BMB 10

Addiction

a chronic disease characterized by drug seeking and use that is compulsive, or difficult to control

these brain changes can be...

persistent

Using appropriate terminology can help reduce stigma

- sigmas discourage people from seeking help and can negatively impact patient care

name some patterns of symptoms caused by using a substance use that reflects current clinical standards and reduces stigma

1.Using more of a substance than intended or using it for longer than you're meant to.

2. Trying to cut down or stop using the substance but being unable to.

3. Experiencing intense cravings or urges to use the substance.

4. Needing more of the substance to get the desired effect — also called tolerance.

5. Developing withdrawal symptoms when not using the substance.

6. Spending more time getting and using drugs and recovering from substance use.

7. Neglecting responsibilities at home, work or school because of substance use.

8. Continuing to use even when it causes relationship problems.

9. Giving up important or desirable social and recreational activities due to substance use.

10. Using substances in risky settings that put you in danger.

11. Continuing to use despite the substance causing problems to your physical and mental

health

DSM

Diagnostic and Statistical Manual of Mental Disorders

- outlines disorders

withdrawal

seen when drug use is terminated and symptoms are the opposite of the drug's effects

dependence

the body has made changes to compensate for drug's presence

-functions normally when the drug is present

severity of both withdrawal and dependent depends on

the drugs and the patterns of use

Addiction and physical dependence may occur ...

together or separately and are often accompanied by shift from impulsive to

compulsive behavior

outline the progression of drug addiction

relapse

return to active drug use after a period of successful abstinence or recovery

conditioned drug tolerance

Returning to a place where drugs were once taken (or even thinking

about a drug) causes conditioned compensatory responses (tolerance/withdrawal), craving, and

relapse

Drugs can change synaptic transmission by acting on the ?

pre and post synaptic membrane

- know what a pre and post synaptic change would look like

pre synaptic effects

Transmitter Production (prevent or increase):

-Alter enzymes making neurotransmitters (1)

- Alter the ability of transport of raw materials (2)

-Alter the storage of transmitters (3)

Transmitter Release (prevent or increase):

-Bind to ion channels (prevent or increase release) (4, 5)

-Bind to pre-synaptic receptors (6)

-Alter release (7)

Transmitter Clearance (prevent or increase):

-Alter re-uptake (8)

-Enzymatic degradation (9)

post synaptic effects

Transmitter Receptors

-Antagonists block postsynaptic receptors from being

activated (1)

- Receptor agonists bind to receptors and activate (2)

Intracellular Postsynaptic Processes

- Receptor up/down regulation (3)

-Target tissue may alter its sensitivity to drug by changing

the number of receptors

- Down-regulation: fewer receptors

-Up-regulation: more receptors

- Second messenger systems (4)

The reward pathway

Mesolimbocortical Pathway

- VTA to Nucleus Accumbens

(many addictive drugs cause a release of dopamine in the nucleus accumbens)

research indicates that the addictive power of drugs comes from what?

stimulating the VTA → nucleus

accumbens pathway

Self-Administration Study

a study that involves testing whether research participants will "give themselves" a drug

Electrical Self-Stimulation Studies

stimulates the nucleus accumbens pathway via electrode when the rat presses the lever

Findings of these studies

The rat will press the level to

stimulate the pathway "at the

expense of other vital behaviors

such as eating or drinking"

Opioids examples

-Morphine (Schedule II)

-Fentanyl (Schedule II)

- Carfentanil (Schedule II)

- Oxycodone (Schedule II)

- Heroin (Schedule I)

Opioid therapeutic uses

Pain management, anesthesia,

cough suppression (back in the day)

Opioid acute effects

euphoria, relaxation, pain relief,

respiratory depression, nausea

-high doses = coma/death

Opioid drug administration

-Pills, IV Injection, Needles (health hazard)

Opioid mechanism of action

Drugs bind to opioid receptors (brain + spinal cord)

-Receptors are activated

- Pain signals are reduced (turn off GABA neurons)

-Indirect increase of dopamine in NAc (disinhibition of

GABAergic neurons in VTA)

- Dopamine creates feelings of pleasure & reward

Opioid withdrawal

Muscle pain, diarrhea, vomiting, nausea, sweating,

anxiety, excessive heart rate, abdominal pain,

insomnia

Desire to avoid withdrawal adds ...

motivation to use

Treatments for Opioid use disorder

Drugs that block opioid receptors can reverse

effects of opioids

- Narcan (naloxone) → immediate, prevent overdose

- Naltrexone → long-term, helps stay drug-free

Medication-assisted treatment (Gold standard)

Harm reduction strategies

- Naracan distbiution

Cognitive Behavioral Therapy (CBT)

what is the golden standard

medication-assisted treatment

- methadone and Buprenorphine

Cannabinoid examples

-Δ9-tetrahydrocannabinol (THC) - main psychoactive compound in marijuana

(Schedule I)

-Dronabinol - synthetic purified version of THC (Schedule II)

-Cannabidiol (CBD) (Not considered a controlled substance under 2018 Farm Bill

(hemp))

Cannabinoid therapeutic uses

epilepsy (CBD & dronabinol) FDA approved, relieve nausea & vomiting, relief from chronic pain, anorexia

Cannabinoid acute effects

-relaxation, mood alterations, increased appetite, impaired

judgement, motor deficits, increased impulsivity (Don't smoke & drive)

-High Doses: pseudo-hallucinations, synesthesia, paranoia, confusion, respiratory

problems, addiction, cognitive decline, short-term memory loss, heart attacks

-No evidence that cannabis causes permanent brain damage

Cannabinoid drug administration

smoking, eating (edibles), topicals

Cannabinoid mechanism of action

Binds to receptors of anandamide, 2-AG

(endogenous transmitters)

- CB1 & CB2 receptors

- Activation of these receptors lead to increased

firing of dopamine neurons

Cannabinoid Withdrawal

Irritability, insomnia, decreased appetite, anxiety

(mild, not life-threatening).

Stimulant examples

-Caffeine (Not a regulated controlled substance)

- Nicotine (Not a regulated controlled substance)

-Cocaine (Schedule II)

Amphetamine/Methamphetamne (Schedule II)

-Adderall, Ritalin, Vyvans

Stimulant therapeutic uses

ADHD, Narcolepsy, Local Anesthetic (rare- cocaine)

Acute effects of stimulant

Increased alertness, focus, energy, elevated HR/BP,

decreased appetite

- High Doses: Neurotoxicity, psychosis, cardiovascular strain, stroke risk, insomnia,

anxiety

Drug administration of stimulations

Smoking, Snorting, Ingestion (Pills)

Explain the addiction potential of stimulants

stimulants have a strong addiction potential

- About 70% of those who experiment with smoking

become addicted, and only 20% of attempts to

stop smoking are successful

Withdrawl of stimulants

Headaches, fatigue, depression, sleep

disturbances, Irritability, anxiety, difficulty

concentrating, strong cravings.

mechanism of action of Nicotine

-Binds to nicotinic acetylcholine receptors (Some

found on dopamine neurons)

- Receptors are activated

- Release of dopamine → pleasure, reward, alertness

mechanism of action cocaine

-Blocks dopamine reuptake transporters

on presynaptic neurons

-Dopamine stays in the synapse longer → more activation of postsynaptic

dopamine receptors

mechanism of action amphetamines

-Reverses DAT transporter (normally it

removes dopamine from synapse)

- Now its pumping dopamine into the synapse → more activation of postsynaptic dopamine receptors

Dopamine and Cocaine

blocks transporters in dopamine from reuptake, leaving more dopamine in the synapse

Alcohol examples

beer, wine, liquor

- Not classified as a controlled substance

- High potential for misuse

Alcohol therapeutic uses

none

Effects of Alcohol

an initial stimulant phase,

followed by a depressant phase (GABA agonist)

-Acute effects: relaxation, lowered inhibition, motor

impairment

-High Doses: liver disease, cardiovascular problems,

brain atrophy, dependence

Alchohol administration

oral

Alcohol mechanism of action

-Classified as a depressant drug (reduces excitability of neurons - not mood!)

-Binds to GABA receptors to make them even

more inhibitory (agonist) & binds to glutamate

receptors preventing glutamate from binding to

the cell (antagonist)

Alcohol withdrawal

Severe and could be life threatening

Treatments for Alcohol use

-Benzodiazepines for withdrawal

- Naltrexone (Vivitrol), acamprosate (Campral), disulfiram (Antabuse)

- Cognitive Behavioral Therapy

Psychedelics examples

-LSD (lysergic acid) (Schedule I)

-Mescaline (peyote cactus) (Schedule I)

-Psilocybin (psilocybe mushrooms) (Schedule I)

-MDMA* (Schedule I)

Psychedelic therapeutic uses

No FDA-approved uses, low addiction

potential

Current Therapeutic Research

-LSD: Anxiety, Depression, Micro-Dosing, Substance-use disorder

- Mescaline: Substance Use Disoders

- Psilocybin: Substance-use disorders, PTSD, depression

-MDMA: PTSD

Psychedelic drug administration

ingestion

acute effects of psychedelic

-Vivid visual hallucinations,

slowing of the sense of time, feelings of

depersonalization, strong emotional reactions, disruption of logical thought

-Long-term effects: "bad trips", dehydration,

serotonin toxicity

Psychedelics Withdrawal

depression and mood swings

LSD mechanism of action

-Binds to serotonin receptors (especially 5-HT2A)

-Activates receptors --> increased serotonin

(agonist at the serotonin receptor)

MDMA mechanism of action

-Enters neurons that release serotonin & dopamine

-Blocks reuptake → increases dopamine & serotonin in

synapse

(indirect agonist on serotonin and dopamine)

Summarize the addiction potential of the drug classes we have discussed...

opioids- very high

stimulants-high

alcohol-high

cannabinoids-moderate to low

psychedelics-very low