Opium Poppy

Opium Poppy: Papaver somniferum

Member of the Papaveraceae, poppy family

Large showy annual with conspicuous flowers (white, pink, red, purple)

Fruit is a capsule that produces latex with several potent alkaloids

Latex is collected from cut capsules (latex oozes out and dries – dried latex scraped off) - dried latex called opium

Fresh capsule of opium poppy

Cut capsule showing latex exuding from cut

Opium Poppy Native to the Mediterranean area Oldest evidence of poppy use was

existence of a poppy capsule found with religious artifacts from a cave in Spain that are dated 7500 years old

Evidence of spread in Europe from 3000 to 5000 years ago

Reasons for use at these sites unknown

Ancient medical use Poppy was revered by several ancient

societies for its analgesic properties and its ability to induce sleep

Opium latex has a long history of use for pain relieve and inducing sleep among Babylonia, Egyptian, Greek, and Roman civilizations Opium eaten, drunk, and smoked Most common method was to dissolve opium in

alcohol – opium wine

Mediterranean societies Writings of Hippocrates, Theophrastus,

Dioscorides, and Galen show evidence of the widespread use of opium

In eastern Mediterranean it seems that poppy also became valued for its narcotic use

Ancient goddess of Crete is depicted wearing a crown with 3 poppy capsules

Opium Alkaloids Many alkaloids have been identified in

opium latex (opiates) - maybe as many as 50

Morphine and codeine most important Morphine first alkaloid identified from any

plant in 1806 and the pain relieving properties soon recognized

Morphine (like raw opium) is strongly addictive and because of this its general medical use declined in 20th century

Still drug of choice for cases of severe pain

Morphine Morphine affects the central nervous

system but also induces drowsiness and can depress respiration - overdose can cause death through respiratory failure

Cause has high physical dependency Has relatively low oral activity Became drug of choice to treat war

injuries during Civil War - created many addicts

Codeine Codeine most widely used opiate Only 1/5 as strong as morphine and

still addictive Effective in oral medication and

often used in combination with non-opiate compounds

Codeine is especially effective in cough syrups because it suppresses the coughing reflex

Heroin In 1898, Bayer Pharmaceuticals

introduced heroin which they thought was a non-addictive opiate and more effective than morphine and codeine

Heroin is a semi-synthetic derivative of morphine - diacetyl morphine

Widely available in over the counter tonics and cough syrups from 1898 to 1914 - mail order catalogs, etc

Heroin Within a few years over 1 million people

addicted to heroin in US alone Soon realized that it was actually more

addictive than morphine - actually six times more addictive

In US use of heroin is illegal placed under Harrison Act of 1914

Heroin still used medicinally in other countries

Heroin addiction a major problem worldwide

Isoquinoline alkaloids

Opiates

Mode of action Opiates bind to opiate receptors in

membrane of neurons of the brain and spinal column (ID’d in 1970s)

The natural ligands that normally bind to these receptors are endorphins and enkephalins (small peptides)

These peptides are released at synapses on neurons involved in transmitting pain signals to the brain

Opiate receptors When enkephalins bind to the opiate

receptors they inhibit neurons from transmitting pain signal - pain signal does not reach brain

Inhibit release of neurotransmitter “Substance P”

Substance P used by the sensory neurons involved in the perception of chronic and/or intense pain

Opiate receptors Peptides and receptors form a

complex neurotransmitter system that plays a major role in controlling pain, euphoria, and motivation

Also involved in other biological events - stress responses, immune regulation, respiration, endocrine responses

Different classes of opiate receptors

Opiate receptors Three (or 4) classes of opiate receptors -

with subtypes of each Opioids exert their effects by activating

one or more of these receptors Pain relief involves activation of one

type receptors in the brain and another in the spinal cord

Other receptors are are involved in respiratory depression and euphoria

Opiate receptors (mu) receptors - analgesia, euphoria (kappa) receptors - sedation, spinal

cord analgesia (delta) receptors - Antitussive

(coughing) properties, emesis (vomiting), and anticholinergic (constipation)

sigma (?) receptors cardiac stimulation

Opiates Morphine and the other opiates

bind these same receptors Morphine especially binds to

receptors Explains why opiates are excellent

pain killers However, they are also highly

addictive