Plant Toxins

STKM4012 Food Toxicologi

Outline Plant  Cannabis sativa and cannabis indica-Marijuana  Erythroxylon coca-cocaine  Papaver

Somniferum-Heroin, morphine  Nicotiana tabacum-Nicotine  Various plant-Caffeine  Other poisonous plant

From Plant to Drug Plant

Crude Extract

Pure Compound

Molecular Structure OH OH

=

HO

O

OH O

OH

OH

O

OH OH

Biological Activity

Al-Mu’minun- Q23: 51

O (you) Messengers! Eat of the Taiyibon [all kinds of Halal (legal) foods which Allah has made legal (meat of slaughtered eatable animals, milk products, fats, vegetables, fruits, etc.)], and do righteous deeds. Verily! I am WellAcquainted with what you do

MARIJUANA  Marijuana-

is a cannabinoid drug  cannabinoids-most potent, delta-9tetrahydro-cannabinol, or THC)

delta-9-tetrahydro-cannabinol

MARIJUANA

Cannabis sativa and cannabis indica

HISTRORY OF MARIJUANA 

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2737 B.C. Early writings in China note prescribing marijuana to treat every thing from gout to absentmindedness. 1600s American Colonies mandated the growth of Cannabis Sativa for the hemp which was needed for rope and fabric among other things. 1765 George Washington thought to use cannabis for hemp product, medicinal, as well as recreational use. As late as 1850 Cannabis Sativa grown for hemp products as well as for medicinal purposes. 1915-1927 Cannabis begins to be prohibited for non-medical use in the U.S.

 2001

United States Supreme Court ruled 8-0 against medicinal marijuana under federal law. Despite the fact that 9 States allow medicinal use of marijuana, United States federal law prohibits medicinal use of marijuana.  In Malaysia-It calls cannabis or ganja and all prohibited drugs are controlled under Malaysian Laws “Akta Dadah Berbahaya 1952”

Malaysian Laws related with drugs AKTA DADAH BERBAHAYA 1952 AKTA PENAGIH DADAH (RAWATAN DAN PEMULIHAN) 1983 AKTA DADAH BERBAHAYA (LANGKAH-LANGKAH PENCEGAHAN KHAS) 1985 AKTA DADAH BERBAHAYA (PERLUCUTHAKAN HARTA) 1988 AKTA RACUN 1952

AKTA DADAH BERBAHAYA 1952 SESEORANG ITU ADALAH DIANGGAP MENGEDAR DADAH SEKIRANYA DIDAPATI DIDALAM MILIKNYA :4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

15 GRAM ATAU LEBIH HEROIN 15 GRAM ATAU LEBIH MORFIN 15 GRAM ATAU LEBIH CAMPURAN HEROIN ATAU MORFIN 1000 GRAM ATAU LEBIH CANDU MASAK 1000 GRAM ATAU LEBIH CAMPURAN CANDU MENTAH ATAU MASAK 200 GRAM ATAU LEBIH GANJA 200 GRAM ATAU LEBIH RESIN GANJA 200 GRAM ATAU LEBIH CAMPURAN GANJA ATAU RESIN GANJA 40 GRAM ATAU LEBIH KOKAIN 2000 GRAM ATAU LEBIH DAUN KOKA 50 GRAM ATAU LEBIH AMPHETAMINE TYPE STIMULANTS (ATS)

HUKUMANNYA IALAH GANTUNG SAMPAI MATI MANDATORI DI BAWAH SEK. 39(B) ADB 1952

AKTA DADAH BERBAHAYA (PERLUCUTAN HARTA) 1988 AKTA INI BERTUJUAN MEMBERI KUASA KEPADA KERAJAAN UNTUK:I

MENGESAN HARTA.

II

MEMBEKU HARTA.

III

MERAMPAS ASET PENGEDAR DADAH

AKTA INI BERKUASA SEKIRANYA TANGKAPAN DIBUAT DIBAWAH : I

SEKSYEN 39B ADB 1952.

II

SEKSYEN 6 (B) ADB 1952.

II

SEKSYEN 3 (1) ADB (LLPK) 1985.

Marijuana  Marijuana

is the dried mix of flowers and leaves form the female Cannabis Sativa plant.  Hashish is the resin, or sap*, harvested from the plant.  Hashish oil is the essential oil of the female Cannabis Sativa plant. *a watery solution of sugars, salts, and minerals that circulates through the vascular system of a plant

Marijuana: Modes of absorption The most common method of absorption is smoking. Either in a loosely rolled cigarette called a joint, or through a pipe or water pipe.  However, it can also be cooked in foods or brewed as a tea.  THC enters the body through the Lungs. The smoke is inhaled and held in the lungs  THC crosses the blood barrier through the capillaries in the lungs 

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Effects are felt as the THC begins to bind to the large numbers of natural cannabinoid receptors in the brain. Cannabinoid receptors are found on the presynaptic nerve terminals and inhibit calcium (Ca++) ion flux*. As a result glutamate ** and neurotransmitter release is inhibited.

*the rate of flow of energy or particles across a given surface **is the most common excitatory neurotransmitter in the brain and spinal cord

Synaptic vesicle

Ca++ channel Post synaptic density

Neurotransmitt er Neurotransmitter re uptake pump

Neurotransmi tter receptors

Exon terminal (presynapse)

Synaptic cleft Dendritic spine (postsynapse)

Receptors in the Basil Ganglia and Cerebellum involved with many forms of movement and postural control, are affected by smoking marijuana In the Cerebral Cortex, cannabinoid receptors are activated which distortions in sense of time, reduces the ability to concentrate and, produces a dream like state. As well as altering how sound and taste are perceived (superficial). The Hippocampus (has a large number of cannabinoid receptors) which is responsible for movement of short term memories into long term memory storage, is affected. Damaging memory formation capabilities

 Smoking

Marijuana during pregnancy has many of the same effect as smoking cigarettes, mild fetal growth retardation.  There have been cases of infants born with THC dependence and withdrawal.

Marijuana Crosses the Placenta

CB1 and CB2 receptor The cannabinoid receptors are a class of receptors under the Gprotein coupled (guanine nucleotide-binding proteins) receptor superfamily  CB1 Cannabinoid receptor type 1-receptors are expressed mainly in the brain, but also in the lungs, liver and kidneys  CB2 Cannabinoid receptor type 2receptors are mainly expressed on T cells of the immune system, on

Marijuana effects Angina- Paroxysmal thoracic pain and choking sensation, especially during exercise Angina pectoris is a squeezing, suffocating, or burning feeling in the chest.

Tolerance and Withdrawal  Tolerance to the effects of Marijuana can develop especially in long term and chronic marijuana.

Treatment Because around 20% of illegal drug users use marijuana in conjunction with other drugs, there is not treatment program specifically for marijuana users.  However, treatments such as psychotherapy with an emphasis in

SHORT-TERM EFFECTS SHORT-TERM EFFECTS

Physical: - relaxation to sedation (a state of reduced excitement or anxiety that is by the administrative of a sedative agent )

- bloodshot eyes - coughing/lung irritation - some pain control - increase in appetite, - loss in muscular coordination - decreased blood pressure bloodshot eyes - decrease in pressure behind the eyes - increased heart rate - increased blood flow through the mucous membranes of the eye - decreased nausea - impaired tracking ability - marijuana can act as a stimulant or depressant, - temporary disruption of the secretion of testosterone

induced

Mental Mild to moderate dose: - confused and separated from the environment - feeling of deja vu - drowsiness - feelings of detachment (disinterest) and being aloof (cold) - difficulty in concentrating - disrupts short-term memory Strong dose: - stimulation, giddiness, distortions of color/time/sound Very strong dose: - feelings of movement, visual hallucinations and hallucinations Mental effects dependent on set, setting, and experience - can exaggerate mood, personality, empathy or suggestibility

LONG TERM EFFECTS Acute mental problems: long-term and lasting problems rare BUT, can trigger pre-existing problems “post hallucinogenic drug perceptual disorder”

MAJOR ISSUES OF CONCERN - decrease in color discrimination - decrease in ocular motor tracking - visual distortion - decreased recognition - decreased analysis of peripheral visual field light stimuli - marijuana and alcohol, polyabuse

Cocaine •Plant name: •Active ChemiCoca call: Cocaine, Cocaine is made from coca shrub.

•Other names: •Charlie, Snow, Coke

•2 different forms: •White powder or Crack (white rocks)

•Consumption: •Cocaine can be eaten, smoked, sniffed or injected.

Erythroxylon coca

Crack and Cocaine Powder

Photo courtesy U.S. Drug Enforcement Administration

What is Cocaine? • Cocaine is a bitter, white, odorless, crystalline drug. • Cocaine has been classified as drug. • Cocaine is extracted and refined from the Coca plant. • A highly addictive stimulant that produces profound feelings of pleasure.

History of cocaine Used by man since 800 A.D.  Cultivated by the Incan  1500s - Coca chewing of the South American Indians  1860s - Isolated from coca leaf by Albert Nieman  1880s - Sigmund Freud’s Uber Coca  1886 - Coca Cola a non-alcoholic medicinal tonic from Atlanta Georgia  1890s – Cocaine containing medicine  1922 – Narcotic Drug Import and Export Act restricted coca imports 

Cocaine Extraction Coca leaves are stripped from the plant and crushed, chopped, and/or pounded  mixed with a solution of alcohol, gasoline, kerosene, or some other solvent that will remove the cocaine from the 

Erythroxylon coca

How is Cocaine Used? Cocaine can be snorted, injected, smoked or eaten. The level and length of the effects depend on how the drug was induced. Onset

Duration

Snorted

1 minute

20-40 minutes

Injected

1-5 seconds

15-20 minutes

Smoked

Immediate

5-15 minutes

Cocaine Methods of Use causes such pleasurable effects as reduced fatigue, increased mental clarity, and a rush of energy  the more one takes cocaine, the less one feels its pleasurable effect  which causes the addict to take higher and higher doses of cocaine in an attempt to recapture the intensity of that initial high 

Cocaine’s effects on the nervous system  one

of the most potent, addictive recreational drugs  Can cause irreversible damage to the nervous system

Cocaine and the brain Dopamine-a monoamine neurotransmitter found in the brain and essential for the normal functioning of the central nervous system http://health.howstuffworks.com/crack6.htm

Cocaine’s Effects on the Brain 

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produces its pleasurable high by interfering with the brains pleasure centers where such chemicals as dopamine are produced drug traps an excess amount of dopamine in the brain, causing an elevated sense of well being

Cocaine Overdose  serious

long-term effects to the central nervous system, including an increased chance of heart attack, stroke, and convulsions, combined with a higher likelihood of brain seizures*, respiratory failures, and, ultimately, death  overdose of cocaine raises blood pressure to unsafe heights resulting in permanent brain *Uncontrolled electrical activity in the brain, which may produce a physical convulsion, minor physical signs, thought disturbances, or a combination of damage symptoms

Cocaine’s Physical Effects Physical side effects that have been known to be caused by cocaine use are: • Decreased Appetite • Increased Body Temperature

• Severe Nose Damage (when snorted) • Violent Behavior

• Increased Heart Rate

• Kidney Failure

• Dilated Pupils

• Seizure and/or Stroke

• Nausea/Vomiting

• Heart Attack

Cocaine’s Physiological Effects • Increased Alertness

• Confused Behavior

• Decreased Fatigue

• Increased Fear

• Increased Concentration

• Severe Anxiety Attacks

• Insomnia

• Hallucinations (in extreme cases)

• Increased Irritability • Increased Psychosis

• Aggressive Behavior

Addiction and Withdrawal Cocaine is one of the most addictive drugs known to man. Those who use cocaine heavily or regularly find it extremely difficult to stop and often suffer through serious withdrawal symptoms such as: • Severe Irritability

• Excessive Sleep

• Chronic Depression

• Eating Disorders

• Paranoia

• Nausea / Vomiting

• Loss of Sex Drive

• Diarrhea

• Insomnia

• Heart Attack

Heroin-Candu-Opium Poppy 

Papaver Somniferum, Sleeping poppy, Sedation, Pain relief, God’s own medicine, Acts on brain’s

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At present, opium poppies are mostly grown in the Middle East, Pakistan, and Afghanistan, and in Asia, especially in the region known as the Golden Triangle straddling Myanmar,

China and the Opium War China wasn’t open to foreigners and new cultures; not much foreign relations/trade except for Guangzhou  They had beautiful goods made of silk, fine china and porcelain, and good quality cotton.  The British imported a lot of tea from China and by doing so, they were losing a lot of money. The British wanted to find a product that they could trade in large amounts.  Opium, made from the poppy plant, was a addictive drug. The British merchants illegally brought in opium to China. 

Opium and its derivatives raw opium extract Natural components (1800)

morphine

codeine

heroin (1898)

thebaine Percadan

Oxycodone

Codeine

Heroin

Oxycodone

Endorphins and morphine

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Morphine is a highly potent opiate ana;gesic drug and is the principal active agent in opium and the prototypical opiate.

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Like other opioids, e.g. Diamorphine (heroin), morphine acts directly on the central nervous system (CNS) to relieve pain, and at synapses of the nucleus accumbens in particular.

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Morphine is highly addictive when compared to other substances, and tolerance and physical and

Nucleus accumbens

Side Effects Morphine has many side effects. The most dangerous is respiratory depression. With higher doses or in frail patients, the respiratory rate decreases, the patient becomes increasingly sedated, and the pupils very small.  Common side effects are nausea and vomiting due to a central action of morphine stimulating one of the centres in the brain concerned with vomiting called the chemotactic trigger zone. 

Side Effects Other central nervous system side effects of morphine are cough suppression, sedation, and dependence leading to addiction.  Morphine also has an effect on the muscle of the bowel and urinary tract, causing the sphincter to contract and reduce the peristalsis (the wavelike movements of the bowel muscle that propel its contents forwards). This results in a delayed emptying of the stomach, constipa tion, and may also lead to urinary retention. 

Side Effects  Morphine

can also cause histamine release, which causes itching of the skin and nose and a mild flushing of the skin.

Heroin  Heroin

is a white or brownish powder that is highly addictive. Heroin can be injected, snorted, or smoked. Heroin bought on the street might be pure or diluted (“cut”) with starch, talcum powder and other impurities.

Heroin structure

Effects from short-term use: • A false sense of euphoria (a feeling of great) and reduced pain • Warm skin • Decrease in appetite • Wakeful and drowsiness • Dry mouth • Shallow breathing • Heavy feeling in the arms and legs • Nausea and vomiting • Severe itchy skin

Effects from long-term use: •Physical and mental dependency •Addiction •Malnutrition •Chronic constipation •Coma •Overdose •Collapsed veins, bacterial infections and scarring from injecting •Women can have irregular periods •Men may become impotent (weak)

N I O R E H N FACTS O •

Babies born to heroin addicted mothers are often premature and under weight, the baby experiences withdrawal at birth. Babies are at an increased risk for contracting hepatitis, HIV and blood contamination from their mothers.

2. When you stop using heroin the withdrawal effects will start within a few hours. These effects will get stronger for 2 to 4 days and then gradually weaken. Depression, insomnia, weakness and stress can last for several weeks to months.

Nicotine is toxic and addictive Don’t Start

Nicotiana tabacum

Cancers attributed to tobacco  Oral  Larynx  Esophagus  Lung  Kidney  Bladder  Cervix  Pancreas  Stomach

Cancer deaths attributed to tobacco  45

developed countries  85% lung cancer deaths, 27% all cancer deaths  Similar patterns in developing countries, 89% of men among patients with lung cancer were ever-smokers in India  Lung cancer risk was two to four times higher among men who smoked compared to men who did

Caffeine  Caffeine

is an alcaloid compoud, purin derivative  Caffeine acts as psychoactive stimulant and diuretic in humans  Pure caffeine is white powder  Caffeine is found in the beans,leaves, and fruit of over 60 plants, where it acts as a natural pesticide. Caffeine – 1,3,7 Trimethylxanthine

Sources Caffeine is a plant alcaloid  Most known plants containing caffeine are cocoa, tea and coffee, yerba maté and guarana  Caffeine has no stereoizomers (Isomers 

which have their atoms connected in the same sequence but differ in the way the atoms are oriented in space - i.e. the difference between two stereoisomers lies only in the three dimensional arrangement of atoms. Stereoisomers can be classed as cis-trans

)  Many natural sources of caffeine also contain varying mixtures of other xantine alkaloids* or polyphenols**, Alkaloids, which contain xanthine as their nitrogenous base which can form insoluble complexes **Polyphenols are a group of chemical substances found in plants, characterized by the with caffeine presence of more than one phenol unit or building block per molecule isomers or optical isomers

Plant alkaloid  Definition:

Any of various organic compounds normally with basic chemical properties and usually containing at least one nitrogen atom in a heterocyclic ring, occurring chiefly in many vascular plants and some fungi. Many alkaloids, such as nicotine, quinine, cocaine, and morphine, are known for their poisonous or medicinal attributes

heterocyclic ring

Coffee

Yerba maté Guarana

Overuse  Caffein

can leave to caffeinism (you became addicted on caffeine)  Caffein dependency combines with nervousnes, irritability, headaches and hearth palpitation (a rapid and irregular heart beat)  Because caffeine increases the production of stomach acid, high usage over time can lead to peptic ulcers (is an ulcer (defined as mucosal erosions equal to or greater than 0.5 )

Tolerance 

Because caffeine is antagonism for the neurotransmiter adenosine of nervous systém, it makes your body more sensitive to adenosine

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Caffeine tolerance develops very quickly, especially among heavy coffee and energy drink consumers. Complete tolerance to sleep disruption effects of caffeine develops after consuming 400 mg of caffeine 3 times a day for 7 days.

oisonous Plants

300 toxic species in New Mexic 1000 toxic species in U.S. $234 million/year

sheep grazing larkspur (any of numerous cultivated

plants of the genus Delphinium

Ranunculaceae – buttercup family Delphinium - larkspur

olanaceae – nightshade family Datura – jimsonweed, thornapple

Fabaceae – pea family “locoweeds” and milkvetches – Astragalus and Oxytropis

Oxytropis

Astragalus

Apiaceae – celery family poison hemlock – Conium maculatum water hemlock – Cicuta maculata Most toxic in North America!

CYANIDE PLANTS

Almonds

250 mg CN/100g plant tissue

Cassava

Wild Cherries

104 mg CN/ 100 g plant tissue 140-370 mg CN/ 100 g plant materi

Glycosides sugar + aglycone (toxic agent) Cyanide is most common toxic glycoside, cytochrome oxidase molecule Inhibits ATP formation, preventing cellular respiration-electro transport chain

Cyanide recognized since antiquity

(ancient time) present in bitter almonds, cassava, and other foods used extensively in industry for fumigation, electroplating, and mining activities

 Several

forms exist; all may have an odor of bitter almonds, but this is not always detectable Gas: colorless, dissipated (dissolve)

rapidly

○ hydrogen cyanide [HCN] and cyanogen

chloride [CNCl, also known as CK]

Liquid: ranges from blue to colorless,

stable

○ hydrocyanic acid; an aqueous solution of

HCN

Solid: white granular powder, stable ○ sodium, potassium, or calcium

72

Clinical signs  Death

within minutes to hours.   Apprehension*, involuntary defecation**, muscle tics (sudden, repetitive) leading to convulsions (An epileptic seizure is a transient symptom of excessive or synchronous neuronal activity

, respiration becomes difficult, champing of the mouth produces frothing(foaming), pupils dilate and coma follows shortly.  Bright red mucous membranes are of particular diagnostic *fearful expectation or anticipation importance. **the elimination of fecal waste through the in the brain)

anus

Treatment: 1) 2) 3) 4) 5) 6)

Activated charcoal Supplemental oxygen/Supportive care Sodium nitrite Amyl nitrite Sodium thiosulfate Hydroxocobalamin

Rosaceae Prunus spp. Almond, Apricot Toxic principal: cyanide in pits

Bromobenzyl-cyanide

Rosaceae Malus spp. Apple, Cyanide in seeds

Lilaceae convallaria majalis Lily of the Valley

Cardioactive glycosides in leaves Clinical sign: Nausea, vomiting, diarrhea, tenesmus, heart complications

Araceae Caladium spp Caladium, Calcium Oxylate crystals in leaves, also a protein-like substance may release histamine