Cannabis sativa L.

   1.1 Scientific name
   1.2 Family
   1.3 Common name(s)
   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
   3.1 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
   4.1 Uses
   4.2 High risk circumstances
   4.3 High risk geographical areas
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
   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
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data Adults 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
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material Simple Qualitative Test(s) Advanced Qualitative Confirmation Test(s) Simple Quantitative Method(s) Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens Simple Qualitative Test(s) Advanced Qualitative Confirmation Test(s) Simple Quantitative Method(s) Advanced Quantitative Method(s) Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis Blood, plasma or serum Urine 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
   9.1 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 CNS Peripheral nervous system Autonomic nervous system Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary Renal 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 Acid base disturbances Fluid and electrolyte disturbances Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
   9.6 Summary
   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
   11.1 Case reports from literature
   11.2 Internally extracted data on cases
   11.3 Internal cases
   12.1 Availability of antidotes/antitoxins
   12.2 Specific preventive measures
   12.3 Other
   13.1 Clinical and toxicological
   13.2 Botanical
    1. NAME
     1.1 Scientific name
       Cannabis Sativa L. (var Indica)
     1.2 Family
     1.3 Common name(s)
       Cañamo de la India (Latin America)
       Chanvre (France)
       Hanfkraut (Germany)
       Herbe (France)
       Indian hemp (USA, UK)
       Maconha   (Latin America)
       Marihuana (Latin America)
       Marijane  (USA, UK)
       Marijuana (Latin America)
    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 
       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 
     2.6 Main toxins
       Marihuana contains approximately 60 active compounds, or 
       cannabinoids; the most important is delta-9-
       Other cannabinoids are: cannabinol, cannabidiol, cannabinolic 
       acid, cannabigerol, cannabicyclol, different isomers  of 

     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 
             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 
             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,
       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 
     3.4 Other chemical contents of the plant
       No data available. 
     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.
     5.1 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 
       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 
       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.
     6.1 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, 

       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 
     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
                     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).
                     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 
       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 
     8.1 Material sampling plan
       8.1.1 Sampling and specimen collection
    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.
    Biomedical analyses
    Arterial blood gas analysis
    Haematological analyses
    Other (unspecified) analyses
       8.1.2 Storage of laboratory samples and specimens
    Toxicological analyses
    Biomedical analyses
    Arterial blood gas analysis
    Haematological analyses
    Other (unspecified) analyses
       8.1.3 Transport of laboratory samples and specimens
    Toxicological analyses
    Biomedical analyses
    Arterial blood gas analysis
    Haematological analyses
    Other (unspecified) analyses
     8.2 Toxicological Analyses and Their Interpretation

       8.2.1 Tests on toxic ingredient(s) of material
    Simple Qualitative Test(s)
    Advanced Qualitative Confirmation Test(s)
    Simple Quantitative Method(s)
    Advanced Quantitative Method(s)
       8.2.2 Tests for biological specimens
    Simple Qualitative Test(s)
    Advanced Qualitative Confirmation Test(s)
    Simple Quantitative Method(s)
    Advanced Quantitative Method(s)
    Other Dedicated Method(s)
       8.2.3 Interpretation of toxicological analyses
     8.3 Biomedical investigations and their interpretation
       8.3.1 Biochemical analysis
    Blood, plasma or serum
    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 
     8.5 Overall Interpretation of all toxicological analyses and 
       toxicological investigations
     8.6 References
     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 
             . the inhalation technique (prolonged and deep 
             inhalation; use of bong, pipes, others),
             . individual and environmental conditions
             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.
             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 
             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 
             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 
             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 
             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 
             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, 
             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 
             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 
             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 
             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 
             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
                     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.
    Peripheral nervous system
                     No data available.
    Autonomic nervous system
                     No data available.
    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 
       9.4.5 Hepatic
             Chronic use may induce the hepatic metabolism of ethanol,
              barbiturates and antipyrine.
       9.4.6 Urinary
                     No data available.
                     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 
       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
     Acid base disturbances
                       No data available.
     Fluid and electrolyte disturbances
                       No data available.
                       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 
              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
      10.1 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 
         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 
      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, 
                Saliva samples can be tested for cannabinoids in some 
                Cigarettes and suspected marihuana should be kept for 
                macroscopical, microscopical and chemical 
         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.
      11.1 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.
      12.1 Availability of antidotes/antitoxins
         No data available.
      12.2 Specific preventive measures
         Not relevant.
      12.3 Other
         No data available.
      13.1 Clinical and toxicological
         Belmore S, Miller LL (1980).  Levels of processing and acute 
         effects of marihuana on memory. Pharm Biochem Behaviour, 13: 
         Brebneisen R, Elsahly MA (1988).  Chromatographic and 
         spectroscopic profiles of cannabis of different origins: 
         Part II.  Forensic Sci 33 (6): 1385-1404.
         Cappel HB, Pline PL (1973).  Volitional control of marijuana 
         intoxication: A study of the ability to "come down" on 
         command. J Abnorm Psycho 82: 428-434.
         Cohen S (1982).  Cannabis: effects on adolescent motivation. 
         From Marijuana and Youth: Clinical Observation on Motivation 
         and Learning. Rockville, Maryland. National Institute on 
         Drug Abuse. 2-11.
         Cone EJ, Johnson RE, Paul BD et al (1988).  Marijuana-laced 
         brownies: behavioural effects, physiologic effects, and 
         urinalysis in humans following ingestion. J Anal Toxicol 12 
         (4): 169-175.
         Dell'Acqua C, Etchechury G, Montenegro A, et al. (1988).  
         Abordaje del uso indebido de drogas con un equipo 
         interdisciplinario: De la teoría a la práctica. Monografía 
         presentada en Centro de Estudios Avanzados de la Universidad 
         de Bs As Argentina.
         Foltin RW et al (1987).  Marijuana and cocaine Interactions 
         in humans: Cardiovascular consequences.  Pharmacol Biochem 
         Behaviour 28: 459-464.
         Gillone A, Miguez L, Castro de la Mata R (1986).   Técnicas 
         terapéuticas en Farmacodependencia. Lima, Perú. Ministerio 
         de Salud.
         Hamadeh R, Ardehali A, Locksley RM, York MK (1988).  Fatal 
         aspergillosis associated with smoking contaminated marijuana 
         in a marrow transplant recipient Chest 94 (2): 432-433.
         Hardin J, & Arena J (1974).  Human Poisoning from native and 
         cultivated plants  2nd. Ed. Duke University Press, Durham, 

         Heyrdrick A et al (1970).  J Pharm Belg 24,37.
         Hollister LE, (1988).  Marijuana and Immunity. J 
         Psychoactive Drugs 20 (1): 3-8.
         Hollister LE (1988). Cannabis. Acta Psychiatric Scand Suppl 
         345: 108-118.
         Jaffe JH (1986).  Drogadicción y Abuso de Drogas in: Goodman 
         LS and Gilman A: "Bases farmacológicas de la terapéutica".  
         7 ed. en español. Ed. Panamericana.
         Johansson E, Agurell S, Hollister LE, Haldin MM (1988).  
         Prolonged apparent half-life of delta-1-
         tetrahydrocannabinoid in plasma of chronic marijuana users. 
         40 (5): 374-375).
         Reynolds EF (1982).  Martindale, The Extra Pharmacopoeia. 
         The Pharmaceutical Press, London. 28th Edit.
         Mikuriya TH, Aldrich MR (1988).  Cannabis 1988. All drugs, 
         new dangers. The potency question. J Psychoactive Drugs. 
         20(1): 47-55. 
         Nahas G (1979).  J Am Med Assoc 242: 2775.
         Nahas G, (1975).  Marihuana: Toxicity and Tolerance. In 
         Richter, EW: Medical Aspects of Drug Abuse. Harper and Row, 
         Norton R, Colliver J (1988).  Prevalence and patterns of 
         combined alcohol and marijuana use.  J Stud Alcohol, 49 (4): 
         Schwartz RH (1987).  Marijuana: an overview. Pediatric 
         Clinics of North America Vol. 34.
         Smith JW, Schmeling G, Knowles PL (1988).  A marijuana 
         smoking cessation clinical trial utilising THC-free 
         marijuana, aversion therapy, and self management 
         counselling.  J Subst Abuse Treat 5 (2): 89-98.
         The Medical Letter on Drug and Therapeutics (1985).  
         Synthetic marijuana for nausea and vomiting due to cancer 
         chemotherapy. 27: 97-98.
         Valbuena Briones A (1987).  Las Toxicomanias. Ed. Salvat, 
         Varma JK, Malhotra AK, Dang R, et al. (1988).  Cannabis and 
         cognitive functions: a prospective study. Drug Alcohol 
         Depend 21(2): 147-152.
         Wu Tzu-Chin et al (1988).  Pulmonary hazards of smoking 
         marijuana as compared with tobaco.  New Engl J Med; 318: 347-

         Zuckerman B, Frank DA, Hingson R, et al (1989).   Effects of 
         maternal marijuana and cocaine use on fetal growth.  New 
         Engl J Med; 320 (12): 762-768
      13.2 Botanical
         Biagioni JR (1979). Caracteres histomorfológicos de interés 
         en la caracterización de Cannabis Sativa L (Cannabinaceae) 
         Var. Indica. Ministerio de Agricultura y Pesca;  Dirección 
         de Sanidad Vegetal; Informe Técnico.  Montevideo, Uruguay.
         Font Quer P: Plantas Medicinales. Edit. Labor. Barcelona, 
    Authors:  Dr Cecilia Dell'Acqua
              Dr Raquel Peyraube
              CIAT 7° piso
              Hospital de Clinicas
              Av. Italia s/n
    Telephone: 598-2-470300
    Telefax:   598-2-470300
    Date:      October 1989
    Peer Review: Adelaide, Australia, April 1991

    See Also:
       Toxicological Abbreviations