January 25, 2025	PSY 340 Brain and Behavior  Class 09: Substance Abuse and Addiction (Outline)

 

 

• DMX (1970-2021). Rapper. Drug-induced (cocaine) heart attack.
  
• Taylor Hawkins (1972-2022). Drummer for Foo Fighters. Apparent heart disease/attack. Multiple drugs found in his system at the time of death included opioids, benzodiazepines, tricyclic antidepressants, and THC (active ingredient in marijuana, see below).
• Jimi Hendrix (1942-1970). Musician. Alcohol & barbiturate overdose. Inhalation of vomit.
  
• Philip Seymour Hoffman (1967-2014). Actor. Heroin overdose.
  
• Whitney Houston (1963-2012). Singer, actress. Accidental drowning. Cocaine + Benadryl, Flexeril, Xanax.
• Michael Jackson (1958-2009). Singer. Homicide. MD administration of propofol, lorazepam, diazepam, & midazolam.
• Heath Ledger (1979-2008). Actor. Accidental. "died of the combined effects of five (5) prescription & one (1) over-the-counter medications: oxycodone, hydrocodone, diazepam, temazepam, alprazolam, and doxylamine (Unisom®)
• Mac Miller (1992-2018). Rapper, songwriter. Accidental overdose of fentanyl, cocaine & alcohol
  
• Prince Rogers Nelson (1958-2016) Accidental overdose of fentanyl
• Lil Peep (Gustav Ahr; 1996-2017). Rapper and singer. Multiple Xanax (alprozalam) pills. Blood showed traces of cannabis, cocaine, tramadol, hydrocodone, hydromorphone, oxycodone, & oxymorphon.

   I. Drug Mechanisms

Types of Drug Effects

• Antagonist: blocks
• Agonist: increases or mimics
  
• Mixed agonist-antagonists
  

Other Qualities of Drugs

• Affinity: tendency of a drug to bind to a receptor (strong to weak)
• Efficacy: tendency of a drug to activate a receptor (high to low)

• Synaptic activity is affected in a lot of different ways. These include

• increasing release of neurotransmitters
• blocking re-uptake
• blocking the effects of enzymes that breakdown the neurotransmitters
• affecting the post-synaptic receptors (stimulating or blocking them), etc.
  

A. Olds & Milner (1954): Dopamine & the Nucleus Accumbens

James Olds & Peter Milner (1954) found areas in rat's brain which leads to continual self-stimulation: reinforcement via the nucleus accumbens.

Most drugs of abuse are likely to increase the release of dopamine and norepinephrine with effects on the n. accumbens.

Dopamine carries more information than simple reinforcement, e.g., helping remember pleasure

Prediction Error Theory: The amount of dopamine released in the brain is a function of whether the value of a reward is greater than, equal to, or less than expected. When we are surprised by an experience (a great party, the ingestion of a new drug, etc.), more dopamine is released.

Kent Berridge (U. Michigan) argues that there are two aspects of reinforcement that are different:

• Liking (giving pleasure) and

• Wanting, Desiring (motivation, grabbing attention, "salience")

His "Incentive Salience/Sensitivity Theory" proposes that

• Dopamine is not associated directly with pleasure, but

• Dopamine IS centrally involved in making an individual desire or want something intensely.

"Liking" or "pleasure" arises from a variety of "hot spots" in the brain (the yellow areas in the diagram on the right).

Attention-getting, Craving, Wanting, or Salience arises from the function of dopamine in the nucleus accumbens and other sections of the mesolimbic system of the brain. Why? The brain has been "sensitized" (= has learned deeply) to all of the cues associated with a drug.

Individuals with addiction will have a powerful urge to get a drug even if there is no pleasure.

Some Drugs of Abuse (not in book) 

   1. Stimulant drugs (e.g., amphetamines, cocaine, etc.)

• produce excitement, alertness, elevated mood, decreased fatigue, and sometimes motor activity. Each of these drugs increases activity at dopamine receptors, especially at D2, D3, and D4 receptors. Stimulant drugs are often highly addictive.

a. Amphetamine increases dopamine (DA) release from presynaptic terminals and also reverses the direction of the dopamine transporter (reuptake gate) which makes more DA available.

b. Cocaine ("coke") blocks the reuptake of DA, NE, and serotonin at the synapse.

c. Methylphenidate (Ritalin®): Stimulant currently prescribed for Attention Deficit Disorder (ADD)

--> the use of Ritalin® when used as prescribed does not lead to the use of other drugs in later life.

e. MDMA (methylenedioxymethamphetamine or "Ecstasy")

   2. Nicotine

• morphine
  

• heroin

• methadone, a synthetic ("man made") drug rather than derived from the poppy plant

• Oxycodone [OxyContin®] & hydrocodone [Zohydro ER, Vicodin, Norco] These are semi-synthetic opioids (see above). Note that Vicodin is a mixture of acetaminophen [Tylenol] & hydrocodone.

• Fentanyl (a very powerful synthetic opioid)
  

Opioid Receptors (= inhibitory G protein-coupled receptors)

• Opioid family of receptors. There are multiple places within the brain, spinal cord, and peripheral nervous system (as well as the digestive track) that are populated by opioid receptors. However, different types of opioid receptors are activated by different types of opioid molecules. There are four general classes of opioid receptors including the μ (mu) receptors which have a high affinity for morphine-like molecules [the other types are δ (delta), κ (kappa), and NOP (noiceptin/orphanin) receptors/]. Each of these types of receptors have a number of subtypes.

• Opioid receptors can be found on both the presynaptic terminal button and the postsynaptic membrane (see figure). Thus they are able to affect both the release of neurotransmitters from the presynaptic neuron and the effects of neurotransmitters on the postsynaptic neuron.

• Opioid receptors within the central nervous system cause hyperpolarization in GABA neurons. Many of these GABA neurons normally restrain or inhibit the release of dopamine neurons.  As a result, opiate receptors overall have the net effect of increasing the release of dopamine in the brain.
  

• Opiates decrease (inhibit) other opiate receptors & cause a range of effects such as analgesia (pain relief), decreased respiration, lowered motility of the GI system (anti-diarrhea), and physical dependence

• Contains the chemical delta-tetrahydrocannabionol (delta-THC) and other cannabinoids (chemicals related to delta-THC); Δ-THC works by attaching to cannabinoid receptors (particularly in hippocampus, basal ganglia, & cerebellum). These receptors are found only on the presynaptic membrane and form negative feedback loops with postsynaptic GABA or glutamate membranes. The cannabinoids tend to slow down or inhibit the release of both neurotransmitters.

• Lipid soluble (dissolves/stored in fatty tissue)

• Heavy use impairs memory significantly.
  

• Adolescents with genetic vulnerability to develop schizophrenia are at greater risk when using marijuana in heavy doses

• Moderate use does seem to lead to some level of tolerance.

A. Alcoholism or alcohol dependence

B. Alcohol (ethanol, ETOH): Inhibits Na⁺ ion flow across the neuron membrane; decreases serotonin activity, facilitates transmission at the GABAA receptor, blocks glutamate receptors, and increases dopamine activity. Thus, alcohol is mostly an INHIBITORY substance.

C. Types

a. Type I Alcoholism

b. Type II Alcoholism

D. Predispositions for Alcoholism & Substance Abuse

i. Alcoholism: Tends to be more likely among those who, as children, were described as impulsive, risk-taking, easily bored, sensation-seeking, & outgoing.

Associated with genes causing

• "long form" dopamine type 4 receptors: these receptors tend to be less sensitive to ETOH and, thus, people tend to consume more, and
  
• more active form of COMT (enzyme breading down DA) leading to lower levels of reinforcement & higher levels of impulsiveness.

ii. Among sons of alcoholics, alcoholism is associated with

• less than average intoxication after drinking a moderate amount of alcohol.
• experiencing more than average relief from tension after drinking alcohol.
• having a smaller than normal amygdala in the right hemisphere

iii. Genetic influences on drug abuse

• Strong evidence for polygenetic influences on alcoholism, cocaine use, and some other drugs.
  

iv. Environmental Influences

• Mothers who drink alcohol during pregnancy have children with a greater risk of alcoholism in later life
• Children with a variant gene for a less sensitive GABA receptor tend to have impulse control problems (including drug use) unless they grow up in families which clear parental supervision.
  

• Medications to Combat Opioid Abuse

• The most effective medical treatment for opioid (heroin, etc.) abuse in patients who have failed to "kick their habit" by more traditional treatment methods is the use of suboxone or methadone.
  

• Suboxone
  

• Methadone
  

• Note that our textbook says, "these drugs do not end the addiction. They merely satisfy the craving in a less dangerous way" (p. 472). When the alternative to suboxone and methadone is so frequently death, it would seem that keeping people alive ought to be the principal goal of health care providers.