2. Outline
1. Addiction!
1. Impact
2. Use vs. Abuse
2. Psychotropic Drugs and the Brain!
1. Common Properties
2. Overview of Addiction Circuitry
3. Classes of Psychotropic Drugs!
1. Hierarchy of Drug Classes
2. Stimulants vs. Depressants
3. Methamphetamine vs. Heroin
4. Medical and Scientific Uses for Illicit Drugs
4. What is a Drug?
Drug: chemical substance that has known biological effects
on humans or other animals (foods excluded)!
Psychoactive Drug: chemical substance that alters a
person’s mood, level of perception, or brain functioning
Psychoactive drugs share many common structural features.
We will discuss these features in upcoming slides.
!
Take Away Message
Not all drugs are psychoactive drugs
5. Addiction: Key Terms
Substance Use: drug consumption!
Substance Abuse: pattern of recurrent drug use despite
interference with ability to fulfill obligations!
Substance Dependence: pattern of repeated drug self-
administration which results in withdrawal, tolerance, and
unpleasant side effects. Also known as addiction.
!
Take Away Message
substance use < substance abuse < substance dependence =
addiction
6. Physiological vs.
Psychological Addiction
• Not all drugs are physiologically addictive
• For example, repeated use of PCP or LSD does not result in development of tolerance.
Many researchers believe that marijuana also falls into this category.
• Tolerance: the need to consume greater amounts of a drug to achieve the initial effect!
• Repeated use of opiates (heroin, morphine), amphetamines, and nicotine does result in
development of tolerance
• But even drugs that are not physiologically addictive can be psychologically addictive
• Psychological addiction: compulsion to take the drug as a way to prepare for certain
activities or relieve negative mood states!
!
Take Home Message
Not all drugs are physiologically addicting, but that doesn’t mean that they aren’t (or don’t have
the potential to be) psychologically addicting.
8. Risk Factors
1. Genetic!
• Lifetime prevalence of drug dependence among parents, siblings, and
children ~3 to 5 times higher than general population (twin and adoption
studies)
2. Individual Variations in Metabolism!
Individuals who need a higher dose to achieve an effect are more likely to
become addicted
3. Social!
• Some cultures prohibit or actively discourage alcohol consumption
• Low socioeconomic status associated with higher prevalence of drug abuse
and dependence
9. 1. Addiction!
1. Impact
2. Use vs. Abuse
2. Psychotropic Drugs and the Brain!
1. Common Properties
2. Overview of Addiction Circuitry
3. Classes of Psychotropic Drugs!
1. Hierarchy of Drug Classes
2. Stimulants vs. Depressants
3. Methamphetamine vs. Heroin
4. Medical and Scientific Uses for Illicit Drugs
11. Drugs and the Brain
• Psychoactive drugs can be agonists or antagonists
of certain neurotransmitters
• Not all drugs act on the same targets
• For example, LSD is a serotonin agonist and
methamphetamine is a dopamine agonist!
• In reality, it’s a little more complicated than that—if you’re interested in learning more, shoot me an email or talk to me after class
• Users report different experiences between the two
drugs
13. Dopamine: Why We Care
• Even though psychoactive
drugs affect many classes of
neurotransmitter, addiction
researchers are particularly
interested in studying the
effect of drugs on dopamine.
• So far, we’ve learned about
dopamine in relation to the
basal ganglia. We know it’s
associated with initiation of
movement.
• Why do addiction care so
much about it?
14. Dopamine: Why We Care
• When dopamine projects onto some
regions of the basal ganglia, the result
is the modulation of movement-related
functions.
• When it projects onto the VTA and
Nucleus Accumbens, the result is
feelings of reward
Take Home Message:
The same chemical that stimulates
movement in the basal ganglia is also
responsible for the rush associated with
being high. The fact that dopamine
modulates two entirely different processes
is not a function of the chemical itself—its
effect varies depending on the cortical
region it’s acting on.
15. Common Properties
• Psychoactive drugs have to be able to pass through the blood-
brain barrier to enter the CNS
• The blood-brain barrier prevents the entrance of large polar
molecules.
• This is one of the body’s clever defense mechanisms for
preventing neuropathogens from entering the CNS.
!
Take Home Message:!
Psychoactive drugs are typically small, non-polar, lipid-like
molecules.
16. Common Properties
• Chemical structure of
psychoactive resembles that
of neurotransmitter
• For example, LSD and psilocin
(mushrooms) bind to the
serotonin receptor
• Observe the structural
similarities between
serotonin (5-HT), LSD, and
psilocin
17. Consequence of Drug Abuse:
Receptor Endocytosis
• The brain is always trying to maintain homeostasis
• It notices if it’s being blasted with neurotransmitter
and tries to adjust its response accordingly
• After repeated use of a drug, the brain tries to
lower the intensity of the response to it by getting
rid of some of its post-synaptic receptors
• Receptors are internalized back into the cell in a
process called receptor mediated endocytosis
18. 1. Addiction!
1. Impact
2. Use vs. Abuse
2. Psychotropic Drugs and the Brain!
1. Common Properties
2. Overview of Addiction Circuitry
3. Classes of Psychotropic Drugs!
1. Hierarchy of Drug Classes
2. Stimulants vs. Depressants
3. Methamphetamine vs. Heroin
4. Medical and Scientific Uses for Illicit Drugs
21. Key Vocabulary
Agonist: Binds to and activates
receptor
Antagonist: Binds to and
prohibits activation of a receptor
!
Note: For the duration of this
lecture, I will operate on the
assumption that you understand
these crucial terms
22. Drug Classes: Outline
• There are many classes of drugs; if I were to list all
of them in the hierarchy diagram it would take up
half of the lecture slides
• I’m going to briefly go over some common
characteristics of drugs in each class.
• But I’m only going to choose one or two drugs
from each category to discuss at length
23. Stimulants
• Increase excitation in central
nervous system by stimulating
action of certain
neurotransmitters
• epinephrin (adrenaline),
norepinephrin, dopamine,
serotonin
• Examples include caffeine,
cocaine, amphetamines, LSD,
PSP, MDMA, nicotine
25. Methamphetamine: How It Works at the Cellular Level!
http://www.youtube.com/watch?v=T-duk-PiIXo
• Binds to VMAT receptors on dopamine-containing vesicles causing dopamine to leak into the
cytoplasm!
• This disrupts the ability of vesicles to store dopamine
• If dopamine can’t be in a vesicle (because meth is bound to VMAT on vesicle), where is it going to go?
• Answer: It will float around in the cytosol
• Chemicals flow from areas of high concentration to areas of low concentration; because the
concentration of cytosolic dopamine is so high, the dopamine will travel out of the cytoplasm into the
synapse
• Dopamine uses the dopamine transporters (DAT) to escape into the synapse. This is not how dopamine
transporters are usually used; in a sober person, DAT is only used for dopamine reuptake. But adding
meth into the mix changes things up.
• Ok, so lots of dopamine is in the synapse… now what?
• Meth binds to and blocks dopamine transporters on the presynaptic cell. This means that
dopamine in the synapse can no longer use these channels to re-enter the pre-synaptic cell.
• Dopamine stays in the synapse (because it has nowhere else to go) and continues to stimulate the
post-synaptic dopamine receptors until the effect of meth wears off.
Stimulants: Meth
28. Depressants: Heroin
• At the level of the spinal cord, opiate receptor
stimulation blocks pain signals from entering the brain
• Weird, right? We have opioid receptors in our
spinal cord, too. Don’t forget that the spinal cord is
part of the central nervous system
• At the level of the cortex, opioid receptor stimulation
causes feelings of euphoria by stimulating the
“pleasure” centers of the brain, such as the ventral
tegmental area (VTA) and the nucleus accumbens
29. Depressants: Heroin
• Heroin binds to and stimulates opiate receptors. In other words, Heroin is
an opiate agonist
• Note that just because a chemical is an agonist to a particular receptor
does not necessarily mean that the chemical itself is a stimulant
• Also note that “pain” refers to both emotional and physical pain.
• Opiate antagonists increase the activity of a circuit which blocks pain
signaling. The overall result of this stimulation is reduction of the excitatory
signaling which would otherwise manifest as a response to painful stimuli
• Heroin not the only chemical that can stimulate these receptors.
Endorphins, known as “endogenous opiates,” also stimulate the same
receptors as heroin
30. Depressants: Heroin
• As mentioned earlier, repeated use of heroin results in build up of
tolerance
• More and more of the drug is needed to achieve the same initial “high”
• Stopping heroin results in withdrawal
• Symptoms of withdrawal can be ameliorated by treatment with a partial
dopamine agonist known as methadone
• Methadone is very addictive. If a non-addict were to consume
methadone, he or she would get high
• To an addict, however, methadone only functions to relieve withdrawal
symptoms
31.
32. Depressants: Heroin
• Just as heroin stimulates
opioid receptors, opioid
receptors can also be blocked
by other compounds
• Naltrexone is an opioid
antagonist
• Naltrexone is sometimes used
as a treatment for alcohol and
opioid dependence
Naltrexone structure
33. Outline
1. Addiction!
1. Impact
2. Use vs. Abuse
2. Psychotropic Drugs and the Brain!
1. Common Properties
2. Overview of Addiction Circuitry
3. Classes of Psychotropic Drugs!
1. Hierarchy of Drug Classes
2. Stimulants vs. Depressants
3. Methamphetamine vs. Heroin
4. Medical and Scientific Uses for Illicit Drugs
35. Medical and Scientific Uses
• Methamphetamine hydrochloride
(trade name Desoxyn) is FDA
approved for treating ADHD and
obesity
• NMDA antagonists such as PCP
and ketamine used to mimic
schizophrenia in rodent and
primate models
• Morphine as an analgesic post-
surgery
• Ketamine analgesic in rodents;
eliminates pain associated with
survival and non-survival surgeries
