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 ADHD and Substance Use Disorders

Psychopharmacology 101

For Non-prescribing

Mental Health Professionals -

A Training Resource

By Jim Messina, Ph.D., CCMHC, NCC, DCMHS-T
Resources for Mental Health Professionals

Attention Disorders

Over the years Labled from Minimal Brain DysfunctionTo Attention-Deficit Hyperactivity Disorder

 

History of ADHD

1902

Sir George Frederick Still worked with a 20  Children of normal intelligence, but exhibited “violent outbursts, wanton mischievousness, destructiveness, and a lack of response to punishment.” BUT: No trauma or illness could be identified to explain “illness.”

1947

Alfred Strauss, Director, School for Disturbed Youth, Racine, Wisconsin described: “Normal brain injured children.”

1952,

DSM-I - Minimal Brain Dysfunction

1956

Ciba-Geigy brought Ritalin® (methylphenidate) to market to Quieten children who suffered with “brain damage syndrome”

1968

DSM-II  Renamed: “Hyperkinetic Reaction of Childhood”

1980

DSM-III (Moved to Medical Disease Model)Renamed: “Attention Deficit Disorder” Inattention, Impulsivity and Hyperactivity But only Hyperactivity needed to be diagnosed

1987

DSM-IIIR Renamed: “Attention Deficit Hyperactivity Disorder” Diagnostic boundaries re-configured; Result: Easier to Diagnose; 23% increase in the number of children with ADHD.At that time, disorder was said to affect 3%-5% of all American children

Today’s ADHD

Most Common Disorder of Children - 3% - 18%

ADHD Risk Factors

  • Low Birth Weight
  • Mal-nutrition during first year of life
  • Fetal Alcohol Exposure
  • Lead Exposure

 

Acetaminophen Use During Pregnancy Tylenol®/acetaminophen

“B” Zeyan, L., et al. (2014). Acetaminophen use during pregnancy, behavioral

problems, and hyperkinetic disorders. JAMA Pediatrics, 168, 313-320.

 

ADHD Cause Hypotheses

Genetic Contributions - Twin studies suggest heritability factor as high as .91 of Chromosome 15q, Polymorphism on the D4 receptor; Decreased Brain Volume in Frontal Lobes; Hypo-activation in pre-frontal and parietal network (via functional imaging); Basal Ganglia – especially caudate – reduced; Corpus Callosum - Disruption in Synaptic Pruning (Process by which unused nerve cells are eliminated to increase efficiency & speed) in  ADHD,  Autism & Intellectual Disability


Neurotransmitters found to play a role in expression of ADHD

  • Dopamine
  • Serotonin
  • Norepinephrine

 

Neurochemistry of ADHD

Start with Dorso-Lateral Prefrontal Cortex (DLPFC) with Inadequate arousal. As a result: Inattention; Hyperactive. Impulsivity

Remedy:for ADHD: Increase NE and DA activity with result of Increase processing in DLPFC

Adults with childhood history of ADHD have increased rates of: Divorce, Head Injuries & Lower Educational Success

 

New ADHD Theory

Norepinephrine: Signal to astrocytes to release fuel & shift blood to area activated with dysfunction in release of fuel implicated in ADHD

 

Alternative Therapies & ADHD

Relative Learning Disabilities Rehab

Secondary Issues Remediation

Depression

Test Anxiety

Behavioral Acting Out

Negative Self-Esteem

Organization Strategies & Study Aids

Parent Training

Family & Behavioral Therapies

United Kindom Mandates: Behavior therapy must be tried prior to drug initiation Alternative

Mindfulness Training & Self-monitoring Strategies www.mindfuleducation.org/mindfulnessforchildren.pdf

Parent Training via Parent-Child Interaction

PRIDE skills (Praise, reflection, imitation, describe, enthusiasm)

Environmental accommodations (lists and reminders, writing down directions, information in multiple formats, reward charts, verbal/physical redirection,

Self-Control Skills (“Stop, Think, Act”)

Retained Primitive Reflexes & ADHD

Brain Balancing Clinics  www.brainbalancecenters.com

 

Multisite Multimodal Treatment Study of Children with ADHD LANDMARK: “The MTA Study” Reaffirmed Stimulant Efficacy

1995, “First major clinical trial” NIMH conducted of a “childhood mental disorder”

N=579 children, 7-10 years of age -14 Month Study

Assigned to Four Groups

  • Medication Management

  • Behavioral Therapy

  • Two treatments Combined

  • Standard Community Care

All groups Improved at end of study

Medication Management SUPERIOR

Investigators continued to follow children

Children were free to seek any treatment they wanted

Three Years Later. . .1998

“Medication use was a significant marker NOT of beneficial outcome, but of deterioration.”

Participants showed increased symptomatology during that interval relative to those not taking medication.

Investigators Continued to Follow Children

Six Years Later. . .2004

Ongoing medication use was “associated with worse hyperactivity-impulsivity and oppositional defiant disorder symptoms; “Greater overall impairment.  Higher delinquency scores; 1” Shorter, Weighed 6 lbs. less

But medicated children performed better on math achievement tests

Children & Behavior Therapy were Less likely to be depressed and Less likely to be anxious

The results not due to “selection bias” since Sub-divided participants into 5 subsets trying to explain confounding outcome.

Final Conclusion:

“There was no evidence of the superiority of actual use of medication in any quintile.”

(Jensen, P., 2007; Molina, B., 2007; Swanson, J., 2008)

 

Stimulants

Stimulants (Analeptics)

Stimulants are NOT cognitive enhancers. (Julien, 2011)

Lower Relaxed Mood

Lower Playfulness

Lower Joy

LowerLaughter

 

Mechanism of Action

Methylphenidate (Ritalin® class)

  • Pseudo-amphetamine

  • Blocks NE and DA uptake (strong affinity for DA)

  • SNDRI Serotonin, Norepinephrine, Dopamine Reup Inhibitor

  • Lowers Brain Derived Neurotropic Growth Factor

  • Increases Inflammation

  • Lowers Copamine (DA) neurons in substantia nigra pars compacta

Amphetamine (d, l -- e.g., Adderall®) looks like dopamine trick terminal button

  • Molecule enters button through transporter

  • Disrupts vesicle; prompting Neurotransmitter (NT) release

  • Reverses transporter allowing NT to enter and flood the cleft

  • Vesicles dock, prime, release NT without action potential

  • At higher doses, MAOI

 

Stimulant Side Effects

Common: Insomnia, headache, nervousness, irritability, overstimulation, tremor, dizziness, increase in tics

Anorexia & weight loss

Abdominal pain

Slow normal growth (secondary to ↓ appetite)

Blurred vision

Rare: psychosis, cardiac problems, seizures, anemia, leukopenia


Need to Rules Outs 4 Variables before putting child on Simulant

(1) Is the child sleep deprived?

(2) Did educational testing find any learning disability or relative strength/weakness?

(3) Did psychological testing find any reason for distress or personality issues?

(4) Did an EKG, MRI or PET Scan show any abnormalities?

If yes, then. . . . if all 4 are ruled out:

(1) Select stimulant drug.

(2) Select concomitant adjunctive therapy.

 

Stimulant warnings

American Heart Association – Reasonable, but not mandatory to get EKG prior to prescribing stimulant

American Academy of Pediatrics – No requirement for EKG

But. . . .Ounce of prevention!

 

Methylphenidate

l-methylphenidate

FDA approved for: ADHD in children ages 6-17; Narcolepsy

Brands: Ritalin®; Ritalin LA®; Daytrana® (apply2 hours ahead of time, wear for 9 hours); Concerta® via OROS (Osmotic [controlled] Release Oral [delivery] System)


Quillivant XR®

Liquid methylphenidate for ADHD

Once daily dosing – 5 mg/mL suspension

Lasts 14 hours – eliminates midday doses at school

Cost: $175 month


d-methylphenidate - Focalin®

FDA approved for:ADHD in children ages 6-17

Active “d” enantiomer of methylphenidate may be more than 2x as efficacious as racemic d,lmethylphenidate

• “d” increase DA in CNS; “l” increas NE in PNS

 

Amphetamines

d-Amphetamine


Dexedrine®, Dexedrine® spansules (once a day dosing)

FDA approved for:  ADHD (ages 3-16); Narcolepsy

d, l-Amphetamine (3:1)


Adderall®, Adderall XR®

FDA approved for: ADHD in children 3-12 (Adderall®);  ADHD in children 6-17 and adults (Adderall XR®) &  Narcolepsy

No Generic

FYI: “d” increases DA in CNS; “l” increases NE in PNS

 

New Stimulants

Aptensio XR® (Ap-TEN-see-oh)

Form of methylphenidate-12-Hour sprinkle cap (Taken whole or “sprinkle on apple sauce.” Option if child cannot swallow


QuilliChew ER® (kwil-ih-CHOO)

First 8 hour Chewable Tab


Adzenys XR® (Ad-ZEN-is)

First Orally Disintegrating tab


Dyanavel XR® (dye-AN-uh-vel)

Suspension

Both above are once-daily forms of extended release amphetamine


Evekeo® (Amphetamine)

Racemic amphetamine - d, l-amphetamine

1:1 Ratio: 50% dextroamphetamine 50% levoamphetamine

 “d” increases DA in CNS; “l” increases NE in PNS

Indications: Narcolepsy; ADHD; Short-term adjunct, weight reduction

No evidence that this drug has any advantage over other stimulants – in spite of hype that it causes fewer problems with sleep and appetite

 

Lisdexamfetamine (Vyvanse®) not a schedule drug

FDA Approved for: ADHD, 6-12 and adults

Prodrug of Dextroampheamine Converted to dextroamphetamine and l-lysine.NE and DA reuptake blocker

Less propensity for abuse, intoxication, or dependence

FDA Approved February, 2015

Binge Eating Disorder (BED) – Added to DSM under its own diagnosis in 2013

 

Atomoxetine (Strattera®)

FDA Approved for: • ADHD, ages 6 and up

No nucleus accumbens action & No Schedule

Mechanism of Action: NRI; NE reuptake also blocks DA reuptake in frontal cortex

As a result, DA is increased in frontal cortex

May take 8 weeks before results

 

Guanfacine (Tenex® & Intuniv®)

Guanfacine (Tenex®, Intuniv®)

FDA approved for: • ADHD, ages 6-17; Hypertension

Mechanism of Action: Post-synaptic alpha (α) 2a receptors in prefrontal cortex

Side effects: sedation, dizziness, dry mouth, constipation, abdominal pain, fatigue, weakness, hypotension.

More tolerable in slow release version

 

Clonidine (Catapres®, Kapvay®) designed for hyperactivity

Clonidine (Catapres ®, Kapvay ®)

FDA approved for: ADHD, ages 6-17 & Hypertension

Mechanism of Action: Post-synaptic alpha (α) 2a receptors in prefrontal cortex

Side effects: sedation, dizziness, dry mouth, constipation, abdominal pain, fatigue, weakness, hypotension.

Similarity of Clonidine & Guanfacine

 

Vayarin® Lipirinen™ (Medical Food)

Omega-3-Long Chain Polyunsaturated Fatty Acids

No sugar, lactose, yeast, or gluten

Avoid with Anti- & Cholinergic Meds

Avoid with shellfish allergies

Composed of 167 mg of Lipirinen™:Phosphatidylserine (PS); Eicosapentaenoic Acid (EPA) & Docosahexaenoic Acid (DHA)

 

Methamphetamine Desoxyn®

Methamphetamine Desoxyn®

Methamphetamine

  • 16 Million Users Worldwide
  • 2nd most widely abused drug (after marijuana)
  • Inexpensive to produce
  • Long-lasting effects (t ½ = 10-12 Hours)
  • Euphoric brain rush

Affects Dopamine Receptors

Significant Structural Damage

Reduced striatal binding (increased Risk of Parkinson’s)

Impaired: Memory, attention, selective attention, inhibition, & decision-making abilities

 

Captagon/fenethyline

Most common in Middle Eastern countries

Allegedly used by military groups in Syria

 

Overdose on Amphetamines

Positive Psychotic Symptoms

Delusions & Hallucinations

 

Wake Promoting Drugs

New Class: Wake Promoting

Modafinil, “Daffy” (Provigil®) & Armodafinil (Nuvigil®, “r” isomer of Provigil)

FDA approved for: Reducing excessive sleepiness for narcolepsy, shift work sleep disorder, and sleep apnea as adjunct For narcolepsy without cataplexy

Mechanism of Action:Unknown; clearly different from amphetamines; Hypothetically: Dopamine Reuptake Inhibitor

Side effects: Headache, EKG changes

Schedule IV Drug

Substance Use Disorders


All substance abuse drugs are NEGATIVELY REINFORCING

manipulates you to do what is even bad for you. In withdrawal punishment comes

Reinforcers vs. Punishers

Reinforcers

  • Increase Probability of Behavior

Punishers

  • Decrease Probability of Behavior

Who would like for me to give you something that makes you feel good?

REINFORCER

It doesn’t matter if its positive or negative.

Actually, negative is a more powerful reinforce.

Who would like for me to give you something that makes you feel good?

REINFORCER

Positive Reinforcer

Who would like for me to give you something that makes you feel BAD?

Punisher

This is NOT a NEGATIVE REINFORCER

Who would like for me to TAKE AWAY something that makes you feel good?

Punisher

Who would like for me to TAKE AWAY something that makes you feel BAD?

Reinforcer

 

NEGATIVE REINFORCER – All drugs are negative reinforcers

TYPE

GIVE

TAKE AWAY

GOOD

Positive Reinforcer

Punisher

BAD

Punisher Negative

Reinforcer

 

Self-Reinforcing Properties

Drugs that take away pain:

Self-Reinforcing

Negatively Reinforcing e.g. Religion, Movies, Disney (takes away the pain)

Increase probability of repeated abuse to stop pain of withdrawal

 

Withdrawal

is

NEGATIVELY REINFORCING!

Increases the probability you will relapse!

Let’s create a Self-Reinforcing Drug. . .

 

CREATE A DRUG. . .

• “Makes me feel good”

• “Chills me out”

• “Forget my troubles”

• “Takes away my pain”

• Would you buy this drug?

 

CREATE A DRUG. . .

• DA Dopamine agonist

  • “Makes me feel good”

• GABA agonist

  • “Chills me out”

• Glutamate antagonist

  • Forget my troubles”

• Mu opiate agonist

    “Takes away my pain” (close to death to reach this point)

• Put it all together: Feel good, Chilled Out, No Worries, No Pain.

Would you buy this drug? – Alcohol C2HO8

 

Why is it Negatively Reinforcing?

Mesolimbic-Dopamine System

• 1 of 6 Dopamine Pathways

• Ventral Tegmental Area (VTA) to Amygdala and Nucleus Accumbens (NA)

• Nucleus Accumbens, reward center of brain

• Amygdala attaches positive valence to abuse

• Hippocampus, memory of drug’s effect

• Activates Glutamate

 

Overview

Substance Abuse

Estimate: 50% of an individual’s likelihood of having a substance abuse associated with genetic predisposition

Likely not “inheritance,” but “genetic predisposition”

 

Alcohol

Central Nervous System Depressant

Wernicke-Korsakoff Syndrome Thiamine deficiency

Ataxia

Confabulation

Oculogyric Problems

Zero-Order Kinetics

Binge Drinking:  5 for Men  4 for Women

 

Alcohol Health Benefits

Decreased: Pro-inflammatory Cytokines; Gallstones; Kidney Stones (also with Caffeine); Diabetes; Heart Disease & Platelet Aggregation

Increased:HDL & Vasodilation

 

Cannabis

Δ9-THC (tetrahydrocannabinol) (isolated in 1964) Unique has its own Classification System


Mechanism of Action

Lowers Adenylate cyclase (catalyzes the conversion of ATP to cAMP, regulator of stored energy); Lowers Glutamate in hippocampus; Lowers ACh, DA, NE, 5-HT ;LowersCa++; AChEse inhibitor in CNS; Facilitates K+ & μ opiate agonist


Stimulates DA firing in VTA & Increases release of DA in nucleus accumbens (self-reinforcing)

Chronic Use: lowered Testosterone; lowered Sperm Count; lowered Viability; lowered Follicle Stimulating Hormone; lowered Luteinizing; Menstrual Cycles Affected &  Anovulatory Cycles


Treatment for. Nausea;  Appetite; Analgesia; Decreases Inter-Ocular Pressure (IOC); Bronchodilation Seizures (Increases Seizure Threshold); Tourette’s; Multiple Sclerosis; Inflammatory & Neuropathic Pain & Menstrual Difficulties

 

Cannabinoid Hyperemesis Syndrome

Characterized by nausea, vomiting, & colicky abdominal pain.

Proposed Disorder, currently unlisted

 

Affects of Cannabis

Age of use significantly affects biological process

Use ‹17 YOA: Smaller whole brain volumes; Less cortical gray matter; Greater amounts of cerebral blood flow

THC increases cognitive effort for simple inhibitory tasks: Slower processing speed; Memory problems & Decreased Attention

 

Cannabis Withdrawal

Symptoms emerge 1 day after discontinuation & Peak at about 1 week & Last up to 3 weeks

Symptoms: Cravings; Anorexia; Irritability; Restlessness & Sleep Disturbances

 

Epidiolex®

Liquid formulation of highly purified cannabidiol (CBD) – 1 of 85 active cannabinoids identified in cannabis

Cannabidiols, 40% of plant extract, lack psychoactivity no interference with psychomotor of psychological functioning

Investigational Drug – Not approved for use by FDA

Orphan drug designation granted for Epidiolex® for: Lennox-Gestaut Syndromes (Fast Track Designation) Dravet Syndrome (Severe Myoclonic Epilepsy of Infancy, SMEI, rare genetic epileptic encephalopathy)

6.3 children per 1000 diagnosed with epilepsy

 

Cannabis & Post Traumatic Stress Disorder

Possible Explanation of Cannabis’s effectiveness in treatment of PTSI

Potentiates GABA in amygdala

Concomitantly antagonizes (blocks) Glutamate in amygdala

Result: Extinguish Fear Memories

Decreases GABA at Ventral Tegmental Area (VTA) which increases DA

Result: Patient feels better!

 

Cannabis & Viagra®

Cannabis & Viagra® Don’t Mix!

Cannabis CYP 3A4 Inhibitor (enzyme needed to breakdown Viagra)

Viagra, metabolized by CYP 3A4

MIX = Cardiac ARREST

 

Cannabis

Recent Cause of Concern

Increae Heart Rate & Increase Blood Pressure

When Lying Down = May Cause Heart to Lose Rhythm

2 Recent Deaths in Colorado

 

Cocaine

MOA: SNDRI Serotonin, norepinephrine, dopamine, reup inhibitor

Long Lasting DA decreaser & Tyrosine hydroxylase decreaser

Damages 5-HT Serotonin fibers in neo-cortex, hippocampus, & striatum

Stereotypies (Pronounced: “Stare-e-ot-o-pees”)

Sympathomimetic

Chronic Use: Long-term deficit in frontal lobe glucose utilization; Decrease gray matter & Decreased attention, verbal memory, & motor function

Cocaine as a Negative Reinforcer

A single dose of cocaine auses up-regulation of receptors; Can last as long as a month and

Leads to craving & drug seeking behavior

Cocaine the Perfect Heart Attack Drug

Sympathomimetic Increases Aortic Stiffness; Increases Systolic Blood Pressure;Increases Thickness of Heart’s Left Ventricle

FYI: Cocaine Causes Hyperthermia: decreases Sweating – Do not feel discomfort & increase Deaths in Summer

 

Caffeine

Mechanism of Action: Adenosine Antagonist at A1 and weakly at A2;

1/16th tsp = 250 mg  3 Red Bulls®

1 tsp = 50 Red Bulls®

Foosh® Energy Mints = 1 Red Bull ®

Stimulant; Absorbed Rapidly, Peak Effects within 30 Minutes

>250 mg per day may interfere with deep sleep

Half Life Caffeine

• t ½ = 3-5 Hours

• t ½ = 10 Hours when mixed with contraceptives

• t ½ = Increased more than 3-5 Hours in Fetus

• t ½ = Increased when mixed with SSRIs

A1 Antagonist

  • decreased Ach acetylcholine - memory

  • decreased NE norepinephrine – energy, alertness

  • decreased DA dopamine - sad

  • decreased 5-HT serotonin - apathy

  • decreased GABA - anxious

Central Nervous System Stimulant

“Zeitgeber” works on hypothalamus; Alert; Insomnia; increased Heart Rate; Diuretic; Constricts Cerebral Blood Vessels (30%); Dilates Peripheral Blood Vessels; Dilates Coronary Arteries; Constricts Cerebral Arteries & Decreases blood flow and pressure in brain by 30%; increase heart rate; increase Body Temperature; increase Blood Pressure; increase Blood flow to skin/extremities; increase Blood Sugar; increase Stomach Acid & increases Urine (diuretic)


Caffeine Suppositories - Tour de France Neurogum® “Optimize Your Body & Mind” Nootropic Chewing Gum $35 (pack of 12)

 

Nicotine

Perfect Nootropic (mind nourishing) – except for one pesky, little side effect!

Most Addictive Psychoactive Substance - Central Nervous System Stimulant

Approximately 90% absorbed = very toxic drug

Mimics Acetylcholine - Biphasic: Stimulates then Blocks

T 1/2 = 90 Minutes

First Cigarette in the Morning the Best (Withdrawal); Lowers Dose, Left Hemisphere = Mental Stimulation; increases Dose, Right Hemisphere = Sedation

Casual vs. Chain Smokers: CYP 1A2 Inducer & 2A6 Inducer; decreases Oxygen to heart Thereby increasing amount of work heart must do: increase Heart Rate; increases Blood Pressure; increases Atherosclerosis (artery wall thickens); Risk of Thrombosis (narrowing & clotting); increases Cognitive Performance (nootropic); increases Arousal & increases Muscle Tone

 

OPIATES

Introduction of Hypodermic Needle 1856

Analgesic – Relieve pain without producing unconsciousness

94% of World Opiate Supply from Afghanistan

Most US Opiates from Columbia & Mexico

Harrison Act, 1914, required physicians to report prescriptions for opiates

Indicators of Opiate Poisoning - The Opioid overdose Triad: Coma, Pinpoint Pupils & Depressed Respiration


OPIATE Receptors

ORL-1, Opiate Receptor Like-1; Mu (μ) (Endorphins) when hit get pain relief, pleasure, hero affect; Found Throughout Brain

High doses act on regulation of respiration in ventral medulla, inhibiting respiratory responses triggered by carbon dioxide – result, respiratory depression


Delta (δ) (Enkephalins) Found in striatum and nucleus accumbens for pleasure; Kappa (_) (Dynorphins); Contributes more to dysphoria & thermoregulation Amygdala, hippocampus, & pituitary; Tolerance; Analgesic effects, rapid tolerance; Constipation & Pinpoint Pupils, limited tolerance

Chronic Use: decrease Testosterone & decrease Estrogen (as much as 50%); decrease Melatonin, Interferes with REM and Δ Delta Sleep; decrease Adenosine; Ataxic/Biot’s Respiration (quick, irregular apnea); Adrenergic Rebound (when come off the drug) and decreaseNorepinephrine in Locus Coeruleus


Natural Narcotics: Morphine & Codeine (prototype Pro drug)

Semisynthetic Narcotics

Heroin; Hydromorphone (Dilaudid®); Oxycodone (OxyContin®; Percodan®; Oxecta®, breaks into chunks, not powder,turns to gel if mixed with H2O, contains sodium laurel sulfate, irritant to nose if snorted)

Totally Synthetic Narcotics

Meperidine (Demerol®); Fentanyl (Sublimaze®) (Lazanda®, fentanyl nasal) (marijuana became legal the Mexican cartels lost money and looked for a drug easy to make which works fast)


Methadone (Dolophine®) (Nazi drug, in WWII, using heroine as drug to kill people with dignity got if from Afghanistan, but when allies cut the path to get opiates from Afghanistan, they created a synthetic opiate and named in his honor Adolf Hitler) (rosh drug offered Christ on cross – head of poppy plant- opiate wine and myhrr)


New Opiate Partial Agonist

Belbuca® (bel-BYOO-kuh) Twice-daily film – hydrophilic polymer that rapidly dissolves on tongue.Joins Butrans® once-weekly patch as another buprenorphine product approved for chronic pain

C-III, lower abuse potential than other opiods; Fewer withdrawal if stopped; Less risky in overdose; Possible analgesic ceiling & Can be abused!

• NOTE: OxyContin® (oxycodone ER) - generic!


 Antagonists

 Naloxone (Narcan®, Evzio®)

 Naltrexone (ReVia®, Vivitrol®)

Mixed Agonist-Antagonist

Buprenorphine (Buprenex®, Subtex®)

Opiate Partial Agonist combined with naloxone (antagonist)

FYI: Contrave® = Naltrexone + Bupropion Weight Loss


PCP & Ketamine

Entheogenics (allow you see the face of God) “To be one with the Universe”

Along with Ecstasy (MDMA), LSD, mushrooms, ketamine and phencyclidine fall broadly under “hallucinogens”

MOA: NMDA Antagonists (Glutamate) Closely Related Compounds; Dissociative Amnesia – “Down the K Hole”; Highly Reinforcing; Paranoia; Catatonia; Convulsions ;Vertical Nystagmus &  Coma with Eyes Open

Overdose

Positive (Delusions & Hallucinations) & Negative (Affect, Anhedonia, inAttention, Alogia, Avolition) Psychotic Symptoms

 

MDMA - Ecstasy

Entacogenic (Latin. “tactus,” to touch)

1914 – Appetite Suppressant

1950s – Tested for “Brainwashing”

1970s – Therapeutic EST (Erhard Seminars Training)

1970s CIA Ultra

MOA: SRI, Stimulates DA, 5-HT > DA (could be used to treat autism-missing mirror neurons)

Damages 5-HT pathways in forebrain; Axons pruned (will regrow, but not same); lowers 5-HT Function

Side Effects: Water toxicity; Trismus – tightening of jaw muscles & Bruxism, teeth grinding

MDMA Side Effects

Mouth (biting inside of mouth)

Death (“Suicide Tuesday,” affinity for 5-HT-2B receptor in heart)

Memory (can last up to 40 days)

Aqua (Hypotonic, water intoxication)

UNIQUE ACTION

Has the ability to uncouple the energy-producing capacity of mitochondria in the body

Mitochondria loses its ability to generate ATP, body’s principal energy currency

Can’t generate ATP, mitochondria waste their energy as heat

Seen mostly in muscles

Males have more muscles; they are more sensitive to this phenomena than females

 

Inhalants

MOA: Not clearly known; Enhances inhibitory GABAA; Inhibits NMDA (Glutamate antagonist); Increases DA in VTA; More brain abnormalities than cocaine, amphetamine, marijuana, opiates & alcohol; Methemoglobinemia

Damage: Highly perfused areas Liver, Kidney, Lungs, Brain (Highly vulnerable), Cognitive Abnormalities &  White matter (myelin) abnormalities; “Sudden Sniffing Death Syndrome” FATAL: 1 whiff = heart arrhythmias

Inhalant ABUSE

Hearing Loss, Peripheral Neuritis, Paresthesia, Cerebellar Signs, Motor impairment, Rhabdomyolysis, Irreversible Hepatic & Renal Damage, GI Distress – Vomiting & Hematemesis, Nausea & Vomiting; Headache, Appetite Decrease, Light Sensitivity, Aches Muscle, Neurons Decreased, Tachycardia (arrhythmias) & Tinnitus, Skin Rash, Sneezing, Sniffling, Slurred Speech

Unsuspecting Parents & Inhalants

Helium & Gasoline 46% of Acute Fatalities

 

Energy vs. Chill Drinks

Energy Drinks:

  • Red Bull®

  • NOS®

  • Monster®

  • Anti-Energy Drinks (“Relaxation Drinks”)

  • Bliss®

  • Just Chill®

  • Dream Water®

  • iChill®

  • Marley’s Mellow Mood®

  • “Drank® – To Slow Your Roll”

Energy Drinks

Ingredients: Ephedrine (in ADHD medicines), Taurine – amino acid regulates heart beats & muscle *, Ginseng – root believed to reduce stress & boost energy, B-Vitamins – Group of vitamins that can convert sugar to energy & improve muscle tone

Side Effects

Cardiac Arrest, Headaches & Migraine, Insomnia, Type 2 Diabetes

Drug Interactions

Addiction, Risky Behavior, Vomiting, Jitteriness & Nervousness, Allergic Reactions

Relaxation Drinks

“Anti-Energy”, Ingredients (usually not listed; combination of): GABA, Melatonin, L-theanine – amino acid in green tea shows some evidence for relaxation, L-threonine, amino acid in proteins, no evidence it facilitates relaxation, 5-HTP – 5-hydroxytryptophan, raises serotonin, Botanicals: Chamomile, passion flower, and valerian, KAVA – GABAA agonist, NDRI, CB1 agonist, MAO-B reversible inhibitor, Na+ &,Ca++ channel inhibitors

Side Effects 

Consumer Reports: “Little evidence these products have been associated with harmful reactions.” But: Drowsiness, Should be avoided by pregnant or nursing women, Not for children, Avoid with alcohol, Sugar Content: 0 to 54 grams


Over-the-Counter & Herbal

Psychopharmacology Natural, not necessarily safe!

Anxiety & Tension

B-Complex

5-HTP

St. John’s Wort

Sage

Valerian

L-theanine

N-Acetyl cysteine (overly promoted prodrug, free radical scavenger)

Depression

St. John’s Wort

5-HTP & tyrosine

Pumpkin Seeds

B-Complex

Vitamin D

Folic Acid

N-Acetyl cysteine

SAMe

Memory

Choline – Aricept

Huperzine-A (HUP-A) work similarly to aricept

Gingko

Ginseng

Sleep

GABA

Melatonin

Valerian

Lavender Oil (Aroma Therapy)

Lemon Balm

Chamomile