Indian Hemp, Cannabis Indica, Cannabis

• Indian hemp consists of the dried flowering tops of pistillate (female) plants of Cannabis sativa L., family Moraceae.

• The plant is an annual dioecious herb (= two houses),

Cannabis

• The typical herbal form of cannabis consists of the flowers , leaves and stalks of mature pistillate plants.

• All parts of the plant, particularly the bracts, stipules, and upper leaves, bear numerous hairs and large stalked glands(glandular hairs).

• The g.h. secretes the adhesive resin.• The drug has a heavy powerful odour, but almost

devoid of taste.

Cannabis glandular hairs

The resin

• The narcotic resin is a brown, amorphous semi solid; insoluble in water, soluble in alcohol, ether....

Constituents

• The main psychoactive (or mind altering) substance of cannabis resin is a "cannabinoid" called THC (9-delta tetrahydrocannabinol).

• THC is responsible for the mental and physical effects of cannabis.

• Cannabis resin contains over 60 cannabinoids .

Cannabis products

• Ganja ……. India• Hashish ....... Arabic, Egypt• Marijuana........USA• Charas or churrus• Hash oil• Hemp• The most common form of cannabis used as a drug is

the dried herbal form.

Ganja

• gañjā, meaning hemp ........ India.• The tops of the female plants only are

compressed into masses by the resinous secretion .

Marijuana

• Marijuana consist of the dry leaves and young tops of male and female plants.

• The plant is dried and not compressed into masses.

• Marijuana may also contain seeds and stems.

• The high quality Indian cannabis (Ganja) have an activity about 10 times as great as that of American cannabis (Marijuana).

Hashish

• Hashish or hash is made from resin that is collected and compressed from the Cannabis plant.

• It can range in colour from brown to black, and may be soft or firm and brittle.

• Hashish which contains significant quantities of leaves and flowering tops is green.

• It generally contains more THC than marijuana.

Charas

• Charas or churrus is the crude resin. It varies in color from black to golden brown depending upon purity.

• The resin contains up to 20% THC content. (UNODC) United Nations Office on Drugs and Crime.

Hash Oil

• Hash oil, also called cannabis oil, is produced by extracting cannabis plant through the use of various solvents.

• Cannabis oil is usually a thick, sticky liquid and can range in colour from gold, to red, to dark brown.

• Cannabis oil is generally smoked.

• According to the United Nations Office on Drugs and Crime (UNODC) cannabis oil contains more than 60% THC content.

Hemp

• The term hemp is often used to refer only to varieties of Cannabis cultivated for non-drug use (used for its fibre).

• Industrial uses of hemp include the production of fabric, paper, food for cattle and cosmetics.

• Industrial hemp contain less than 1% THC.

How Does Cannabis Affect the Body?

• After using cannabis……..

• THC is absorbed into the blood stream and it travels to the brain.

• In the brain, THC binds to specific receptors, called cannabinoid receptors.

• This binding reaction in the brain produces the effects felt by the user.

• THC is stored in fat cells. • It takes a long time to completely clear from

the body. • Although this does not produce long-lasting

psychoactive effects.......• It can result in a positive drug test for a long

period after the drug has been taken.

Potency

• According to the United Nations Office on Drugs and Crime (UNODC)

• The amount of THC present in a cannabis sample is generally used as a measure of cannabis potency.

Short-Term Effects

Long-Term Effects

• Cannabis is the most widely used illegal drug worldwide.

• Cannabis smoke irritates the respiratory passages. This can lead to bronchitis, especially if used regularly.

• Cannabis smoke combined with tobacco smoke can cause cancer.

Long-Term Effects(cont.)

• Frequent cannabis use affects motivation and concentration. It can interfere with school and job performance.

• Long-term heavy use may cause schizophrenia in individuals with genetical history.

Legality of cannabis

• Since the beginning of the 20th century, most countries have laws against the cultivation, possession, or transfer of cannabis.

• But there are many regions where, under certain circumstances, handling of cannabis is legal or licensed.

Medical use• The most well known uses of Cannabis :• Control nausea and vomiting. One of the most

important things when treating cancer with chemotherapy or when treating AIDS.

• Control the eye pressure and keep glaucoma from causing blindness. Glaucoma is the second leading cause of blindness, caused by uncontrollable eye pressure.

• Control multiple sclerosis and helps to stop spasms, produced by this disease. Multiple Sclerosis is a disease where the body's immune system attacks nerve cells.

Detection and estimation

• A wide variety of methodologies has been recommended for the detection and determination of Cannabis : TLC , HPLC , GC and GC-MS, immunological method (Enzyme-Linked Immunosorbent Assay) (ELISA), radio immunoassay (RIA) .

• Microscopical examination.

Intoxication

• On its own, cannabis intoxication is not lethal.• THC has an extremely low toxicity and the amount that

can enter the body through the consumption of cannabis plants poses no threat of death.

• However, cannabis interferes with concentration, reaction time, and coordination.

• These effects impair a person's ability to drive safely or operate any machinery.

• Alcohol and cannabis intensify each other's effects.

• Combined use may result in severe impairment and is a factor in many injuries and deaths.

Duration and route of administration

• Smoked• When smoked, the short-term effects of cannabis

manifest within seconds and are fully apparent within a few minutes, typically lasting for 2-3 hours.

• Oral• When taken orally, the psychoactive effects take

longer time to manifest and generally last longer, typically lasting for 4-10 hours after consumption.

Psychoactive drug

A psychoactive drug is a chemical substance that acts primarily upon the central nervous system where it alters brain function, resulting in changes in mood, consciousness and behavior. The user may find pleasant (e.g. euphoria) Many psychoactive substances are among the abused drugs.

Addiction in medicine• Is a chronic neurobiological disorder that has

psychosocial, and environmental dimensions.• It is characterized by :• The continued use of a substance despite its

detrimental or harmful effects.• Impaired control over the use of a drug

(compulsive or uncontrolable behavior). • The use of a drug for non-therapeutic

purposes.

Drug addiction

• Tolerance to a drug and• Dependence • Both typically accompany addiction to certain

drugs.

Tolerance

• Tolerance is a pharmacologic phenomenon where the dose of a medication needs to be continually increased in order to maintain its desired effects.

• Individuals with severe chronic pain taking opiate medications (like morphine) will need to continually increase the dose in order to maintain the drug's analgesic effects.

Dependence

• Dependence is a state resulting from chronic use of a drug that has produced tolerance and where symptoms of withdrawal result from abrupt discontinuation or dosage reduction.

• Many drugs used for therapeutic purposes produce withdrawal symptoms when abruptly stopped, e.g. oral steroids, certain antidepressants, opiates and opioids.

Withdrawal symptoms

• Symptoms include increased heart rate and/or blood pressure, sweating, and tremors.

• More serious withdrawal symptoms such as confusion, seizures, and visual hallucinations indicate a serious emergency and the need for immediate medical care.

Types of addiction

• A positive addiction is a beneficial habit.• Examples : exercise, eating healthy etc..• A negative addiction is a detrimental habit• Examples : drug addiction (e.g. alcoholism,

nicotine addiction), overeating, shopping addiction, computer addiction,, television addiction. etc…,

• A neutral addiction is a habit in which it is not clear if the humanbeing benefits from this activity.

Drug abuse prevention

• A concept known as:"environmental prevention“

• focuses on changing community conditions so that the availability of substances is reduced .

Drug abuse prevention(cont.)

• Drug abuse prevention typically focuses on:• Alcohol.• Tobacco.• Cannabis.• based on gateway drug theory.

Gateway drug theory

• Known also as gateway theory, gateway hypothesis .

• Proposes that these three substances (alcohol,tobacco,cannabis) are typically used first and may ultimately lead to the use of "hard drugs" like cocaine or heroin.

• (crime).

Plants containing toxic glycosides

Glycosides

• Glycosides are compounds containing a carbohydrate and a non carbohydrate residue in the same molecule.

• The carbohydrate residue is attached by an acetal linkage at carbon atom 1 to a non carbohydrate residue or AGLYCONE.

• The non sugar component is known as the AGLYCONE. The sugar component is called the GLYCONE.

• If the carbohydrate portion is glucose, the resulting compound is a GLUCOSIDE

I- Cardiac glycosides

• The term is derived from the Greek word

• kardiā, meaning heart.

Presence of Cardiac glycosides • Cardiac glycosides are found in diverse plants including: • Digitalis purpurea (foxgloves) and D. lanata,• Nerium oleander (common oleander), • Thevetia peruviana (yellow oleander),• Convallaria majalis (lily of the valley), • Urginea maritima and Urginea indica (squill),• Strophanthus gratus, • Apocynum cannabinum (dogbane), • Cheiranthus cheiri (wallflower). • In addition, the venom gland of toad (Bufo marinus).• Venom; poison

General Structure of Cardiac Glycosides

• Cardiac glycosides are type of STEROID Steroids form an important group of compounds

based on the fundamental saturated tetracyclic hydrocarbon : cyclopentanoperhydrophenanthrene (sterane)

Steroid skeleton

Types of Cardiac Glycosides

• The Cardenolides: • The Digitalis group and the Strophanthus

group.• The Bufadenolides:• The squill-toad group (scillarins and the toad

poison Bufotoxin).

The Cardenolides• The aglycones of the cardenolides are (23) C-

steroids with methyl groups at C-10 and C-13 and a five-membered lactone at C-17.

• Digitoxigenin is given as a typical example of cardenolides genin.

•

The Cardenolides(cont.)

• They are widely distributed in plants mainly as glycosides.

• They are either toxic or insect deterrents.(Digoxin)

•

The Bufadenolides• The aglycones of the bufadenolides are (24) C

- steroids with a six-membered lactone ring at C-17.

• Hellebrigenin is a typical example of bufadenolides genin.

The Bufadenolides(cont.)

• They have been isolated from plants and animals. • They are important for their cardiotonic activity.• They possess insecticidal and antimicrobial properties.• Bufadenolides produced by the toad skin are strongly

poisonous.

The Bufadenolides

• The aglycones of the bufadenolides differ from those of the cardenolides in having

at position 17 a six – membered doubly unsaturated lactone ring .

The Digitalis and the Strophanthus group

Example Genus Digitalis• Family Scrophulariaceae.• It has now been placed in the much enlarged

family Plantaginaceae.

• The best-known species is the Common Foxglove الثعلب .Digitalis purpurea L , كف

• The scientific name means "finger-like".

• The flowers vary in colour with species, from purple to pink, white, and yellow.

• It is from the ornamental plants.

Digitalis purpurea Common Foxglove

Digitalis purpurea

• The use of Digitals purpurea extract for the treatment of heart conditions was first described in the medical literature, in 1785, which is considered the beginning of modern therapeutics.

Digitalis purpurea

• The fresh plant contains:• 1ry glycosides (tetraglycosides)• purpurea glycoside A and • purpurea glycoside B.

Digitalis purpurea(cont.)

• On drying, enzyme degradation takes place with loss of the terminal glucose to give the major glycosides of the foxglove digitoxin and gitoxin.(2ry glycosides).

Some cardiac glycosides of D. purpurea

Sugar Aglycone Glycosides

- (Digitoxose)3 – glucose

Digitoxigenin Purpurea glycoside A

- (Digitoxose)3 – glucose

Gitoxigenin Purpurea glycoside B.

- (Digitoxose)3 Digitoxigenin Digitoxin

- (Digitoxose)3 Gitoxigenin Gitoxin.

D. lanata

D. lanata(cont.)

• Digitalis lanata is used for manufacture of pure glycosides particularly digoxin and lanatoside C.

• With the exception of D-glucose and L-rhamnose, all the other sugars that are found

in cardiac glycosides are uncommon deoxy-sugars e.g., Digitoxose,Cymarose, Thevetose.

• Digitoxose (deoxy – sugar).• (Keller Killiani's reaction)

Chemical tests for identification of cardiac glycosides

• Tests for the steroidal nature, Libermann’s and Salkoviski’s colour reaction.

• Tests with alkaline solutions of aromatic nitro - compounds namely Kedde’s reagent, Raymond’s R., Baljet’s R., Legal’s R., all these nitro - compounds react with the active methylene group of the 5-member lactone ring (in alkaline medium) to give characteristic colours. (c/f cardenolides and bufadenolides).

• Keller Killiani's test for deoxy – sugars.

Medicinal use

• 1- They are used as an antiarrhythmic agent to control the heart rate (pulse), particularly in the irregular(often fast) atrial fibrillation.(rapid irregular heartbeat)

• 2- They are used to increase cardiac contractility or force of contraction (it is a positive inotrope) .

• (inotrope,contraction of heart)

Medicinal use (cont.)

• Digitalis glycosides are prescribed for patients in atrial fibrillation, especially if they have been diagnosed with heart failure.

• Heart failure, also called congestive heart failure.• It is a condition in which the heart can no longer

pump enough blood to the rest of the body.• The most common cause of heart failure is coronary

artery disease and narrowing of the small blood vessels that supply blood and oxygen to the heart.

Mechanism of the inotropic effect Sodium-Potassium pumps

• A well-established observation that cells contain relatively high concentrations of potassium ions but low concentrations of sodium ions.

• The mechanism responsible for keeping this balance is the sodium-potassium pump which moves these two ions in opposite directions across the plasma membrane.

• It is now known that the carrier is an ATP-ase (adenosine triphosphatase).(normal function)

• Na+/K+ - ATPase (Na+/K+ pump, or sodium pump,) is an enzyme located in the plasma membrane.

• The Na+ K+ - ATPase can be pharmacologically modified by administrating exogenous drugs .

• Na+ K+ - ATPase found in the membrane of heart cells is an important target of cardiac glycosides .For example digoxin (Digitalis) and ouabain (Strophanthus).

• Digitalis glycosides works by inhibiting sodium-potassium - ATPase.

• This results in an increased intracellular concentration of sodium, which in turn increases intracellular calcium. – reduction of Ca expulsion from the cell by the Na-

Ca exchanger caused by the Na increase.• The increased intracellular calcium gives a

positive inotropic effect ( increase cardiac contractility ).

• slowing down the Na+- K+ pump results in a permanently-higher Ca++ level in the muscle, which will eventually lead to stronger contractions.

Mechanism of the antiarrhythmic effect

• Arrhythmia• An arrhythmia is a disorder of the heart rate

(pulse) or heart rhythm .• Parasympathetic innervation of the heart

(atrium) is mediated by the vagus nerve. • The vagus nerve acts to lower the heart rate.

• Digitalis glycosides increase the parasympathetic vagal tone.

• They are used to slow the ventricular rate during atrial fibrillation and so treat cardiac arrhythmias.

• Digitalis glycosides• 1- inhibit Na+/K+ pump.• 2- increase the parasympathetic vagal tone.

Digitalis toxicity (Digitalis intoxication)

• Digitalis glycosides are amongst the most toxic drugs.

*Toxicity due to cardenolides contents: Concentrations required to enhance cardiac

contractility frequently cause cardiac arrhythmias.

(narrow therapeutic Index) TI = ( LD50 / ED50 ).

Digitalis toxicity

*Toxicity due to saponin contents:Many saponins are capable of altering the

nature of the phospholipids of the cell membranes.

The cells become abnormally leaky to ions; (lysis of cells).

Complications of Digitalis therapy• Risks include taking digitalis medications along

with medications that interact with digitalis. • Reduced kidney function will cause digitalis to

build up (accumulation) in the body rather than to be removed normally through urine. (high levels of digitalis in the body).

• Decreased tolerance to the drug (individual variation).

Medications that interact with digitalis.

• Be cautious with this combination (cardiac glycosides and Liquorice)

• Large amounts of liquorice can decrease potassium levels in the body. (hypokalemia).

• Low potassium levels can increase the side effects of digoxin (Lanoxin).

• Many diuretics can cause potassium loss.

• Digitalis toxicity• Hypokalemia• Liquorice• diuretics

• Fatal accidents, also involve children drinking the water in a vase containing digitalis plants.

• Herbal cardiac glycosides found in Asian herbal products are source of human toxicity.

Symptoms of Digitalis toxicity Digitalis toxicity causes:• Anorexia (loss of apetite), nausea, vomiting

and diarrhea.

• sometimes resulting in xanthopsia (yellow vision) and the appearance of blurred outlines or rings of light around objects .

• causes either bradycardia (lowered heart rate) or tachycardia (increased heart rate) and heart block .

• Because a frequent side effect of digitalis is reduction of appetite, some individuals have used the drug as a weight loss aid.

Treatment of Digitalis intoxication.

• If toxicity is due to a recent, acute single exposure, treatment may involve:

• * Gastric lavage (Tube through the mouth into the stomach to wash out the stomach).

• *Activated charcoal• Digitalis blood levels may be lowered with repeated

doses of charcoal, given after gastric lavage.• In severe cases, medications called digoxin-specific

antibodies may be prescribed. Hemodialysis may be required to reduce the levels of digitalis in the body.