Cannabis sativa L.
| 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
Cannabis Sativa L. (var Indica)
1.2 Family
Cannabinaceae
1.3 Common name(s)
Cañamo de la India (Latin America)
Chanvre (France)
Charas
Chira
Ganja
Gauja
grass
Grifa
Guaza
Hanfkraut (Germany)
Hashish
Hasis
Hemp
Herbe (France)
Indian hemp (USA, UK)
Juana
Kif
Maconha (Latin America)
Marihuana (Latin America)
Marijane (USA, UK)
Marijuana (Latin America)
Pot
reefer
tea
weed
Yerba
2. SUMMARY
2.1 Main risks and target organs
The main target organ is the CNS.
Acute or prolonged psychotic states, distress and anxiety may
occur.
Traffic and occupational accidents may be related to acute
effects of marihuana use.
Larynx and bronchopulmonary neoplasm have been attributed to
smoking marihuana.
The possibility of immunologic, chromosomal, reproductive and
foetal abnormalities is under research.
2.2 Summary of clinical effects
Acute intoxication - depends upon several facts such as (e.g.
emotional state, past experiences, psychological state,
association with other drugs. Marihuana may produce:
apprehensive states, panic, anxiety, hallucinations and
prolonged psychotic states (acute delirious psychosis,
paranoic reactions, flashbacks, excitation with auto or
heteroagressiveness, mental confusion and depersonalization).
Severe headaches and abdominal discomfort are common.
On clinical examination: motor incoordination, reduction of
reflex responses, distortion of the perception of time and
space, conjunctival irritation, dryness of mouth and throat,
pulmonary irritation (hacking cough, bronchial hypersecretion,
bronchospasm) tachycardia and tremor.
Note: The effect sought by the consumer is a dishinhibition
state with euphoria, unmotivated laugh, relaxed sensation and
pleasant drowsiness. After the lethargic phase, changes in
humour and depression may be observed.
Chronic use may be asssociated with the induction of
"amotivational syndrome" and loss of memory, amongst many
other possible effects (see section 9).
2.3 Diagnosis
On clinical examination: motor incoordination, reduction of
reflex responses, distortion of the perception of time and
space, conjunctival irritation, dryness of mouth and throat,
pulmonary irritation (hacking cough, bronchial hypersecretion,
bronchospasm) tachycardia and tremor.
Sample collection:
specimen of the plant or seeds for identification.
marijuana cigarettes.
urine for determination of cannabinoids (can be positive even
three days after a single use and four weeks or more after
chronic use).
saliva for determination of cannabinoids (experimental)
Toxicological analysis: detection of cannabinoids in urine by
thin layer chromatography, immunoassay or EMIT test.
2.4 First-aid measures and management principles
Treat psychiatric symptoms: calm the patient, make him feel
protected and safe, prescribe rest in a noise-free shady room.
Induce a sense of security and trust using a soft and
monotonous voice ("talking down"). In case of severe
excitation, administer diazepam 10 mg IM. When psychotic
phenomena predominate, haloperidol 5 mg IM is recommended. The
patient should be kept well hydrated.
2.5 Poisonous parts
The active principles are contained in all parts of the plant,
but mostly in the brown resin secreted by hairs in female
influorescences.
2.6 Main toxins
Marihuana contains approximately 60 active compounds, or
cannabinoids; the most important is delta-9-
tetrahydrocannabinol.
Other cannabinoids are: cannabinol, cannabidiol, cannabinolic
acid, cannabigerol, cannabicyclol, different isomers of
tetrahydrocannabinol.
3. CHARACTERISTICS
3.1 Description of the plant
3.1.1 Special identification features
Only macroscopic details will be described.
Indian hemp is an annual dicotyledon herb that can reach
up to 3 metres high or more with suitable humidity and
soil. The stem is covered by rigid hairs, rough to the
touch. Species are male and female; the latter has more
leaves. The leaves are long-stalked, palmate, with 3-7
narrow and toothed leaflets. The upper leaves are
alternate and the low ones, opposite.
Flowers are very small, green and have axillary branches
(Hardin & Arena, 1974). The fruit is oval, flat, 5 to 6
mm long and 4 mm wide, with a light green colour. It has
an herbaceous strong smell and taste.
3.1.2 Habitat
It grows in well-irrigated lands with warm weather,
blooming in the spring and summer.
3.1.3 Distribution
The plant is originally from the Caspian and Black Sea
area, and was taken to Persia and India eight centuries
ago.
The Cannabis sativa native to Central Asia has a world
wide distribution. It is cultivated in North, Central
and South America, in Asia, Europe and North and Central
Africa. Major producers include Mexico, Brasil, Paraguay,
Colombia, Peru, New Zealand and Arabia.
The Indian variety is cultivated in the Orient, Asia and
North Africa.
3.2 Poisonous parts of the plant
The active principles of this plant are contained in the brown
resin secreted by hairs located in female influorescences.
Although the active principles are located in the whole plant,
the major concentration is in the blooming buds. The so
called "seed" or fruit, has a lower concentration, but leaves
and blooming parts have a higher concentration. When they are
new, they contain more active principles and are called
"Kifi". The dried leaves and buds (less rich), are called
"bhang". The resin of the buds, the part with major
pharmacological activity, is called "hashish"; this can be
extracted and stored in blocks.
The common "street" marihuana is usually a mixture of dried
flowers, leaves and ocassionally seeds. It has a brownish
green colour, depending on dryness and maturity of the plant.
3.3 The toxin(s)
3.3.1 Name(s)
Indian hemp contains more than 60 cannabinoids
including: cannabinol, cannabidiol, cannabinolic acid,
cannabigerol, cannabicyclol, and various
tetrahydrocannabinol isomers, the most important is
delta-9-tetrahydrocannabinol (delta-9-THC).
3.3.2 Description, chemical structure, stability
CAS number = 1972-08-3
Molecular weight = 172
Structural formula:
Solubility: Practically insoluble in water, soluble 1 in
1 in alcohol and ketones, and 1 in 3 of glycerol. It is
soluble in fixed oils.
Stability: decreases with time, specially in the case of
hashish, but may resist high temperatures without
inactivation.
The concentration of delta-9-THC in a sample depends
upon the genetic structure of the plant, local
conditions of growth, storage methods and time elapsed
between harvest and use.
Street marihuana, called "sin semilla" (seedless) has
usually higher concentrations of delta-9-THC of 7 - 14%.
Hashish, the oily dark substance obtained after
dissolving the marihuana paste contains 20 to 30% of
delta-9-THC. One drop induces an effect similar to one
cigarette. It is generally commercialized as fragments
of solid resin called "chocolate" (Reynolds, 1982; Jaffe,
1986).
3.3.3 Other physico-chemical characteristics
It has a penetrating, sweetish aroma, very persistant,
that impregnates clothes and hair of users.
Cannabinoids are soluble in alcohol, ether and other
organic solvents, but non-soluble in water and mineral
acids.
3.4 Other chemical contents of the plant
No data available.
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
Medicinal: delta-9-THC and some synthetic analogues are
used therapeutically, e.g. for nausea and vomiting
produced by antineoplastic chemotherapy. Synthetic
cannabinoids used therapeutically include "Dronabinol",
nabilone and "Levonamtradol".
A further possible indication is to reduce intra-ocular
pressure in the treatment of open angle glaucoma.
Some synthetic cannabinoids are undergoing clinical
trial as analgesics and anticonvulsants.
Cannabis sativa has been mixed with other plants in the
preparation of anti-asthma cigarettes.
Medical uses have been limited by adverse effects
similar to those observed after smoking marihuana, but
Dronabinol and nabilone have been approved by
regulkatory authorities in the United States for
therapeutic use (Reynolds, 1982).
Abuse: marihuana is the most frequently abused drug in
the world after alcohol and tobacco, and it is the main
illegal drug of abuse.
Religious: some cultures accept its use for a defined
religious purpose (e.g. some Buddhist and Tibetan sects,
and groups in the north of Africa).
4.2 High risk circumstances
As in every case of drug abuse, several determining factors
should be considered at individual, family and social levels.
Therefore, the high risk circumstances of use and abuse will
vary according to the country or region.
4.3 High risk geographical areas
Abuse of marihuana is worldwide, but it is more common in
cities than in rural areas.
5. ROUTES OF ENTRY
5.1 Oral
Not common in cases of abuse bnut it is the usual route of
administration for medical purposes.
5.2 Inhalation
The commonest way of consuming marihuana and hashish. The
inhaled smoke of one cigarette ("joint") contains 0.5-0.7 g
delta-9-THC.
Marihuana can be smoked directly or through small pipes or
"bongs". They are similar to those used with opium, where
refrigeration by air or water reduces the irritative effects
on the tracheo-bronchial tract allowing a deeper and prolonged
inhalation.
The usual technique consists in inhaling very deeply and
mantaining the smoke in the lungs for 20 or 30 seconds to
maximise the absorption of cannabinoids; the extraction is
about 50% of the cannabinoid content.
5.3 Dermal
No data available.
5.4 Eye
No data available.
5.5 Parenteral
There are some reports of experimental intravenous injection
of marihuana solutions and of cannabinoids in clinical trials.
5.6 Others
No data available.
6. KINETICS
6.1 Absorption by route of exposure
Oral administration
Absorption from the gastrointestinal tract is almost complete.
Peak blood levels and maximal pharmacological effects occur
later after oraladministration than after inhalation (Cone,
1988). Symptoms become apparent within 30 - 120 minutes,
reaching a peak after 2 - 3 hours (Schwartz, 1987; Jaffe,
1985).
Inhalation
After inhalation, peak plasma concentrations are achieved
within a 7 - 10 minutes; subjective effects appear in 20 or 30
minutes but rarely persist for more than 2 - 3 hours.
No data are available on other routes of absorption.
6.2 Distribution by route of exposure
Delta-9-THC is metabolised by the liver. It is intensively
lipophilic and high concentrations accumulate in fatty tissues
in great quantities; these are liberated slowly into the
circulation (Jaffe, 1986).
6.3 Biological half-life by route of exposure
The half-life of delta-9-THC is 3 days. Jaffe (1985) reported
that plasma concentrations of delta-9-THC and 11 hydroxydelta-
9-THC fall rapidly (in a few minutes) due to their
redistribution in the fatty tissues; afterwards there is a
slow decline with a half-life of 30 hours due to the
metabolism and gradual elimination of the drug. The half-life
maybe increased in chronic users to 4.1 days (range 2.9 and
5.0 days) (Johansson, 1988).
6.4 Metabolism
After oral administration but not after inhalation, delta-9-
THC undergoes first-pass hepatic metabolism via enzymatic
hydroxylation and carboxylation to the active metabolite 11-
hydroxy- delta-9-THC, then carboxylation to the more polar
inactive metabolite, 11-nordelta-9-THC acid. Enterohepatic
circulation occurs and only 35% is excreted in the urine.
Around 80 cannabinoid metabolites can be identified from a
similar metabolic pathway; the most important one is 11-
hydroxy-delta-9-THC which is metabolised to non-cannabinoid
metabolites such as terpenes and alkenes.
Delta-9-THC and its metabolites persist in human plasma for
several days or weeks (Jaffe, 1986) but repetitive ingestion
or smoking over weeks is not followed by clinically apparent
accumulation; this suggests that the persistent metabolites
are inactive.
Chronic marihuana smokers metabolise delta-9-THC more rapidly
than non-smokers.
6.5 Elimination by route of exposure
35% of delta-9-THC and its metabolites is eliminated in the
urine compared with 65% in the faeces.
Metabolites can be detected in urine even 2 - 3 days after one
exposure and, in cases of chronic use, after 4 - 5 weeks of
abstinence.
7. TOXICOLOGY/TOXINOLOGY/PHARMACOLOGY
7.1 Mode of action
No specific mechanism or site of action has been demonstrated.
The effects on the CNS can be determined by a diminution of
cholinergic activity at neuronal level. Psychological effects
do not depend on dopaminergic or noradrenergic action.
The cardiovascular effects (tachycardia, decubitus systolic
hypertension and orthostatic hypotension) are counteracted by
propranolol (Jaffe, 1986).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
The average toxic dose is 0.035 mg/kg
(Schwartz, 1987). The minimal effective dose of
delta-9-THC is 5 mg. A 0.5 - 1 g marihuana
cigarette contains 0.5 - 11% delta-9-THC, (Jaffe,
1986). Assuming that the average concentration
is 5% delta-9-THC and that 50% is destroyed by
pyrolysis during smoking, the total inhaled dose
is approximately 25 mg; of this, approximately
60% is absorbed by inhalation.
Nahas (1975) estimates that the lethal dose by
intravenous injection is 2 g for a 70 kg person.
The minimum plasma concentration of delta-9-THC
which produces psychotropic effects is 25 ng/ml
(Hollister, 1988).
7.2.1.2 Children
No data available.
7.2.2 Animal data
With Cannabis extract, the LD50 in mice is:
oral 21.6 g/kg
dermal 11g/kg
IV 0.18g/kg
(Valbuena Briones, 1987)
7.2.3 Relevant in vitro data
No data available.
7.3 Carcinogenicity
Marihuana smoking and hashish abuse produce histological
changes and affect the bronchial epithelium in the young
animal.
In animals, the tar produced by marihuana pyrolysis is more
carcinogenic than that of tobacco (Jaffe, 1986). High
temperature burning corresponding with deep inhalation into
the lungs, together with smoking until the end of the
cigarette, all increase the carcinogenic risk of delta-9-THC
and polyaromatic hydrocarbons.
7.4 Teratogenicity
Cannabinoids cross the placental barrier and may affect fetal
development. When mothers are exposed to cannabis during
pregnancy, both the human and animal newborn may show
postpartum behavioural effects such as altered response to
stimuli and impairment of learning (Jaffe, 1986).
In a prospective study of 1226 mothers, of which 27% were
users, urine metabolites of cannabis were found in 16% of
cases, and there were alterations in foetal development,
weight and height, with values lower than those of a child
born to non-smoking mothers (Zucherman, 1989).
7.5 Mutagenicity
Comparative studies between marihuana smokers and non-smokers
show that more than 60% of the former have a significant
increase of chromosomal alterations: in smokers the average
was 3.4% of leucocytes, and in non-smokers only 1.2%.
7.6 Interactions
Abuse of marihuana may lead to the use of other drugs and
alcohol. It is important to determine whether other drugs have
been consumed in case of acute intoxication. Unfortunately,
only a few interactions are well-known, so the physician must
be alert to the possible variety of clinical presentations.
Clinical features other than the typical symptoms should be
evaluated in order to determine the possible association with
other drugs.
Delta-9-THC enhances the metabolism of barbiturates,
antipyrine, and ethanol.
The combination of cocaine and marihuana reportedly
significantly increases heart rate and arterial pressure
(Foltin, 1987). This finding is important if we consider the
frequent association between marihuana and cocaine abuse. The
authors conclude that this combination in a non-controlled
situation and in high doses may cause severe cardiovascular
toxicity.
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
Collect sample of the plant, seed, leaves, dried
preparation, cigarettes or other suspected
specimen (e.g. resin) for pharmacognostical or
analytical identification.
Biological specimens (urine) should be collected
in clean flasks and sent to the laboratory.
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
The clinical presentation is similar to that produced by
inhalation (see section 9.1.2) though there are
differences in the time to onset of symptoms, which may
be delayed by 30 minutes to 1 hour.
9.1.2 Inhalation
The acute effects of cannabis depend on:
. the concentration of delta-9-THC in plasma
. the concentration of delta-9-THC in the marihuana
cigarette
. the inhalation technique (prolonged and deep
inhalation; use of bong, pipes, others),
. individual and environmental conditions
Individual
Conditions depending upon the person, such as previous
experiences, attitude, expectations for the actual
experience, and personality. In this way, unexperienced
young persons, fearing to be discovered, can present
acute anxiety reactions and panic, fear of losing self-
control and unpleasant sensations. Young people with
unstable personalities and acute affective disorders,
such as depression or a psychotic background (unrelated
to drugs), have a higher risk of developing adverse
effects and permanent psychosis.
Environment
Conditions due to the environment (confidence in
partners, link between users and other participants,
comfort, safety, etc).
Interactions between cannabis and other drugs of abuse
and alcohol may provoke unpredictable effects in
individuals and the response to delta-9-THC may be very
complex.
The usual clinical picture appears after smoking a
cigarette with 2% of THC, or after a 20 mg dose of
delta-9-THC. After a few minutes, the first effects on
humour, motor coordination, sensitivity, auto-perception,
cognitive capacity, attention and time perception
occur. Feelings of well-being, euphoria, laughing and
relaxation are common; somnolence is observed when the
individual is alone.
Tasks that require intermediate steps before reaching
the objective are difficult to perform (time
misperception). There is a tendency to mix past, present
and future with a strange feeling of unreality and
depersonalization. Motor coordination (balance and
reaction time) is always affected, even at low doses,
and thereis therefore a higher risk of accidents.
Perception of colour, distance, and depth, and visual
acuity is impaired. These effects are more persistent
than the subjective disorders, and they last for 4 - 24
hours.
Marihuana smokers frequently experience hunger, dryness
of the mouth and throat, vivid visual images,
hyperacusia, and increased sensations of touch, taste
and smell. There is a reduction of empathy and
perception of other people's emotions, conversation may
be unclear and communication may be interrupted by
unrelated words and ideas.
At higher doses the patient may have: hallucinations,
delirium, paranoia and variable degrees of anxiety
culminating in panic and toxic psychosis.
There is an increase in heart rate, with high supine
systolic blood pressure and orthostatic hypotension.
Conjunctival irritation is usually seen.
The patient's body temperature is increased by
inhibition of sweating.
Respiratory effects are related to the chronic use of
marihuana; the acute effect is bronchodilatation both in
healthy and asthmatic individuals. But in the latter,
irritative effects may precipitate an asthmatic crisis.
A painful, itching or burning sensation of mouth and
throat produces irritating cough.
Hashish smokers develop inflammation and swelling of the
uvula.
The cannabis "trip" may be interrupted easily
voluntarily, so that the person may look normal, even in
his affective relations and in the speed and contents of
speech.
After 2 or 3 hours, the user may gradually "leave" the
intoxicated state and develop clumsiness (physical and
mental), irritability (that may turn into rage),
somnolence and deep sleep. Depression may occur.
During this "comming down" phase, the avidity for food
rich in carbohydrates, sweets and cola soft drinks is
common. Once the "trip" is over, there is practically no
hangover.
Only two physical signs persist: tachycardia and
conjunctival irritation (although the latter can be
avoided by use of eye drops).
Although the effects of marihuana are usually pleasant,
adverse effects may be observed even when the consumer
is experienced, and may be seen also after a single dose,
even if it is low.
Adverse effects are:
acute toxic psychosis with: excitation, confusion,
disorientation, illusions, depersonalization, visual
hallucinations and delirium.
acute panic reactions ("bad trip") accompanied by
abdominal pain, headaches, anxiety, depression with
excessive fear of being discovered, fear of dying and
uncontrollable agressive feelings with paranoid ideas.
"flashback" reactions are not frequently associated with
cannabis but some cases have been reported (Schwartz,
1986).
affective disorders
chronic psychosis
9.1.3 Skin exposure
No data available.
9.1.4 Eye contact
Conjunctival irritation is usually seen due to the
direct effects of smoke contact.
9.1.5 Parenteral exposure
In cases where parenteral administration has been
observed experimentally, the clinical picture is
similarto that produced by social use, although the
symptoms develop faster and more intensely.
9.1.6 Other
No data available.
9.2 Chronic poisoning
9.2.1 Ingestion
No data available.
9.2.2 Inhalation
The chronic effects of Cannabis are controversial, but
believed to be more important the younger the patient
starts with the abuse. They may consist of:
amotivational syndrome: although marihuana may be a
primary or secondary factor inducing amotivational
syndrome, it is not the main one: a drug that produces
passiveness is effective only in the predisposed
individual (Cohen, 1982).
The syndrome consists of:
loss of interest, apathy, passiveness
lack of interest in work and productivity without any
concern
lassitude and loss of energy
lack of tolerance and easy frustration
melancholy, bad temper and whims.
loss of concentration and inability to process any new
information.
shabby look
a life style that is based on a search for the drug.
Use of other drugs: some authors believe that marihuana
may lead to abuse of other drugs, a phenomenon that has
been called "escalation".
Impairment of memory, loss of concentration, a loss of
faith in themselves, in judgement and ambitions;
deterioration of relationships with family, teachers and
other authorities has been recognized by most chronic
abusers after treatment.
crime: chronic abusers may be involved more frequently
in illegal activities.
Tolerance and dependence are mainly due to functional or
pharmacodynamic adaptations of the CNS, rather than to
faster metabolism and excretion. Tolerance develops to
emotional changes, tachycardia, body temperature and
psychomotor tasks; tolerance of the cardiac effects may
develop in just a few days.
Experienced abusers may have more intense subjective
effects than beginners, but will have lesser
deterioration of perceptive and motor functions.
After chronic abuse at high doses, sudden
discontinuation produces: irritability, restlessness,
nervousness, loss of weight, insomnia, tremors, rise of
body temperature and shivering.
Symptoms may start a few hours after withdrawal, and
last a few days (Schwartz, 1987; Jaffe, 1986).
Car accidents may be an indirect consequence of acute
abuse. In those who smoke marihuana more than 6 times
per month, the risk of car accidents is increased 2.4-
fold (Schwartz, 1987).
Endocrine effects have been reported following chronic
use, including impairment of gonadotrophin secretion
(FSH and LH), reduction in testosterone levels and a
direct effect on cytochrome P 450 of the Leydig cells
with inhibition of testosterone synthesis. Both
mechanisms will lead to olisgospermia and possibility of
subfertility (Nahas, 1975).
In the woman, alteration of menstrual cycles
(amenorrhoea and anovulatory cycles), and also a
reduction in plasma levels of prolactine have been
reported.
Chromosomal alterations have been observed in germinal
cells and lymphocytes.
Effects on the respiratory system:
chronic bronchitis, sinusitis, asthma, rhino-pharyngitis,
uvular inflammation.
bronchopulmonary histological changes that may lead to
squamous cell metaplasia and hyperplasia of basal cells
with changes in subepithelial glandules and infiltration
of mononuclear leucocytes in the alveoli and pulmonary
interstitium. These anomalies are similar to those
considered as pre-cancerous in tobacco smokers and have
been found in marihuana smokers who do not smoke
tobacco.
Wu (1988) reported higher levels of carboxyhemoglobin in
marihuana smokers than in tobacco smokers.
Histological alterations at cerebral levels have been
described by some authors (Jaffe, 1986).
Alterations on the immune system are possible, although
evidence is not conclusive. The immune response may be
suppressed due to a reduction of T- lymphocytes
secondary to alteration in DNA production.
chronic diarrhoea, abdominal pain and loss of weight are
frequent in marihuana abusers.
Note: It is important to stress that some of the
symptoms described as "chronic effects" may be
experienced by teenagers undergoing an 'adolescent
crisis' and should not, therefore, be readily attributed
to use of marihuana.
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
No data available.
9.3 Course, prognosis, cause of death
The normal course of acute poisonings is usually uneventful,
once the subjective effects have ceased. Motor coordination
and reflexes may take a few hours to come back to normal.
The prognosis may be uncertain in case of psychotic reactions
and only follow-up of the patient will allow diagnosis of a
permanent psychosis. Adequate treatment and avoidance of
futher exposure usually gives a favourable prognosis which is
more dependent on the psychiatric features of the patient than
on the marihuana use.
Tachycardia will rarely exceed 140 or 150/min, but patients
with previous cardiovascular impairment may be at risk of
acute cardiac failure.
The evolution and prognosis of chronic abuse depends upon
adequate treatment and consideration of other factors
associated with the use of drugs. Most effects are reversible
once abuse has ceased.
Chronic use of cannabis may cause bronchopulmonary cancer
which may appear earlier than in tobacco smokers (Valbuena
Briones, 1987).
The clinical course and prognosis will be worse if other drugs
and alcohol have also been taken.
The usual cause of death is by accident or clinical
complications, as it is extremely rare to have lethal over-
dose (the lethal dose is very high).
Cases of acute marihuana poisoning and overdose by other more
dangerous drugs should be managed as a poisoning by the
associated drug.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Tachycardia, increased systolic pressure (in decubitus);
orthostatic hypotension, vasodilatation.
9.4.2 Respiratory
Acute irritative effects, cough, and asthmatic crisis in
predisposed patients.
Chronic use may produce chronic bronchitis, sinusitis,
rhinopharyngitis, bronchopulmonary and laryngeal cancer.
Acute on chronic use may also lead to acute bronchitis
and pneumonia.
9.4.3 Neurological
9.4.3.1 CNS
Acute intoxication: motor incoordination,
alterations of emotional states, impairment of
self-perception and perception of the
enviromment (hallucinations, illusions),
impairment of cognitive functions, memory
deficits and decreased attention. Chronic use
may produce amotivational syndrome and chronic
psychosis. Acute use in chronic abuser can
produce adverse reactions if the patient was
already a psychosis or amotivational syndrome.
9.4.3.2 Peripheral nervous system
No data available.
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
No data available.
9.4.4 Gastrointestinal
Acute abuse induces dry mouth, thirst and a desire to
eat carbohydrates and sweet soft drinks. Chronic abuse
may produce diarrhoea, abdominal pain and loss of
weight.
9.4.5 Hepatic
Chronic use may induce the hepatic metabolism of ethanol,
barbiturates and antipyrine.
9.4.6 Urinary
9.4.6.1 Renal
No data available.
9.4.6.2 Others
No data available.
9.4.7 Endocrine and reproductive systems
Chronic effects on man are: infertility due to
oligospermia, impotence, and chromosomal alterations in
germinal cells. Theoretically, aggravated oligospermia
may occur as an acute on chronic effect.
In the woman: amenorrhoea, anovulatory cycles,
chromosomal alterations in germinal cells and
diminution of prolactin serum levels.
Endocrine effects have been described after chronic use.
Impairment of gonadotrophin secretion (FSH and LH),
reduction in testosterone levels and also a direct
effect on cytochrome P 450 of the Leydig cells with
inhibition of testosterone synthesis. Both mechanisms
will lead to olisgospermia and possibility of
subfertility (Nahas, 1975).
In the woman, alteration of menstrual cycles (amenorrhea
and anovulatory cycles), and also a reduction in plasma
levels of prolactin have been reported.
9.4.8 Dermatological
Skin dryness occurs during acute poisoning.
9.4.9 Eye, ears, nose, throat: local effects
In acute poisoning: conjunctival irritation, itch and
burning sensation of throat, dryness of mouth.
In chronic poisoning: swelling and inflammation of the
uvula.
9.4.10 Haematological
Anaemia by nutritional deficiency has been reported in
chronic abusers.
9.4.11 Immunological
Immune deficiency due to diminished numbers of T-
lymphocytes has been reported in chronic abusers.
9.4.12 Metabolic
9.4.12.1 Acid base disturbances
No data available.
9.4.12.2 Fluid and electrolyte disturbances
No data available.
9.4.12.3 Others
Hyperthermia may occur if the patient is in a
hot enviromment (Jaffe, 1985).
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
Abstinence syndrome:
After chronic abuse at high doses, sudden
discontinuation produces:
irritability, restlessness, nervousness, loss of weight,
insomnia, tremors, rise of body temperature and
shivering.
Symptoms may start a few hours after withdrawal, and
last a few days (Schwartz, 1987; Jaffe, 1986).
9.4.15 Special risks
In drug abusing patients it is necessary to investigate
HIV serological positivity, because there may be a
possible association with intravenous use of other
drugs as well as with other high risk situations
related to drug abuse.
Pregnancy: impaired fetal development and decreased in
growth have been described (Zuckerman, 1989).
9.5 Others
Cannabis may be contaminated with:
Paraquat: abuse of contaminated marihuana without secondary
ill-effects has been reported (Schwartz, 1987).
Aspergillus fumigatus: a fatal case of pulmonary aspergillosis
was reported in a heavy marihuana smoker; the fungus found in
the marihuana and obtained from pulmonary biopsy was the same
(Hamadeh, 1988).
9.6 Summary
10. MANAGEMENT
10.1 General principles
Management of psychiatric disturbances is based on sedation
and antipsychotic treatment.
There is no risk of death in cases of pure acute Cannabis
intoxication. However, the cardiovascular and respiratiory
functions should be monitored carefully in order to detect
possible severe tachycardia or bronchial asthma.
If abuse of other drugs or alcohol is suspected, vital
functions should be monitored and drug treatment should be
avoided or used with care due to the risk of potential
interactions.
In cases of chronic abuse, patient management should have
two main objectives:
i) evaluation and treatment of organic consequences, and ii)
psychological and social assistance by an interdisciplinary
staff.
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
Blood: if general evaluation of the patient is
required, blood should be collected as usual for
routine exams. Urine for detection of cannabinoids:
first-voided urine contains the highest concentration
of cannabinoids. It can be refrigerated, frozen or
even stored at room temperature for up to three days
until it can be sent to a reliable and carefully
supervised medical laboratory for testing (Schwartz,
1987).
Saliva samples can be tested for cannabinoids in some
countries.
Cigarettes and suspected marihuana should be kept for
macroscopical, microscopical and chemical
identification.
10.2.2 Biomedical analysis
No biomedical analysis is considered relevant for
diagnosis, prognosis and treatment of this acute
intoxication. If the patient is a chronic abuser of
drugs, the following could be necessary for prognosis
and therapy:
Chest X-ray
Otorhinolaryngological evaluation and laryngoscopy
according to the clinical picture
Serological studies for HIV
Echographic diagnosis and monitoring of pregnancy
10.2.3 Toxicological/toxinological analysis
(In preparation)
10.2.4 Other investigations
As required by the patient's clinical condition.
10.3 Life supportive procedures and symptomatic treatment
Life-support procedures are not usually necessary, but some
clinical states may require them:
If cardiovascular effects (tachycardia) are present, cardiac
monitoring is necessary and propranolol can be administered
in the usual dosage (80-180 mg orally or IV, according to
the clinical situation).
In case of bronchoconstriction, inhalation of
bronchodilators may be necessary. Dosage will depend upon
the drug and clinical severity of the case.
The psychological and psychiatric consequences may require:
(i) hospitalization in a quiet and comfortable room
(ii) if sedative measures are necessary, the first step will
be the "talking down" technique in order to give confidence
and calm down the patient. This may be followed, if needed,
with diazepam 5 - 10 mg IM.
(iii) If psychotic reactions occur, haloperidol 5 mg IM may
be administered.
It may be useful to consult a psychiatrist, especially in
difficult cases.
Physical measures of restraint are not recommended because
psychological support giving security and confidence to the
patient in a monotonous and smooth voice is frequently
enough to overcome the panic crisis.
10.4 Decontamination
No procedures for decontamination are available.
10.5 Elimination
There is no procedure to accelerate elimination.
10.6 Antidote/antitoxin treatment
10.6.1 Adults
No data available.
10.6.2 Children
No data available.
10.7 Management discussion
The management of acute marihuana intoxication is
symptomatic and depends upon the experience of the treating
physician. Differences in treatment will be seldom
important. Perhaps the only symptoms that may influence
prognosis are those related to some psychotic reactions, in
which case a wrong evaluation and treatment can lead into a
chronic psychiatric illness.
The main controversy is over the treatment of chronic users:
some consider that hospitalization is needed in every case;
others that users only of marihuana do not need treatment.
Between these extremes, various possibilities include:
individual psychotherapy, out-patient management, group
therapy, and uni-, multi- or interdisciplinary treatment.
Further informationis required on the possible teratogenic,
mutagenic and oncogenic effects of marihuana. Bearing in
mind the extended use and abuse of marihuana, clinical and
biochemical research is important but it should be
scientifically sound and well documented.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Note: published case reports do not describe the usual cases
of marihuana smoking, except when abnormalities arise due to
complications or associated abuse of other drugs.
A 21 year old man from Angola who used great amounts of
hashish from the age of 11. He used other drugs only
occasionally. He was hospitalized in the psychiatric unit of
a prison hospital with a severe depressive syndrome and
suicide attempt. When he gave up hashish abuse, all the
clinical evidences of depression disappeared (Valbuena
Briones, 1986).
Fatal pulmonary aspergillosis occurred in a patient who had
undergone bone marrow transplantation who smoked
contaminated marihuana. He was 34 years old; he developed
pulmonary aspergillosis on the 75th day after bone marrow
transplantation for chronic myelocytic leukemia. He had
smoked marihuana heavily for several weeks prior to hospital
admission. The cultures of marihuana revealed aspergillosis
fumigatus with identical morphology and growth to a sample
grown from an open lung biopsy specimen (Hamadeh, 1988).
11.2 Internally extracted data on cases
A 21 old woman who was a heavy marihuana abuser (five or
more cigarettes per day for 5 years) asked for help to give
up the abuse. She had also used amphetamines and smoked
tobacco (less than 10 cigarettes a day). The most relevant
clinical findings were: loss of weight, amotivational
syndrome, irritability, frequent problems with the police
and paranoid ideation. All the biological parameters were
normal and she was HIV negative. Three months later she
began treatment and presented a severe disphonia resistant
to usual therapy. The evaluation by otorhinolaryngologist
showed a chronic inflamatory process of vocal cords with
squamous metaplasia. Unfortunately, as the patient gave up
the treatment, we were unable to follow-up the case.
The management of this patient was based upon symptomatic
treatment and psychological assistance. No antipsychotic
drugs were needed as she had an acceptable evolution when
gave up the drug with psychological support. Ketazolam 12 mg
twice a day were needed to reduce anxiety at the begining of
treatment (one month).
11.3 Internal cases
To be added by the PCC.
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes/antitoxins
No data available.
12.2 Specific preventive measures
Not relevant.
12.3 Other
No data available.
13. REFERENCES
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14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Authors: Dr Cecilia Dell'Acqua
Dr Raquel Peyraube
CIAT 7° piso
Hospital de Clinicas
Av. Italia s/n
Montevideo
Uruguay
Telephone: 598-2-470300
Telefax: 598-2-470300
Date: October 1989
Peer Review: Adelaide, Australia, April 1991