In summary

Can CBD interact with cocaine? Can it help overcome drug addiction?

  • A 2019 study revealed that CBD was able to reverse the toxicity and seizures caused by cocaine, as well as the motivation to take cocaine and methamphetamine (meth) in the non-clinical setting(1).
  • It also showed that CBD could be a promising treatment for substance use disorders(2).
  • Observational studies also imply that CBD “may reduce problems related to crack-cocaine addiction, such as withdrawal symptoms, craving, impulsivity and paranoia (Fischer et al., 2015).”(3)
  • Another research conducted by Friedbert Weiss, PhD of Scripps Research Institute focused on the development of behavioural methods that can accurately model certain aspects of human drug-seeking behaviour in animals. During the behavior tests, which included stressful and anxiety-provoking situations, the rats did not display any sign of drug-seeking behavior. Five months later, the involved animals still proved to be free from relapse caused by stress or drug cues(4).
  • Clinical trials and human subjects studies are still needed to fully gauge CBD’s potential to treat substance abuse and disorders.
The full article

Does CBD Interact with Cocaine?

What is Cocaine

Cocaine is a strongly-addictive stimulant drug that can have a detrimental effect on the mental health of the user. It is brewed from the leaves of the coca plant which originally came from South America. Although it can serve as local anesthesia for surgeries, cocaine is known as an illegal recreational drug.

Cocaine is known to give short-term pleasurable effects which is one of the main reasons why cocaine abuse has become a global phenomenon. 

What is CBD

Cannabinoids, like CBD and tetrahydrocannabinol (THC), are chemicals found in cannabis plants. The most popular kinds of cannabis plants are marijuana and hemp plants.

Cannabidiol or CBD is the second active ingredient of cannabis. CBD can be pressed out from either marijuana or hemp. Hemp plants, or industrial hemps, contain a high amount of CBD, and a lesser percentage of THC, the primary psychoactive compound that brings about euphoria. Hemps naturally has 0.3% THC.

Medical marijuana, or medical cannabis, is the marijuana plant used to treat health issues.

Can CBD Be Taken with Cocaine?

Individually, cocaine and marijuana can already be damaging to the user. Thus, taking cannabinoids along with cocaine can have detrimental effects. The risks of using them together are amplified, which may even lead to a cocaine overdose(5).

Stimulants like cocaine, amphetamines, methamphetamine (meth), methylphenidate (MPH), and amphetamine-dextroamphetamine are often used and misused to boost physical strength, improve performance at work or school, control one’s appetite or lose weight.

A 2014 study by The U.S. National Library of Medicine National Institutes of Health which presents that the combination of low to moderate dosages of MPH and THC resulted in a significantly higher heart rate which caused an increase in cardiovascular strain(6).

In the same manner as with THC, using CBD along with any kind of stimulant must be only upon the prescription of a medical professional. 

Can CBD Treat Cocaine Craving and Reduce Addiction Relapse?

A 2019 study reveals that CBD could be a promising treatment for substance use disorders(7). CBD was able to reverse the toxicity and seizures caused by cocaine, as well as the motivation to take cocaine and methamphetamine in the scarce amount of human clinical studies available. Observational studies also imply that CBD “may reduce problems related to crack-cocaine addiction, such as withdrawal symptoms, craving, impulsivity and paranoia (Fischer et al., 2015).”(8)

A team from Scripps Research Institute also facilitated a research to verify if it can decrease cocaine craving and treat cocaine addiction. The recent studies conducted by the Scripps Research Institute in Neuropsychopharmacology explained that CBD activates the brain’s serotonin receptors(9).

The leader of the investigative team, Friedbert Weiss, and his research associate, Gustavo Gonzalez-Cuevas, focused on the development of behavioural methods that can accurately model certain aspects of human drug-seeking behaviour in animals. 

Since drug cravings and relapse in humans take place when they are exposed to drug-related environmental stimuli and stressful settings, Weiss’s team experimented on rats that had become dependent on cocaine and alcohol, which led to substance addiction. 

The researchers then applied a gel which contained CBD to the skin of the rats being studied. The team repeated the process once daily for an entire week. 

During the behaviour tests, which included stressful and anxiety-provoking situations, the rats did not display any sign of drug-seeking behaviour. Five months later, the involved animals still proved to be free from relapse caused by stress or drug cues. 

Friedbert Weiss pointed out, “The results provide proof of principle supporting the potential of CBD in relapse prevention along two dimensions: beneficial actions across several vulnerability states, and long-lasting effects with only brief treatment.”

He added, “Drug addicts enter relapse vulnerability states for multiple reasons. Therefore, effects such as these observed with CBD that concurrently ameliorate several of these are likely to be more effective in preventing relapse than treatments targeting only a single state.”

While the results of these studies are on the affirmative, clinical trials and studies (currently lacking) are still needed to fully gauge CBD’s potential to treat substance abuse and disorders.

Effects of Cocaine Addiction

Generally, cocaine consumption affects all systems in the body, but its primary target is the central nervous system (CNS). 

Cocaine blocks the reuptake of neurotransmitters in the neuronal synapses, and this mechanism affects the CNS(10).

Some of the short-term side effects of substance abuse include:

  • Extreme happiness
  • Nausea
  • Paranoia
  • Sensitivity to touch, sound, and sight
  • Loss of appetite
  • Irritability or anger
  • Fast or irregular heartbeat
  • Tremors and muscle twitches

However, heavy and frequent usage of cocaine can lead to more severe health issues, such as:

  • Seizures and convulsions
  • Heart disease, heart attack, or stroke
  • Mood swings
  • Lung damage
  • Memory loss
  • Sleep problems

Using cocaine can be destructive to anyone, but the injurious effect can be greater for pregnant women. 

American Addiction Centers stated that pregnant women who abuse cocaine consumption may suffer from anemia, skin infections, and malnutrition. It may also cause anxiety, severe postpartum depression, and suicidal thoughts. (11)

It can also affect the unborn baby. Taking cocaine during the early stage of the pregnancy may yield to miscarriage, and can also cause placental abruption, decrease blood flow in the uterus, and preterm labor(12).

What Causes Cocaine Addiction?

The National Survey on Drug Use and Health (NSDUH) revealed in a 2014 survey that there were close to 1.5 million cocaine users in the United States aged 12 or older (6 out of 10 of the population)(13).

In a latter report, the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) said nearly 1.9 million people aged 12 or older used cocaine in 2016, and almost half a million people engaged in using crack cocaine (crystal form of cocaine)(14).

A 2006 review published by the U.S. National Library of Medicine National Institutes of Health emphasized results that the endocannabinoid system (ECS) has a crucial role in the neurobiological mechanism underlying drug addiction. It engages in the rewarding effects of nicotine, cannabinoids, opioids, and alcohol(15).

Once cocaine is inhaled, snorted, or injected, the drug increases the amount of dopamine in the body. It serves as the chemical messenger into the parts of the brain which control pleasure. As a result, the body experiences heightened alertness and increase in energy, or what is generally known as “high.”

In an attempt to continuously experience the same high, people tend to use cocaine more frequently and in an increased dosage until it becomes a habit. Eventually, trying to stop using drugs can become painful and can cause intense cravings and withdrawal symptoms. 

According to The National Institute of Drug Abuse (NIDA), withdrawal happens when a drug-dependent person suddenly stops using substances after a long time. Withdrawal symptoms include insomnia, muscle and bone pain, cold flashes, and vomiting. It may also come with depression or dysphoria (opposite of euphoria) which can last for weeks(16).

Treatments for Cocaine Addiction

Behavioural therapy may be used to help treat cocaine addiction.

Behavioural therapy includes:

  • cognitive-behavioural therapy, or psychotherapy with a mental health counsellor
  • Incentive-based initiatives for recovering addicts who remain substance-free
  • 12-step programs for addiction recovery

According to the National Institute of Drug Abuse (NIDA), there are currently no government-approved medicines available to treat cocaine addiction(17).

Conclusion

Despite the benefits of CBD, Peter Grinspoon, MD, a professor of medicine at Harvard Medical School, advises the public through a Harvard health article to be wary of the health risks that it may pose. Some of the side effects of CBD include nausea, fatigue, and irritability(18). It may also increase the level of blood thinners like coumadin. 

Notably, CBD is primarily sold as a dietary supplement and not a medicinal alternative. The Food and Drug Administration (FDA) does not regulate nutritional supplements. FDA also discourages the “use of CBD, THC, and marijuana in any form during pregnancy and while breastfeeding.”(19)

It is always highly encouraged to consult a licensed medical professional for general health care advice or to alleviate symptoms of specific ailments.


  1. Lopez, C. C., Pardo, M. P. G., & Aguilar, M. A. (2019). Cannabidiol Treatment Might Promote Resilience to Cocaine and Methamphetamine Use Disorders: A Review of Possible Mechanisms. Molecules, 24(14). doi: https://doi.org/10.3390/molecules24142583
  2. Ibid.
  3. Gonzalez-Cuevas, G. et al. Unique treatment potential of cannabidiol for the prevention of relapse to drug use: Preclinical proof of principle, Neuropsychopharmacology DOI: 10.1038/S41386-018-0050-8
  4. National Institute on Drug Abuse. Source: https://www.drugabuse.gov/publications/drugfacts/marijuana
  5. U.S. National Library of Medicine National Institutes of Health. Published online 2014 Aug 7. doi: 10.1016/j.jsat.2014.07.014. An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250392/
  6. Cannabidiol Treatment Might Promote Resilience to Cocaine and Methamphetamine Use Disorders: A Review of Possible Claudia Calpe-Lopez, et al., 2019) Retrieved from https://www.researchgate.net/publication/334517310_Cannabidiol_Treatment_Might_Promote_Resilience_to_Cocaine_and_Methamphetamine_Use_Disorders_A_Review_of_Possible_Mechanisms
  7. Lopez and Pardo, op. cit.
  8. Gonzalez-Cuevas, G., op.cit.
  9. Gonzalez-Cuevas, G., op.cit.
  10. U.S. National Library of Medicine National Institutes of Health. Int J Clin Pharmacol Ther Toxicol. 1993 Dec;31(12):575-81. Cocaine and the Nervous System. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/8314357
  11. American Addiction Centers. Dangers of Cocaine in Pregnancy. Retrieved from https://americanaddictioncenters.org/cocaine-treatment/dangers-pregnancy
  12. American Addiction Centers. Dangers of Cocaine in Pregnancy. Retrieved from https://americanaddictioncenters.org/cocaine-treatment/dangers-pregnancy
  13. National Institute on Drug Abuse. What Is the Scope of Cocaine Use in the United States? Source: https://www.drugabuse.gov/publications/research-reports/cocaine/what-scope-cocaine-use-in-united-states
  14. Substance Abuse and Mental Health Services Administration. (2017). Key substance use and mental health indicators in the United States: Results from the 2016 National Survey on Drug Use and Health (HHS Publication No. SMA 17-5044, NSDUH Series H-52). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. Retrieved from https://www.samhsa.gov/data/
  15. Pharmacol Biochem Behav. 2005 Jun;81(2):396-406. The role of endocannabinoid transmission in cocaine addiction. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/15925401
  16. National Institute on Drug Abuse https://www.drugabuse.gov/about-nida/frequently-asked-questions)
  17. National Institute on Drug Abuse (May 2016). How Is Cocaine Addiction Treated? Source: https://www.drugabuse.gov/publications/research-reports/cocaine/what-treatments-are-effective-cocaine-abusers
  18. Harvard Health Publishing, Harvard Medical School. (2019, August 27). Peter Grinspoon, MD. Source: https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-2018082414476
  19. U.S. Food and Drug Administration Source: https://www.fda.gov/consumers/consumer-updates/what-you-should-know-about-using-cannabis-including-cbd-when-pregnant-or-breastfeeding

More Info

Less Info

Does CBD interact with cocaine, and can CBD help with cocaine addiction?
Cocaine is a strongly-addictive stimulant drug concocted from the leaves of the coca plant native to South America. Although medical professionals can sometimes use it as local anesthesia for surgeries, recreational cocaine use is illegal.

Cocaine abuse is a global phenomenon, with the highest rates of consumption in the Americas.

According to the National Survey on Drug Use and Health (NSDUH), there were about 1.5 million cocaine users in the United States aged 12 or older (6 out of 10 of the population) in 2014.

A new study published by the National Institutes of Health (NIH) demonstrated that CBD is effective in reducing cocaine intake in animal models, providing new perspectives in using CBD as a therapeutic tool against cocaine addiction.

However, there are adverse effects when cannabinoids are used with cocaine.

While cocaine and marijuana have health risks when used alone, the risks are amplified when they are used together, possibly leading to a cocaine overdose.

While results from cannabis compounds may be promising, scientists would still need high-quality evidence from longitudinal research to validate the benefits of CBD oil in treating cocaine addictions safely.

Cocaine Side Effects
The U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) said that 2.2 million people in 2016 used cocaine at least once in the month before the survey, and close to half a million people smoked crack cocaine (crystal form of cocaine).

Cocaine’s short-term effects include extreme happiness, mental alertness, irritability, sensitivity (to sound, sight, and touch), and unreasonable distrust of others.

The substance also has other health effects, such as:

nausea
dilated pupils
fast or irregular heartbeat
raised body temperature and blood pressure
constricted blood vessels
tremors and muscle twitches
The use of cocaine carries risks for anyone, but the risks intensify when abused by pregnant women.

According to the American Addiction Centers, pregnant women who abuse cocaine may be prone to malnutrition, anemia, and skin infections.

What Causes Cocaine Addiction?
Results from recent studies performed by the Scripps Research Institute showed that CBD activates the brain’s serotonin receptors. This interaction was known to be directly linked to reduce drug-seeking behavior by the user.

The National Institute on Drug Abuse (NIDA) explains that cocaine amplifies the levels of dopamine, a natural chemical messenger in the brain linked to the regulation of movement and reward.

Typically, dopamine recycles back to the cells that released it, blocking off the signals between nerve cells.

However, cocaine stops dopamine from being reused, causing substantial amounts to build up in the space between two nerve cells, preventing their regular communication.

The excess of dopamine in the brain’s reward circuit intensifies drug-taking behaviors because the reward circuit ultimately adapts to the massive amounts of dopamine caused by cocaine, becoming less sensitive to it.

As a result, people take more frequent and increased doses of cocaine in an attempt to feel the same high, as well as to achieve relief from withdrawal.

Withdrawal symptoms include fatigue, slowed thinking, increased appetite, depression, insomnia, and having unpleasant dreams.

CBD can regulate the body’s dopamine receptors through the body’s endocannabinoid system (ECS), controls homeostasis (stability or balance) through the nervous system. Thus, CBD is effective in alleviating withdrawal symptoms with minimal side effects.

Treatments for Cocaine Addiction
Drug Abuse Warning Network (DAWN) revealed that, in 2011, cocaine was involved in over one in three visits to hospitals’ emergency departments for drug misuse or drug abuse.

Behavioral therapy may be used to help treat cocaine addiction.

Behavioral therapy includes:

cognitive-behavioral therapy, or psychotherapy with a mental health counselor
motivational incentives, or rewarding patients who remain substance-free, providing drug-free accommodations where people in recovery from substance use help each other
12-step programs
Currently, there are no government-approved medicines available to treat cocaine addiction, according to the NIDA.

What is CBD?
Cannabinoids, like cannabidiol (CBD) and tetrahydrocannabinol (THC), are a group of naturally-occurring compounds in the cannabis plant. Cannabis plants include both marijuana and hemp plants.

CBD can be extracted from either hemp or marijuana.

Hemp plants are naturally high in CBD, and they have less than 0.3% THC, the primary psychoactive compound that induces a euphoric high.

Medical marijuana, or medical cannabis, is the marijuana plant used to treat health issues.

CBD is sold in the form of oils, salves, tinctures, gummies, gels, and supplements.

CBD Benefits and Side Effects
CBD is used to help with numerous ailments and disorders, such as seizures, inflammation, nausea and vomiting, and anxiety.

Typical side effects of CBD include low blood pressure, dry mouth, drowsiness, and lightheadedness.

Note that cannabidiol is possibly unsafe to use when pregnant or breastfeeding.

There have been no clinical studies on the risks of CBD use by pregnant women. However, the U.S. Food and Drug Administration (FDA) discourages “the use of CBD, THC, and marijuana in any form during pregnancy or while breastfeeding.”

CBD and Cocaine Addiction
CBD has been the subject of several studies that examine its potential in treating several diseases and disorders.

There have also been several studies done to investigate CBD’s possible effect on cocaine addiction.

A review highlights results indicating that the endocannabinoid system (ECS) may promote certain aspects of cocaine addiction.

Few studies examined the effects of CBD, and researchers found that it may have therapeutic properties on opioid, cocaine, and psychostimulant drug addiction.

In a review, the authors found that, in some cases, CBD could treat substance use disorder more effectively when used in conjunction with THC.

In another study, the authors assessed the effects of CBD on brain reward function and the reward-facilitating effect of morphine and cocaine. Results showed that CBD inhibited the reward-facilitating effect of morphine, but not cocaine.

Moreover, a group of researchers also investigated the impact of THC and CBD on cocaine-induced conditioned stimulants in animal models.

Results indicate that although CBD does not seem to influence stimulants’ rewarding effect, the compound may impact addictive behaviors during the relapse phase.

CBD and Cocaine Interactions
People sometimes take cocaine and marijuana together to lower the intensity of cocaine ‘high.’

However, even though users are not feeling the effects of the cocaine as strongly, the drug is still affecting their body in the same way, leading to a cocaine overdose.

Also, since THC, a psychoactive component, lowers one’s inhibitions, the user is more inclined to take more cocaine than he or she would usually consume and over a shorter length of time.

The combination of THC and cocaine can also raise heart rate and blood pressure, which may amplify the risk of stroke and heart attack.

A review indicates that marijuana can also weaken the efficacy of prescription antipsychotics or lead to heart disorders when combined with antidepressants.

As most CBD products contain trace amounts of THC, experts warn CBD users to take note of the adverse effects that come with combining cocaine and THC.

Conclusion
ClinicalTrials.gov, a database of clinical studies conducted around the world, lists numerous studies on cannabinoids, CBD, and cocaine-related disorders. However, there has been no high-quality evidence indicating that CBD can help with cocaine addiction.

CBD and cocaine, when used either alone or together, bring about varying degrees of risk.

Medical experts advise people to first consult with their doctor if they are looking to try CBD for general health care or to alleviate symptoms of specific ailments.

——————————————————————————————————————————————————————————————————————–

Cocaine
1. NAME
1.1 Substance
1.2 Group
1.3 Synonyms
1.4 Identification numbers
1.4.1 CAS number
1.4.2 Other numbers
1.5 Main brand names, main trade names
1.6 Main manufacturers / importers
2. SUMMARY
2.1 Main risks and target organs
2.2 Summary of clinical effects
2.3 Diagnosis
2.4 First aid measures and management principle
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
3.2 Chemical structure
3.3 Physical properties
3.3.1 Colour
3.3.2 State/form
3.3.3 Description
3.4 Other characteristics
3.4.1 Shelf-life of the substance
3.4.2 Storage conditions
4. USES
4.1 Indications
4.1.1 Indications
4.4.2 Description
4.2 Therapeutic dosage
4.2.1 Adults
4.2.2 Children
4.3 Contraindications
5. ROUTES OF EXPOSURE
5.1 Oral
5.2 Inhalation
5.3 Dermal
5.4 Eye
5.5 Parenteral
5.6 Other
6. KINETICS
6.1 Absorption by route of exposure
6.2 Distribution by route of exposure
6.3 Biological half-life by route of exposure
6.4 Metabolism
6.5 Elimination and excretion
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
7.1.1 Toxicodynamics
7.1.2 Pharmacodynamics
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
7.2.1.2 Children
7.2.2 Relevant animal data
7.2.3 Relevant in vitro data
7.3 Carcinogenicity
7.4 Teratogenicity
7.5 Mutagenicity
7.6 Interactions
7.7 Main adverse effects
8. TOXICOLOGICAL ANALYSIS AND BIOMEDICAL INVESTIGATIONS
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
9.1.2 Inhalation
9.1.3 Skin exposure
9.1.4 Eye contact
9.1.5 Parenteral exposure
9.1.6 Other
9.2 Chronic poisoning
9.2.1 Ingestion
9.2.2 Inhalation
9.2.3 Skin exposure
9.2.4 Eye contact
9.2.5 Parenteral exposure
9.2.6 Other
9.3 Course, prognosis, cause of death
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
9.4.2 Respiratory
9.4.3 Neurological
9.4.3.1 CNS
9.4.3.2 Peripheral Nervous System
9.4.3.3 Autonomic Nervous System
9.4.3.4 Skeletal and smooth muscle
9.4.4 Gastro-intestinal
9.4.5 Hepatic
9.4.6 Urinary
9.4.6.1 Renal
9.4.6.2 Other
9.4.7 Endocrine and Reproductive Systems
9.4.8 Dermatological
9.4.9 Eye, ear, nose, throat, local effects
9.4.10 Haematological
9.4.11 Immunological
9.4.12 Metabolic
9.4.12.1 Acid-Base Disturbance
9.4.12.2 Fluid and electrolyte disturbances
9.4.12.3 Others
9.4.13 Allergic Reactions
9.4.14 Other clinical effects
9.4.15 Special risks
9.5 Other
9.6 Summary
10. MANAGEMENT
10.1 General Principles
10.2 Life supportive procedures and symptomatic/specific treatment
10.3 Decontamination
10.4 Elimination
10.5 Antidote Treatment
10.5.1 Adults
10.5.2 Children
10.6 Management discussion
11. ILLUSTRATITIVE CASES
11.1 Case reports from literature
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
12.2 Other
13. REFERENCES
14. AUTHORS

Cocaine

International Programme on Chemical safety
Poisons Information Monograph 139
Pharmaceutical

1. NAME

1.1 Substance

Cocaine

1.2 Group

Nervous system; anesthetics;
local; esters of benzoic acid (N01BC01)

1.3 Synonyms

(-)-cocaine; ß-cocaine;
Benzoylmethylecgonine;
Ecgonine methyl ester benzoate;
L-cocaine; Methylbenzoylecgonine;
cocaina; Erytroxylin;
Kokain; Kokan; Kokayeen;
Neurocaïne; Bernice;
Bernies; Blow; Burese;
C; Cadillac of drugs;
Carrie; Cecil;
Champagne of drugs; Charlie;
Cholly; Coke; Corine;
Crack; Dama blanca;
Eritroxilina; Flake; Girl;
Gold dust; Green gold;
Happy dust; Happy trails;
Her; Jam; Lady;
Leaf; Nose candy;
Pimp’s drug; Rock; She;
Snow; Star dust;
Star-spangled powder; Toot;
White girl; White lady;
liquid lady (alcohol + cocaine);
speed ball (heroine + cocaine)

1.4 Identification numbers

1.4.1 CAS number

50-36-2 (cocaine)

1.4.2 Other numbers

CAS cocaine hydrochloride: 53-21-4
ATC codes:

R02AD03
S01HA01
S02DA02

1.5 Main brand names, main trade names

mélange de Bonain

1.6 Main manufacturers / importers

Merck (Germany); Stepan Chemical Company (Mazwood,
New-Jersey, USA)

2. SUMMARY

2.1 Main risks and target organs

The target organs are Central Nervous System (CNS) and
the Cardio-vascular (CV) system.
Abuse of cocaine leads to strong psychological
dependence.

2.2 Summary of clinical effects

Effects depend on the dose, the other substances taken,
the route of administration and individual
susceptibility.
In low doses acute intoxication causes euphoria and
agitation.

Larger doses cause hyperthermia, nausea, vomiting, abdominal
pain, chest pain, tachycardia, ventricular arrhythmia,
hypertension, extreme anxiety, agitation, hallucination,
mydriasis. These can be followed by CNS depression with
irregular respirations, convulsions, coma, cardiac
disturbances, collapse and death.

Chronic intoxication produces euphoria, agitation
psychomotor, suicidal ideation, anorexia, weight loss,
hallucinations and mental deterioration.

A withdrawal syndrome with severe psychiatric effects can
occur (euphoria, depression).
Physical signs of withdrawal have been described.

2.3 Diagnosis

Clinical features:

Acute cocaine poisoning produces signs similar to acute
amphetamine poisoning: psychiatric disturbance (agitation,
hallucinations), neurological effects (mydriasis,
convulsions), cardiovascular problems (tachycardia, raise in
blood pressure, arrhythmia and acute coronary insufficiency)
and respiratory difficulties (cardio-respiratory arrest).
When agitation, convulsions, acute coronary insufficiency are
seen in a young patient without previous cardiovascular
problems, cocaine poisoning should be suspected.
Headaches may be due to stroke or transient ischemic attack
or to intra-cerebral or subarachnoid haemorrhage. Spontaneous
cerebral haemorrhage can occur in normotensive subjects.

Laboratory: by detection of urinary metabolites of cocaine.

2.4 First aid measures and management principle

In case of ingestion, gastric emptying, may provoke
convulsions and is dangerous. Ipecac should not be used.

Treatment of acute intoxication is symptomatic.

If there are convulsions or agitation, 2.5 to 5 mg diazepam
by slow intravenous injection can be given, and repeated
every 10 to 15 minutes up to a maximum of 30 mg; in status
epilepticus, thiopentone with intubation and mechanical
ventilation is used.
In acute psychiatric disturbance, 2 to 5 mg haloperidol
intramuscularly may be required.
Betablockers may correct cardiac arrhythmia but may aggravate
coronary or systemic vasoconstriction. Antiarrhythmic and
cardioversion can be used but intravenous lidocaine should be
avoided because it can provoke convulsions.
Severe arterial hypertension can be corrected with
intravenous nitroprusside, phentolamine or labetolol, or with
oral nifedipine.

Myocardial ischemia is treated in the usual manner with
nitrates and betablockers, or calcium channel blockers.
Hyperthermia is treated by removal of clothing, a calm
atmosphere and cooling blanket.
Cardio-respiratory resuscitation may be required.

Cardiovascular collapse is treated by molar sodium lactate if
the QRS complex is wider than 120 milliseconds and by the
cautious administration of catecholamines (dopamine or
norepinephrine).
Monitoring of CPK activity is required because
cocaine-induced rhabdomyolysis and hypotension pose a high
risk of acute renal failure and require treatment.

3. PHYSICO-CHEMICAL PROPERTIES

3.1 Origin of the substance

Cocaine is one of 14 alkaloids extracted from the leaves
of 2 species of coca: Erythroxylum coca (found in South
America, central America, India and Java) and Erythroxylum
novogranatense (in South America).

Local manufacture:
The leaves are steeped in alkaline, sulphuric acid, paraffin
or other solvents: the mixture forms a thick brown paste,
“coca paste”, which contains 40 to 91% cocaine.
Subsequently, the alkaloids are precipitated with sodium
carbonate and then dissolved in dilute hydrochloric acid to
produce cocaine hydrochloride containing 40% cocaine.
Extraction of cocaine hydrochloride with ether in aqueous or
alkaline solution produces “freebase” or “crack”, which
contains 85 to 90% of pure cocaine (Jeri, 1984; Ellenhorn &
Barceloux, 1988; Farrar & Kearns, 1989; Goldfrank, 1990).

Pharmaceutical manufacture:
Cocaine is a semi-synthetic drug obtained from ecgonine, a
product of the saponification of coca alkaloids; the ecgonine
is esterified with methyl alcohol in the presence of an
excess of chlorine. It is made from the resulting methyl
ecgonine by treatment with benzoic anhydride (Dorvault,
1987).

Street cocaine used by addicts can be mixed with a number of
diluants (“cut”), and these include amphetamines,
anti-histamines, benzocaine, inositol, lactose, lidocaine,
mannitol, opiods, phencyclidine, procaine, sugars,
tetracaine, and sometimes arsenic, caffeine, quinidine, and
even flour or talc. These adulterants can themselves be the
cause of poisoning (Cregler, 1986; Van Viet et al.,
1990).

3.2 Chemical structure

Chemical names:
Benzoylmethylecgonine;
(1R,2R,3S,5S)-2-Methoxycarbonyltropan-3-yl benzoate;
2ß-carbomethoxy-3ß-benzoxytropane;
1aH, 5aH-tropane-2ß-carboxylic acid 3ß-hydroxy-methyl ester
benzoate;
3-tropanylbenzoate-2-carboxylic acid methyl ester;
3-(benzoyloxy)-8-methyl-8-azabicyclo-(3.2.1.)
octane-2-carboxylic acid methyl ester;

Molecular Weight= 303.4
Molecular formula: C17 H21 N O4

(Clarke, 1986; Reynolds, 1989)

3.3 Physical properties

3.3.1 Colour

Cocaine hydrochloride:
colourless or white

Cocaine freebase:
white

3.3.2 State/form

Cocaine hydrochloride:
solid-crystals

Cocaine freebase:
solid-crystals

3.3.3 Description

Cocaine hydrochloride:
Hygroscopic odourless bitter tasting crystals
Solubility in water: 200 grams per 100 mLs
In alcohol: 25 grams per 100 mLs
In ether: insoluble
Melting point: 197°C
1% solution is of neutral pH (Pharmacopée française,
1982; Clarke, 1986; Dorvault, 1987)

Cocaine freebase:
Slightly volatile, anhydrous, bitter tasting crystals
Solubility in water: 0.17 grams per 100 mL
In alcohol: 15.4 grams per 100 mL
In ether: 28.6 grams per 100 mL
Melting point 98°C
Boiling point 187 to 188°C
pH: alkaline
(Budavari, 1989)

Street cocaine used by addicts can be mixed with a
number of diluents (“cut”), and these include
amphetamines, anti-histamines, benzocaine, inositol,
lactose, lidocaine, mannitol, opioids, phencyclidine,
procaine, sugars, tetracaine, and sometimes arsenic,
caffeine, quinidine, and even flour or talc.

3.4 Other characteristics

3.4.1 Shelf-life of the substance

No data

3.4.2 Storage conditions

Cocaine hydrochloride should be kept in a
tightly shut recipient away from light and moisture
(Pharmacopée française, 1982; Reynolds, 1989).

4. USES

4.1 Indications

4.1.1 Indications

4.4.2 Description

Cocaine hydrochloride is now used only for
anaesthesia of the respiratory tract (Baschard &
Richard, 1984; Clarke, 1986; Goldfrank, 1990; Goodman
& Gilman, 1990), though concentrations of 1 to 20%
were in the past used as anaesthesia for the middle
ear, pharynx, larynx, mucosae of the nose, urinary
tract and rectum, the cornea and the iris.
The value of cocaine in analgesic mixtures (such as
“the Brompton cocktail”) used for terminal care is
controversial, and current opinion does not favour it
(Ellenhorn & Barceloux, 1988; Fleming et al., 1990).
The major use of cocaine at present is as an illegal
drug of abuse.

4.2 Therapeutic dosage

4.2.1 Adults

The recommended dose is between 1 and 3
milligrams per kilogram (Loper, 1989; Reynolds, 1989).

4.2.2 Children

No data available

4.3 Contraindications

Cocaine hydrochloride should not be used intra-ocularly,
because it can provoke corneal ulceration (Goodman & Gilman,
1990). Solutions of cocaine should not be applied to burnt or
abraded skin or tissue supplied by terminal arterioles,
because of the risks of ischaemia and tissue necrosis.

5. ROUTES OF EXPOSURE

5.1 Oral

The use of oral cocaine in analgesic mixtures intended
for terminal care is controversial and not at present
recommended (Ellenhorn & Barceloux, 1988; Fleming et al.,
1990). Cocaine can be abused by the oral or sublingual route
(Cregler, 1986), and drug smugglers, called “mules” or “body
packers”, sometimes swallow the product in packages of
variable composition (for example, condoms) which may leak or
rupture and cause massive intoxication (Ellenhorn &
Barceloux, 1988).

5.2 Inhalation

There is no therapeutic use for this route.
Crack cocaine is abused by inhaling the vapour from
cigarettes (in which it is mixed with tobacco or marijuana)
or after heating in a device called a cocaine pipe. Coco
paste can also be smoked.
Most drug abusers at present take cocaine by the nasal route,
and cocaine hydrochloride can be “sniffed” or “snorted” in
“lines” on a flat surface such as a mirror. This route leads
to pulmonary complications (Jéri, 1984; Cregler & Mark, 1987;
Derlet, 1989; Haddad & Winchester, 1990).

5.3 Dermal

Not described.

5.4 Eye

The intra-ocular route is not used therapeutically.

5.5 Parenteral

There is no therapeutic use for parenteral cocaine
administration.
Drug abusers inject cocaine hydrochloride subcutaneously,
intramuscularly or intravenously alone or with heroin (“speed
ball”) or with other drugs (Jeri, 1984; Cregler & Mark,
1987).

5.6 Other

Cocaine can also be administered rectally, vaginally,
and urethrally (Cregler, 1986). Cocaine has been used
therapeutically for local anaesthesia of the upper
respiratory tract (Fleming et al., 1990).

6. KINETICS

6.1 Absorption by route of exposure

Cocaine is absorbed by all routes of administration, but
the proportion absorbed depends on the route (Haddad &
Winchester, 1990).
After oral administration, cocaine appears in blood after
about 30 minutes, reaching a maximum concentration in 50 to
90 minutes (Clarke, 1986).
In acid medium, cocaine is ionised, and fails to cross into
cells. In alkaline medium, there is less ionisation and the
absorption rapidly increases. (Ellenhorn & Barceloux,
1988).
By the nasal route, clinical effects are evident 3 minutes
after administration, and last for 30 to 60 minutes, the peak
plasma concentration being around 15 minutes.
By oral or intra-nasal route, 60 to 80% of cocaine is
absorbed (Ellenhorn & Barceloux, 1988; Stinus, 1992).
By inhalation, the absorption can vary from 20 to 60%, the
variability being related to secondary vasoconstriction.
Freebase does not undergo first-pass hepatic metabolism, and
plasma concentrations rise immediately to 1 to 2 mg per
litre. The effects on the brain occur very rapidly, after
about 8 to 12 seconds, are very violent (“flash”), and last
only 5 to 10 minutes (Burnat & Le Brumant-Payen, 1992;
Stinus, 1992).
By the intravenous route blood concentrations rise to a peak
within a few minutes (Clarke, 1986).

6.2 Distribution by route of exposure

Cocaine is distributed within all body tissues, and
crosses the blood brain barrier (Ellenhorn & Barceloux,
1988).
In large, repeated doses, it is probably accumulated in the
central nervous system and in adipose tissue, as a results of
its lipid solubility (Cone & Weddington, 1989).
The volume of distribution is, according to different
authors, between 1 and 3 litres per kilogram (Clarke, 1986;
Ellenhorn & Barceloux, 1988; Baselt, 1989).
Cocaine crosses the placenta by simple diffusion, and
accumulates in the fetus after repeated use (Finster &
Pedersen, 1991).

6.3 Biological half-life by route of exposure

The observed half life depends on the route of
administration, dosage, and individual subject. It is of the
order of 0.7 to 1.5 hours (Clarke, 1986). After oral
administration, it appears to be 0.8 hours (Baselt, 1989),
nasal administration, 1.25 hours (Baselt, 1989; Ellenhorn &
Barceloux, 1988), parenteral administration 0.7 to 0.9 hours

(Ambre et al., 1988; Ellenhorn & Barceloux, 1988; Burnat & Le
Brumant-Payen, 1992).
For therapeutic doses there is no tolerance to the effects of
cocaine, but when used in abuse it may lead to dose
escalation to obtain the same euphoriant effects
(psychological tolerance); and there are anecdotal cases of
abusers taking more than the recognised lethal dose
(Ellenhorn & Barceloux, 1988).

6.4 Metabolism

Cocaine metabolism takes place mainly in the liver,
within 2 hours of administration. The rate of metabolism
varies according to plasma concentration (Baselt, 1989;
Haddad & Winchester, 1990).
There are 3 routes of bio-transformation:
– the major route is hydrolysis of cocaine by hepatic and
plasma esterases, with loss of a benzoyl group to give
ecgonine methyl ester. Esterase activity varies
substantially from one subject to another (Fleming et al.,
1990),
– the secondary route is spontaneous hydrolysis, probably
non-enzymatic, which leads to benzoylecgonine by
demethylation (Fleming et al., 1990).
The final degradation of cocaine, which is a sequel to both
the principle and secondary routes of metabolism, leads to
ecgonine (Burnat & Le Brumant-Payen, 1992).
N-demethylation of cocaine is a minor route leading to
norcocaine (Fleming et al., 1990).
The principle metabolites are therefore benzoylecgonine,
ecgonine methyl ester, and ecgonine itself, which are
inactive; and norcocaine which is active, and may be relevant
after acute intoxication (Baselt, 1989; Burnat & Le
Brumant-Payen, 1992).
In the presence of alcohol, a further active metabolite,
cocaethylene is formed, and is more toxic then cocaine itself
(Nahas et al., 1992).
The rate of cocaine metabolism is reduced in pregnant women,
aged men, patients with liver disease, and those with
congenital choline esterase deficiency (Cregler, 1986;
Slutsker, 1992).

6.5 Elimination and excretion

1 to 9% of cocaine is eliminated unchanged in the urine,
with a higher proportion in acid urine. The metabolites
ecgonine methyl ester, benzoylecgonine, and ecgonine are
recovered in variable proportions which depend on the route
of administration (Clarke, 1986).
At the end of 4 hours, most of the drug is eliminated from
plasma, but metabolites may be identified up to 144 hours
after administration (Ellenhorn & Barceloux, 1988).

Unchanged cocaine is excreted in the stool and in saliva
(Clarke, 1986; Cone & Weddington, 1989).
Cocaine and benzoylecgonine can be detected in maternal milk
up to 36 hours after administration, and in the urine of
neonates for as much as 5 days. (Chasnoff et al., 1987,
1989).
Freebase cocaine crosses the placenta, and norcocaine
persists for 4 to 5 days in amniotic fluid, even when it is
no longer detectable in maternal blood (Stinus, 1992).

7. PHARMACOLOGY AND TOXICOLOGY

7.1 Mode of action

7.1.1 Toxicodynamics

The main target organs are the central nervous
system and cardiovascular system. Effects depend on
the dose, other substances taken, the route of
administration, and individual susceptibility (Jeri,
1984).

Cardiovascular effects:
the mechanism of cardiovascular toxicity is unclear.
Increased circulating catecholamine concentrations
cause excessive stimulation of alpha- and
beta-adrenoceptors (Derlet, 1989). The cardiovascular
effects are dose-dependent. At low doses there is
vagal stimulation with bradycardia (Baschard &
Richard, 1984). At moderate doses, because of
adrenergic stimulation, there is a rapid increase in
cardiac output, myocardial oxygen consumption, and
blood pressure (followed by a fall).
This may have several consequences:
– there is a risk of myocardial infarction, both the
subjects with coronary atheroma and those with
normal coronary arteries (when it is unclear if
the mechanism is thrombosis, embolism, or
spasm),
– there is a risk of spontaneous cerebral
haemorrhage, which may occur even in subjects with
normal blood pressure. This may be a consequence
of arterial malformation, ischaemia, arterial
vasoconstriction, cerebral vasculitis, cardiac
rhythm disturbance, or myocardial infarction
(Cregler & Mark, 1987; De Broucker et al., 1989;
Derlet, 1989; Isner & Chokshi, 1989; Stenberg et
al., 1989; Guérin et al., 1990; Kloner et al.,
1992).
– at very high doses, cocaine can cause cardiac
arrest by a direct toxic effect on the
myocardium.

Cocaine can cause intestinal ischaemia or gangrene.
The intestinal vasculature contains alpha receptors,
which are stimulated by norepinephrine, leading to an
increase in arterial resistance, intense vaso
constriction, and a reduction in cardiac output (for
example, in body packers).

Action on the central nervous system:
the neurotoxic actions of cocaine are complex and
involve several sites and mechanisms of action.
Euphoria, confusion, agitation, and hallucination
result from an increase in the action of dopamine in
the limbic system (Nahas et al., 1987). Cortical
effects lead to pressure of speech, excitation, and a
reduced feeling of fatigue; stimulation of lower
centres leads to tremor and tonic-clonic convulsion;
brain stem effects lead to stimulation and then
depression of the respiratory vasomotor and vomiting
centres.
Cocaine causes hyperthermia as a result of 2
mechanisms: the increase in muscular activity and a
direct effect on thermal regulatory centres (Baschard
& Richard, 1984; Goodman & Gilman, 1990).

The visceral effects on liver and kidney are due to
dopaminergic action of cocaine, or its metabolites, or
to impurities (Guérin et al., 1989). The abrupt
increase intra-alveolar pressure can cause alveolar
rupture and pneumomediastinum.
Rhabdomyolysis occurs as a result of several different
mechanisms: direct effect on muscle and muscle
metabolism, tissue ischaemia, the effects of drugs
taken with cocaine, such as alcohol and heroin (Roth
et al., 1988; Skluth et al., 1988; Singhal et al.,
1990).

7.1.2 Pharmacodynamics

The principle effects of cocaine are the result
of its sympathetic action: cocaine prevents the
re-uptake of dopamine and noradrenaline, which
accumulate and stimulate neuronal receptors (Amin et
al., 1990; Kloner et al., 1992).
At the same time, the release of serotonin a
“sedative” neurotransmitter, is inhibited (Derlet,
1989).
The inhibition of catecholamine re-uptake does not
explain the duration of action of cocaine, which may
also result from an increase in calcium flux,
potentiating cellular responses and causing receptor
hypersensitivity. There may also be a direct effect
on peripheral organs (Fleming et al., 1990; Goldfrank,
1990).

Applied locally, cocaine blocks neuronal transmission:
this results in a powerful local anaesthetic action at
the level of sensory nerve terminals (Derlet, 1989;
Lange et al., 1989; Goodman & Gilman, 1990; Kloner et
al., 1992).
Anabolic experiments have shown that there is no true
physical tolerance to the effects of cocaine, but a
very marked psychic tolerance which leads animals to
auto-inject cocaine to obtain the desired
psychological effects, even though this may lead to
death (Stinus, 1992).

7.2 Toxicity

7.2.1 Human data

7.2.1.1 Adults

Lethal doses are estimated at 0.5 to
1.3 grams per day by mouth; 0.05 to 5 grams
per day by the nasal route, 0.02 grams of
cocaine by the parenteral route (Baschard &
Richard, 1984; Haddad & Winchester, 1990;
Burnat & Le Brumant-Payen, 1992).
Cocaine addicts can tolerate doses up to 5
grams per day.
Toxic effects can be manifest with plasma
concentrations equal to or above 0.50 mg per
litre; deaths have been reported with
concentrations of 1 mg per litre (Clarke,
1986).

7.2.1.2 Children

No data.

7.2.2 Relevant animal data

The LD50 for the rabbit is 15 mg per kilogram
by the intravenous route, and 50 mg per kilogram by
the nasal route; the intravenous LD50 for the rat is
17.5 mg per kilogram (Budavari, 1989).

7.2.3 Relevant in vitro data

Experiments on animal heart tissue show a
direct, reversible, depressant effect of cocaine on
ventricular myocardium (Chokshi et al., 1989).
Experiments on rats prove that alcohol potentiates the
toxic effects of cocaine (Nahas et al., 1992).

7.3 Carcinogenicity

No data available.

7.4 Teratogenicity

The studies in animals are contradictory (Shepard, 1986;
Ellenhorn & Barceloux, 1988). A recent meta-analysis shows an
increase in congenital malformation rate in the offspring of
cocaine-users, particularly for abnormalities of the limbs,
the genito-urinary tract, and the cardiovascular,
neurological, and digestive systems (Kain et al.,
1992).

7.5 Mutagenicity

No data available.

7.6 Interactions

Patients with choline esterase deficiency may develop
severe reactions (Ellenhorn & Barceloux, 1988).
Interactions can occur with adrenaline, alpha- and
beta-blockers, vasoactive amines, antidepressants,
chlorpromazine, guanethidine, indomethacin, monoamine oxidase
inhibitors, methyldopa, naloxone, psychotropic medicines, and
reserpine (Reynolds, 1989; Fleming et al., 1990; Carlan et
al., 1991).
There are metabolic interactions with other local
anaesthetics, cholinesterase inhibitors and cytotoxic drugs
(Fleming et al., 1990).

7.7 Main adverse effects

Not applicable.

8. TOXICOLOGICAL ANALYSIS AND BIOMEDICAL INVESTIGATIONS

9. CLINICAL EFFECTS

9.1 Acute poisoning

9.1.1 Ingestion

Acute intoxication causes intense agitation,
convulsions, hypertension, rhythm disturbance,
coronary insufficiency, hyperthermia, rhabdomyolysis,
and renal impairment.
Intestinal ischaemia has been described.

9.1.2 Inhalation

Acute intoxication causes intense agitation,
convulsions, hypertension, rhythm disturbance,
pulmonary oedema with acute respiratory distress
syndrome, coronary insufficiency, hyperthermia,
rhabdomyolysis, and renal impairment.

9.1.3 Skin exposure

Not applicable.

9.1.4 Eye contact

Not applicable.

9.1.5 Parenteral exposure

Acute intoxication causes intense agitation,
convulsions, hypertension, pulmonary oedema with acute
respiratory distress syndrome, coronary insufficiency,
hyperthermia, rhabdomyolysis, and renal
impairment.

9.1.6 Other

By the intranasal route, acute intoxication
causes intense agitation, convulsions, hypertension,
rhythm disturbance, pulmonary oedema, stroke, coronary
insufficiency, hyperthermia, rhabdomyolysis, and renal
impairment.

9.2 Chronic poisoning

9.2.1 Ingestion

Chronic ingestion of cocaine can cause thoracic
pain, changes on the electrocardiogram with transient
elevation of the ST segments and re-polarisation
abnormalities; and convulsions (Zimmerman et al.,
1991). Erosion of the teeth has been noted with
chronic oral ingestion (Krutchkoff et al.,
1990).

9.2.2 Inhalation

During inhalation of “crack”, chest pain with
changes on the electrocardiogram (re-polarisation
abnormalities and transient ST segment elevation), and
convulsions can occur (Zimmerman et al., 1991).
Reversible cardiomyopathy with hypotension, hypoxaemia
and tachycardia, has been described (Chokshi et al.,
1989). A number of other symptoms have been described,

though their aetiology is not always clear. Cough,
black or blood-stained sputum, dyspnoea, thoracic
pain, spontaneous pneumothorax, spontaneous
pneumomediastinum, and asthma (in a few cases) or
immunoallergic lung disease, have been described.
Pulmonary granulomas and fibrosis, bronchiolitis
obliterans, and isolated arterial hypertension have
also been observed (Kevorkian & Guérin, 1993).
Chronic cocaine intoxication causes anorexia, which
leads to weight loss, physical exhaustion, behavioural
problems, and depression.

9.2.3 Skin exposure

Application of cocaine to skin or mucous
membrane can cause necrotic lesions.

9.2.4 Eye contact

Repeated application of cocaine can cause
necrotic lesions.

9.2.5 Parenteral exposure

Cocaine addicts can develop HIV infection and
AIDS as a result of sharing needles and syringes
(Burnat & Le Brumant-Payen, 1992; Rubin & Neugarten,
1992; Kevorkian & Guérin, 1993).

9.2.6 Other

Intranasal administration of cocaine can cause
necrosis and perforation of the nasal septum, atrophy
of the nasal mucosa, chronic sinusitis, and anosmia
(Baschard & Richard, 1984; Burnat & Le Brumant-Payen,
1992).

9.3 Course, prognosis, cause of death

In patients who are moderately poisoned, the symptoms
have often spontaneously resolved before emergency admission,
and most patients leave hospital within 36 hours (Rubin &
Neugarten, 1992).

Serious cocaine intoxication evolves in 3 phases:
– an early phase of stimulation,
– a second phase of hyper-stimulation with tonic-clonic
convulsions, tachyarrhythmias, and dyspnoea,
– a third phase of depression of the central nervous system,
with loss of vital function, paralysis, coma, and
respiratory and circulatory collapse.

Two-thirds of deaths occur within 5 hours of administration,
and one-third within one hour after absorption of the drug,
whatever the route of administration.

Important factors include:
– the quantity absorbed,
– the rapidity with which the serum concentration
increases,
– the occurrence of hyperthermia secondary to
vasoconstriction,
– the prior cardiovascular state of the patient: large
intravenous doses of cocaine can cause immediate death as
a result of arrhythmia, myocardial infarction, circulatory
failure, or direct myocardial depression (Goodman &
Gilman, 1990).
Also recognized are acute pulmonary complications (acute
respiratory distress syndrome) which can lead to death within
a few hours of poisoning by the parenteral route. Post mortem
examination often reveals intra-alveolar haemorrhage
(Baschard & Richard, 1984).
The occurrence of convulsions, which are secondary to cardiac
effects (particularly ventricular fibrillation or
tachycardia), can appear whatever the dose absorbed, and are
responsible for one-third of the deaths.
Chronic intoxication by cocaine leads to anorexia, weight
loss, physical exhaustion, behavioural problems, and
depression.

9.4 Systematic description of clinical effects

9.4.1 Cardiovascular

The following have been described with chronic
intravenous abuse or inhalation:
– precordial pain, of unknown aetiology in 80% of
cases;
– palpitation;
– arterial hypertension;
– tachycardia;
– ventricular and supraventricular tachyarrhythmias,
atroventricular block;
– acute coronary insufficiency and myocardial
infarction;
– digital, renal, intestinal and spinal cord
ischaemia;
– dilated cardiomyopathy and myocarditis, rupture of
the ascending aorta;
– asystole;
– circulatory collapse;
– endocarditis affecting the tricuspid valve;
– superficial thrombophlebitis;

– electrocardiographic changes: widening of the QRS
complex, re-polarisation changes, ST segment
elevation.

(Baschard & Richard, 1984; Cregler & Mark, 1987;
Wiener & Putman, 1988; Derlet, 1989; Guérin et al.,
1990; Zimmermann et al., 1991).

9.4.2 Respiratory

The following features have been observed:
cough, chest pain, haemoptysis, dark sputum, dyspnoea,
cyanosis, pneumothorax, surgical (subcutaneous)
emphysema, pneumopericardium, spontaneous
pneumomediastinum, non-cardiogenic pulmonary oedema,
and cardiogenic pulmonary oedema secondary to acute
coronary insufficiency, rhythm disturbance, or
cardiomyopathy.
Death has occurred from renal insufficiency and from
acute respiratory distress syndrome (Baschard &
Richard, 1984; Cregler & Mark, 1987).
During chronic poisoning, the following have been
observed:
pulmonary fibrosis and granulomatosis, bronchiolitis
obliterans, and isolated pulmonary hypertension. There
are also non-specific complications: inhalation
pneumonia, related to reduced consciousness; pulmonary
abscesses secondary to infective endocarditis; and
pulmonary complications related to AIDS. There are a
few cases reported of asthma and of immunoallergic
lung disease (Kevorkian & Guérin, 1993).

9.4.3 Neurological

9.4.3.1 CNS

The following consequences have been
described: tremor, headaches, transient
ischaemic attacks, cerebrovascular ischaemia
or haemorrhage, intracerebral and
subarachnoid haemorrhage, intracerebral
infarction; syncopy, epileptic fits, optic
neuritis, mental confusion and insomnia,
intellectual stimulation, mania, pressure of
speech, agitation, excitement, anxiety,
irritability, euphoria, depression, suicidal
ideation; visual hallucination,
hallucinations of parasites leading to
scratching; paranoia, irrational fear,
persecution complex, “acting out”, psychotic
states, destruction of the personality; and
anorexia leading to weight loss and physical
exhaustion (Baschard & Richard, 1984;

Cregler, 1986; Bismuth et al., 1989; De
Broucker et al., 1989; Goldfrank, 1990;
Guérin et al., 1990; Vaille, 1990; Stinus,
1992).

9.4.3.2 Peripheral Nervous System

Local anaesthesia, muscular
paralysis and abolition of reflexes occur
(Baschard & Richard, 1984).

9.4.3.3 Autonomic Nervous System

Cocaine can cause tachycardia,
arterial hypertension, vomiting, “cocaine
fever”, and occasionally
hypothermia.

9.4.3.4 Skeletal and smooth muscle

Contraction of facial, digital and
intestinal smooth muscle occurs. There may be
myalgia and muscular weakness, and
rabdomyolysis (Cregler, 1986; Bismuth et al.,
1989; Herzlich & Arzura, 1989; Brody et al.,
1990).

9.4.4 Gastro-intestinal

Anorexia leading to weight loss and physical
exhaustion occur; as do nausea, vomiting, diarrhoea,
abdominal pain, and intestinal ischaemia (Burnat & Le
Brumant-Payen, 1992). Drug smugglers (“mules” or “body
packers”) can develop intestinal obstruction from
packages.

9.4.5 Hepatic

Hepatocellular insufficiency,
hyperbilirubinaemia, anti-hepatocellular necroses have
been described (Guérin et al., 1989).

9.4.6 Urinary

9.4.6.1 Renal

Both acute renal insufficiency
secondary to rhabdomyolysis, and renal
infarction, have been described (Cregler,
1986; Roth et al., 1988; Van Viet et al.,
1990).

9.4.6.2 Other

Haematuria, glycosuria, and
proteinuria are seen.

9.4.7 Endocrine and Reproductive Systems

In small doses, cocaine delays ejaculation and
orgasm, increases libido, and improves sexual
performance. In large and repeated doses, impotence
and complete loss of libido occur.

9.4.8 Dermatological

In therapeutic doses, cocaine has a local
anaesthetic action, and application to the skin and
mucous membranes (eye, nose) can cause necrotic
lesions. Hallucinations of parasites can lead to
scratching. Crack smokers can lose eye lashes and
eyebrows, as a result of the hot vapours which burn
them. Cocaine can also provoke porphyria (Cregler,
1986; Dick, 1987).

9.4.9 Eye, ear, nose, throat, local effects

The contact of cocaine with the cornea leads to
ulceration and prevents its therapeutic use as an eye
salve.
During acute intoxication, local action can cause
pupillary dilation, anaesthesia, and vasoconstriction
of mucous membranes.
During chronic intranasal intoxication, there may be:
deformity, atrophy, necrosis, perforation of the nasal
septum or base of the tongue or epiglottis, retraction
of the palette, chronic sinusitis, a change in the
voice, anosmia, and blindness.
Dental erosion can follow oral cocaine ingestion.
(Baschard & Richard, 1984; Cregler, 1986; Bezmalinovic
et al., 1988; Deutsch & Millard, 1989; Krutchkoff et
al., 1990; Vaille, 1990; Burnat & Le Brumant-Payen,
1992).

9.4.10 Haematological

Disseminated intravascular coagulation has
been observed in subjects: platelet aggregation and
thromboxane A2 levels are increased and prostacyclin
inhibited by cocaine (Roth et al., 1988; Guérin et
al., 1989).

9.4.11 Immunological

Opportunist infections such as cerebral
mycosis, and infectious lung disease, have been
described in intravenous cocaine users, who have no
other pre-disposing factors; needle sharing,
prostitution and homosexuality greatly increase the
risk of infection with HIV in cocaine addicts
(Cregler, 1986; Kevorkian & Guérin, 1993).

9.4.12 Metabolic

9.4.12.1 Acid-Base Disturbance

Acid-base disturbances are caused
by hypoxia in cocaine addicts, particularly
when there are repeated convulsions (Bismuth
et al., 1989).

9.4.12.2 Fluid and electrolyte disturbances

Electrolyte disturbances are the
consequence of vomiting and
diarrhoea.

9.4.12.3 Others

Poor nutrition, failure to adhere
to therapeutic regimes, a sensitivity to
epinephrine which mobilises glucose cause
abnormalities of glucose homeostasis in
patients who repeatedly consume cocaine
(Cregler, 1986).

9.4.13 Allergic Reactions

Asthma and an immunoallergic lung disorder
have been described in some subjects without preceding
asthma or atopy, during prolonged crack intoxication;
the relevant allergen may be cocaine itself, or
excipients in inhaled preparations (Kevorkian &
Guérin, 1993).

9.4.14 Other clinical effects

No data

9.4.15 Special risks

Pregnancy: cocaine causes uterine
hypercontractility, a reduced uterine blood flow, and
placental vasoconstriction. Thus, women cocaine
addicts can develop hypertension of pregnancy,

spontaneous abortion, placental abruption, premature
delivery, and complications at delivery (Burnat & Le
Brumant-Payen, 1992; Kain et al., 1992).
Risks in the fetus: the offspring of mothers who are
cocaine addicts has an increased risk of
genito-urinary, cardiovascular, gastrointestinal, and
neurological malformations; even a single exposure to
cocaine during pregnancy can lead to cerebral
infarction or haematoma, or to failure of development
of the blood supply or nerve supply to fetal
structures.
In the new-born: ventricular tachycardia, cerebral
infarction, convulsion, hypertension, and unilateral
hypotonia are seen with increased frequency. Sudden,
unexplained death in the babies of cocaine addicted
mothers can occur during the first few weeks of life
(Cregler, 1986; Chavez et al., 1989; Kain et al.,
1992).
Breast feeding: cocaine and benzoylecgonine are
found in maternal milk up to 36 hours after the use of
cocaine (Chasnoff et al., 1987).
Enzyme deficiencies:
Subjects who are deficient in pseudocholinesterase can
die suddenly after cocaine.

9.5 Other

Cocaine use causes hypersensitivity of the autonomic
nervous system and changes to the structure and function of
the brain; there is very marked psychological dependence
without physical dependence or tolerance, because the same
dose causes the same psychological effects. Nonetheless,
cocaine abuse can lead to the consumption of increasingly
large quantities to obtain euphoriant effects; there are
anecdotal cases of addicts taking doses above the theoretical
lethal dose. Addicts can take cocaine at intervals of 10 to
45 minutes during the course of a “run”, which may last for
several days, when there is loss of control of the frequency
and duration of the pleasurable phase (Ellenhorn & Barceloux,
1988; Stinus, 1992).

Withdrawal syndrome:
there are 3 distinct phases:
– when the drug wears off, 15 to 30 minutes after the last
dose, there is a “crash” when the addict becomes
dysphoric, depressed, irresistibly sleepy, agitated, and
anxious with a strong desire (“craving”) for cocaine,
– after about 2 hours, there is a phase of sleeping and
exhaustion so intense that even the desire for cocaine is
unable to overcome it;
– during the next several weeks there is a period of
dysphoria, anhedonia, depression and “extinction” or
“cocaine blues”.

9.6 Summary

10. MANAGEMENT

10.1 General Principles

The treatment of cocaine poisoning varies according to
the clinical severity; most patients do not require admission
to hospital, because symptoms resolve rapidly and
spontaneously. The emergency treatment of severe
intoxications requires the maintenance of vital functions,
and the treatments of complications due to cocaine, or to
adulterants of the drug. There is no antidote.
The measurement of serum creatine kinase activity is
necessary to detect rhabdomyolysis; but neither the creatine
kinase nor the electrocardiogram necessarily give information
on the likelihood of chest pain being due to myocardial
infarction (Amin et al., 1990; Brody et al., 1990; Guérin et
al., 1990). Plain abdominal x-rays may show evidence of
packets of cocaine.

10.2 Life supportive procedures and symptomatic/specific treatment

Vital function, particularly cardiorespiratory
function, has to be maintained. According to the
circumstances this may require:
– electrocardiographic monitoring of arrhythmias;
– intubation and assisted ventilation;
– alkalinisation with sodium bicarbonate;
– reversal of cardiovascular collapse with molar sodium
lactate if the QRS complex is wider than 120 milliseconds
and by the cautious administration of catecholamines
(dopamine or norepinephrine)
If creatine kinase is elevated above 10,000 international
units per litre then rehydration, diuresis with frusemide,
and alkalinisation of the urine have been advised, and
haemodialysis may be required (Guérin et al., 1989).

Symptomatic treatment of moderately severe cases requires the
following measures:
– the patient should be placed in a calm environment;
– hyperthermia should be corrected by undressing;
– hydration should be sufficient to induce a diuresis and
prevent rhabdomyolysis;
– moderate doses of diazepam (5 to 10 mg intravenously,
which may have to be repeated after 10 minutes) if there
are convulsions or severe agitation;
– ventilation with the administration of thiopentone or
clonazepam may be necessary to control status
epilepticus;
– neuroleptics such as haloperidol (2 to 5 mg
intramuscularly) may be required for psychosis or
agitation;

– arterial hypertension may require diazoxide, phentolamine,
labetalol or sodium nitroprusside for its control;
– arrhythmias: betablockers may correct cardiac arrhythmias
but may aggravate coronary or systemic vasoconstriction;
antiarrhythmics, cardioversion and over-pacing can be used
but intravenous lidocaine should be avoided because it can
provoke convulsions;
– dexamethasone and positive pressure of ventilation may be
required in the case of alveolar haemorrhage.
(Baschard & Richard, 1984; Bismuth et al., 1989; Derlet,
1989; Bouchi et al., 1992).

10.3 Decontamination

Gastric lavage is dangerous because of sudden
occurrence of convulsion, and syrup of ipecacuanha is even
worse, because the effects can be delayed, and the subject
meanwhile may lose consciousness. Activated charcoal is
recommended.
For drug smugglers (“mules” or “body packers”), gentle
laxatives (avoid liquid paraffin) and activated charcoal are
recommended rather than endoscopy, which risks rupturing the
sachets, leading to massive acute intoxication. Repeat x-rays
are required to be certain that all packets have been
eliminated. Intestinal irrigation with polyethylene glycol
has been used. Surgical intervention is requrired only in
exceptional cases.
(Caruana et al., 1984; Bismuth et al., 1989; Baud, 1991; Marc
et al., 1992).

10.4 Elimination

Given the large volume and distribution and short half
life of cocaine, there is no role for methods of increasing
the rate of elimination.

10.5 Antidote Treatment

10.5.1 Adults

There is no specific antidote.

10.5.2 Children

There is no specific antidote.

10.6 Management discussion

The following drugs have been suggested in the
literature for treating the syndrome of intense adrenergic
activity:

amitriptyline, propranolol, labetalol, calcium channel
blocking drugs, and phentolamine (an alpha-1 receptor
antagonist).
Combination of diazepam and enalaprilat or diazepam and
propranolol has also been used to prevent both cardiovascular
and neurological disturbance.

Withdrawal symptoms have been treated with amantadine, and
dopamine agonist such as bromocriptine.

There may be a place for dantrolene in treating the muscular
hypertonia, hyperthermia, and rhabdomyolysis that occur in
cocaine poisoning. Heparin and fresh frozen plasma have been
shown to be ineffective in treating the rhabdomyolysis.
(Dackis & Gold, 1985; Cregler, 1986; Trouvé et al., 1988;
Fox, 1989; Pike, 1989; Baud, 1991).

Research:
Research in this field includes neurobiological studies of
the effects of the drug, and the development of experimental
models of cocaine dependence with a view to developing
treatments for cocaine addiction (Beckeman et al.,
1991).

11. ILLUSTRATITIVE CASES

11.1 Case reports from literature

Local application of 30 mg of cocaine in a 14 month old
child prior to bronchoscopy caused mydriasis, agitation,
euphoria, tachypnoea, tremor, and flushing. The child was
treated with rectal diazepam, intramuscular meperidine
(pethidine) and rectal methohexitone (methohexital); it had
recovered 18 hours after exposure (Schou et al., 1987).

12. ADDITIONAL INFORMATION

12.1 Specific preventive measures

Providing the public with information to contradict the
myths surrounding cocaine: that it is benign, aphrodisiac,
and does not cause dependence.

12.2 Other

Treatments suggested for chronic intoxication include:
a programme of detoxification; maintainence treatment; self
control methods; exercise sessions and abstainence programmes
and tranquillizers. Relapse is possible many years after
cessation of drug taking, and some teams suggest providing
support for as long as 5 years (Jeri, 1984).

13. REFERENCES

Ambre J, Ruo TI, Nelson J & Belknap S (1988) Urinary
excretion of cocaine, benzoylecgonine, and ecgonine methyl ester
in humans. J Anal Toxicol, 12: 301-306.

Amin M, Gabelman G, Karpel J & Buttrick P (1990) Acute myocardial
infarction and chest pain syndromes after cocaine use. Am J
Cardiol, 66: 1434-1437.

Baschard P & Richard D (1984) La cocaïne. Act Pharm, 212:
49-56.

Baselt RC (1989) Disposition of toxic drugs and chemicals in man,
2nd ed, Davis, California, Biomedical publications, 208-213.

Baud F (1991) Drogues. Intoxications aiguës et chroniques,
principes du traitement d’urgence. Rev Prat, 41(15): 1412.

Beckman KJ, Parker RB, Hariman RJ, Gallastegui JL, Javaid JI &
Bauman JL (1991) Hemodynamic and electrophysiological actions of
cocaine. Circulation, 83 (5): 1799-1807.

Bezmalinovic Z, Gonzalez M & Farr C (1988) Oropharyngeal injury
possibly due to free-base cocaine. N Engl J Med, 319 (21):
1420-1421.

Bismuth C, Baud FJ, Conso F, Fréjaville JP & Garnier R (1989)
Toxicologie clinique, 5ème éd, Paris, éd. Médecine-Sciences
Flammarion, p 116.

Bouchi J, El Asmar B, Couetil JP, Gédéon E & Bouchi N (1992)
Hémorragie alvéolaire après inhalation de cocaïne. Presse Med, 21
(22): 1025-1026.

Brody SL, Wrenn KD, Wilber MM & Slovis CM (1990) Predicting the
severity of cocaïne-associated rhabdomyolysis. Ann Emerg Med, 19:
1137-1143.

Brody SL, Slovis & Wrenn KD (1990) Cocaine related medical
problems: consecutive series of 233 patients. Am J Med, 88:
325-331.

Burnat P & Le Brumant-Payen C (1992) Intoxication par la cocaïne.
Lyon Pharm, 43 (3): 149-156.

Budavari S ed. (1989) The Merck Index: an encyclopedia of
chemicals, drugs and biologicals, 11th ed. Rahway, New Jersey,
Merck and Co, Inc.

Carlan SJ, Stromquist C, Angel JL, Harris M & O’Brien WF (1991)
Cocaine and indomethacin: fetal anuria, neonatal edema and
gastrointestinal bleeding. Obstet and Gynecol, 78 (3):
501-503.

Caruana DS, Weinbach B, Goerg D & Gardner LB (1984) Cocaine-packet
ingestion. Diagnosis, management and natural history. Ann Intern
Med, 100 (1): 73-74.

Chasnoff IJ, Lewis DE & Squires L (1987) Cocaine intoxication in a
breast-fed infant. Pediatrics, 80 (6): 836-838.

Chasnoff IJ, Lewis DE, Griffith DR & Willey S (1989) Cocaine and
pregnancy: clinical and toxicological implications for the
neonate. Clin Chem, 35 (7): 1276-1278.

Chavez GF, Mulinare J & Cordero JF (1989) Maternal cocaine use
during early pregnancy as a risk factor for congenital urogenital
anomalies. JAMA, 262 (6): 795-798.

Chokshi SK, Moore R, Pandian NG & Isner JM (1989) Reversible
cardiomyopathy associated with cocaine intoxication. Ann Intern
Med, 111 (12): 1039-1040.

Clarke EGC (1986) Clarke’s isolation and identification of drugs
in pharmaceuticals, body fluids, and post-mortem materials, 2nd
ed, London, The Pharmaceutical Press.

Cone EJ & Weddington WW (1989) Prolonged occurrence of cocaine in
human saliva and urine after chronic use. J Anal Toxicol, 13:
65-68.

Cregler LL, Mark H (1987) [Risques cardiovasculaires et cocaïne].
J Intern Med, 100 (suppl): 6-8.

Cregler LL (1986) Medical complications of cocaine abuse. N Engl J
Med, 315 (23): 1495-1500.

Dackis CA & Gold MS (1985) Bromocriptine as treatment of cocaine
abuse. Lancet, 18 mai: 1151-1152.

De Broucker Th, Verstichel P, Cambier J & De Truchis P (1989)
Accidents neurologiques après prise de cocaïne. Presse Med, 18
(10): 541-542.

Derlet RW (1989) Cocaine intoxication. Postgrad Med, 86 (5):
245-253.

Deutsch HL & Millard DR (1989) A new cocaine abuse complex. Arch
Otolaryngol Head Neck Surg, 115: 235-237.

Dick AD (1987) Cocaine and acute porphyria. Lancet, 8568 (2):
1150.

Dorvault F (1987) L’officine, XXIIème édition, éd. Vigot, Paris,
pp 368-371.

Ellenhorn MJ ed. & Barceloux DG ed. (1988) Medical Toxicology:
diagnosis and treatement of human poisoning. New York, Elsevier
science publishing compagny, Inc., 644-661.

Farrar HC & Kearns GL (1989) Cocaine: clinical pharmacology and
toxicology. J Pediatr, 115 (5): 665-675.

Finster M & Pedersen H (1991) Maternal and fetal effects of
cocaine abuse. Adv Biosciences, 80: 233-238.

Fleming JA, Byck R & Barash PG (1990) Pharmacology and therapeutic
applications of cocaine. Anesthesiology, 73: 518-531.

Fox AW (1989) More on rhabdomyolysis associated with cocaine
intoxication. N Engl J Med, 321 (18): 1271.

Goldfrank LR (1990) Management of acute neuropsychiatric
manifestations of cocaine intoxication. Intensive Care and
Emergency Medicine, 10 ed. J. L Vincent, Springer-Verlag.

Goldfrank LR, Flomenbaum NE, Lewin NA, Weisman RS & Howland MA ed.
(1990) Goldfrank’s toxicologic emergencies, 4th ed, Prentice-Hall
Inc.

Goodman LS & Gilman A ed (1990) Goodman and Gilman’s: the
pharmacological basis of therapeutics, 8th ed., New-York, Pergamon
Press.

Guérin JM, Barbotin-Larrieu F, Lutsman C & Lerebours F (1990)
Intoxication par la cocaïne: les complications cardio-vasculaires.
Concours Médical, 112 (36): 3251-3253.

Guérin JM, Barbotin-Larrieu F, Lutsman C & Aoula D (1989)
Complications neurologiques de l’intoxication par la cocaïne.
Concours Médical, 111 (19): 1603-1605.

Guérin JM, Barbotin-Larrieu F, Lutsman C & Aoula D (1989)
Complications viscérales multiples lors d’une intoxication par la
cocaïne. Rev Med Interne, 10: 561-562

Haddad LM & Winchester JF (1990) Clinical management of poisoning
and drug overdose, 2nd ed, Philadelphia, London, Montreal,
Toronto, Sidney, Tokyo, WB Saunders Company Inc.

Herzlich B & Arsura E (1989) Acute rhabdomyolysis associated with
cocaine intoxication. N Engl J Med, 320 (10): 667-668.

Isner JM & Chokshi SK (1989) Cocaine and vasospasm. N Engl J Med,
312 (23): 1604-1606.

Jeri FR (1984) La fumerie de pâte de coca dans certains pays
d’Amérique latine: une forme de toxicomanie grave et soutenue.
Bulletin des stupéfiants, 1984, 25 (2): 17-34.

Kain ZN, Kain TS & Scarpelli EM (1992) Cocaine exposure in utero:
perinatal development and neonatal manifestations. Review. J
Toxicol Clin Toxicol, 30 (4): 607-636.

Kevorkian JP & Guérin JM (1993) Complications pulmonaires de
l’intoxication par la cocaïne. Concours Médical, 115 (07);
523-526.

Kloner RA, Hale S, Alker K & Rezkalla S (1992) The effects of
acute and chronic cocaine use on the heart. Circulation, 85 (2):
407-419.

Krutchkoff DJ, Eisenberg E, O’Brien JE & Ponzillo JJ (1990)
Cocaine induced dental erosions. N Engl J Med, 8: 408.

Lange RA, Cigarroa RG, Yancy CW, Willard JE, Popma JJ, Sills MN,
MacBride W, Kim AS & Hillis LD (1989) Cocaine-induced
coronary-artery vasoconstriction. N Engl J Med, 321 (23):
1557-1562.

Loper KA (1989) Clinical toxicology of cocaine. Med Toxicol
Adverse Drug Exp, 4 (3): 174-185.

Marc B, Baud FJ, Maison-Blanche P, Leporc P, Garnier M & Gherardi
R (1992) Cardiac monitoring during medical management cocaine body
packers. J Toxicol Clin Toxicol, 30 (3): 387-397.

Nahas G, Latour C & Trouvé R (1992) Potentialisation des effets
toxiques aigus de la cocaïne par l’alcool éthylique. Bull Acad
Natl Med, 176 (2): 193-197.

Nahas G, Trouvé R, Manger W, Vinyard C & Goldberg S (1987) Cocaïne
et toxicité des neurotransmetteurs endogènes. Bull Acad Nat Med,
171 (6): 669-673

Pharmacopée Française (1982) 10ème éd, Paris, Maisonneuve S. A.
ed.

Pike RF (1989) Cocaine withdrawal. An effective three-drug
regimen. Postgrad Med, 85 (4); 115-121.

Reynolds ed. (1989) Martindale the Extra Pharmacopoeia, 29th ed.
Londres, The Pharmaceutical Press.

Roth D, Alarcon FJ, Fernandez JA, Preston RA & Bourgoignie JJ
(1988) Acute rabdomyolysis associated with cocaine intoxication. N
Engl J Med, 319 (11); 673-677.

Rubin RB & Neugarten J (1992) Medical complications of cocaine:
changes in pattern of use and spectrum of complications. J Toxicol
Clin Toxicol, 30 (1): 1-12.

Schou H, Krogh B & Knudsen F (1987) Unexpected cocaine
intoxication in a fourteen month old child following topical
administration. J Toxicol Clin Toxicol, 25 (5): 419-422.

Shepard TH (1986) Catalog of teratogenic agents, 5th ed,
Baltimore, London, the John’s Hopkins University Press.

Singhal PC, Rubin RB, Peters A, Santiago A & Neugarten J (1990)
Rhabdomyolysis and acute renal failure associated with cocaine
abuse. J Toxicol Clin Toxicol, 28 (3): 321-330.

Skluth HA, Clark JE, Ehringer GL (1988) Rhabdomyolysis associated
with cocaine intoxication. Drug Intelligence and Clinical
Pharmacy, 22: 778-780.

Slutsker L (1992) Risks associated with cocaine use during
pregnancy. Obstet Gynecol, 79 (5): 778-789.

Stenberg RG, Winniford MD, Hillis LD, Dowling GP & Buja LM (1989)
Simultaneous acute thrombosis of two major coronary arteries
following intraveinous cocaine use. Arch Pathol Lab Med, 113:
521-524.

Stinus L (1992) La dépendance à la cocaïne. Rev Prat, 6 (179):
1203-1210.

Trouvé R, Sitbon M, Latour C & Nahas G (1988) Combinaison
enalaprilat + valium comme antidote de l’intoxication cocaïnique.
J Toxicol Clin Exp, 8 (1): 61.

Vaille C (1990) Cécité due à la cocaïne. Presse Med, 19 (10):
446.

Van Viet H, Chevalier P, Sereni C, Bornet Ph, Bautier P, Degos CF
& Rullière R (1990) Accidents neurologiques liés à l’usage de la
cocaïne. Presse Med, 19 (22): 1045-1049.

Welch RD, Todd K, Krause GS (1991) Incidence of cocaine-associated
rhabdomyolysis. Ann Emerg Med, 20 (2): 154-157.

Wiener MD & Putman CE (1988) [Douleur thoracique chez un
cocaïnomane]. JAMA, 13 (170): 1017-1019.

Zimmermann JL, Dellinger RP & Majid PA (1991) Cocaine-associated
chest pain. Ann Emerg Med, 611 (330): 33-37.

14. AUTHORS

Authors: Dr Anne Claustre
Dr Isabelle Bresch-Rieu
Nathalie Fouilhé, Interne
Unité de Toxicologie Clinique et Centre Anti-Poisons
(Docteur V Danel)
Service de Médecine Interne et Toxicologie (Pr JL
Debru), Hopital Albert-Michallon BP 217 38043 GRENOBLE
CEDEX FRANCE
Tél. 33 4 76 76 56 46
Fax 33 4 76 76 56 70

Date: April 1993

Peer review: Cardiff, United Kingdom, February 1994 (Dr
C. Alonzo, Dr V. Danel, Dr J. de Kom, Dr R. Ferner, Dr A. Furtado
Rahde, Dr J. Hodgson, Dr Z. Kolacinski, Dr P. Myrenfors)

Translation from French to English: R Ferner, MO Rambourg Schepens
(1997)

First revision and update: Drs V Danel, R Ferner, MO Rambourg
Schepens (1998)

Finalised and edited by Dr MO Rambourg: February 1999

See Also:
Cocaine (PIM 139F, French)

Erythroxylum coca Lam
1. NAME
1.1 Scientific name
1.2 Family
1.3 Common name(s)
2. SUMMARY
2.1 Main risks and target organs
2.2 Summary of clinical effects
2.3 Diagnosis
2.4 First-aid measures and management principles
2.5 Poisonous parts
2.6 Main toxins
3. CHARACTERISTICS
3.1 Description of the plant
3.1.1 Special identification features
3.1.2 Habitat
3.1.3 Distribution
3.2 Poisonous parts of the plant
3.3 The toxin(s)
3.3.1 Name(s)
3.3.2 Description, chemical structure, stability
3.3.3 Other physico-chemical characteristics
3.4 Other chemical contents of the plant
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
4.2 High risk circumstances
4.3 High risk geographical areas
5. ROUTES OF ENTRY
5.1 Oral
5.2 Inhalation
5.3 Dermal
5.4 Eye
5.5 Parenteral
5.6 Others
6. KINETICS
6.1 Absorption by route of exposure
6.2 Distribution by route of exposure
6.3 Biological half-life by route of exposure
6.4 Metabolism
6.5 Elimination by route of exposure
7. TOXICOLOGY/TOXINOLOGY/PHARMACOLOGY
7.1 Mode of action
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
7.2.1.2 Children
7.2.2 Animal data
7.2.3 Relevant in vitro data
7.3 Carcinogenicity
7.4 Teratogenicity
7.5 Mutagenicity
7.6 Interactions
8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their interpretation
8.5 Overall Interpretation of all toxicological analyses and toxicological investigations
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
9.1.2 Inhalation
9.1.3 Skin exposure
9.1.4 Eye contact
9.1.5 Parenteral exposure
9.1.6 Other
9.2 Chronic poisoning
9.2.1 Ingestion
9.2.2 Inhalation
9.2.3 Skin exposure
9.2.4 Eye contact
9.2.5 Parenteral exposure
9.2.6 Other
9.3 Course, prognosis, cause of death
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
9.4.2 Respiratory
9.4.3 Neurological
9.4.3.1 CNS
9.4.3.2 Peripheral nervous system
9.4.3.3 Autonomic nervous system
9.4.3.4 Skeletal and smooth muscle
9.4.4 Gastrointestinal
9.4.5 Hepatic
9.4.6 Urinary
9.4.6.1 Renal
9.4.6.2 Others
9.4.7 Endocrine and reproductive systems
9.4.8 Dermatological
9.4.9 Eye, ears, nose, throat: local effects
9.4.10 Haematological
9.4.11 Immunological
9.4.12 Metabolic
9.4.12.1 Acid base disturbances
9.4.12.2 Fluid and electrolyte disturbances
9.4.12.3 Others
9.4.13 Allergic reactions
9.4.14 Other clinical effects
9.4.15 Special risks
9.5 Others
9.6 Summary
10. MANAGEMENT
10.1 General principles
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
10.2.2 Biomedical analysis
10.2.3 Toxicological/toxinological analysis
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic treatment
10.4 Decontamination
10.5 Elimination
10.6 Antidote/antitoxin treatment
10.6.1 Adults
10.6.2 Children
10.7 Management discussion
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
11.2 Internally extracted data on cases
11.3 Internal cases
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes/antitoxins
12.2 Specific preventive measures
12.3 Other
13. REFERENCES
13.1 Clinical and toxicological
13.2 Botanical
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)

POISONOUS PLANTS
1. NAME
1.1 Scientific name
Erythroxylum Coca Lam
1.2 Family
Erythroxylaceae
1.3 Common name(s)
Coca Brazil
Coca France
Coca shrub England
Cuca Peru
Epadu Brazil
Hayo Brazil, Venezuela, some indigenous tribes of the Andes
Huaunuco Coca Bolivia
Ipadu Brazil
Spadic Colombia
Ypadu Brazil
2. SUMMARY
2.1 Main risks and target organs
The leaves of E. Coca are used as a stimulant in Western South
America. For centuries the indians of Peru and Bolivia have
chewed coca leaves, often mixed with ashes of plants or
limestone. This is the most common manner of use but the
chewing of the powdered plant, the smoking, or the swallowing
in various infusions are also practised (Morch, 1963).

Chewing the leaves releases the alkaloid cocaine in contact
with the saliva. The chewing habit (named “coqueio”) induces
a mild stimulation, enabling the user to withstand strenuous
work, walking, hunger, or thirst.

The contact with the mucous membranes of mouth and stomach
produces local anaesthesia. The psychological and
physiological effects are lighter than the administration of
pure extracted alkaloid cocaine. The hazards of this pattern
of use are considerably diminished.

Other effects are related to the potentiation of responses of
sympathetically innervated organs to catecholamines, and to
sympathetic nerve stimulation causing tachycardia and
mydriasis (Goodman & Gilman, 1985).

According to the amount of cocaine ingested by the habitual
users of coca chewing – 60 grams of leaves a day – (Phillips,
1980) the various effects include mainly local anaesthesia,
slight euphoria and diminishing of fatigue.

The greatest hazard is addiction. For many centuries the
populations of the Andes region have used coca leaves as part
of the social and religious habits. Changing the pattern of
use to the administration of pure cocaine is another permanent
risk.

The target organs are the central nervous system, and the
cardiovascular system.

2.2 Summary of clinical effects
Chewing coca leaves rarely induces acute effects but chronic
effects are often observed.

The manifestations of acute poisoning are dose-related and are
well understood from the description of the clinical effects
induced by ingestion of the pure alkaloid:
Acute poisoning – With small amounts, cocaine users
experience euphoria, restlessness, excitability. There is a
lessened sense of fatigue, and increased capacity for muscular
work. Later, hallucinations, tachycardia, dilated pupils,
arterial hypertension and abdominal pain develop. The
stimulation is followed by depression of the nervous system.
Irregular respiration, convulsions, coma, and circulatory
failure are observed.

Chronic poisoning – Impaired sensibility of mucous membranes
of mouth; the irritating and vasoconstricting properties may
cause ulceration of the mucous membranes; weight loss; altered
character; hallucinations and mental deterioration have been
described.
2.3 Diagnosis
An initial excitatory phase produces euphoria and
restlessness; this is followed by hallucinations and
tachycardia. Later, CNS depression occurs, with
abnormal respiration, coma and circulatory failure;
convulsions may also occur.

Remnants of leaves, vomitus or gastric aspirate should be
collected in clean bottles for identification purposes.
2.4 First-aid measures and management principles
First-Aid Measures:

Remove any leaves present in the mouth. Wash the mouth
thoroughly with water or a saline solution. Induce vomiting
by giving syrup of ipecac.

Dose of syrup of ipecac (this should be taken with a glass of
water and may be repeated after 20 minutes if necessary).

Children: 6 to 18 months 10 ml
18 months to 12 years 15 ml
Adults: 30 ml

Do not induce vomiting if consciousness is impaired or if fits
occur.

Management principles

The treatment of acute overdose is basically symptomatic and
supportive. Ensure patient’s airway and ventilation.
Supportive measures include: oxygen, artificial respiration,
intravenous fluids with vasopressors (dopamine) and control of
agitation and seizures with intravenous diazepam.
2.5 Poisonous parts
The leaves are the poisonous parts of the plant. Description

of the leaves: Lively green, or greenish brown and clear brown,
smooth, slightly glossy, opaque, oval and more or less
tapering at the extremities. They are 1.5 – 3 cm wide, and
2.5 to 11 cm long. Characteristically, the leaves have an
areolate portion bounded by two longitudinal curved lines one
on each side of the midrib, and more evident on the under face
of the leaf.

When chewed they have a pleasant, pungent taste. Dried leaves
are uncurled, deep green on the upper surface, grey-green on
the lower, and have a strong tea-like odour (Morch, 1963; Cruz,
1982 Hoehne, 1978).
2.6 Main toxins
Cocaine (methylbenzoylecgonine) is one of at least 12
alkaloids extracted from the leaves of E. coca. All have
ecgonine as common constituent.

Some other alkaloid are: cinnamylcocaine, hygrine,
tropococaine, truxillines, isotropylcocaine, cocaicine.
3. CHARACTERISTICS
3.1 Description of the plant
3.1.1 Special identification features
The wild coca shrub often grows to a height of 3 to 5.5
m (12 to 18 feet). The cultivated plant is usually kept
to 6 meters. Diameter of the stem is about 16
centimetres. The plant is very hardy and its roots can
penetrate 2 to 3 m into the soil. The reddish branches
are straight, alternate. The stem has a whitish bark.

The leaves are lively green, or greenish brown, and
clear brown, smooth, slightly glossy, opaque, oval or
elliptical, and more or less tapering at the
extremities. The leaves are 1.5 to 3 cm wide, and .5 to
11 cm long. A special characteristic of the leaf is an
areolate portion bounded by two longitudinal curved
lines one on each side of the midrib, and more evident
on the under face. The taste is bitter and faintly
aromatic. Dried leaves are uncurled, deep green on the
upper surface, grey-green on the lower, and have a
strong tea-like odour. The flowers are succeeded by red
berries. These fruits are drupaceous, oblong, measuring
around 1 cm; these produce only one seed (monospermous).
The main characteristic of the plant is the perennial
renewal of the branches, after cutting, in a geometrical
progression (Morch, 1963; Cruz, 1982).
3.1.2 Habitat
The wild coca shrubs develop well in tropical humid
climates, preferably zones such as clearings in forests,
or on the wet side of mountains. Wild species are
commonly found in altitudes of 300 to 2000 m.
Cultivated plants can thrive in different climatic
conditions.
3.1.3 Distribution
Erythroxylum coca grows throughout the tropical regions
in the Eastern Peruvian Andes, mainly Peru, Ecuador and
Bolivia. It also grows in Colombia, Chile, and in the

Brazil Amazon region, and to a lesser extent in Mexico,
and the West Indies. It is cultivated in Indonesia.
3.2 Poisonous parts of the plant
The leaves are the poisonous parts of the plant.
3.3 The toxin(s)
3.3.1 Name(s)
The alkaloid cocaine (methylbenzoylecgonine) is the
active principle obtained from the leaves of E. coca.
It is one of at least 12 alkaloids extracted from the
leaves. All toxins have ecgonine as common constituent.
Cocaine is synthetically obtained from ecgonine. Other
toxins are cinnamylcocaine, truxillococaine,
isotropylcocaine, cocaicine, tropococaine (Merck Index,
1983; Reynolds, 1989).
3.3.2 Description, chemical structure, stability
Cocaine is methybenzoylecgonine.

CAS number: 50-36-2
Molecular weight: 303.4
Structural formula: C17H24N04

Colourless odourless crystals, or white crystalline
powder, with a numbing taste. It is slightly volatile.

Stability: Melting point from 96 °C to 98 °C. Should
be protected from light (Reynolds, 1989).
3.3.3 Other physico-chemical characteristics
Cocaine is soluble in water, alcohol, arachis oil,
castor oil, chloroform, ether, liquid or soft paraffin,
oleic acid. Practically insoluble in glycerol. The
saturated solution in water is alkaline to
phenolphthalein. Only a mild degree of heat is used to
prepare oily solutions (Reynolds, 1989).
3.4 Other chemical contents of the plant
In addition the leaves contain:-

Dextrin and sugars
Starch
Protein
Crude fibre
Volatile oils.

Nutritional analysis shows that 100 g of leaves contain 305
calories (Phillips & Wynne, 1980).
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
The tradition of chewing of coca leaves is deeply fixed
among the Andes Indians, farmers and miners, who use it
to arouse physical energy, and to fight against pain,
hunger and thirst.

Some countries in South America, for example, Peru and
Bolivia, have legal plantations of coca shrub, to supply
this local and traditional use.

From the leaves the alkaloid cocaine is extracted, for

limited medical use as an ophthalmic anaesthetic.

One of the reported uses of the coca leaves is as an
ingredient in the composition of soft drinks, cocaine
being previously removed.

The most important use of cocaine is an illegal one, as
defined by all countries and the United Nations. The
free base, the paste and cocaine are extracted from coca
leaves. “Crack” is a potent smokable form of cocaine.
The illicit use of cocaine has increased dramatically
because of its accelerated use among all social classes
(Ellenhorn, 1988).
4.2 High risk circumstances
poisoning may occur in association with the traditional
chewing of leaves in some well-defined geographical areas, and
due to ingestion by children who chew or swallow the leaves.

The use of infusions is a minor risk for poisoning, because
the concentration of the alkaloid is very low.

This monograph will not discuss the use of the alkaloid
cocaine. Readers are referred to Cocaine.
4.3 High risk geographical areas
Especially the regions of the Andes (Peru, Bolivia, Ecuador,
Columbia, Chile) and the Amazon region of Brazil.
5. ROUTES OF ENTRY
5.1 Oral
Ingestion is commonly by chewing, sucking or swallowing the
leaves entire or in powdered form. Leaves can also be
ingested in the form of infusion: ‘coca tea’ is very popular
in the Andes.
5.2 Inhalation
Smoking the leaves is not a current practice. Although pure
leaves can be used as cigars, the concentration of alkaloids
is very low. This use is different from making cigars with
the basic paste.
5.3 Dermal
Folk medicine uses leaves or infusions as topical treatment of
burns or skin diseases.
5.4 Eye
Infusions are used in traditional medicine.
5.5 Parenteral
Not described.
5.6 Others
Not described.
6. KINETICS
6.1 Absorption by route of exposure
When coca leaves are chewed there is absorption from the
mucous membranes of the mouth and from the gastrointestinal
tract. The exact sites of absorption (stomach or duodenum)
are not known. Systemic absorption is 30 to 40% after oral
doses (Grabowski, 1984).

The extent of absorption after smoking the leaves is unknown
though the absorption of smoked cocaine and crack has been

extensively studied.
6.2 Distribution by route of exposure
Distribution occurs throughout the tissues of the body.
Cocaine easily diffuses across the blood-brain barrier. The
significance of enterohepatic circulation is still undefined
(Gosselin, 1984). The volume of distribution of cocaine is
1.2 to 1.9 L/kg (Ellenhorn, 1988).
6.3 Biological half-life by route of exposure
6.4 Metabolism
Cocaine is rapidly and extensively metabolized by the liver
although absorption from the mucous membranes of the mouth
avoids some presystemic hepatic metabolism. Enzyme esterases,
specifically the plasma cholinesterase, play an important
role in the metabolism of cocaine and the activity of
cholinesterase can vary greatly between individuals.

Cocaine is hydrolysed to water soluble metabolites. The major
products of metabolism are ecgonine methyl ester (32 to 49%)
and benzoylecgonine (29 to 45%). The latter may be hydrolysed
nonenzymatically. Other metabolites, including hydroxycocaine,
methylecgonidine, and norcaine, have been identified
(Gillenhorn, 1988).
6.5 Elimination by route of exposure
The metabolites are excreted in urine, and can be identified
up to 48 hours after oral ingestion (Noji & Kelen, 1989).
After metabolism, 1 to 9 % of cocaine is excreted unchanged in
the urine (Gosselin, 1984).
7. TOXICOLOGY/TOXINOLOGY/PHARMACOLOGY
7.1 Mode of action
The main effects of cocaine result from sympathetic
stimulation. Cocaine inhibits the reuptake of catecholamines,
particularly norepinephrine (noradrenaline) and dopamine, at
the nerve terminal. The effects of sympathetic
neurotransmitters are therefore enhanced due to the
persistence of catecholamines in the synaptic cleft.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
There is considerable individual variation in
the susceptibility to cocaine. The toxicity of
cocaine may be lower if it is ingested orally by
chewing coca leaves (Grabowski, 1984). The
lethal oral dose of the alkaloid is 1,200 mg for
adults (Noji & Kelen, 1989), but it has been
reported that chronic users consume 5 to 10
g/day.

The leaves of the South American plants contain
0.5% to 1% of the alkaloid cocaine.

Coca leave chewers may use 20 to 80 g of leaves
per day. This corresponds to an ingestion of
0.16 to 0.64 mg/day of the alkaloid. The lethal
dose is not achieved by chewing the leaves.
7.2.1.2 Children
Data on oral absorption and toxicity of cocaine

after chewing of leaves in children are not
available.
7.2.2 Animal data
Estimates of oral acute LD50 in animals are not
available. The approximate LD50 in the rabbit is: 15
mg/kg IV; 50 mg/kg intranasally (Gosselin, 1984)

The LD50 IV in the rat is 17.5 mg/kg (Merck Index,
1983).
7.2.3 Relevant in vitro data
In vitro, cocaine is hydrolysed by human hepatic and
plasma esterase to ecgonine methyl ester. Treated the
same way, norcocaine yields norecgonine methyl ester
(Reynolds, 1989).
7.3 Carcinogenicity
No data available.
7.4 Teratogenicity
The evidence from animal studies is conflicting (Ellenhorn,
1988).

Congenital malformations are more common among children born
to mothers who abuse cocaine (Reynolds, 1989).
7.5 Mutagenicity
Not available.
7.6 Interactions
Patients with esterase deficiencies may develop severe
reactions (Ellenhorn, 1988). Interactions are possible with
methyldopa, tricyclic antidepressants, monoamine oxidase
inhibitors, chlorpromazine, reserpine, guanethidine,
adrenaline, and alpha- and beta-adrenoreceptor blocking agents
(Reynolds, 1989).
8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)

8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
Full blood count
8.3.1.2 Urine
Urinalysis to detect red and white blood cells;
and glucose, protein.
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
Arterial p02 and pCO2 and acid-base balance.
8.3.3 Haematological analyses
Serum electrolytes, blood urea nitrogen, creatinine,
glucose, phosphorus, bilirubin, serum glutamic-
oxaloacetic transaminase, and serum glutamic-pyruvic
transaminase.
8.3.4 Interpretation of biomedical investigations
ECG.
8.4 Other biomedical (diagnostic) investigations and their
interpretation
8.5 Overall Interpretation of all toxicological analyses and
toxicological investigations
Oral doses of 2 mg/kg produce an average peak plasma
concentration of 0.21 mg/l in one hour. After ingestion of
cocaine filled condoms (‘body-packing’), the serum cocaine
level in one patient was 2 mg/l. Postmortem cocaine blood
levels range from 0.1 to 2.11 mg/l and blood concentrations
are highest in patients who die after oral ingestion
(Ellenhorn, 1988).

Blood: Leukocytosis commonly occurs after large doses of
cocaine (Ellenhorn, 1988).

Urine: Red blood cells in urine; electrolytes, blood urea
nitrogen, and glucose show changes after large doses of
cocaine (Ellenhorn, 1988). Glucose and protein are increased.

Severe overdoses cause hypoxaemia and hypercarbia due to
respiratory depression and seizures. Acid-base abnormalities
follow hypoxaemia (Ellenhorn, 1988).

The most frequent ECG changes are tachycardia and ventricular
arrhythmias (Noji & Kelen, 1989).
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
The onset of action after ingestion is 2 to 5 minutes.
Clinical features include: restlessness, excitability,

hallucinations, mydriasis, chills, abdominal pain,
vomiting, numbness and muscular spasms.
9.1.2 Inhalation
Acute poisoning after inhalation of the smoking of
leaves has not been reported.
9.1.3 Skin exposure
Not relevant.
9.1.4 Eye contact
Not relevant.
9.1.5 Parenteral exposure
Not described.
9.1.6 Other
Not described.
9.2 Chronic poisoning
9.2.1 Ingestion
Chronic ingestion or chewing of the leaves may produce
some specific clinical features, including physical
exhaustion, weight loss, impaired sensitivity of mouth
mucous membranes, pallor, tremors, hallucinations,
mental deterioration and altered personality.
9.2.2 Inhalation
Effects in chronic smokers of leaves have not been
reported.
9.2.3 Skin exposure
Not described.
9.2.4 Eye contact
Not described.
9.2.5 Parenteral exposure
Not described.
9.2.6 Other
Not described.
9.3 Course, prognosis, cause of death
The course of cocaine poisoning has 3 phases: an early phase
of stimulation, a second phase of late stimulation and a third
phase of depression.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Acute: Tachycardia.

Chronic: Arrhythmias.
9.4.2 Respiratory
Acute: Tachypnoea.
9.4.3 Neurological
9.4.3.1 CNS
Acute: Euphoria, headache, vertigo, tremor,
restlessness, hyperreflexia.

Chronic: Hallucinations, mental deterioration.
9.4.3.2 Peripheral nervous system
Local application of cocaine blocks nerve
conduction.
9.4.3.3 Autonomic nervous system
Mydriasis and cycloplegia.
9.4.3.4 Skeletal and smooth muscle
Muscular tremor and hyperactivity. Increased
contraction of intestinal smooth muscles.

9.4.4 Gastrointestinal
Acute: Nausea, vomiting, diarrhoea, abdominal cramps.
9.4.5 Hepatic
Hepatoxicity is not a well recognized complication
(Ellenhorn, 1988).
9.4.6 Urinary
9.4.6.1 Renal
Haematuria.
9.4.6.2 Others
Not available.
9.4.7 Endocrine and reproductive systems
Not available.
9.4.8 Dermatological
Not relevant.
9.4.9 Eye, ears, nose, throat: local effects
Acute: Mydriasis by local action. Anaesthesia and
vasoconstriction of mucous membranes.

Chronic: Sneezing and coryza-like symptoms.
9.4.10 Haematological
Acute: Leukocytosis after large doses.
9.4.11 Immunological
Not described.
9.4.12 Metabolic
9.4.12.1 Acid base disturbances
Acid base disturbances occur after hypoxemia.
9.4.12.2 Fluid and electrolyte disturbances
Vomiting and diarrhoea may result in loss of
fluids.
9.4.12.3 Others
Higher temperature is observed due to
vasoconstriction that reduces the amount of
heat loss.
9.4.13 Allergic reactions
Not described.
9.4.14 Other clinical effects
Chronic: Psychiatric complications of addiction:
dysphoric agitation, acute psychoses.
9.4.15 Special risks
There is evidence that the risk of congenital
malformations is increased in mothers who abuse
cocaine; perinatal mortality is also greater (Ellenhorn,
1988).

During pregnancy there is a decrease of cholinesterase
activity which increases cocaine toxicity (Grabowski,
1984). Cocaine is excreted breast milk.
9.5 Others
Not relevant.
9.6 Summary
10. MANAGEMENT
10.1 General principles
Supporting symptomatic treatment. Remove any leaves present
in the mouth. Wash the mouth with water or saline.
Ingested leaves should be removed from the stomach by
gastric lavage or emesis.

10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
(In preparation).
10.2.2 Biomedical analysis
As indicated. Choline esterase blood levels.
10.2.3 Toxicological/toxinological analysis
(In preparation)
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic treatment
Monitor pulse, respiration, and blood pressure. Maintain a
fluid balance chart.

Respiration: assess ventilation and establish an adequate
airway. Correct anoxia by mechanical ventilation and oxygen.

Convulsions: Diazepam 10 mg (0.1 to 0.3 mg/kg) IV mg for an
adult.
10.4 Decontamination
Remove any leaves present in the mouth. Wash the mouth
thoroughly with water or a saline solution. If convulsions
are not imminent, induce vomiting or perform gastric lavage.

Gastric lavage may be performed if emesis fails, bearing in
mind the risk of imminent convulsions.

Activated charcoal is indicated.
10.5 Elimination
Due to its very short half-life and large volume of
distribution, measures to enhance the elimination of cocaine
are not indicated.
10.6 Antidote/antitoxin treatment
10.6.1 Adults
10.6.2 Children
10.7 Management discussion
Management is mainly symptomatic. There are few case
reports of ingestion of leaves or the consequences of
chewing the leaves. Scientific papers refer primarily to the
use of the pure alkaloid.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Zapata Ortiz (1952) describes the chronic use of E. coca
among the Andean miners:

“Although it is true that the chewing of coca leaf
diminishes fatigue and by exerting a stimulating effect may
increase the output of work within the short period of a
particular experiment, the result in no way shows that coca
addicts are capable of doing more work and achieving a
greater output over the protracted period required for their
customary tasks and much less that they have a greater
capacity for work than persons who do not consume coca and
who receive proper nourishment”.
11.2 Internally extracted data on cases
11.3 Internal cases
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes/antitoxins

12.2 Specific preventive measures
Know the botanical name of the house and yard plants or
trees.

Teach children never to put leaves, stems, bark, seeds, nuts,
or berries from any plant into their mouths.

Keep poisonous house plants out of the reach of all
children.

Never eat a wild plant unless you are sure of its identity.

Do not assume that plant is safe because birds or animals
eat it.

Cooking seldom do not destroy active principles of the
plant.

Do not smoke plant materials.
12.3 Other
13. REFERENCES
13.1 Clinical and toxicological
Dreisbach RH, Robertson WO (1987). Handbook of poisoning;
prevention, diagnosis, and treatment. 12th ed Norwalk:
Appleton & Lange, p. 589.

Ellenhorn MJ, Braceloux DG (1988). Medical Toxicology:
Diagnosis and treatment of human poisoning. New York:
Elsevier, p. 1512.

Gillam AG, Goodman LS, Rall TW, Murad F, eds. Goodman and
Gilman’s The Pharmacological Basis of Therapeutics. 7th.ed.
New York, Toronto, London: Macmillan, 1985. p. 1839.

Gosselin RE, Smith RP, Hodge HC (1984). Clinical toxicology
of commercial products. 5th Ed. Baltimore: Williams &
Wilkins.

Grabowski J (1984). Cocaine; Pharmacology, effects, and
treatment of abuse. Washington: National Institute on Drug
Abuse. (NIDA Research Monograph, 50).

Merck Index (1983). An encyclopedia of chemicals, drugs
and biologicals. 10th ed. Rahway: Merck, p. 10000.

Noji EK, Kelen GD (1989). Manual of toxicological
emergencies. Chicago, London, Boca Raton: Year Blood Medical
Publishers, p. 850.

Phillips JL, Wynne RW (1980). Cocaine – the mystique and
the reality. New York: Avon Bloods, p. 318.

Reynolds JEF (ed). Martindale, The Extra Pharmacopoeia. 29th
Ed. London: Pharceutical Press, 1989. p. 1896.

Zapata-Ortiz V (1952). The problems of the chewing of the

coca leaf in Peru. Bulletin of Narcotics: 26-33.
13.2 Botanical
Cruz Gl (1982). Dicionario de plantas uteis do Brazil. 2nd
Ed Rio de Janeiro: Civilizaçåo Brasileria, p. 599. (in
Portuguese).

Hoehne FC (1978). Plantas e substancias vegetais toxicos e
medicinais. Reimpressao, Sao Paulo, (1st Ed. 1939) (in
Portuguese).

Morch ET (1963). Cocaine. In: Encyclopedia Britannica,
vol.5. chicago, London, Toronto, Geneva: William Benton
Publisher, p. 993-4.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Authors: M.S.C. de Medeiros and A. Furtado Rahde
Rua Riachuelo 677 ap 201
90010 Porto Alegre
Brazil

Tel: 55-512 275419
Fax: 55-512 391564/246563
Telex: 051 2077 FUOC BR

Date: September 1989

Peer Review: Strasbourg, France, April 1990

Neonatal Hair Test for Cocaine: Toronto Experience

In large US cities, an estimated 10% to 45% of women cared for at teaching hospitals use cocaine during pregnancy. Between June 1990 and December 1991, we conducted a prevalence study of cocaine use during pregnancy in one inner-city and two suburban metropolitan Toronto hospital nurseries and found 37 of 600 (6.25%) infants tested positive for cocaine.

Since the neonatal hair test for cocaine was established in 1989 and its use as a research tool for ascertaining the prevalence of use in the Toronto area was confirmed, physicians, hospital nurseries, and social welfare agencies (e.g., Children’s Aid) have increasingly requested analysis of neonatal hair to corroborate or refute clinical suspicion of cocaine use during pregnancy when urine test results were negative.

This report should help establish the sensitivity of clinical suspicion of in utero exposure to cocaine as validated by hair testing.

The hypothesis underlying this research was that use of the hair test in cases of clinical suspicion but negative urine test results would yield a substantially higher prevalence rate than expected in the general population.

Samples for Neonatal Hair Test for Cocaine

Between October 1991 and April 1995, we analyzed hair samples from 192 neonates and four mother-infant pairs. Among the neonatal hair samples provided for analysis, 10 did not contain sufficient hair to analyze for cocaine metabolites, but 55 (30%) of the remaining 182 samples tested positive for the cocaine metabolite benzoylecgonine. Most samples (72%) were sent from hospital nurseries and clinics. The rest were sent from social welfare agencies and privately practicing physicians.

Neonatal Hair Test for Cocaine: The Results

Whether all newborns should be screened for exposure to cocaine is continually under debate. The complex relationships between maternal and fetal rights and the extremely heterogenous views on drug testing in western societies make it unlikely that routine screening will ever take place.

Our results suggest strongly that it might be sufficient to test suspected cases based on nonspecific signs of cocaine exposure and not take on the enormous cost and ethical-legal liabilities inherent in universal testing.

Confirmation of in utero exposure to cocaine might allow for earlier intervention to ensure proper care for both baby and mother.

Both mother and infant should be closely followed with postnatal care, supportive counseling, contraceptive counseling, public health nurse visits, and training in parenting skills. Evidence shows that interventions such as home visits benefit children’s early development.

Publications on Recreational/Social Drugs: Cocaine

Morris P, Binienda Z, Gillam MP, Klein J, McMartin K, Koren G, Duhart HM, Slikker W Jr, Paule MG: The effect of chronic cocaine exposure throughout pregnancy on maternal and infant outcomes in the rhesus monkey. Neurotoxicology & Teratology. 19(1):47-57, 1997 Jan-Feb.

Koren G, Graham K, Shear H, Einarson T: Bias against the null hypothesis; The reproductive hazards of cocaine. Lancet 2: 1440-1442, 1989.

Nulman I, Rovet J, Altman D, Bradley C, Einarson T, Koren G: Neurodevelopment of adopted children exposed in utero to cocaine. Can Med Assoc J 151: 1591-1597, 1994.

Eliopoulos C, Klein J, Koren G: Neonatal markers for intrauterine exposure to cocaine and nicotine. Can J Obstet Gynecol 6: 615-620, 1994.

Forman R, Graham K, Klein J, Greenwald M, Koren G: Accumulation of cocaine in fetal hair; The dose response curve. Life Sci 50: 1333-1341, 1992.

Forman R, Klein J, Meta D, Barks J, Greenwald M, Koren G: Maternal and neonatal characteristics following exposure to cocaine in Toronto. Reprod Toxicol 7: 619-622, 1993.

Forman R, Klein J, Meta D, Barks J, Greenwald M, Koren G: Prevalence of fetal exposure to cocaine in Toronto 1990-1991. Clin Invest Med 17: 206-211, 1994.

Graham K et al: Pregnancy outcome and infant development following gestational cocaine use by social cocaine user. Koren G (ed): Maternal-Fetal toxicology, 2nd edition, Marcel Dekker, NY 371-386, 1994.

Graham K, Demitrakoudis D, Pellegrini E, Koren G: Pregnancy outcome following first trimester exposure to cocaine in non addict social users in Toronto. Vet Hum Toxicol 31: 143-148, 1988.

Graham K, Klein J, Forman R, Flynnk, Sakuma T, Davidson W, Koren G: Potential misclassification of a case of SIDS: Maternal and neonatal hair analysis for cocaine and heroin. Maternal Fetal Med 2: 91-93, 1993.

Graham K, Koren g, Klein J, Schneiderman J: Determination of gestational cocaine exposure by hair analysis. JAMA 262: 3328-3330, 1989.

Graham K, Koren G: Characteristics of pregnant women exposed to cocaine in Toronto between 1985 and 1990. Can Med Assoc J 144: 563-568, 1991.

Graham K, Koren G: Maternal cocaine use and risk of sudden infant death J Pediatr 115: 333, 1989.

Johnson D, Schwartz H, Forman R, Klein J, Jacobson, S, Greenwald M, Koren G: Assessment of in utero exposure to cocaine; Radioimmunoassay testing for benzoylecgonine in meconium, neonatal hair and maternal hair. Can J Clin Pharmacol 1: 83-86, 1994.

Addis A, Moretti M, Syed FA, Einarson TR, Koren G. Fetal effects of cocaine: an updated meta-analysis. Reprod Toxicol 15 (4): 341-69, 2001.

Nulman I, Rovet J, Greenbaum R, Loebstein M, Wolpin J, Pace-Asciak P, Koren G. Neurodevelopment of adopted children exposed in utero to cocaine: the Toronto Adoption Study. Clin Invest Med 2001 Jun;24(3):129-37

Klein J, Eliopoulos C, Ursitti F, Koren G: Issues in measuring cocaine and nicotine in neonatal hair. NIDA monograph (In Press)

Klein J, Forman R, Eliopoulos C, Koren G: A method of simultaneous measurement of cocaine and nicotine in neonatal hair. Ther Drug Monit 16: 67-70, 1994.

Klein J, Greenwald M, Becker L, Koren G: Fetal distribution of cocaine: Case analysis. Ped Pathol, 12: 463-468, 1992.

In Book:

Koren G et al: Biological markers of intrauterine exposure to cocaine and cigarette smoking. Koren G (ed): Maternal-Fetal Toxicology, 2nd edition, Marcel Dekker, NY 387-398, 1994.

Koren G, Klein J, Forman R, Graham K, My-Khan P: Biological markers of intrauterine exposure to cocaine and cigarette smoking. Dev Pharmacol Ther 18: 228-236, 1992.

Koren G, Klein J, Forman R, Graham K: Hair Analysis of cocaine: Differentiation between systemic exposure and external contamination. J Clin Pharmacol 32: 671-675, 1992.

In Book:

Koren G, Klein J, Graham K, Forman R: Hair test to verify gestational cocaine exposure. In: Recent Developments in TDM and Clin Toxicology Marcel Dekker, NY 569-574, 1992.

Koren G: Cocaine use by pregnant women in Toronto; An alarming note. IM Paint 11: 20-21, 1995 (Winter).

Koren G: Cocaine and the human fetus: The concept of teratophilia. Neurotoxicol & Teratol, 15: 301-304, 1993. No abstract available.

Levy M, Koren G: Obstetric and neonatal effects of drugs of abuse. Emerg Med N Amer 8: 633-652, 1990.

In Book:

Lutiger B et al: Relationship between gestational cocaine use and pregnancy outcome. Koren G (ed): Maternal-Fetal Toxicology, 2nd edition, Marcel Dekker, NY 353-370, 1994.

Lutiger B, Graham K, Einarson T, Koren G: Relationship between gestational cocaine use and pregnancy outcome: A meta-analysis. Teratology 44: 405-414, 1991.

Koren G, Gladstone D, Robeson C, Robieux I: The perception of teratogenic risk of cocaine. Teratology 46: 567-571, 1992.

Potter S, Klein J, Valiante G, Stack DM, Papageorgiou A, Stott W, Lewis D, Koren G, Zelazo PR: Maternal cocaine use without evidence of fetal exposure. J Pediatr 125: 652-654, 1994.

Ursitti F, Klein J, Koren G: Clinical utilization of the neonatal hair test for cocaine: a four-year experience in Toronto. Biology of the Neonate 1997;72(6):345-351

CBD Clinicals is reader-supported. When you buy through links on our site, we may earn an affiliate commission. Learn more

Featured Posts


Spruce CBD Oil Review

Spruce is a family-owned business based out of Raleigh, North Carolina. The company was founded in 2018 in the belief that modern medicine is broken and that there is a need for alternatives to dangerous pharmaceuticals. Spruce’s lab-grade CBD oil is 100% natural and tested by a third-party lab in...

Read more

Best CBD Oil for High Blood Pressure (Hypertension)

Why People Are Taking CBD for High Blood Pressure? According to the Centers for Disease Control and Prevention (CDC), high blood pressure can harden the arteries, which decreases the flow of blood and oxygen to the heart, leading to heart disease(5). In a 2015 study conducted by researchers from the...

Read more

NuLeaf Naturals Review

Based in Colorado, USA, and founded in 2014, NuLeaf Naturals is one of America’s top pioneering hemp companies. NuLeaf Naturals wellness products are derived from specially bred therapeutic hemp (Cannabis Sativa) plants grown on licensed farms in Colorado. Their hemp CBD plants are 100% organic whole-plant extracts and grown with...

Read more

Best CBD for Neuropathy (Nerve Pain)

As medical cannabis products have become more popular, people are turning to them to treat everything from anxiety to depression to chronic pain. Individuals who are suffering from neuropathy may show interest in trying CBD oil. What Is CBD? CBD comes from a plant that is part of the Cannabaceae...

Read more

SabaiDee Review

SabaiDee CBD products are tested both in-house and by independent laboratories to verify the quality of every batch. Their products all come with SabaiDee’s Happiness Guarantee. 

Read more

Best CBD Oil for Dogs With Cancer

Why Some People are Using CBD for Dogs with Cancer? An article posted by the American Kennel Club (AKC) says that there is no conclusive scientific data on using cannabidiol (CBD) to treat dogs specifically. However, there is anecdotal evidence from dog owners suggesting that CBD can help with neuropathic...

Read more

CBD Oil for Kids with Anxiety

Why People are Turning to CBD for Children with Anxiety? CBD has become a popular OTC treatment that parents give their children, says Doris Trauner, M.D., professor of neurosciences and pediatrics at the University of California San Diego School of Medicine and a physician at San Diego’s Rady Children’s Hospital....

Read more

CBD Oil for Candida

Why People are Turning to CBD for Candida? Candidiasis or thrush is a medical condition caused by Candida albicans, a yeast-like fungus. This type of fungus spreads over within the mouth and throat, and it usually infects men and women alike. Certain cannabinoids, like CBD, have been shown as a...

Read more