1. Opium Poppy

2. 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

4. Fresh capsule of opium poppy Cut capsule showing latex exuding from cut

5. 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

6. 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

7. 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

8. 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 20 th century Still drug of choice for cases of severe pain

9. 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

10. 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

11. 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

12. 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

13. Isoquinoline alkaloids

14. Opiates

15. 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

16. 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

18. 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

19. 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

20. 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

21. 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