1. Reminder: What Information Will be Covered for EVERY Drug: What is drug? Why is it used? How is it administered? How much is used? Metabolism? Affects on the cell? Addiction? Benefits? Harms? Individual experience may vary

2. Review: Cocaine and caffeine, but NOT nicotine…. 1.Cause vasoconstriction 2.Stimulate the reward pathway 3.Bind antagonistically to brain molecules 4.Impact recycling transporters 5.Are metabolized by CYP 450 enzymes 6.Lead to dependence (and resultant withdrawal symptoms) Yep!

3. Which explains a person whose caffeine use makes them sleepy? 1.They have weak CYP1A2 2.They have strong CYP1A2 3.Their adenosine production is excessively strong 4.Their adenosine receptors bind caffeine as an agonist Yep!

4. Nicotine Caffeine (it IS a drug!) Cocaine Amphetamines Lesson 18 Ecstasy (MDMA) Antidepressants http://www.graphicaddicts.net/tutorials/hitler.jpg

5. What are amphetamines? Activity 2 CH 3 http://www.heroinaddiction.com/Pictures/speed.jpg All images WikimediaCommons (public domain)

6. How about herbal stimulants?

7. Once more with the Methyls… CH 3 Dopamine < amphetamine < methamphetamine Theobromine (chocolate) < caffeine

8. Why do people take amphetamines? Euphoriant All images WikimediaCommons (public domain)

9. How are amphetamines administered? Activity 3 Oral Smoked Intravenous All images WikimediaCommons (public domain)

10. Injecting amphetamine intravenously will: 1.Hurt! 2.Speed delivery to the brain 3.Result in greater addiction 4.Expose a user to blood- borne pathogens 5.All of the above Yep!

11. Amphetamine Dosage? 5 – 60 mg orally. Why difference? Lethal dose Effective dose Few exposuresRegular exposures Ritalin has been associated with 25 overdose deaths (19 of which were children) and dozens more heart attacks and strokes.

12. Amphetamine metabolism? Activity 4 CYP2D6 HO Half life ~ 1 hour Hydroxyamphetamine

13. How do amphetamines work on a cell? Activity 5 Endogenous amphetamine NH 2 Produce alertness Treat narcolepsy, fatigue, obesity, ADHD Euphoriant

15. Amphetamines block the same molecule type as: 1.Opiates 2.Nicotine 3.Caffeine 4.Cocaine 5.Alcohol 6.Cannabis 7.None of the above Yep!

16. How addictive are amphetamines? Activity 6 Reward Tolerance Dependence? Craving to reuse Neurotransmitter depletion Turn down endogenous amphetamine (phenylethylamine)

17. Amphetamine Benefits? Activity 7 Euphoriant

18. What are amphetamine’s side effects? Activity 8 Extremely high tolerance Amphetamine challenge – can push a borderline psychotic over the edge – give full blown symptoms

19. Methamphetamine and Brain Loss Media/meth/meth.jpg Damage to Limbic – 11% Hippocampus – 8% STUDY: 4 grams per week for 10 years, smoked, 22 people, 21 controls Increases seen in glial proteins that respond to neuron injury

20. Long term effects on neuron? Receptor density Post-synaptic membrane density PMID 14686913

21. Why was Ephedra recently banned? 1% supplement sales – 64% serious side effects

22. Individual Experience may vary… Activity 9 DAT (Dopamine transporter) gene Gene for enzyme CYP2D6 Gene that produces glial factor-derived growth factor Previous history of amphetamine use

23. Lab Wrap Up What CONTROL would you expect us to test on the worms? Placebo in our case = pond water- which flask do you think was the control? A1A2B1B2C1D1E1 Pond Water Caffeine Nicotine Ethanol Aspirin (NSAID) What do you think the others were? Stimulants? Depressants?