W HICH EXPLAINS A PERSON WHOSE CAFFEINE USE MAKES THEM SLEEPY ? A.T HEY HAVE WEAK CYP1A2 B.T HEY HAVE STRONG CYP1A2 C.T HEIR ADENOSINE PRODUCTION IS EXCESSIVELY STRONG D.T HEIR ADENOSINE RECEPTORS BIND CAFFEINE AS AN AGONIST

AMPHETAMINES ARE…. Amphetamine – general category

HOW ABOUT HERBAL STIMULANTS? ” Catha edulis ” Catha edulis” active ingredient – cathine (cathidine) HydroxycutMetabalife FDA – 50+ deaths, high blood pressure, stroke, heart attack, one death NOT regulated Packaged as food suppleme nt to avoid regulation, inaccurat e dosage info…

Q: I F AMPHETAMINES FOLLOW THE SAME RULE AS XANTHINES WITH REGARD TO THE NUMBER OF METHYLS, WHICH AMPHETAMINE IS MOST POTENT - DEXTROAMPHETAMINE, EPHEDRA, OR CATHINE ? A: EPHEDRA

Orally Ephedra & cathine Pills/Capsules Smoked Insufflated Intravenous

I NJECTING AMPHETAMINE INTRAVENOUSLY WILL : A.H URT ! B.S PEED DELIVERY TO THE BRAIN C.R ESULT IN GREATER ADDICTION D.E XPOSE A USER TO BLOOD - BORNE PATHOGENS E.A LL OF THE ABOVE

ED50= 5– 60 mg orally Lethal dose Effective dose Few exposuresRegular exposures Dosage Initial TI of 100 is common  long-time users often are taking in a dose that is only different from the LD by a factor of 10

Q: W HICH MECHANISM WOULD ACCOUNT FOR THE RAPID TOLERANCE THAT LEADS TO DECREASING IMPACT WHILE BLOOD LEVEL OF AMPHETAMINE IS STILL INCREASING ? A: DECREASING RECEPTOR BINDING. I T CAN ’ T BE INCREASING METABOLIC ENZYME - BECAUSE THE AMPHETAMINE LEVEL WOULD DECREASE IF METABOLIC ENZYME DECREASED.

CYP2D6 HO Half life ~ 1 hour dextro- amphetamine hydroxy- amphetamine

Endogenous amphetamine NH 2 Produce alertness Activate the sympathetic nervous system Treat narcolepsy, fatigue, obesity, ADHD Euphoriant Activate the Reward Pathway

Receptor density Post-synaptic membrane density PMID Study suggests rewiring or change in the brain of someone who used Ritalin Might increases probability of having drug addiction Why? Reuptake transporters could be e back to pre-Ritalin efficient state Cells have been permanently changed by Ritalin use Natural euphoric events are less rewarding

TOC Q: C OME UP WITH TWO REASONS FOR METHAMPHETAMINE BEING MORE ADDICTIVE THAN DEXTRO AMPHETAMINE. ( DIAGRAM ABOVE HAS A HINT ) A: SPEEDIER TO THE BRAIN ( INJECTED ) & EXTRA METHYL GROUP MAKES IT MORE INTENSE

In the ADHD subject above less red area= less dopamine receptor occupancy suggests less dopamine availability Thus inhibiting dopamine recycling might diminish the deficit in focusing

A MPHETAMINES CAN HAVE A SERIOUS PSYCHOLOGICAL HEALTH RISK A MPHETAMINES CAN HAVE A SERIOUS PSYCHOLOGICAL HEALTH RISK DO HAVE THE POTENTIAL TO PUSH A BORDERLINE PSYCHOTICS OVER THE BRINK. B RING ON SYMPTOMS THAT WERE LURKING BUT NOT FULLY EXPRESSED.

BRAIN DAMAGE CAN ALSO BE DETECTED BY ASSAYING FOR CHEMICALS MADE BY GLIAL CELLS IN RESPONSE TO NEURON DAMAGE. BRAIN DAMAGE CAN ALSO BE DETECTED BY ASSAYING FOR CHEMICALS MADE BY GLIAL CELLS IN RESPONSE TO NEURON DAMAGE. C HOLINE AND MYOINOSITOL ARE INCREASED GLIAL - MADE CHEMICALS THAT HAVE BEEN SHOWN TO BE INCREASED WITH NEURON DAMAGE THESE ARE INCREASED IN METHAMPHETAMINE - EXPOSED CELLS.

METHAMPHETAMINE AND BRAIN LOSS Media/meth/meth.jpg Limbic – 11% loss of tissue Hippocampus – 8% loss of tissue Subjects studied: ~ 30 years old 4 grams per week for 10 years-Smoked 22 people, 21 controls Increases seen in glial proteins that respond to neuron injury

Q: E PHEDRA IS “ HERBAL ”. M ANY THEREFORE CLAIM IT IS NATURAL AND HAS NO RISK. F OR THIS AND MANY OTHER REASONS, COMPANIES MARKET AND SOLD EPHEDRA AS A FOOD SUPPLEMENT. F OOD SUPPLEMENTS DO NOT HAVE TO GO THROUGH RIGOROUS SAFETY TESTING THAT DRUGS DO. H OW, THEN, CAN THEY BE DETERMINED TO BE UNSAFE? A: F OOD SUPPLEMENTS ARE DETERMINED TO BE UNSAFE IF THEY ARE ASSOCIATED WITH A LOT OF COMPLAINTS RELATING TO POOR HEALTH.

Q: U PON ENTERING, WHAT HAPPENS TO DOPAMINE ? A. IT IS RECYCLED BACK INTO THE CELL B. IT LEAVES THE CELL C. IT IS METABOLIZED D. IT IS CONVERTED INTO AMPHETAMINE Q: D OPAMINE IN THE SYNAPSE DOES WHAT WHEN A PERSON USES AMPHETAMINE ? A. IT IS QUICKLY RECYCLED B. IT IS QUICKLY METABOLIZED C. IT STAYS IN THE SYNAPSE DUE TO BLOCKED RECYCLING TRANSPORTERS D. IT STAYS IN THE SYNAPSE DUE TO INHIBITED METABOLIC ENZYMES