1. Hung Kay LEE Department of Chemistry The Chinese University of Hong Kong The Chemistry of Some Common Soft Drugs 10 th April, 2006

2. Drugs Physiological changes Emotional changes Behavioural changes Medicines — Chemicals Against Diseases?

3. "Good" Drugs "Bad" Drugs vs Penicillin Morphine Aspirin Heroin Cocaine Amphetamines

4. Chemists always stride in modifying the chemical structure of a compound in order to remove those undesirable properties while retaining the desirable ones. Chemistry: The Central Science

5. How do drugs work? 1.Drug action at enzymes 2.Drug action at receptors

6. Neurotransmitters and Receptor Molecules

7. Drug Action at Receptors Cell Receptor Nucleus Signal Nerve Response

8. Pain-killing drugs that also induce euphoria N ARCOTIC A NALGESICS Powerful central nervous system depressants that can induce sleep and reduce anxiety

9. The Opium Alkaloids A number of alkaloids can be isolated from the juice obtained from seed pods of the opium poppy.

10. Three important opiates are: They are the most effective pain-killers!

11. M ORPHINE The most important narcotic analgesic in medicine — used for the relief of severe pain. When pure, it is an insoluble, odourless, white crystalline solid with a bitter taste. The principal alkaloid (~10% w/w) of raw opium. First isolated in 1805. But it is an additive!

12. H EROIN Also known as diacetyl morphine or diamorphine. Heroin is a semi-synthetic opiate drug which was introduced commercially in 1898 after a pioneering clinical research work by the German pharmacologist Heinrich Dreser at Friedrich Bayer and Co.

13. It can be readily prepared by heating morphine with acetic acid: Acetylation

14. Heroin was found to be a highly effective medication in the treatment of coughs, chest pains and the discomfort of tuberculosis. Dreser called it heroin, a name derived from the German word for “heroic”. In terms of pain-killing activity, heroin is about 2–3 times stronger than morphine.

15. Abusers often feel a surge of pleasurable sensation, followed by drowsiness for several hours. Heroin crosses the blood–brain barrier soon after inhalation or injection. It is converted to morphine in the brain and binds rapidly to opiate receptors. Effects of heroin

16. Treatment The methadone treatment As a synthetic opiate, methadone was developed by the Nazis during World War II when the supply of opium was cut off. The most effective form of treatment for addiction to heroin and other narcotics. Methadone

17. S TIMULANT D RUGS Caffeine A cup of tea or coffee?

18. S TIMULANT D RUGS CocaineAmphetamines Ecstasy

19. C OCAINE — The most potent stimulant of natural origin Cocaine is extracted from the leaves of coca plants, that grows almost exclusively on the South American Andes.

20. It was first used as a local anesthetic in eye surgery. It was also useful in surgery of the nose and throat. However, it is seldom used nowadays due to the development of safer anesthetic drugs.

21. Coca-cola was introduced in 1886 as "a valuable brain-tonic and cure for all nervous afflictions".

22. Four basic routes to coca intoxication: (1)Chewing coca leaves (mixed with lime and ashes) or brewing a cup of coca-tea for refreshment by the South America Indians.

23. (2)Cocaine sulfate — a low-grade stuff in the preparation of cocaine hydrochloride crystals from coca leaves.

24. (3)Cocaine hydrochloride — an odourless, white crystalline solid with a bitter taste. (4)“Crack” — a street name given to cocaine free base.

25. A MPHETAMINES Amphetamine is a powerful stimulant drug that increases the activity of the central nervous system. Its effect is similar to that of adrenaline, but amphetamine acts for a much longer time in the body. “Ice”

26. Amphetamines can be acquired legally by prescription. It has once been used extensively for weight reduction and treatment of mild depression. Nowadays, it has been used to treat narcolepsy (a rare form of sleeping sickness) and childhood hyperactivity. Amphetamine can induce an extremely high blood pressure that strokes or even heart failure may result.

27. MDMA (3,4-Methylenedioxymethamphetamine) (ECSTASY) A synthetic, psychoactive drug possessing stimulant and hallucinogenic properties. A close structural analogue of amphetamine.

28. MDMA was first synthesized and patented by E. Merck & Co., Germany in 1914 as an appetite suppressant. The compound was never marketed.

29. H ALLUCINOGENS

30. Marijuana: Some Chemistry of Cannabis The plant Cannabis sativa, which grows wild throughout most of the tropic and temperate regions of the world, has long been useful. e.g.Stem  tough fibers for making rope. Marijuana refers to the leaves and flowering tops of the cannabis plant.

31. Cannabis contains a variety of chemical substances known as cannabinoids. Among the cannabinoid compounds, tetrahydrocannabinol (THC) is believed to be the active ingredient responsible the psychoactive effects of cannabis. Tetrahydrocannabinol (THC)

32. Smoking Cannabis increases the pulse rate, distorts the sense of time, impairs motor functions, and leads to hallucinations. There is evidence that marijuana causes brain damage (brain lesions). Unlike alcohol, THC can persist in the bloodstream for several days as it is soluble in fats. Effect of cannabis

33. Chemists can monitor the levels of THC in the bloodstream and can identify its degradation products. Marijuana has some medical uses. e.g. For treatment of glaucoma (high eye pressure) and for the control of nausea that afflicts cancer patients undergoing radiation treatment and chemotherapy.

34. Lysergic Acid Diethylamide (LSD) The most potent hallucinogen and mood-changing chemical known to man. It was originally synthesized by Albert Hoffman at the Sandoz Laboratories in Switzerland in 1938, but its hallucinogenic effects were known in 1943 when Hoffman accidentally ingested some.

35. Lysergic acid is isolated from ergot fungus and can be easily converted to LSD by replacing the acid with a —N(CH 2 CH 3 ) 2 group. LSD is produced in crystalline form, or diluted as a solution for production in ingestible forms.

36. At the time when LSD was first reported, the new chemical appeared not to have any particularly useful medical properties, although it has been noted that “the experimental animals became restless during the narcosis”. Self-experiments by Hoffman: 17:00:Beginning dizziness, feeling of anxiety, visual distortions, symptoms of paralysis, desire to laugh.

37. It is generally believed that as a part of the structure of LSD is similar to that of serotonin (a brain amine), this may account for its fantastic neurophysiological effects. Because of its similarity to serotonin, LSD has been used to study mental illness in the 1950’s and 1960’s. How does LSD work? The mechanism by which LSD causes hallucination still has not been established.

38. K etamine A general anaesthetic for veterinary use. Its hallucinatory effects are short-acting, lasting for an hour or less. However, it can affect the sense, judgement, and coordination for 18 to 24 hours.

39. Ketamine Synthesis of Ketamine

40. Right: Drug usersLeft: Normal people far less serotonin activity