PSYCH207 Final Exam

1. Neurotransmitter Systems

1.1. Cannabinoids

1.1.1. Types

1.1.1.1. Synthetic Cannabinoids

1.1.1.1.1. Potent factory produced chemicals sold as incense

1.1.1.2. Phytocannabinoids

1.1.1.2.1. THC

1.1.1.2.2. CBD

1.1.1.2.3. CBGa

1.1.1.2.4. More: cannabinol, N-alkamide, etc

1.1.1.3. Endocannabinoids

1.1.1.3.1. Receptors

1.1.1.3.2. Neurotransmitters

1.1.1.3.3. New Topic

1.2. Adenosine

1.2.1. Antagonized by caffeine

1.2.2. Agonized by acetate

1.2.2.1. ethanol -> acetaldehyde -> acetate

1.3. Opioids

1.3.1. Endogenous Opioid System

1.3.1.1. Endogenous Opioid Receptors

1.3.1.1.1. Kappa-opioid

1.3.1.1.2. Delta-opioid

1.3.1.1.3. Mu-opioid

1.3.1.1.4. NOP-R

1.3.1.2. How opioids inhibit pain

1.3.1.2.1. Post synaptic inhibition

1.3.1.2.2. Axoaxonic inhibition

1.3.1.2.3. Presynaptic Autoreceptors

1.3.1.3. Periaqueductal Gray

1.3.1.4. Endogenous Opioid Neuropeptides

1.3.1.4.1. Endorphins

1.3.1.4.2. Nociceptin

1.3.1.4.3. Proenkephalin

1.3.1.4.4. Dynorphin

1.3.2. Exogenous Opioid System

1.4. GABAergic

1.4.1. Purkinje cell

1.4.1.1. GABAergic neurons located in the cerebellum

1.4.1.2. Found to be associated with endocannabinoid release

1.4.2. LSD

1.4.2.1. LSD and alcohol have opposite effects on the GABA system

1.4.2.1.1. Alcohol binds as a positive modulator to GABAa to inhibit GABA release

1.4.2.1.2. LSD agonizes serotonin receptors on GABA neurons

1.4.2.2. 5HT2A Rs increase activity of glutamate and GABA neurons

1.4.2.2.1. ^ glutamate -> ^ PFC activation

1.4.2.2.2. ^ GABA -> dec. sensory info filtering

1.4.3. Benzos increase GABA effect

1.5. Serotonergic

1.5.1. Metabolite: 5-HIAA

1.5.1.1. Heavy MDMA users have lower 5-HIAA levels in CerSpinFluid suggesting less serotonin production in their NSs

1.5.2. SSRIs

2. Drugs

2.1. Psychostimulants

2.1.1. Types

2.1.1.1. Ephedra

2.1.1.1.1. Derived from medicinal herb

2.1.1.2. Amphetamine

2.1.1.2.1. Synthesized in lab

2.1.1.3. Methamphetamine

2.1.1.3.1. Derived from ephedrine in the lab

2.1.1.4. Methylphenidate

2.1.1.4.1. Improves the action of catecholamines in the brain

2.1.1.5. Cathinones

2.1.1.6. Cocaine

2.1.2. Pharmacokinetic Properties

2.1.2.1. Administration

2.1.2.1.1. Therapeutic: oral

2.1.2.1.2. Recreational: intravenous, insufflation, inhalation

2.1.2.2. Biotransfomation

2.1.2.2.1. Active metabolites produced in liver

2.1.2.3. Elimination

2.1.2.3.1. Half-life length: methamphetamine > amphetamine >methylphenidate >cathinones >

2.1.3. Addiction

2.1.3.1. Treatment Types

2.1.3.1.1. Disulfiram

2.1.3.1.2. Modafinil

2.1.3.1.3. Imipramine

2.1.3.1.4. Topirimate

2.1.3.1.5. Vaccinations

2.1.3.2. Risk Factors

2.1.3.3. Stages of Recovery

2.1.3.3.1. Abstinence

2.1.3.3.2. Relapse

2.2. Psychedelics

2.2.1. MDMA

2.2.1.1. Characteristics

2.2.1.1.1. Enactogen: means "touching within" Empathogen: means "enhanced empathy"

2.2.1.1.2. Use most common among high school and college students

2.2.1.1.3. Developed during efforts to develop amphetamine derivatives

2.2.1.1.4. Hallucinogen-stimulant

2.2.1.2. Therapeutic Use

2.2.1.2.1. First clinical trial for MDMA published relatively recently. Mithoefer and colleagues (2011) reported that MDMA assisted therapy for patients with posttraumatic stress disorder (PTSD).

2.2.1.2.2. The DEA scheduling not only eliminated all therapeutic MDMA use but also for practical purposes precluded clinical studies with MDMA.

2.2.1.2.3. Although dependence doesnt build normally, half of MDMA users meet criteria for substance use disorder

2.2.1.3. Pharmacodynamics

2.2.1.3.1. Effects

2.2.1.3.2. Half life: 9 hours

2.2.1.4. Pharmacokinetics

2.2.1.4.1. Deficiencies in the CYP2D6 enzyme (such as those caused by taking certain SSRIs) lead to accumulation of MDMA in the body.

2.2.1.5. Studies

2.2.1.5.1. Chronic usage is toxic to monkeys (Hatzidimitriou 1999)

2.2.1.5.2. MDMA users do worse on verbal working memory tasks that may fail to improve over time (Brown 2010)

2.2.1.5.3. MDMA shares subjective effects with d-amphetamine, and mCPP (Tancer & Johanson, 2003)

2.2.1.5.4. Monkeys self administer MDMA less than meth indicating lower reinforcing effects (Fantegrossi 2002)

2.2.2. LSD

2.2.2.1. Characteristics

2.2.2.1.1. Non-addictive by any criteria

2.2.2.1.2. Users are hyper-suggestible

2.2.2.1.3. Ergot that grows on rye discovered in 1943 by Hoffman

2.2.2.1.4. Tested on interrogating prisoners, use as a chemical weapon, psychotherapy

2.2.2.2. Pharmacokinetics

2.2.2.2.1. Metabolized in liver

2.2.2.2.2. Half life of 3 hours but can last up to 12 hours

2.2.2.2.3. Oral administration is very small doses

2.2.2.2.4. Serotonin receptor agonist with some DA receptor affinity

2.2.2.2.5. Human lethal dose of 14 grams

2.2.2.3. Pharmacodynamics

2.2.2.3.1. Effects on Brain Structure

2.2.2.3.2. Subjective Effects

2.2.2.3.3. Addiction

2.2.2.4. Studies

2.2.2.4.1. Marsh Chapel Experiment (Doblin)

2.2.2.4.2. Stimulus generalization between LSD, psilocybin, and DMT in rats (Winter 2007)

2.2.3. Psilocybin

2.2.3.1. Psilocybin makes offenders less likely to commit more crimes (Leary et al)

2.2.4. Salvia Divinorum

2.2.4.1. History

2.2.4.1.1. First documented in 1939 but it took longer to be identified to the Mazetec secrecy over the growing sites

2.2.4.1.2. Very few wild plants can be found in the wild because the plant produces few viable seeds even when it does flower

2.2.4.2. Subjective Effects

2.2.4.2.1. Rapid Onset

2.2.4.2.2. Rated by participants as very much to exptremely intense

2.2.4.2.3. Uniqueness from normal experience

2.2.4.2.4. Hallucinations

2.2.4.2.5. Depersonalization Loss of perceived control over thoughts and actions

2.2.4.2.6. Distorted body ownership

2.2.4.2.7. Altered reality monitoring; inability to track concensus reality while immersed in the experience

2.2.4.3. Papers

2.2.4.3.1. Dynorphins Regulate Fear Memory: from Mice to Men (Bilkei-Gorzo et al 2012)

2.2.4.3.2. The subjective experience of acute, experimentally-induced Salvia divinorum inebriation (Addy et al., 2015)

2.2.5. DMT

2.2.5.1. posterior cingulate cortex activation

2.2.5.1.1. PSC: central node of default mode network

2.2.5.1.2. Studies suggest it can cause thinning of PCS

2.3. Alcohol

2.3.1. Pharmacodynamics

2.3.1.1. Effects

2.3.1.1.1. Behavioral Effects

2.3.1.1.2. Adverse Effects

2.3.1.1.3. Physiological Effects (MOA)

2.3.1.2. Addiction

2.3.1.2.1. Tolerance

2.3.1.2.2. Withdrawal

2.3.1.2.3. Treatments

2.3.2. Characteristics

2.3.2.1. Standard drink = 14grams of pure alcohol

2.3.2.2. Sumerians used alcohol as a vehicle for medicines

2.3.3. Pharmacokinetics

2.3.3.1. Highly soluble in water and fat so easily absorbs into tissue

2.3.3.2. Metabolism

2.3.3.2.1. 95% in liver

2.3.3.2.2. 5% released by lungs

2.3.3.3. Absorption

2.3.3.3.1. Highly soluble in water and fat

2.3.4. History

2.3.4.1. 18th Amendment

2.3.4.2. 21st Amendment

2.3.5. Addiction

2.3.5.1. Type I (>25)

2.3.5.2. Type II (< 25)

2.3.5.3. Physiological Dependence

2.3.5.3.1. Associated with increased glutamate NMDA receptors and decreased GABAa receptors

2.4. Marijuana

2.4.1. Pharmacodynamics

2.4.1.1. Effects

2.4.1.1.1. Physiological

2.4.1.1.2. Subjective

2.4.1.1.3. Adverse

2.4.2. Pharmacokinetics

2.4.2.1. Absorption

2.4.2.1.1. Joint - 50%

2.4.2.1.2. Vape - 80%

2.4.2.1.3. Edibles - 25-20%

2.4.3. Medical Uses

2.4.3.1. Cancer

2.4.3.1.1. Tentative evidence for using medical marijuana to treat cancer

2.4.3.1.2. Marinol and Sativex prescribed to treat chemo patients

2.4.3.2. Multiple Sclerosis

2.4.3.2.1. Sativex 1:1 THC:CBD reduced spasticity

2.4.3.2.2. Sativex is currently approved in the United Kingdom, Spain, and Canada for the treatment of muscle spasms and stiffness in multiple sclerosis.

2.4.3.2.3. Anti-inflammatory effect can help with overactive immune system (same with arthritis)

2.4.3.3. Parkinsons

2.4.3.3.1. Cannabis can reduce the side effects of Parkinsons medication

2.4.3.4. HIV/AIDS

2.4.3.4.1. Reduces neuropathic pain

2.4.3.5. Anorexia

2.4.3.5.1. Treated with marinol

2.4.3.5.2. Stimulates appetite

2.4.3.6. Glaucoma

2.4.3.6.1. Reduces intraocular pressure

2.4.4. Epilepsy

2.4.4.1. CBD and THC reduce frequency and severity of seizures by unclear mechanisms

2.4.5. Addiction

2.4.5.1. Tolerance

2.4.5.1.1. Regular users find tolerance to many of the behavioral and subjective effects

2.5. Caffeine

2.5.1. Pharmacodynamics

2.5.1.1. Tolerance develops for positive effects

2.5.1.2. A1 and A2 adenosine antagonist

2.5.1.3. Effects

2.5.1.3.1. Physiological

2.5.1.3.2. Behavioural

2.5.1.3.3. Adverse Effects

2.5.1.4. Withdrawal

2.5.2. Pharmacokinetics

2.5.2.1. Active Metabolites

2.5.2.1.1. Theophylline

2.5.2.1.2. Theobromine

2.5.2.1.3. Paraxanthine

2.5.2.2. Oral administration

2.5.2.3. Absorbed across intestinal walls

2.5.2.4. Peak effects at 40 minutes after ingestion

2.5.2.5. Metabolized in the liver

2.6. Nicotine

2.6.1. Characteristics

2.6.1.1. Belongs to the xanthine family

2.6.1.2. Cigarettes are neurodegenerative, nicotine itself has some moderate neuroprotective benefits

2.6.1.3. Because of upregulation, acute effects of nicotine differ greatly from chronic effects

2.6.2. History

2.6.2.1. Religious use by Mayans, Incas, Aztecs

2.6.2.2. Widespread use in 1600s when introduced to Europe

2.6.2.3. Doubts about health outcomes in the 1700s

2.6.2.4. Early 20th century - focus on adverse effects

2.6.3. Administration

2.6.3.1. Absorbed by mouth, throat, lungs

2.6.3.2. Inhalation is most effective

2.6.3.3. Peak absorption

2.6.3.3.1. Cigarettes: 5-7 minutes

2.6.3.3.2. Other methods: 20-30 mins

2.6.4. Pharmacokinetics

2.6.4.1. Crosses BBB

2.6.4.2. Eliminated in urine

2.6.4.3. Metabolized in liver

2.6.4.4. Active Metabolite: cotinine

2.6.4.5. Mentholation slows metabolism

2.6.5. Effects

2.6.5.1. Causes NS dysfunction in small animals and used as incesticide

2.6.5.2. Effects negative for naive users and positive for habitual users

2.6.5.2.1. Chippers (social smokers) don't show this effect

2.6.5.3. Positive Subjective Effects

2.6.6. Risks

2.6.6.1. Risks conveyed in second and third hand smoke

2.6.6.2. Increased pregnancy complications

2.6.6.3. Increased cancer and cardiovascular disease risk

2.6.6.3.1. Nitrosamines

2.6.6.4. increased rate of pulmonary disease

2.6.6.4.1. Emphysema

2.6.7. Pharmacodynamics

2.6.7.1. Desensitizes receptors and cholinergic agonist at nicotinic receptors

2.6.7.2. Nicotine and acetylcholine compete for binding

2.6.7.3. Cells upregulate acetylcholine receptors and multiply

2.6.7.4. Acute tolerance effect, first cig of the day is strongest

2.6.7.5. Distribution of Nicotinic Receptors

2.6.7.5.1. PNS

2.6.7.5.2. CNS

2.7. Opiates

2.7.1. Terminology

2.7.1.1. Natural Narcotics

2.7.1.1.1. Morphine

2.7.1.1.2. Codeine

2.7.1.1.3. Thebaine

2.7.1.2. Semisynthetic Narcotics

2.7.1.2.1. Heroin

2.7.1.2.2. Hydromorphone

2.7.1.2.3. Oxycodone

2.7.1.2.4. Desomorphine (Krokodil)

2.7.1.2.5. Etorphine

2.7.1.3. Synthetic Narcotics

2.7.1.3.1. Laudanum

2.7.1.3.2. Pentazocine

2.7.1.3.3. Meperidine

2.7.1.3.4. Fentanyl

2.7.1.3.5. Methadone

2.7.1.3.6. LAAM

2.7.1.4. Harrison Act

2.7.2. Pharmacodynamics

2.7.2.1. Nociception

2.7.2.1.1. Ascending pathway

2.7.2.1.2. Descending pathway

2.7.2.2. Subjective Effects

2.7.2.2.1. Rush: rapid onset euphoria

2.7.2.2.2. High: feelings of joy and ease

2.7.2.2.3. Nod: calm, disinterest, unawareness

2.7.2.2.4. Straight: Normalcy

2.7.2.3. Objective Effects

2.7.2.3.1. Cough reflex suppression

2.7.2.3.2. Opioid Overdose

2.7.2.3.3. Dysphoria, restlessness, anxiety, and nausea

2.7.2.3.4. Constipation

2.7.3. History

2.7.4. Treating Addiction

2.7.4.1. Tolerance/Withdrawal

2.7.4.1.1. cAMP

2.7.4.2. Maintenance/Replacement

2.7.4.2.1. RadioLigand Binding Assay

2.7.4.3. Detoxification

2.7.4.3.1. Long Term

2.7.4.3.2. Short Term

2.7.4.3.3. Rapid

2.7.4.3.4. Ultra-rapid

2.7.5. Pharmacokinetics

2.7.5.1. Absorption/Metabolism

3. Brain Structures

3.1. Forebrain (Prosencephalon)

3.1.1. Telencephalon

3.1.1.1. Basal Ganglia

3.1.1.1.1. The Reward Circuit

3.1.1.2. Cerebral Cortex

3.1.1.2.1. Lobes

3.1.2. Diencephalon

3.1.2.1. Globus pallidus

3.1.2.2. Ventral pallidum

3.1.2.3. Thalamus

3.2. Midbrain (Mesencephalon)

3.3. Hindbrain (Rhombencephalon)

3.3.1. Metencephalon

3.3.1.1. Pons

3.3.1.2. Cerebellum

3.3.2. Myelencephalon

3.3.2.1. Medulla