
 D.O. Warner, M.A. Warner, R.D. Barnes, K.P. Oﬀord, D.R. Schroeder,
D.T. Gray, J.W. Yunginger, Perioperative respiratory complications in patients
with asthma, Anesthesiology 85 (1996) 460e467.
 A. Zakrzeska, T. Grędzi
nski, W. Kisiel, E. Chabielska, Cannabinoids and hae-
mostasis, Postepy Hig. Med. Dosw. 70 (2016) 760e774.
 C.F. Schaefer, D.J. Brackett, C.G. Gunn, et al., Decreased platelet aggregation
following marihuana smoking in man, J. Oklahoma State Med. Assoc. 72
 E.A. Formukong, A.T. Evans, F.J. Evans, The inhibitory eﬀects of cannabi-
noids, the active constituents of Cannabis sativa L. on human and rabbit
platelet aggregation, J. Pharm. Pharmacol. 41 (1989) 705e709.
 C. Coetzee, R.A. Levendal, M. van de Venter, C.L. Frost, Anticoagulant eﬀects of
a cannabis extract in an obese rat model, Phytomedicine 14 (5) (2007) 333e337.
 V. De Angelis, A.C. Koekman, C. Weeterings, et al., Endocannabinoids Con-
trol Platelet Activation and Limit Aggregate Formation under Flow, Freson K,
ed, PLoS One 9 (9) (2014) e108282.
 R. Levy, A. Schurr, I. Nathan, A. Dvilanski, A. Livne, Impairment of ADP-
induced platelet aggregation by hashish components, Thromb. Haemostasis
36 (1976) 634e640.
 E. Deusch, H.G. Kress, B. Kraft, S.A. Kozek-Langenecker, The procoagula-
tory eﬀects of delta-9-tetrahydrocannabinol in human platelets, Anesth. Analg.
99 (4) (2004) 1127e1130.
 A.B. Shang, T.J. Gan, Optimising postoperative pain management in the
ambulatory patient, Drugs 63 (2003) 855e867.
 C. Jayr, Retentissement de la douleur post op
eratoire et b
eﬁces attendus des
traitements. [Repercussions of postoperative pain. Expected the therapeutic
beneﬁts], Ann. Fr. Anesth. Reanim. 17 (1998) 540e554.
 F. Bonnet, E. Marret, Postoperative pain management and outcome after sur-
gery, Best Pract. Res. Clin. Anaesthesiol. 21 (2007) 99e107.
 M.E. Lynch, F. Campbell, Cannabinoids for treatment of chronic non-cancer
pain; a systematic review of randomized trials, Br. J. Clin. Pharmacol. 72 (5)
 E.B. Russo, Cannabinoids in the management of diﬃcult to treat pain, Ther-
apeut. Clin. Risk Manag. 4 (1) (2008) 245e259.
 F. Bauer, W. Donohoo, A. Tsai, L. Silveira, H. Hollis, F. Husain, Marijuana
use and outcomes in the bariatric population, Surg. Obes. Relat. Dis. 12 (7)
 C.M. Rummel, L.J. Heinberg, Assessing marijuana use in bariatric surgery
candidates: should it Be a contradiction? Obes. Surg. 10 (2014) 1764e1770.
 K.K. Saules, A. Wiedemann, V. Ivezah, J.A. Hopper, J. Foster-Hartsﬁeld,
D. Schwartz, Bariatric surgery history among substance abuse treatment pa-
tients: prevalence and associated features, Surg. Obes. Relat. Dis. 6 (2010)
 J.I. Mechanick, R.F. Kushner, H.J. Sugerman, et al., American Association of
Clinical Endocrinologists, the Obesity Society, and American Society for
Metabolic and Bariatric Surgery medical guidelines for clinical practice for
the perioperative nutritional, metabolic, and nonsurgical support of the bariat-
ric surgery patient, Surg. Obes. Relat. Dis. 4 (2008) S109eS184.
 R.J. Hancox, R. Poulton, M. Ely, et al., Eﬀects of cannabis on lung function: a
population-based cohort study, Eur. Respir. J. 35 (2010) 42e47.