1. Julien’s Primer of Drug Action 40th Anniversary Edition
Claire D. Advokat, Joseph E. Comaty, Robert M. Julien
Julien’s Primer of Drug Action
Thirteenth Edition
40th Anniversary Edition
Chapter 7
Cocaine, the Amphetamines, and Other Psychostimulants
Copyright © 2014 by Worth Publishers

2. Table 7.1
Claire D. Advokat, Joseph E. Comaty, Robert M. Julien: Julien’s Primer of Drug Action, Thirteenth Edition Copyright © 2014 by Worth Publishers

3. Structures of cocaine and the products of cocaine metabolism. A
Structures of cocaine and the products of cocaine metabolism. A. Normal metabolism to benzoylecognine. B. Metabolism to the abnormal, active metabolite cocaethylene, formed from the interaction between cocaine and alcohol. Cocaethylene is the ethyl ester of benzoylecognine.
Figure 7.1
Claire D. Advokat, Joseph E. Comaty, Robert M. Julien: Julien’s Primer of Drug Action, Thirteenth Edition Copyright © 2014 by Worth Publishers

4. Skin Reactions to Adulterated Cocaine
Dr. Noah Craft
Skin Reactions to Adulterated Cocaine
The U.S. Department of Justice has reported that up to 70 percent of cocaine in the United States is contaminated with the drug levamisole, which is cheap, widely available, and commonly used for deworming livestock. Levamisole had been prescribed for humans in the past but was discon-tinued after patients developed side effects similar to those found in the cocaine users. There are recent reports of patients who developed purple-colored patches of necrotic skin on their ears, nose, cheeks, and other parts of their body and, in some instances, suffered permanent scarring after they had used cocaine. Twenty-three cases were recently described, with symptoms of fever, body aches, and sore throats, in addition to necrotic lesions (Vagi et al., 2013).

5. Dopamine nerve terminal and transporter proteins involved in the active uptake of dopamine (DA). A. Two transporters are shown. The first is a vesicular DA transporter (VMAT) located in the cytoplasm of the presynaptic neuron, bound to DA-containing storage vesicles. This transporter carries DA from the cytoplasm into storage. The second type of DA transporter (the DAT) is found on the synaptic membrane of the presynaptic neuron and functions to transport DA from the synaptic cleft into the presynaptic nerve terminal, recycling the transmitter and ending the process of synaptic transmission. B. It is the DAT that is blocked by cocaine, prolonging the action of DA in the synaptic cleft. [Adapted after Katzung et al., 2009, Figure 32-5, p. 732/e1547.]
Figure 7.2
Claire D. Advokat, Joseph E. Comaty, Robert M. Julien: Julien’s Primer of Drug Action, Thirteenth Edition Copyright © 2014 by Worth Publishers

6. A graph of brain regions demonstrating a significant association between the decrease in gray matter volume and duration of cocaine use. Individuals who had been using cocaine for longer periods of time had greater extent of gray matter volume reduction in the anterior and middle cingulate gyrus, middle frontal cortex (orbital part), rectus gyrus, supplementary motor area, superior temporal gyrus, insula, cerebellum and in the left caudate (r = –0.75, P < 0.001). [Ersche et al., 2011, Figure 2, p ]
Figure 7.3
Claire D. Advokat, Joseph E. Comaty, Robert M. Julien: Julien’s Primer of Drug Action, Thirteenth Edition Copyright © 2014 by Worth Publishers

7. The basic sympathomimetic amine nucleus (phenylethylamine), the neurotransmitters dopamine, norepinephrine and epinephrine, and the structures of amphetamine and methamphetamine.
Figure 7.4
Claire D. Advokat, Joseph E. Comaty, Robert M. Julien: Julien’s Primer of Drug Action, Thirteenth Edition Copyright © 2014 by Worth Publishers

8. Mechanism of action of amphetamine on dopamine nerve terminals
Mechanism of action of amphetamine on dopamine nerve terminals. Amphetamine blocks the dopamine (DA) transporter (DAT), preventing reuptake of DA. Amphetamine is also taken up into the terminal by the DAT, where it interferes with the DA transporter of the synaptic vesicles (VMAT). This depletes the vesicles, and increases DA levels in the cytoplasm of the terminal. As a result, the direction of the DAT reverses, which means more DA is released into the synaptic cleft. Not shown is an additional effect of amphetamine, a weak block of the enzyme MAO. Amphetamine also has comparable effects on the norepinephrine transporter (NET) [Adapted after Katzung, et al., 2009, Figure 32-5, p. 732/e1547.]
Figure 7.5
Claire D. Advokat, Joseph E. Comaty, Robert M. Julien: Julien’s Primer of Drug Action, Thirteenth Edition Copyright © 2014 by Worth Publishers

9. Two-and-a-Half Years of Meth Abuse
Multnomah County Sheriff’s Office/Faces of Meth™
Two-and-a-Half Years of Meth Abuse
One of the most striking effects of meth is the change in the physical appearance of meth users. Because meth causes the blood vessels to constrict, it cuts off the steady flow of blood to all parts of the body. Heavy usage can weaken and destroy these vessels, causing tissues to become prone to damage and inhibiting the body’s ability to repair itself. Acne appears, sores take longer to heal, and the skin loses its luster and elasticity. Some users are covered in small sores, the result of obsessive skin-picking brought on by the hallucination of having bugs crawling beneath the skin, a disorder known as formication.

10. Heringlake, DDS, St. Cloud Correctional Facility
Meth Mouth
Users with “meth mouth” have blackened, stained, or rotting teeth, which often cannot be saved, even among young or short-term users. The exact causes of “meth mouth” are not fully understood. Various reports have attributed the decay to the corrosive effects of the chemicals found in the drug, such as anhydrous ammonia (found in fertilizers), red phosphorus (found on matchboxes), and lithium (found in batteries), which when smoked or snorted might erode the tooth’s protective enamel coating; however, it is more likely that this degree of tooth decay is brought on by a combination of side effects from a meth high. The drug causes the salivary glands to dry out, which allows the mouth’s acids to eat away at the tooth enamel, causing cavities. Teeth are further damaged when users obsessively grind them, binge on sugary food and drinks, and neglect to brush or floss for long periods of time.

11. Comparison of brain structure volumes in methamphetamine abusers (MA) and healthy control persons (CTL). Mean values and mean percentage gains/losses (percent) are shown for the volumes of the hippocampus (A), ventricles (B), total cerebral gray matter (C), and white matter (D). In general, hippocampal and gray matter volumes decrease and are compensated for by increases in ventricle and white matter volumes. NS = nonsignificant increase/decrease. The hippocampal volume deficits correlate with word recall (memory) performance. [Modified data from Thompson et al. (2004), Figure 3, p ]
Figure 7.6
Claire D. Advokat, Joseph E. Comaty, Robert M. Julien: Julien’s Primer of Drug Action, Thirteenth Edition Copyright © 2014 by Worth Publishers

12. Structures of two naturally occurring catecholamine psychostimulants—ephedrine (from Ephedra, or ma-huang) and cathinone (from Catha edulis, or khat)—and four synthetic noncatecholamine psychostimulants—methylphenidate (Ritalin), pemoline (Cylert), modafinil (Provigil), and armodafinil (Nuvigil).
Figure 7.7
Claire D. Advokat, Joseph E. Comaty, Robert M. Julien: Julien’s Primer of Drug Action, Thirteenth Edition Copyright © 2014 by Worth Publishers

13. How the cocaine vaccine works
How the cocaine vaccine works. This pair of diagrams shows the difference between a patient’s immune system with and without protection from antibodies against cocaine. In the unprotected immune system (left part of figure), the normal condition, cocaine molecules (circles) enter the bloodstream and then cross unimpeded from the blood into the brain. In the protected immune system (right part of figure), a series of vaccines has stimulated the patient’s immune system to produce cocaine antibodies in the blood (Y symbols). They attach to most of the molecules of cocaine and prevent them from reaching the brain. [After
Figure 7.8
Claire D. Advokat, Joseph E. Comaty, Robert M. Julien: Julien’s Primer of Drug Action, Thirteenth Edition Copyright © 2014 by Worth Publishers