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Chapter: Modern Medical Toxicology: Neurotoxic Poisons: Deliriants

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Cannabis - Deliriant Neurotoxic Poisons

Cannabis - Deliriant Neurotoxic Poisons
Cannabis is among the earliest mind-altering drugs known to man and has been around for at least 4000 years.

Cannabis

Cannabis is among the earliest mind-altering drugs known to man and has been around for at least 4000 years. Today, it is the world’s most commonly used illicit drug, with more than 300 million regular users. In terms of popularity ratings, it stands 4th among psychoactive drugs (after caffeine, nicotine, and alcohol).

Source

Cannabis preparations (vide infra) are derived from Indian hemp plant (Cannabis sativa) (Fig 15.5), which is a hardy, aromatic annual herb that grows wild under most climatic conditions. The plant grows to a height of 5 to 15 feet, and is characterised by an odd number of leaflets on each leaf (varying from 5 to 9), all having serrated or saw-tooth edges. The male and female flowers are borne on separate plants. After pollination, the male plants die back.


Toxic Principles

The main active principle is d9 (delta-9) tetrahydrocannabinol (THC) which is a cannabinoid found in both the male and female plants. The concentration of THC is highest in the bracts, flowers, and leaves, while it is practically non-existent in the stem, root, and seeds. The THC content of the plant varies greatly, and is probably controlled more by the type of seed than by the soil or climatic conditions. Apart from THC, Cannabissativa contains a number of other cannabinoids, includingcannabidiol, cannabinol, cannabidolic acid, cannabicyclol, and cannabigerol. So far, more than 60 of these cannabinoids have been identified.

Uses

·              The durable fibres of the woody trunk of cannabis, referred to collectively as Indian hemp, has been used for centuries to produce rope and twine, as well as fine or rough cloth. The cannabis plant is possibly the most efficient source of paper pulp, producing up to 5 times as much cellulose per acre per year, as trees.

·      Cannabis seeds are used as food by man, poultry, and other birds, as well as furnishing hemp-seed oil for paint and soap.

·      Therapeutic uses:

1.           THC in the form of a synthetic oral cannabinoid (“dron-abinol”) has been shown to be effective in controlling the nausea and diarrhoea associated with AIDS, as well as the nausea and vomiting caused by chemotherapy for cancer or AIDS. It also increases appetite and produces weight gain in both AIDS and cancer patients.

2.           Since smoked cannabis lowers intraocular pressure, it has been suggested that this effect though short-lived (3 to 4 hours), can be utilised for treating glaucoma.

3.           Some studies suggest a possible role for cannabis in the treatment of multiple sclerosis, epilepsy, and dystonic states, though convincing scientific evidence is lacking.

4.           THC possesses analgesic properties and has been tried in the treatment of pain due to cancer.

Mode of Poisoning

Toxic effects arise mainly from the abuse of various cannabis preparations for their mind-altering properties.

·      Marijuana: The term “marijuana” refers to any part of theplant or its extract that is used to induce psychotomimetic or therapeutic effects. Synonyms include Mary Jane, MJ, maconha, pot, weed, grass, puff and dagga.

·      Ganja: Although some texts refer to ganja as beingsynonymous with marijuana, while others consider it to be a resinous mass composed of leaves and bracts, in India (where the term actually originated), it is used to refer to crushed leaves and inflorescences of female plants (Fig15.6). It is usually smoked in a pipe (“chillum”) or in theform of cigarettes (“reefer” or “joint”). Ganja is said to contain 1 to 2% THC.


·              Bhang: Bhang consists of dried mature leaves and flowerstems that are ground with water and mixed with milk (Fig15.7) or fruit juice. It is consumed by Hindus in India duringfestivals such as Holi and Shiv Ratri.


·      Hashish (Charas): This preparation is made out of driedresin collected from flower tops, and contains varying concentrations of THC up to 10% (Fig 15.8). It is popular in the Middle East and North Africa. Hashish oil or “liquid hashish” is an alcohol or petrol extract which occurs as a dark green viscous liquid with the consistency of tar. It is the most potent of all cannabis preparations and contains 20 to 30% (or more) THC.


·      Sinsemilla: It is the most popular form of cannabis in theUSA, and refers to seedless (unpollinated female) plant which averages 5% of THC.

·      Marijuana “Blunts”: This is nothing but cheap cigarssliced open, packed with cannabis, and resealed. The harsh stench of the cigar masks the characteristic sweet smell of cannabis. Blunts are very popular among the youth in some parts of the USA.

Mode of Action

·     Recently a receptor site has been identified in rat brain that binds reversibly and selectively with cannabinoids. Receptor binding was also found in the peripheral B lymphocyte-rich areas such as the marginal zone of the spleen, nodular corona of Peyer’s patches, and cortex of lymph nodes.

·              Another recent development has been the isolation of an endogenous cannabinoid-like ligand within the brain, named “anandamide”.*

·              A cannabinoid antagonist was also discovered that antago- nises cannabinoid-induced inhibition of adenylcyclase and smooth muscle contraction.

·              All this suggests the presence of a cannabinoid neuro- chemical pathway.

o     It appears that cannabinoids exert many of their actions by influencing several neurotransmitter systems and their modulators. These include GABA, dopamine, acetylcholine, histamine, serotonin, noradrenaline, and prostaglandins.

o     Cannabinoid receptor location and density in animal models has correlated well with clinical effects in humans. The highest density of receptors occurs in the basal ganglia and molecular layer of cerebellum, which correlates with its interference in motor coordination. Intermediate levels of binding were found in the hippocampus, dentate gyrus, and layers I and IV of cortex, consistent with effects on short-term memory and cognition. Low receptor density is noted in the brainstem areas controlling cardiovascular and respiratory functions, which correlates with the cannabinoids’ known lack of lethality.

o     After binding to receptors, cannabinoids also produce effects through second-messenger systems including inhibition of adenylcyclase and calcium channels, and also probably by enhancing potassium channels activity. 

Toxicokinetics

Smoking cannabis generally produces immediate effects, while ingestion results in slow and unpredictable effects due to the instability induced by the acidic environment of the stomach. The most important factor in determining the bioavailability of THC happens to be the smoking dynamics (manner in which the cannabis is smoked). It takes about 15 seconds for the lungs to absorb the THC and transport it to the brain. Peak effects are seen in 10 to 30 minutes and may last for 1 to 4 hours. The mean terminal half-life of THC in plasma of frequent cannabis smokers is 4.3 days (range: 2.6–12.6 days).

Drug Interactions

·              Concomitant use of cannabis and ethanol produces additive effects on psychomotor performance.

·              Concomitant use of cannabis and cocaine can greatly increase the heart rate.

·              Concomitant use of cannabis and phencyclidine (“super- grass” or “superweed”) produces an intensely vivid hallu- cinogenic experience.

Clinical (Toxic) Features

Acute Poisoning:

·              Euphoria with increased garrulity and hilarity, espe-cially when smoked in a social group setting.

·              Temporal and spatial disorientation with intensification of sensation (colours become brighter, sounds become more distinct, music is heard with heightened fidelity) and increased clarity of perception.

·              At high doses, the user experiences hallucinations, sedation, and sometimes dysphoria characterised by unpleasant sensations, fear, and panic.

·              Sometimes an acute toxic psychosis is precipitated with suicidal ideation, anxiety, and paranoia. Occasionally, schizophrenic symptoms occur. Flashback phenomena have been reported.

·              Tachycardia, palpitations, hypotension (high doses).

·              Stimulation of appetite.

·              Bloodshot eyes due to conjunctival congestion.

·              Pupils are usually not affected.

Chronic Poisoning:

Chronic users of cannabis demonstrate tolerance to most of the physical effects, while this is not very apparent in the case of mood and behavioural changes.

·              Amotivational Syndrome: Chronic indulgence is said to induce an amotivational syndrome characterised by apathy, poor concentration, social withdrawal, and lack of motivation to study or work. However, the actual existence of such a syndrome is being questioned by had not attempted to adequately distinguish between the effects of cannabis and pre-existing psychological status. In other words, it is difficult to determine which came first, the drug or the amotivation.

·              Heavy cannabis users demonstrate an increased tendency to develop manic, schizophreniform, and confusional psychoses over a period of time. The development of acute psychosis after chronic use is controversial because of questions about the contribu- tion of premorbid personalities and multiple-drug use.

·              Medical Complications:

––  Chronic lung disease and carcinogenesis. Experiments have revealed that cannabis smoking can cause a five-fold increase in blood CoHb level and three-fold increase in the amount of tar inhaled when compared with tobacco.

––  Cancers of mouth and larynx.

––  Aspergillosis: Studies have shown that cannabis is often contaminated with

––  Aspergillus spores which can cause aspergillosis in immunocompromised individuals.

––  Digital clubbing has been reported in chronic hashish users.

Usual Fatal Dose

There are no authentically documented cases of lethality from cannabis intoxication alone. The few cases of fatality that have been reported have not adequately ruled out the possibility of multiple-drug intoxication. In spite of such lack of documented fatalities, some authors have suggested that the fatal dose for IV cannabis is about 1 to 2 grams, while it is 700 grams for ingestion (of bhang).

Diagnosis

Clinical:

·              Symptomatology

·              Characteristic ‘burnt rope’ odour in the breath of a recent smoker.

Identification of suspected specimen: Suspend leaf orstem fragments in several drops of chloral hydrate (10%) on a microscope slide and examine under low power for characteristic “cystolith hairs”. These hairs look like bear claws or elephant tusks. At the base of these claws is a wart-like cluster composed of calcium carbonate deposit. Add a drop of 20% HCl and note the gentle effervescent release of carbon dioxide gas in tiny bubbles.

Urine levels of cannabinoids:

·      THC is hydrophobic and accumulates in adipose tissue. Screening tests may be positive for up to 70 or more days, depending on the cut-off levels used and the individual’s lipid stores of THC. Some investigators state that after using three or more joints per day, an individual who then stops smoking cannabis completely and adopts an excessive fitness programme mobilising body fat, will test positive for urinary THC (at 50 to 100 ng/ml) for more than 2 months. An individual who smokes an occasional joint will test positive (at 500 to 1000 ng/ml) f3 to 4 days.

·              False positive results may occur with therapeutic use of ibuprofen, fenoprofen, and naproxen. False negatives may result from dilution, diuretic use, common salt, or other contaminants. Concomitant testing of urine specific gravity, pH, temperature, and creatinine could help in eliminating these confounders.

Treatment

Acute Poisoning:

·              Decontamination measures in cases of ingestion.

·              Acute psychotic reactions respond to benzodiazepines.

·              Supportive measures.

Chronic Poisoning:

·              Psychosocial therapy consisting of attempts to promote realistic and rewarding alternatives to the drug and associated life styles, along with a commitment to abstinence from self-administered or unprescribed psychotropic drugs. A combination of interventions is recommended, including urine testing, participation in multi-step programmes, education about drug effects, drug counselling, psychotherapy, and family therapy.

·              Drug-focussed group therapy comprising strategies such as social pressure to reinforce abstinence, teaching socialisation and problem solving skills, reducing stress and the sense of isolation common with drug abuse, relapse prevention exercises, and varying degrees of confrontation.

·              Short-term use of anxiolytic agents such as benzodiaz-epines may be necessary in some cases when anxiety symptoms are severe.

·              Short-term use of antipsychotic medication may be required if there are persistent delusional ideas or frightening flash backs.

Medicosocial and Forensic Issue

·              Cannabis has been around for thousands of years, initially touted for its “medical” uses, and later condemned for its abuse potential. The first reference to the medical use of cannabis is in a pharmacy book written about 2737 BC by the Chinese Emperor Shen Nung, who recommended it for “absent-mindedness, female weakness, gout, rheu- matism, malaria, beri beri, and constipation”.

·              The mind-altering properties of cannabis probably did not receive wide attention until about 1000 BC when it became an integral part of Hindu culture in India. After AD 500, cannabis began creeping westward, and references to it began appearing in Persian and Arabic literature.

·              Cannabis was brought to Europe by Napoleon’s soldiers returning from Egypt in the early part of 19th century. It made its entry into the USA at about 1920 when Mexican labourers smuggled the weed across the border into Texas. Its popularity spread quickly, and by 1937 most of the American states had enacted laws prohibiting the use or possession of marijuana. Today, inspite of all efforts at minimising the abuse of cannabis, the drug is the most commonly used illicit substance in the USA.

·              The use of cannabis among youth reached its peak in the 1960s when the drug became associated with social protest. The hippie generation (“flower people”) was particularly fond of cannabis, to whom it was a “gateway drug” opening the doors to more potent “hard drugs” such as opiates and hallucinogens.

·              Recent reports of medical uses of cannabis have led to the resurgence of “pot culture” beginning with the 1990s. Consumption of cannabis in various forms has always been popular in India. Sanyasis and temple poojaris use it to induce a trance-like state for the purpose of religious meditation. There are several festivals such as Holi and Shiva Ratri when widespread consumption occurs even among the general populace.

·              While long-term cannabis use can cause serious health problems (vide supra), acute intoxication sometimes leads to medicolegal complications. The danger lies in the capacity of cannabis to interfere with motor skills and judgement. Operating a motor vehicle or other machinery under the influence of the drug could lead to potential loss of life or limb.

·              Occasional acute psychotic reactions precipitated by long- term heavy cannabis use can cause the user to “run amok” in homicidal frenzy. This became well known during the Vietnam war when several American soldiers began suffering from acute toxic psychosis arising out of heavy abuse. Cannabis is also known to induce suicidal ideation brought on by anxiety and paranoia.

·              While cannabis does not appear to have teratogenic effects on the foetus, some studies have indicated that infants whose mothers had used the drug during pregnancy exhib- ited impaired foetal growth.


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