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99
in blood carboxyhemoglobin levels, a threefold increase in inhaled tar compounds,
and an increased tar compound retention [22]. In addition, cannabis inhalation is
known to impair airway ciliated cells responsible for the mobilization of mucus, and
THC has immunosuppressive properties, which may contribute to airway health. A
retrospective study examined 35,114 individuals for respiratory-related emergency
room (ER) visitations and observed that cannabis users had a signicantly increased
risk of respiratory-related ER visit or hospitalization (OR 1.22, 95% CI 1.13–1.31)
[23]. Despite this increase, cumulative marijuana use does not appear to contribute
to the adverse changes in spirometry typically observed with tobacco smoking [24].
It does increase the risk of severe bronchitis at low exposure and increase airway
resistance without evidence of airow obstruction or impairment of gas exchange
[25]. Mechanical ventilation may be affected by both an increase in sedation require-
ments related to cross-tolerance with sedative-hypnotic agents and airway hyperre-
activity that may result in ventilator dyssynchrony issues [26].
Gastrointestinal
Due to its many effects on the gastrointestinal tract, cannabis has been promoted for
the treatment of inammatory bowel disease, nausea, and anorexia. While there is
partial evidence to support cannabis usage in certain GI diseases, there are several
GI effects that must be considered in the ICU setting. Cannabis slows gastric empty-
ing and increases fasting gastric volume through its effect on cannabinoid receptors
in the mesenteric nervous system [27]. Paradoxically, chronic cannabis smokers
may experience cannabis- induced hyperemesis syndrome. This syndrome is thought
to be related to the abuse of high-potency cannabinoids or via adrenocorticotropic
hormone- mediated release of stored cannabinoids in adipocytes. For mild cases, the
use of hot showers or capsaicin is effective in managing symptoms via stimulation
of transient receptor potential vanilloid 1 (TRPV1) receptors. More severe cases
may require the use of antiemetics, benzodiazepines, or anti-dopaminergic agents,
such as haloperidol or droperidol [28]. There is incomplete evidence regarding the
effect of cannabis on the liver. Although not directly hepatotoxic, stimulation of
CB1 receptors may be associated with increased steatosis and brosis. Conversely,
CB2 receptor stimulation has been associated with decreased rates of liver inam-
mation. Clinical studies have demonstrated both harm and benet with cannabis
usage in the setting of comorbid liver disease [29].
Renal
There has been limited research regarding the effects of cannabis on renal disease.
To date, there is no link between cannabis usage, acute kidney injury (AKI), or the
worsening of end-stage renal disease (ESRD) [30]. At least one study has demon-
strated an increased risk of diabetes-related kidney disease in type 2 diabetes mel-
litus patients who consumed recreational cannabis [31].
7 The Impact ofCannabis Use Disorder onCritical Illness
100
Hematological
Similar to other illicit compounds, the data regarding the impact of cannabinoid
compounds on the hematological system is scant. Chronic synthetic cannabi-
noid use has been associated with alterations in function, morphology, distribu-
tion, and index of circulating blood cells, evidence of higher levels of
inammatory cells and subclinical megaloblastic anemia with iron deciency
[32]. The ndings of increased red cell indices have been previously observed
to contribute to a higher risk of venous thrombosis [33]. Similarly, indirect pre-
clinical evidence investigating endocannabinoid 2-arachidonoylglycerol (2-AG)
found increased platelet aggregation and deformation, suggesting enhanced
platelet aggregation [34]. Cannabinoid- positive urine tests are associated with
increased hospitalization for vaso-occlusive crisis in patients harboring sickle
cell disease. The authors suggested that this was not related to an underlying
increase in the severity of sickle cell disease but rather as a signal of either the
severity of the underlying disease (as cannabinoids were used for adjunctive
pain relief) or the combined use of cannabinoids with other illicit substances,
resulting in poor decision-making regarding disease management [35]. Although
the etiology remains unclear, patients with cannabis use disorders have been
observed to have a higher 90-day perioperative thromboembolic incidence and
odds following primary total knee arthroplasty [2.79% vs. 1.78%; OR= 1.58
(95% CI 1.25–1.99) p<0.0001] suggesting an aggressive approach to thrombo-
prophylaxis in the ICU may be warranted [36].
Endocrine
The impact of cannabinoids on the endocrine system has focused on its association
with fertility (male predominant; reduction in circulating plasma testosterone and
sperm counts) and hormonal imbalances (polycystic ovarian syndrome); however, it
appears to widely impact the endocrine system [37]. Chronic cannabinoid use does
not appear to impact thyroid function but may have modulatory effects on cortisol
[38]. Acute cannabis toxicity may increase cortisol secretion, but chronic cannabis
users exhibit elevated basal cortisol levels and disrupted diurnal cortisol secretion,
suggesting that chronic cannabis use blunts the hypothalamic-pituitary-adrenal axis
[39, 40]. The implications of this hypercortisolemia in the critically ill are unclear,
but practitioners should remain cautious of this phenomenon during the care of
chronic cannabis users. Acute consumption of cannabis has been shown to induce
glucose intolerance in pre-clinical and healthy volunteer studies. This is countered
by both epidemiological studies that have found a lower prevalence of obesity and
diabetes mellitus in chronic cannabis users and clinical studies that have observed
increased insulin release and decreased fasting blood glucose levels in chronic can-
nabis use.
Z. J. Carr and E. Strand
101
Infectious Disease
Little is known regarding the effect of endocannabinoids or exogenous cannabis
use on the immune system’s response to infection. Healthy volunteer studies have
demonstrated altered monocyte phenotype and reduced tumor necrosis factor-α
(TNF- α) in patients with chronic cannabis use (5 or more uses/week) [41].
Similarly, pre-clinical evidence in mice treated with cannabidiol (CBD) observed
reduced systemic inammation in a lipopolysaccharide (LPS)-induced cytokine
storm model of sepsis [42]. A myriad of studies have demonstrated the anti-
inammatory activity of exogenous THC and CBD via suppression of pro-inam-
matory mediators and immunomodulatory activity, but it is not fully understood if
this negatively impacts the complex immunological cascade related to sepsis.
Endocannabinoid signaling systems reduce inducible nitric oxide synthase (iNOS)
activity, Interleukin-6 (IL-6), TNF-α, IL-1β, and inhibit neutrophil chemotaxis
[43]. Clinical studies of the endocannabinoid system, namely, anandamide (AEA)
and 2-AG, found that lower AEA was associated with longer hospital length of
stay [OR: 23.59 (95% CI: 3.03–183.8) p=0.003] in patients with conrmed sep-
sis [44]. A retrospective cohort analysis of perioperative outcomes after spine
surgery in patients with or without the diagnosis of cannabis use disorder found
similar perioperative mortality but higher rates of perioperative septicemia or sep-
sis [OR 1.5 (95% CI: 1.0–2.5) p= 0.031] and length of stay (7.1 vs. 5.2 days,
p<0.001) [45]. Similar perioperative ndings have been demonstrated in patients
with active cannabis use and perioperative complications after ruptured intracra-
nial aneurysms, observing a higher length of stay, sepsis, and acute kidney
injury [46].
Conclusion
It is important to note that cannabis remains classied as a schedule I controlled
drug by the federal government. Under this classication, prospective clinical
studies have been severely limited. Natural cannabis products are also heteroge-
nous in their concentrations of various cannabinoids and terpenes, producing
issues of clinical reproducibility. Numerous areas of both exogenous and endog-
enous cannabinoid research are needed to further characterize ICU care and man-
agement (Fig.7.1). Supportive evidence for medicinal cannabis extracts has been
demonstrated for the symptomatic treatment of subtypes of chronic pain, seizure
disorders, muscle spasticity, nausea/emesis syndromes, and appetite stimulation
[47, 48]. Cannabis-related negative physiological effects may directly impact ICU
care and mandate an understanding of its potential negative effects. Neurological
manifestations of acute cannabis complications may complicate sedation manage-
ment due to sedative-hypnotic cross-tolerance, require enhanced delirium man-
agement strategies, and disrupt sleep synchrony in the ICU.Acute intoxication
7 The Impact ofCannabis Use Disorder onCritical Illness
102
Neurologic/ Psychiatric
Neurologic/ Psychiatric
Cardiovascular
Pulmonary
Gastrointestinal
Endocrinological
Hematologic
Infectious disease
Impaired judgement and cognition,
anxiety, delirium, psychosis, insomnia
CB1 mediated tachycardia, increased risk
of tachyarrhythmias, demand-related
myocardial ischemia, vasodilation
Delayed gastric emptying, increased
fasting gastric volume
Acute hypercortisolemia, insulin resistance
Suppression of inflammatory mediators
Acute intoxication
Cross tolerance with sedative-hypnotics,
higher analgesic requirements, cannabis
withdrawal syndrome
Higher risk for cardiovascular adverse
events (atrial fibrillation, atrioventricular
blocks, ventricular dysrhythmias
Upper airway hyper-reactivity, ciliary
dysfunction, elevated carboxyhemoglobin
levels
Cannabis-induced hyperemesis
syndrome,
gastroparesis, hepatic dysfunction
Possible increased risk of perioperative
thromboembolic events
Associations with increased risk of
perioperative septicemia
Chronic usage
Implications of Acute and Chronic Cannabis Usage on Intensive Care Management
Increased fasting gastric volume (increase
d
risk of pulmonary aspiration), airway
hyper-reactivity
Chronic hypercortisolemia, diurnal axis
disruption
Cardiovascular
Pulmonary
Gastrointestinal
Endocrinological
Infectious disease
Fig. 7.1 A synopsis of acute and chronic implications of cannabis usage on intensive care
management
may precipitate superimposed tachycardia and heighten the risk of tachyarrhyth-
mias and demand- related myocardial ischemia in admitted patients. Although not
proven, chronic cannabis users requiring mechanical ventilation may require
aggressive pulmonary care to reduce the risk of ventilator-associated pneumonia,
given its depressant effects on the immune system and ciliary activity. Hyperemesis
syndromes in patients with acute cannabis use should be monitored and diagnosed
to avoid distracting from other more serious primary gastrointestinal disorders.
The cannabinoid’s myriad downstream effects on the immune system need better
characterization of its clinical relevance to ICU practitioners. Particularly con-
cerning is the evidence regarding the increased incidence of sepsis and the
increased length of stay after sepsis diagnosis. The relationship to the chronic
hypercortisolemia exhibited in chronic cannabis users is unclear. Although there
is no evidence of increased mortality, further characterization of cannabis-related
complications during sepsis and other medical conditions is urgently required to
identify mitigating strategies. Exploratory ndings have suggested an increased
risk of thromboembolic phenomena in chronic cannabis users, ICU practitioners
should remain vigilant regarding thromboprophylaxis regarding this newly char-
acterized problem. The relatively limited scientic knowledge and vast number of
active compounds in botanical cannabis need substantial further clinical and pre-
clinical research to determine their impact on ICU care.
Z. J. Carr and E. Strand
103
References
1. Peacock A, Leung J, Larney S, Colledge S, Hickman M, Rehm J, etal. Global statistics on
alcohol, tobacco and illicit drug use: 2017 status report. Addiction. 2018;113(10):1905–26.
2. Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin
Pharmacokinet. 2003;42(4):327–60.
3. Elsohly MA, Gul W, Wanas AS, Radwan MM.Synthetic cannabinoids: analysis and metabo-
lites. Life Sci. 2014;97(1):78–90.
4. Zou S, Kumar U.Cannabinoid receptors and the endocannabinoid system: signaling and func-
tion in the central nervous system. Int J Mol Sci. 2018;19(3):833.
5. Patel J, Marwaha R. Cannabis use disorder. [Updated 2022 Jul 11]. StatPearls Publishing;
2023; 2022.
6. Moore THM, Zammit S, Lingford-Hughes A, Barnes TRE, Jones PB, Burke M, Lewis
G. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic
review. Lancet (London, England). 2007;370(9584):319–28.
7. D’Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT, etal. The psychotomi-
metic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications
for psychosis. Neuropsychopharmacology. 2004;29(8):1558–72.
8. Crippa JA, Derenusson GN, Chagas MH, Atakan Z, Martín-Santos R, Zuardi AW, Hallak
JE.Pharmacological interventions in the treatment of the acute effects of cannabis: a system-
atic review of literature. Harm Reduct J. 2012;9:7.
9. Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, et al. Cannabidiol in
patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol.
2016;15(3):270–8.
10. Campbell FA, Tramer MR, Carroll D, Reynolds DJ, Moore RA, McQuay HJ. Are cannabi-
noids an effective and safe treatment option in the management of pain? A qualitative system-
atic review. BMJ (Clin Res Ed). 2001;323(7303):13–6.
11. Giossi R, Carrara F, Padroni M, Bilancio MC, Mazzari M, Enisci S, etal. Systematic review
and meta-analysis seem to indicate that cannabinoids for chronic primary pain treatment have
limited benet. Pain Ther. 2022;11(4):1341–58.
12. Nasser Y, Biala S, Chau M, Partridge ACR, Yang JY, Lethebe BC, etal. Baseline cannabinoid
use is associated with increased sedation requirements for outpatient endoscopy. Cannabis
Cannabinoid Res. 2022;95:AB50.
13. Lynn RSR, Galinkin JL. Cannabis, e-cigarettes and anesthesia. Curr Opin Anaesthesiol.
2020;33(3):318–26.
14. Davidson EM, Raz N, Eyal AM.Anesthetic considerations in medical cannabis patients. Curr
Opin Anaesthesiol. 2020;33(6):832–40.
15. Holmen IC, Beach JP, Kaizer AM, Gumidyala R.The association between preoperative canna-
bis use and intraoperative inhaled anesthetic consumption: a retrospective study. J Clin Anesth.
2020;67:109980.
16. McLaren-Blades A, Ladha K, Goel A, Manoo V, Kotteeswaran Y, Gee YY, etal. Perioperative
pain and addiction interdisciplinary network (PAIN): protocol for the perioperative manage-
ment of cannabis and cannabinoid-based medicines using a modied Delphi process. BMJ
Open. 2020;10(7):e036472.
17. Jamal N, Korman J, Musing M, Malavade A, Coleman BL, Siddiqui N, Friedman Z.Effects of
pre-operative recreational smoked cannabis use on opioid consumption following inamma-
tory bowel disease surgery: a historical cohort study. Eur J Anaesthesiol. 2019;36(9):705–6.
18. Page RL 2nd, Allen LA, Kloner RA, Carriker CR, Martel C, Morris AA, et al. Medical
marijuana, recreational cannabis, and cardiovascular health: a scientic statement from the
American Heart Association. Circulation. 2020;142(10):e131–e52.
19. Rezkalla S, Kloner RA. Cardiovascular effects of marijuana. Trends Cardiovasc Med.
2019;29(7):403–7.
7 The Impact ofCannabis Use Disorder onCritical Illness
104
20. Richards JR, Blohm E, Toles KA, Jarman AF, Ely DF, Elder JW.The association of cannabis
use and cardiac dysrhythmias: a systematic review. Clin Toxicol (Phila). 2020;58(9):861–9.
21. Richards JR, Bing ML, Moulin AK, Elder JW, Rominski RT, Summers PJ, Laurin EG.Cannabis
use and acute coronary syndrome. Clin Toxicol (Phila). 2019;57(10):831–41.
22. Wu TC, Tashkin DP, Djahed B, Rose JE.Pulmonary hazards of smoking marijuana as com-
pared with tobacco. N Engl J Med. 1988;318(6):347–51.
23. Vozoris NT, Zhu J, Ryan CM, Chow CW, To T. Cannabis use and risks of respiratory and
all-cause morbidity and mortality: a population-based, data-linkage, cohort study. BMJ Open
Respir Res. 2022;9(1):e001216.
24. Kempker JA, Honig EG, Martin GS.The effects of marijuana exposure on expiratory airow.
A study of adults who participated in the U.S. National Health and Nutrition Examination
Study. Ann Am Thorac Soc. 2015;12(2):135–41.
25. Gracie K, Hancox RJ.Cannabis use disorder and the lungs. Addiction. 2021;116(1):182–90.
26. Flisberg P, Paech MJ, Shah T, Ledowski T, Kurowski I, Parsons R.Induction dose of propofol
in patients using cannabis. Eur J Anaesthesiol. 2009;26(3):192–5.
27. Camilleri M.Cannabinoids and gastrointestinal motility: pharmacology, clinical effects, and
potential therapeutics in humans. Neurogastroenterol Motil. 2018;30(9):e13370.
28. Perisetti A, Gajendran M, Dasari CS, Bansal P, Aziz M, Inamdar S, etal. Cannabis hyper-
emesis syndrome: an update on the pathophysiology and management. Ann Gastroenterol.
2020;33(6):571–8.
29. Cohen L, Neuman MG. Cannabis and the gastrointestinal tract. J Pharm Pharm Sci.
2020;23:301–13.
30. Potukuchi PK, Moradi H, Park F, Kaplan C, Thomas F, Dashputre AA, etal. Cannabis use and
risk of acute kidney injury in patients with advanced chronic kidney disease transitioning to
dialysis. Cannabis Cannabinoid Res. 2023;8(1):138–47.
31. Porr CJ, Rios P, Bajaj HS, Egan AM, Huot C, Batten R, etal. The effects of recreational can-
nabis use on glycemic outcomes and self-management behaviours in people with type 1 and
type 2 diabetes: a rapid review. Syst Rev. 2020;9(1):187.
32. Guzel D, Yazici AB, Yazici E, Erol A. Alterations of the hematologic cells in synthetic can-
nabinoid users. J Clin Lab Anal. 2017;31(6):e22131.
33. Rezende SM, Lijfering WM, Rosendaal FR, Cannegieter SC. Hematologic variables and
venous thrombosis: red cell distribution width and blood monocyte count are associated with
an increased risk. Haematologica. 2014;99(1):194–200.
34. Baldassarri S, Bertoni A, Bagarotti A, Sarasso C, Zanfa M, Catani MV, et al. The endocan-
nabinoid 2-arachidonoylglycerol activates human platelets through non-CB1/CB2 receptors. J
Thromb Haemost. 2008;6(10):1772–9.
35. Ballas SK.The use of cannabis by patients with sickle cell disease increased the frequency of
hospitalization due to vaso-occlusive crises. Cannabis Cannabinoid Res. 2017;2(1):197–201.
36. Vakharia RM, Sodhi N, Anis HK, Ehiorobo JO, Mont MA, Roche MW. Patients who have
cannabis use disorder have higher rates of venous thromboemboli, readmission rates, and costs
following primary total knee arthroplasty. J Arthroplast. 2020;35(4):997–1002.
37. Meah F, Lundholm M, Emanuele N, Amjed H, Poku C, Agrawal L, Emanuele MA. The
effects of cannabis and cannabinoids on the endocrine system. Rev Endocr Metab Disord.
2022;23(3):401–20.
38. Bonnet U. Chronic cannabis abuse, delta-9-tetrahydrocannabinol and thyroid function.
Pharmacopsychiatry. 2013;46(1):35–6.
39. van Leeuwen AP, Creemers HE, Greaves-Lord K, Verhulst FC, Ormel J, Huizink
AC.Hypothalamic-pituitary-adrenal axis reactivity to social stress and adolescent cannabis
use: the TRAILS study. Addiction. 2011;106(8):1484–92.
40. Ranganathan M, Braley G, Pittman B, Cooper T, Perry E, Krystal J, D’Souza DC.The effects
of cannabinoids on serum cortisol and prolactin in humans. Psychopharmacology (Berl).
2009;203(4):737–44.
41. Lisano JK, Kisiolek J, Flores V, Smoak P, Pullen NA, Stewart LK.Chronic cannabis use is
associated with altered monocyte phenotype, immune response, and depression in physically
active individuals. Can J Physiol Pharmacol. 2023;101(6):316–26.
Z. J. Carr and E. Strand
105
42. Maayah ZH, Ferdaoussi M, Alam A, Takahara S, Silver H, Soni S, etal. Cannabidiol sup-
presses cytokine storm and protects against cardiac and renal injury associated with sepsis.
Cannabis Cannabinoid Res. 2022.
43. Dinu AR, Rogobete AF, Bratu T, Popovici SE, Bedreag OH, Papurica M, etal. Cannabis sativa
revisited-crosstalk between microRNA expression, inammation, oxidative stress, and endo-
cannabinoid response system in critically ill patients with sepsis. Cells. 2020;9(2):307.
44. Šahinović I, Mandić S, Mihić D, Duvnjak M, Loinjak D, Sabadi D, etal. Endocannabinoids,
anandamide and 2-arachidonoylglycerol, as prognostic markers of sepsis outcome and compli-
cations. Cannabis Cannabinoid Res. 2022;8:802.
45. Chiu RG, Patel S, Siddiqui N, Nunna RS, Mehta AI.Cannabis abuse and perioperative com-
plications following inpatient spine surgery in the United States. Spine (Phila Pa 1976).
2021;46(11):734–43.
46. Chiu RG, Fuentes AM, Patil SN, Chiu R, McGuire LS, Mehta AI.Cannabis abuse and periop-
erative complications after treatment of intracranial aneurysms: a nationwide analysis. World
Neurosurg. 2022;158:e184–e95.
47. Legare CA, Raup-Konsavage WM, Vrana KE.Therapeutic potential of cannabis, cannabidiol,
and cannabinoid-based pharmaceuticals. Pharmacology. 2022;107(3–4):131–49.
48. Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, etal. Cannabinoids
for medical use: a systematic review and meta-analysis. JAMA. 2015;313(24):2456–73.
7 The Impact ofCannabis Use Disorder onCritical Illness
107© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2024
K. Karamchandani, J. E. Grant (eds.), Substance Use Disorders in Adult
Critically Ill Patients, https://doi.org/10.1007/978-3-031-67069-5_8
Chapter 8
Stimulant Use Disorder
KristinReinaker
andJamiJohnson
Abbreviations
ACC: American College of Cardiology
AHA: American Heart Association
AKI: Acute kidney injury
BB: Beta blocker(s)
CAACS: Cocaine-associated acute coronary syndrome
CNS: Central nervous system
ECG: Electrocardiogram
EF: Ejection fraction
GDMT: Goal-directed medical therapy
HF: Heart failure
ICD: Implantable cardioverter debrillator(s)
IM: Intramuscular
Kg: Kilogram
LVAD: Left ventricular assist device(s)
MDA: 3,4-methylenedioxyamphetamine
MDE: 3,4-methylenedioxy-N-ethylamphetamine
MDMA: 3,4-methelenedioxymethamphetamine
Ng: Milligram
MI: Myocardial infarction
K. Reinaker (*)
Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy,
Rutgers, The State University of New Jersey, Ewing, NJ, USA
e-mail: kbohnenberger@pharmacy.rutgers.edu
J. Johnson
Oklahoma Center for Poison and Drug Information, University of Oklahoma
College of Pharmacy, Oklahoma City, OK, USA
108
NSDUH: National Survey on Drug Use and Health
NSTE-ACS: Non-ST segment elevation acute coronary syndromes
PVCs: Premature ventricular contractions
SC: Synthetic cathinones
US: United States
VF: Ventricular brillation
VT: Ventricular tachycardia
Epidemiology
The use of stimulants, such as cocaine and amphetamines, accounts for numerous emer-
gency department visits each year [1]. In recent years, increased rates of emergency
department visits, hospitalizations, and deaths from stimulant overdose have been
reported [1, 2]. According to the National Survey on Drug Use and Health (NSDUH),
cocaine was used by 4.8 million people over the age of 12in the United States (US) in
2021 [3]. Globally, the World Drug Report 2020 reported that cocaine was used by 21.5
million people in the preceding year [4]. Amphetamine use in North America was nota-
bly higher than that of the global prevalence (3.9% vs. 0.7%) in 2020, with amphet-
amine and “ecstasy-type” substances reportedly used in 34 million people and 20
million people aged 15–64 years, respectively [4]. In the US, methamphetamine was
used by 2.5 million people (1% of the population) over the age of 12in 2021 [3].
Furthermore, deaths in the US attributed to methamphetamine increased from several
hundred per year in the 1990s to over 32,000in 2021 [5].
History
Cocaine
Cocaine is an alkaloid contained within the leaves of the coca plant (Erythroxylon
coca), a bush which grows extensively in Columbia, Peru, and the Plurinational State
of Bolivia [4, 6]. Thought to be a gift from the royal son god Manco Cepac, leaves
were mixed with lime and chewed in traditional Incan religious ceremonies as early
as the sixth century [6, 7]. Additionally, native South Americans discovered that chew-
ing coca leaves alleviated fatigue and altitude sickness, thus establishing the plant
within social practices as well [7]. Following the introduction of the leaves to Europe
by explorers, the alkaloid cocaine was isolated, puried, and named in 1860 [6, 7].
Thereafter, cocaine’s stimulant and anesthetic properties led to its role as a pharma-
ceutical tool. In 1883, it was used to alleviate fatigue in Bavarian soldiers [6]. In 1884,
after experimenting with its use to alleviate his own depression, Sigmund Freud pro-
posed that cocaine be used as a stimulant, aphrodisiac, local anesthetic, and to manage
K. Reinaker and J. Johnson
109
asthma, digestive disorders, cachexia, and alcohol and morphine dependence [6]. The
successful use of cocaine as a local anesthetic during ocular surgery and as a regional
nerve block cemented its use in modern medicine in the same year [6]. Shortly there-
after, cocaine from the coca leaf and caffeine from the kola nut were incorporated into
an elixir and marketed as Coca-Cola™ to become one of the most popular elixirs in
the US [6, 7]. It wasn’t until 1906 that the company agreed to use decocainized leaves
in its formula [6]. With its incorporation into numerous products, the widespread use
of cocaine made the penchant for addiction apparent. The Pure Food and Drug Act
helped curtail its use when it required the disclosure of all constituents on medication
labels [7]. Eight years later, in 1914, recreational use of cocaine was made illegal with
the passage of the Harrison Narcotics Act, which limited the use of cocaine to medical
use for local anesthesia of the mucus membranes of the nasal, oral, or laryngeal cavi-
ties [7]. This placed cocaine under strict control and subjected its use to similar penal-
ties as opium, morphine, and heroin [6].
Despite its legal limitation to medical use, the illicit use of cocaine remains prev-
alent [3, 4]. Following an increase in amphetamine-related deaths in the 1960s and
early 1970s, the use of cocaine rose sharply due to its role as a substitutive psycho-
stimulant [7]. Intravenous cocaine rose in popularity as users sought to substitute
injectable amphetamines. The advent of freebase and crack formulations in the late
1970s afforded new options which provided users with a similar “rush” as would be
achieved with the intravenous formulation [8]. Given the propensity of rapid plasma
elevations to result in addiction, it was predicted that these reports of cardiovascular
toxicity would surmount [9]. As predicted, the rst case of cocaine-associated myo-
cardial infarction (MI) in the US was reported in 1982, followed by similar reports
in the years that followed [10]. Recreational use of cocaine remains a major issue.
Cultivation of coca reached a record high in 2021, climbing 35% from the previous
year, demonstrating the sharpest year-to-year increase since 2016 [11]. The increase
in supply is in response to a steep growth in demand, with the world’s largest con-
sumer market for cocaine being North America, followed by Europe [4].
Amphetamines
Amphetamine was rst synthesized by G.A.Alles in 1927 while researching eco-
nomic alternatives to ephedrine [12]. Like many other substances of abuse, amphet-
amine use began medicinally, with mixed success, for ailments ranging from
morphine addiction and myasthenia gravis to seasickness and night blindness in the
1930s and into the 1940s. During this time, amphetamines were concomitantly sup-
plied in substantial quantities to soldiers during World War II to enhance alertness
and combat fatigue, with 72 million Benzedrine tablets distributed to British sol-
diers alone [13]. This led to more widespread recreational use of amphetamines in
the 1950s and 1960s, when growing concerns over addiction led to increased regu-
lation [12]. While the legitimate use of amphetamines declined in the 1970s and
1980s, their illicit use, especially methamphetamine, began to drastically rise. In
recent decades, illicit use of amphetamines has remained a challenge, and
8 Stimulant Use Disorder