Drug Addiction

Addiction

biomedical disorder characterized by compulsive urge to use a substance or substances

• Behavioral syndrome in which drug procurement and use seem to dominate the individuals motivation and where the normal constraints (Control) on behavior are largely ineffective. May or not be accompanied by the development go physical dependence on the drug (Bozarth)

Substance use disorder

Involving actions individuals continuously perform despite negative consequences

• Cluster of cognitive, behavioral and physiological symptoms

Symptoms of SUDS (DSM-5)

1. Taking the substance in larger amounts or for longer than intended

2. Want to reduce substance use but not managing to do so

3. Spending increasing amounts of time procuring, using or recovering from substance use

4. Experiencing cravings and urges to use the substance

5. Having difficulty managing work/school and personal responsibilities

6. Continuing substance use despite causing relationship issues

7. Abandon social, occupational or recreational activities to use the substance

8. Continuing substance use despite repeatedly being placed in dangerous situations

9. Continue to use drugs when they know they have an existing physical or psychological issue can be exacerbated by substance use

10. Need more of substance to achieve desired effect (tolerance)

11. Developing withdrawal

    • 2-9 psychological dependence

    • 10-11 physical dependence

      • Mild: 2-3 symptoms

      • Moderate: 4-5 symptoms

      • Severe: 6+ symptoms

Intoxication

Alteration in consciousness, cognition, perception and behavior

Tolerance

Decrease in drug effect or increase in amount to achieve the same drug effect

Withdrawal

Symptoms, physical changes in physiology that are unpleasant

Physical Drug Dependence

Tolerance and withdrawal

Psychological Drug Dependence

obsession to acquire drugs and neglect other activities

Relapse

follows short or long period of abstinence

Overdose

died or could have died

Substance Use Disorder by WHO (ICD-11)

Must have 3 of 6

1. Have a strong desire or compulsion to take substance

2. Have difficulty in controlling when to take the substance, how much of the substance to take and when to stop using

3. Develop withdrawal

4. Needing more of the substance to get desired effect

5. Neglect other interest because time taken up by drug

6. Continue substance use even when harmful consequences

   Meet category of harmful use, one must be met

   1. Use of substance where impairment could be dangerous

   2. Continue use despite of physical, psychological or cognitive issues

   3. Detrimental behaviors and social problems related to use

      • All or none diagnosis

DEA Schedule of Drugs

Federal evaluation of the social effects (legality). Based on 2 factors

1. Is there medical use for the drug?

2. Abuse Potential: focus on abuse as harm, dependence liability/addiction liability

   • Policed by DEA

   • Regulated by congress with Controlled Substance Act (1970)

Schedule 1

No medical use/highest potential for dependence

• heroin,

• lysergic acid diethylamide (LSD),

• marijuana (cannabis), 3,4-methylenedioxymethamphetamine (ecstasy)

• methaqualone,

Schedule 2

Some medical use/highest potential for dependence

• hydrocodone per dosage unit (Vicodin),

• cocaine,

• methamphetamine,

• methadone,

• hydromorphone (Dilaudid),

• oxycodone (OxyContin),

• fentanyl,

• Adderall,

• Ritalin

Schedule 3

Some medical use/ moderate potential for dependence

• Codeine per dosage unit (Tylenol with codeine)

• ketamine,

• anabolic steroids,

• testosterone

Schedule 4

Some medical use/ low risk potential for abuse/Rdependence

• Xanax,

• Valium,

• Tramadol

Schedule 5

Some medical use/ lower risk potential for abuse/dependence

• cough preparations with less than 200 milligrams of codeine or per 100 milliliters (Robitussin AC),

• Lomotil,

• Lyrica,

Route of Administration

A notable feature of drug effect lies in route of administration

Determine

1. How Fast

2. How Much

3. How Long

ROA: Oral or GI

1. How fast- one of the slowest, 30-90 min

2. How much- one of the lowest, high degrees of metabolism and excretion

3. How long- one of the longest

ROA: Transdermal (Skin)

1. How Fast: one of slowest 30min-24hr

2. How much: one of lowest, very long path, variable capillary access

3. How long: one of longest

ROA: Sublingual or Buccal (Nasal, Rectal, vaginal)

1. How fast: one of the slowest, 30-90 min

2. How much: one of the lowest, non-soluble barrier, time spread, metabolism, excretion

3. How Long: one of the longest 24hr

ROA: Injection (Subcutaneous (SC), Intramuscular(IM), intra-peritoneal (IP), IV and intracerebreal (IC)

1. How Fast: fastest IC>IV» SC = IM=IP

2. How much: Most IC>IV» SC = IM=IP

3. How Long: shortest IC>IU» SC = IM=IP

ROA: Inhalation (Smoking)

1. How Fast: one of the fastest, secondary to IC, equal to IV

2. How much: Close to most, 2nd to IC, = to IV

3. How Long: short, equal to IV

Concurrent Drug Use

the use of more than one drug over the past year, month or lifetime (exploratory)

Simultaneously Polydrug Use

Use of more than one drug at same time (combined or consecutively) over the past year, month or lifetime

• extending or enhancing high or inhibiting side effects

The Nervous System

3 parts, central, peripheral, enteric

• Built on networks/pathways

• CNS and PNS are connected

• Interconnected like serial pathways

• Basic unit of a pathway is a neuron

Enteric Nervous System

Digestive tract, muscular and mucousal parts, Each plexus has nodes of cell bodies (ganglia)

Neuron

Information processing.

• Long and short distance communication

• Connected into pathways by intercellular signals (neurotransmitters)

Sensory Neuron

specialized nerve cells that transmit sensory information from the body's receptors to the central nervous system (brain and spinal cord). 

Motor Neuron

regulate voluntary and involuntary movements via transmitting signals from the brainstem and sensory systems to muscle cells.

Interneurons

the central nodes of neural circuits, enabling communication between sensory or motor neurons and the central nervous system (CNS)

• Only in CNS

• Local

Projection Neurons

Motor and sensory neurons (only in peripheral nervous system)

Afferent

Incoming projection

Efferent

Outgoing projection

Somatic Nervous System

Connect Central Nervous System to skin, joints and bones (sensory) and striated muscle (motor)

• Spinal nerves and cranial nerves

• Each nerve contains 1 sensory (S) nerve and 1 motor nerve (M)

• S uses glutamate as Neurotransmitter

• M uses acetylcholine as neurotransmitter

• Topographically organized- a spatial map

• 42 pairs of nerves (21 on each side of body)

Autonomic Nervous System

2 systems Sympathetic and Parasympathetic

• Connect to most organs

• Sensory/motor neuron innervation targets vary

• Sensory for hollow organs

• Fewer ANS nerves

  • each nerve contains 1 sensory nerve and 2 motor nerves

  • Peripheral ganglia connect motor neuron 1 and motor neuron 2

    • Topographically organized but not very well, enter and exit different nerves

• Sensory neurons use Glutamate

Sympathetic Nervous System

Motor contraction, sensory organ function and touch

• Fight or flight

• Sympathetic ganglia near spinal cord

• Motor neurons use acetylcholine and then norepinephrine

Parasympathetic Nervous System

Motor relaxation, sensory-organ function

• Rest and digest

• Parasympathetic ganglia closer to organs

• Motor neurons uses acetylcholine in both neurons

• Vagus nerve, goes to every organ

Central Nervous System

the primary control center of the body, consisting of the brain and spinal cord. It receives, processes, and sends signals to coordinate all bodily functions. 

In the CNS

Grey matter and white matter (myelinated)

Nuclei and tract

Interneurons (unmyelinated) and projection neurons (afferent and efferent, few myelinated)

Peripheral Nervous System

The peripheral nervous system is a network of nerves that runs throughout the head, neck, and body. It carries messages to and from the central nervous system (the brain and spinal cord).

In the PNS

Ganglia and nerves

None ———--Projection neurons (sensory and motor)

Glial Cells

Structure, support, communication

• Act as barriers

• Provide information to neurons

• Help out with long and short distance communication in different ways

• Astroycte, microglia, ogliodendrocyte, Schwann cell and ependymal cell

Cell Body

Function: listen and keep cell alive/integrate information

Includes:

Nucleus- protein recipes (DNA, Genes)

Mitochondria- gather, store and release energy

Rough Endoplasmic Reticulum- build proteins

Smooth Endoplasmic Reticulum-build/add on lipids

Golgi apparatus- local transport

Endosomes- recycle proteins

Lymsosomes- collect cellular waste

Microtubules and non-tubules- long distance transport

Receptors

Dendrites

Project off of cell body

-Dendritic spines contain receptors, spines can change

-Receptors

Function:Listen/integrate information

Excitatory

Activate cell activity (EPSP)

Inhibitory

Inhibit cell activity (IPSP)

Neurotransmitters

bind and activate the receptors

• Are natural endogenous ligands that produce the intended and expected effect on the receptor

Receptors

Transmembrane protein embedded in phospholipid membranes.

• receptors transduce biochemical message (neurotransmitter) into:

1. Bioelectric message

2. Another biochemical message

Ligand Gated Ionotropic Receptor (channels)

Different kinds, specific to charge and favor molecule.

• Common ions are sodium (Na+), Chloride (Cl-), and Potassium (K). Fast and carry message

• This receptors transduce. Carry forward- the ongoing message in the pathway

Lingand Gated Metabotropic Receptors (G-proteins)

Several kinds, most common is G-protein

• Slow, tweak next message

• G-protein receptors, 3 types Gs, Gq and Gi

• Activate of inhabit enzymes that in turn activate a 2nd messenger (Neurotransmitter is the 1st messenger)

• Each type activates a different 2nd messenger

• These receptors help the post-synaptic neuron REMEMBER, important for memory

• G-proteins structure has 3 parts: Alpha, Beta, Gamma

• Receptor activation releases alpha—> biochemical domino effect

Gs

Alpha release is excitatory and activated adenyl cyclase enzyme

• Adenyl cyclase increase cAMP (adenosine monophosphate) which is the 2nd messenger

• Function:

  1. Opens sodium (Na+) channels that can detect cAMP.

  2. Activates PKA protein (protein kinase A) another enzyme that changes biochemical activities

Gi

Alpha release is inhibitory and opposes Gs (inhibits ongoing adenyl cyclase activity)

• Net consequence decrease cAMP 2nd messenger

• Function: decrease all functions

Gq

Alpha release is excitatory and activates phospholipase c (PLC) enzyme

• PLC increases PIP2 (Phosphatidylinositol,4, 5, bisphosphate) Changes biochemical activities

• PIP2 activates IP3 (Inositol triphosphate) and DAG (diacylgycerol) both 2nd messengers that increase calcium (Ca++)

Axon

Projects to the next cell over short (interneuron) or long (projection neuron)

• No dendritic spines

• Myelin on many projection neurons

• Tapered-thicker at beginning

• The thicker part is the Axon Hillock- integration

• Branchy ends branch out to multiple large branches

• Specialized to regenerate bioelectric signals with great precision and machinery and messages (microtubules)

  Function- integrate and transmit

Biochemical Transmission

Between cells (intercellular)

• Involves presynaptic cell (axon terminal) where the message comes from to go to the post-synaptic cel

• Action potentials collapse into graded potentials (EPSP) in axon terminals—→ calcium-gated channels (receptors)

Bioelectircal Transmission

Within cell (intracellular)

Secretory (Volumetric) Exocytosis

• Larger vesicles

• extrasynaptic space

• Slower

• need bigger Ca++ signal

• Common

  • Fills up more space quicker

Synaptic Exocytosis

• Smaller vesicles

• Synaptic space

• Fast

• Needs less Ca++ signal

• Unique/specific to one synapse

  • Drugs take synaptic exocytosis and make it more volumetric which can lead to addiction

Exocytosis

1. Neurotransmitters are stored in small sacs called synaptic vesicles. 

2. When a neuron is active, a vesicle fuses with the cell membrane. 

3. The contents of the vesicle are released into the synaptic cleft, the space between neurons. 

Acetylcholine

Function- is important for controlling multiple processes in the peripheral nervous system, such as heart rate. One of its most important roles is controlling skeletal muscles.
Within the central nervous system, is important for keeping us alert and sustaining our attention, and it has been shown to be an important mediator of learning and memory.

Chemical Structure- Amine

Synthesis:-  made from two things: the precursor choline and acetyl-coenzyme A. The enzyme choline acetyltransferase converts choline and acetyl-coenzyme A into Acetylcholine

Synthesis Location: Axon terminal

Receptors: Nicotine Receptors (Ionotropic)- Na+ channels, excitatory (EPSP)

Muscarinic Receptors (Metabotropic)- M1,M3,M5: Gq 2nd messenger, excitatory (activates IP3 and DAG)

• M2,M4: Gi 2nd messenger, inhibits cAMP (pre and post synaptic)

Release: Synaptic

Stored: Vesicles via VAChTs

After Release: Extracellular: enzymatic degradation. an enzyme called acetylcholinesterase. Acetylcholinesterase breaks down acetylcholine into choline and acetic acid. Choline reuptake, acetic acid is excreted

Location in CNS: Basal forebrain and dorsolateral tegmental

Dopamine (DA)

Function- Reward learning, movement, executive functioning, arousal, motivation, lactation and nausea.

Chemical Structure- Catecholamine

Synthesis: from tyrosine

Synthesis Location: Axon terminal

Receptors: 1.  All dopamine receptors are metabotropic.

-              of D 1 and D 5 receptors, which are G s -coupled. Excitatory (activate cAMP 2^nd messenger) The excitatory D 1 -like receptors are located on the postsynaptic neuron only,

-              of D 2 , D 3 , and D 4 receptors, and they are G i -coupled and inhibit cAMP. D 2 -like receptors are located on both dendrites of the postsynaptic neuron and on the presynaptic neuron.

Release: Synaptic

Stored: Vesicles via VMATS

After Release:

-              Extracellular: Reuptake via DAT

-              Intracellular: Monoamine oxidase (MAOA/MAOB) and COMT, vesicularuptake by VMATS

Location in CNS: Ventral tegmental and substantial Nigra

Norepinephrine (NE)

Function- Fight or flight response. Norepinephrine is the major neurotransmitter of the parasympathetic nervous system. Prepares us to respond to a stressful situation. Vigilance, wakefulness, attention and memory.

Chemical Structure- Catecholamine

Synthesis: From tyrosine. Dopamine is a precursor to norepinephrine.

Synthesis Location: Axon terminal

Receptors: 1.       Metabotropic Type: Peripheral Nervous System

-              A1, B1: Gs excitatory (activate cAMP)

A2-Gi inhibitory (inhibits cAMP). Pre and post synaptic

Release: Synaptic

Stored: Vesicles via VMATS

After Release:

• Extracellular: Reuptake via NET

• Intracellular: Monoamine oxidase (MAOA/MAOB) and COMT, vesicular uptake by VMATS

Location in CNS: Locus coeruleus

Serotonin (5-HT)

Function- Control mood, sleep, appetite, bowel movements and nausea. Cognition. Mostly found in GI tract (ENS)

Chemical Structure- Indolamine

Synthesis: From tryptophan

Synthesis Location: axon terminal

Receptors: 1.        Ionotropic Type: Only 5 HT3 receptor: Na+ channel

2.        Metabotropic Type: Serotonin receptors are metabotropic

-              Most 5-HT receptors are excitatory- Gs excitatory (activate cAMP)

-              5-HT 1 and 5- HT 5 families- Gi inhibitors (inhibit cAMP) both pre and post synaptic.

Release: Synaptic

Stored: Vesicles via VMATS

After Release: Serotonin Transporter (SERT)

-              Extracellular: reuptake via SERT

-              Intracellular: Monoamine oxidase (MAOA/MAOB) and vesicular reuptake by VMATS

Location in CNS: Raphe Nuclei

Glutamate

Function- Major excitatory. Learning and memory. Sensation, as many neurons transmitting information about vision, hearing and pain

Chemical Structure- Amino acid

Synthesis: Synthesized from the amino acid glutaminase. I

Synthesis Location: axon terminal

Receptors: Can bind to either metabotropic or ionotropic receptors

1.        Ionotropic Type:  

•         AMPA receptors, Na+ channel, excitatory pre and post synaptic.

•         l NMDA , Na+

  •    NMDA receptors is that they are dependent on AMPA receptors to function. .

• Kanic- Ca++ and Na+

2.        Metabotropic Type:

-              mGluR 1 and mGluR 5 , which are excitatory G q -coupled (IP3 and DAG) and located on the postsynaptic neuron.

-              mGluR 2 and mGluR 3- Gi inhibitory (inhibits cAMP) pre and post synaptic

-              mGluR 4 , mGluR 6 , mGluR 7 , and mGluR 8 . Gi inhibitory (inhibits cAMP) pre and post synaptic

-              The Group II and Group III metabotropic receptors can function as heteroreceptors or as autoreceptors.

Release: Synaptic

Stored: Vesicle via VGluTs

After Release:

-              Extracellular: Excitatory amino acid transporters EAATS take up glutamate into astrocytes

Intracellular (astrocytes):enzymatic degradation with glutamine synthetase

Location in CNS: -              Transmission is everywhere

-              Mostly projection neurons- move from nucleus to nucleus

-              Cortico- brainstem pathways (descending) prefrontal cortex to monoamine nuclei in brain

-              Cortico-striatal pathway (descending) prefrontal cortex to basal ganglia (cortico-accumbens and cortico-striatal)

-              Thalamic- cortical pathway- (ascending) to all of cortex

-              Cortico-thalamic pathway- (descending) from all cortex

-              Cortico-cortico pathways- between columns in the cortex

·      Glutamate part of cortico-striatal thalamic loop

GABA

Function- Major inhibitory in nervous system. Regulating release of other neurotransmitters. Specific roles in growth and sleep.

Chemical Structure- Amino acid

Synthesis: Synthesized from glutamate via glutamic acid decarboxylase

Synthesis Location: axon terminal

Receptors: 1.  Ionotropic Type:  GABA A five subunits. There are approximately 16 different possible subunits: six alpha, four beta, four gamma, one delta, and one epsilon. most GABA A receptors are composed of two alpha subunits, two beta subunits, and one gamma subunit. Once GABA has activated the receptor, the ion channel opens, allowing Cl- to enter the cell. This inhibits the neuron

2.        Metabotropic Type: GABA B inhibitory These receptors are located on both the pre and the postsynaptic neurons. Inhibits cAMP, Gi

Release: Synaptic

Stored: Vesicles vis VGAT

After Release:

-              Extracellular: reuptake using GAT

-              Intracellular: enzymatic degradation GABA GABA transaminaseglutamate

Location in CNS: everywhere in CNS

-              Interneurons- all CNS nuclei

-              Projection neurons

o   Subcortical to cortical (ascending)

o   Cerebellar output (Purkinje cells)

o   Subcortical projection neurons: Hippocampus, amygdala, striatum, hypothalamus, olfactory bulb

Endogenous Opioids (endorphins, enkephalins and Dynorphins )

Function- Pain reduction

Chemical Structure- peptide

Synthesis: Protein synthesis of large pro peptides cleaved in vesicles or extracellular to NT.

Synthesis Location: Cell body

Receptors:    Metabotropic Type:

• Mu: endorphin and enkephalin

• Delta: endorphin and enkephalin

• Kappa: dynorphin

• NOP: Nociceptin

  • All Gi inhibits cAMP

-              Gi couples and inhibit cAMP

Release: Secretory (volumetric)

Stored: Vesicles (propetide) stored in cell body and transported to terminal

After Release: Once released into the synapse, the endogenous opioids bind to their respective receptors before they are quickly metabolized.

-              Extracellular: enzymatic degradation endopeptides

Location in CNS: -   Mostly interneurons in CNS nuclei, and enteric NS

-              One known projection neuron (b-endorphin): hypothalamus to brainstem nuclei and spinal cord.

Endocannabinoids (Anandamide and 2-AG)

Function- Appetite, pain suppression, motor control and cognition

Chemical Structure- Lipid

Synthesis: Cell membrane lipids using phospholipase D and C

Synthesis Location: Post synaptic membrane (intracellular)

Receptors:   Metabotropic Type:

-              CB 1 receptors are found primarily in the central nervous system, Gi inhibits cAMP

-               CB 2 are located in the peripheral nervous system.

Release: Diffusional to extra and intracellular areas

-              Intracellular: acts like a 2^nd messenger, modifies activity of ion channels

-              Extracellular: acts like a neurotransmitter (retrograde)

Stored: Not stored, on demand

After Release: Intracellular, Excess anandamide is degraded primarily by the enzyme fatty acid amide hydrolase (FAAH) into ethanolamine, but it can also be oxidized by other lipid metabolic enzymes

Location in CNS: CB1R dense at neocortex, hippocampus, basal ganglia, cerebellum, brainstem

• Found in most cells

Adenosine

Synthesis: From AMP with 5-nucelotidase

Synthesis Location: axon terminal or synaptic cleft

Chemical Structure: Nucleoside

Storage: Not stored, on demand release, diffusional to extra and intracellular areas

-              Extracellular: Adenosine mono phosphate (AMP) ecto-5-nucleotidase adenosine

-              Intracellular: same using a soluble enzyme

Release: Intracellular, synaptic and volumetric, cellular transporter

Receptors: Metabotropic

-              A1 (P1) or A3 (p3)- Gi inhibits cAMP, pre and post synaptic

-              A2a-Gs activates cAMP pre and post synaptic

After Release: Reuptake through nucleoside transporter and enzymatic degradation into uric acid or changed to ADP recycle

Location: Hippocampus, cortex, cerebellum, less in striatum

Drug Action: Cocaine

Block transporters (reuptake) DAT> NET»> SERT

• Directly impacts dopamine system

Drug Action: Methylphenidate

Block transporters (reuptake) DAT> NET»> SERT

• Directly impacts dopamine system

• Same as cocaine

Drug Action: Methamphetamine/ Amphetamine

Reverses cellular reuptake and vesicular transporters (VMATS). Stronger at VMATS (more release)

• Directly impacts dopamine system,

• DAT=NET»SERT

• Increase neurotransmitter release thru cellular transporters, decrease reuptake

• Also inhibits MAO activity

Drug Action: MDMA

everses cellular reuptake and vesicular transporters (VMATS). Stronger at VMATS (more release)

• Directly impacts dopamine system,

• SERT» DA=NE

• Increase neurotransmitter release thru cellular transporters, decrease reuptake

• Also inhibits MAO activity

Drug Action: Nicotine

AChNR agonist

• enhances DA release in basal ganglia

• Enhances glutamate release in basal ganglia→ glutamate increases DA activity

Drug Action: Opioids

Opiod receptor agonists

• In the Ventral Tegmental nucleus (midbrain), inhibit GABA release which which “disinhibits” DA neuron activity. Increase DA release in basal ganglia

• Indirect

Drug Action: Benzodiazepines and Barbituates

GABAa receptor modulators (potentiate GABAa receptor response to GABA)

• In the basal ganglia, increase Dopamine, vis disinhibition

• Indirect

Drug Action: Alcohol

Modifies the activity of many receptors depending on dos

• indirect

• Opioid receptor activation

• Lower dose: potentiate GABA, receptor response to GABA and inhibit NDMA receptors

• Higher dose: facilitate opioid receptor activation

• Very high doses: disrupts the structure of the cellular brain so most receptors are disabled

Drug Action: Hallucinogens (LSD and Psilocybin)

5-HT2a agonists and MGlu2R

• Serotonin increases DA release via 5-HT2a receptor, but not MGlu2r except possibly psychotic states

• Indirect

Drug Action: Hallucinogens (Dissociative Anesthetics, Ketamine/PCP)

NMDA antagonists, noncompetitive

• Seem to displace Mg++ (magnesium) and then not voltage sensitive

• In basal ganglia (spinal cord), these drugs work on presynaptic NMDA receptors on GABA neurons—> decrease GABA release and increase DA and glutamate then glutamate can activate DA neurons

• Indirect

Agonist

substance or drug that binds to a specific receptor in the brain and activates it, mimicking the effects of the natural neurotransmitter that normally binds to that receptor. 

Antagonist

a chemical substance that blocks the activation of receptors on cells. This prevents a biological response. 

Drug Action:Cannabis

CB1 Partial Agonist

• increases DA by inhibiting GABA release

Drug Action: Inhalants

multiple mechanisms

• Toluene- increases 5HT2a activity, GABA activity and decrease NMDAR activity

Drug Action: Caffeine

A1, A2a- competitive antagonists

• enhances the sensitivity of dopamine receptors

Pharmacotherapies for Nicotine

• Nicotine gum/patches- agonist therapy

  • All delivery at lower and slower dose

  Vacreline (Chantix)- partial agnosts, agonist therapy

• Bupropion (Zyban)- blocks DA and NE transporterrs and uncompetitive antagonists at the AChN receptor, enhance activity—> decrease dopamine

• Rimonabant (Acompra)- off label, CB1 inverse agonist, decrease CB1 activity—> increase GABA activity—> decrease dopamine

Pharmacotherapies for Alcohol

• Disulfiram (Antabuse)- blocks aldehyde dehydrogenase and the full metabolism of alcohol, leaving aldehyde dehydrogenase (TOXIC)

• Naltrexone (revia)- competitive antagonist at opioid receptors, antagonist treatment

• Acamprosate (Acampral)- NMDA competitive antagonist and GABA agonist

• Bupropion (Zyban)- blocks DA and NE transporterrs and uncompetitive antagonists at the AChN receptor

• Modafinil (Provigil)- weak DAT blocker-agonist treatment

• Topiramate- inhibits voltage gated Na+ channels (inhibits AP) anti-seizure medication

Pharmacotherapies for Opioids

• Methadone- agonist therapy, slower onset

• Burprenorphine (Bupex)- agonist therapy

  • Partial agonist, stave off withdrawal but provides a weak high

• Naltrexone- competitive agonist, antagonist therapy

• Suboxone- buprenorphine and naloxone- antagonist therapy, administered sublingual

  • Dose of naloxone big enough to block receptor if injected but not if taken orally

Pharmacotherapies for Psychostimulants

• Cocaine- D- amphetamine (meth) low doses, agonist therapy

  • Disulfiram- MAO inhibitor, fail to degrade DA so you have a bit more

• Caffeine- coffee, tea, energy drinks, stave off withdrawal

Pharmacotherapies for Cannabinoids

• Rimonabanat- off label, CB1 antagonist

  • Counteracts CB1 effects-antagonist therapy

• Synthetic THC- agonist therapy

• Naltrexone- competitive agonist

• N-acetyclysteine- decrease glutamate activity and oxidate stress metabolism

Nigrostriatal Pathway

Substantia nigra (midbrain) to dorsal striatum (basal ganglia)

• Dopamine pathway

Dopamine Neural Pathways

Involved in reward

• 4 pathways

Mesolimbic Pathway

Ventral tegmental Area (midbrain) to nucleus accumbent (ventral stratum in basal ganglia)

• Dopamine pathway

Mesocortical Pathway

Ventral tegmental area (midbrain) to prefrontal cortex

• Dopamine pathway

Mesocorticolimbic Pathway

Paths 2 and 3 Mesolimbic and mesocortical pathways combined