Effect of Drug Abuse

on the
Nervous system
Phitchayin Wisawachaiwat, MD
Department of Medicine, Rajavithi Hospital
June 14, 2021
INTRODUCTION
Drug dependence is of two types
Psychic dependence (addiction) : craving and
drug-seeking behavior
Physical dependence : an adaptive state in
which abrupt cessation of drug use results in
somatic withdrawal symptoms
Tolerance : the need for increasing doses of drug
to produce a desired effect or to avoid withdrawal
Abuse : the perception that use of a drug, or the
manner in which it is used, whether licit or illicit,
is harmful
Drugs DEPENDENCE
of Opioids
Psychostimulants
Sedatives
Marijuana
Hallucinogens
Inhalants
Phencyclidine
Anticholinergics
 OPIOIDS
Drug dependence is ofCommonly
two types Used Opioids
Psychic dependence (addiction) : craving and drug-seeking behavior
AGONIST
Camphorated tincture of opium (paregoric) Hydromorphone (Dilau
Physical dependence :
Morphinean adaptive state in which abrupt cessation
Oxycodone of
Meperidine
drug use results inMethadone (Demerol)
somatic withdrawal symptoms Hydrocodone
Propoxyphene (Darvon
Tolerance : the needFentanyl
for increasing doses of drug to produce Heroin a desired
effect or to avoid withdrawal
ANTAGONIST
Naloxone (Narcan)
Abuse : the perception that use of a drug, or the manner in which it is
Naltrexone

used, whether licit orMIXED

illicit, is harmful
AGONIST - ANTAGONIST
Pentazocine (Talwin)
Butorphanol (Stadol)
Buprenorphine (Buprenex)
 OPIOIDS
Drug dependence is of two types
Psychic dependence
DESOMORPHINE (addiction) : craving and drug-seeking behavior
Physical dependence : an adaptive state in which abrupt cessation of
drug use results in somatic withdrawal symptoms
Opioid
Tolerance : the need for increasing doses Southeast
of drugAsian tree
to produce a desired
"Crocodile" for the green-black skin Mitragynine, which has opioid-like as
effect or to avoid withdrawal
lesions found on parenteral users well as serotonergic & noradrenergic
Abuse
Made by :cooking
the perception that use
crushed codeine pillsof a drug, or the manner in which it is
effects
used, whether
Vascular licit organgrene
damage causes illicit, &
is harmful Usually smoked
multiorgan failure Stimulatory effects at low doses & opioid
Life expectancy is estimated at 2 years effects at higher doses
 OPIOIDS
Drug dependence Rushis of two types Pruritis
Psychic dependence (addiction) : craving and drug-seeking behavior
Euphoria or dysphoria Cough suppression
Physical dependence : an adaptive state in which abrupt cessation of
Drowsiness, "nodding" Hypothermia
drug use results in somatic withdrawal symptoms
Analgesia
Tolerance : the need for increasing doses of drug to Respiratory
produce a depression
desired
Acute Effects of
effect orvomiting
Nausea, to avoid withdrawalOpioid Agonists Postural hypotension
Abuse : theMiosis
perception that use of a drug, or the manner in which
Constipation
it is
used, whether licit or illicit, is harmful
Dryness of the mouth Biliary tract spasm
Sweating Urinary retention
 OPIOIDS
Treatment of Opioid Overdose
Drug dependence is of two types If hypotension does not respond promptly to
Respiratory support ventilation, IV fluids (pressors rarely needed)
Psychic dependence (addiction) : craving and drug-seeking behavior
Physical dependence
If respiratory depression : an adaptive state in which abrupt cessation of
Naloxone 2 mg IV, IM, or SC, and then 2 to 4
drug use results in somatic withdrawal symptoms mg repeated
as needed up to 20 mg
Tolerance : thedepression
If no respiratory need for increasing doses of drug to produce a desired
Naloxone 0.4 to 0.8 mg IV,
effect or to avoid withdrawal IM or SC, and if no response,
2 mg repeated as needed
Abuse : the perception that use of a drug, or the manner in which it is
used, whether licit or illicit, is harmful
Consider additional drug overdose, e.g., alcohol or cocaine

Hospitalization and close observation, with additional naloxone as needed

 OPIOIDS
Drug dependence is of two types
Psychic dependence (addiction) : craving and drug-seeking behavior
Physical dependence : an adaptive state in which abrupt cessation of
Symptoms
and
drug use results in somatic withdrawal symptoms
Signs
Tolerance
Drug craving :
Anxiety, the need
irritability for
Lacrimation increasing
Anorexia, doses
nausea, of
vomiting drug
Diarrhea to produce
Abdominal a desired
Rhinorrhea Yawning Sweating Mydriasis Myalgia,
muscle spasms Piloerection Erection, orgasm
cramps Productive coughing Hot flashes Fever
Tachycardia Tachypnea Hypertension
of
effect or to avoid withdrawal Opioid
Abuse : the perception that use of a drug, or the manner in which it
Withdraw is
used, whether licit or illicit, is harmful al
 OPIOIDS
Drug dependence is ofOpioidtwo typesdependence is treated pharmacologically
with maintenance doses of methadone
Psychic dependence (addiction) : craving and drug-seeking behavior or
buprenorphine
Physical dependenceTreatment
: an adaptive state in which abrupt cessation
failure is most often attributable to of
drug use results in somatic withdrawal
inadequate dosagesymptoms
Tolerance : the need forDespite FDAdoses
increasing approval, oral
of drug to treatment
produce awith the
desired
opioid
effect or to avoid withdrawal antagonist naltrexone has limited
usefulness in treating opioid dependence
Abuse : the perception that use of a drug, or the manner in which it is
used, whether licit or illicit, is harmful
Proposed alternative therapies : injectable extended-release
naltrexone, slow-release oral morphine, injectable heroin,
acupuncture and deep brain stimulation
PSYCHOSTIMULANTS
Dextroamphetamine
Methamphetamine
Ephedrine
Pseudoephedrine
Methylphenidate (Ritalin)
Pemoline (Cylert)
Phenmetrazine (Preludin)
Phentemine
Methylenedioxymethamphetamine (ecstasy)
Cocaine
Cathinone, methcathinone
 PSYCHOSTIMULANTS

Cocai Methamphetamine
ne
Alkaloid "Speed", "crystal meth"
Erythroxylon coca Pseudoephedrine
Local anesthetic "Ice" smoked
Intended effects of cocaine and methaphetamine include alert euphoria with
increased motor activity and endurance
Taken parenterally or smoked, they produce a rush distinguishable from that of
opioids
With repeated use there is stereotypic activity progressing to bruxism & dyskinesias
& paranoia progressing to frank hallucinatory psychosis
 PSYCHOSTIMULANTS
Acute Toxic Effects of Cocaine and Amphetamine-Like Psychostimulants

PSYCHIATRIC CARDIOPULMONARY
Anxiety, insomnia, paranoia, Chest pain, dyspnea, palpitations,
agitation, violence, depression, sweating, pulmonary edema, cardiac
suicide, hallucinations, psychosis arrhythmia, myocardial infarction,
cardiac arrest

NEUROLOGICAL OTHER
Dizziness, syncope, vertigo, mydriasis, Nasal congestion, nausea,
headache, paresthesias, tremor, vomiting, abdominal pain, fever,
stereotypy, bruxism, chorea, dystonia, chills, myalgia, rhabdomyolysis,
myoclonus, seizures, coma, ischemic or myoglobinuria
hemorrhagic stroke
 PSYCHOSTIMULANTS
Treatment of Psychostimulant Overdose
Sedation with IV benzodiazepine
Oxygen
Sodium bicarbonate for acidosis
Anticonvulsants
Antihypertensives
Nitroprusside or alpha-adrenergic blockers
Avoid beta-adrenergic blockers
Ventilatory support
Blood pressure support
Cardiac monitoring and treatment of cardiac arrhythmia
Treatment of hyperthermia
For rhabdomyolysis
Vigorous hydration
Sodium bicarbonate
 PSYCHOSTIMULANTS
Withdrawal from these agents produces fatigue, hunger,
craving, and depression
Objective signs are few, but depression can be suicidal

The phenylalkylamine 3,4-methylenedioxymethamphetamie (MDMA,

“Ecstasy”), appears to combine the psychostimulant properties of
amphetamine-related agents and the hallucinogenic properties of drugs such
as LSD
Undesired effects : anxiety, tremor, muscle tightness, sweating, profuse
salivation, blurred vision, and ataxia
Methamphetamine, overdose causes hypertensive crisis, hyperthermia,
tachyarrhythmia, psychosis, delirium, seizures, and rhabdomyolysis
Treatment is similar to that for psychostimulant toxicity
 SEDATIVES
SEDATIVE DRUGS
Barbiturates Benzodiazepines Miscellaneous
LONG-ACTING TRANQUILIZERS
Buspirone
Phenobarbital Barbital Primidone Alprazolam Chlorazepate
Diazepam Chloral hydrate
Lorazepam
Chlordiazepoxide
Oxazepam
Paraldehyde
INTERMEDIATE- Diphenhydramine
ACTING HYPNOTICS Ethchlorvynol
Amobarbital Butalbital Glutethimide
Flurazepam Temazepam Triazolam
Hydroxyzine
SHORT-ACTING
ANTICONVULSANT
Meprobamate
Pentobarbital Secobarbital Methaqualone
Clonazepam
Zolpidem
ULTRA-SHORT-ACTING ANESTHESIA INDUCTION Zaleplon
Methohexital Thiopental Midazolam
Gamma-hydroxybutyric acid
 SEDATIVES
Intended effects and overdose
Resemble ethanol intoxication, but respiratory depression is
much less with benzodiazepines than with barbiturates
Treatment of Sedatives Overdose Respiratory support

Severe benzodiazepine poisoning, specific antagonist flumanazil

can reverse coma, but its action is brief and it can trigger seizures
As with ethanol, sedative withdrawal causes tremor, seizures, or
delirium tremens; treatment can require intensive care and very
high-titrated doses of a benzodiazepine
MARIJUANA
Cannabis sativa
Marijuana is usually smoked but can be eaten
The plant contains more than 60 cannabinoid compounds, of
which delta-9-tetrahydrocannabinol (delta-9-THC) is the
principal psychoactive ingredient
In Europe and Canada, pharmacological agents containing
delta-9-THC and a nonpsychogenic cannabinoid,
cannabidiol, are available for treating spasticity and pain in
multiple sclerosis
In the US, only pure delta-9-THC (dronabinol) FDA-
approved for anorexia and chemotherapy-induced nausea but
not for neurological disease
MARIJUANA
Acute Effects of Marijuana
Relaxation, euphoria, jocularity Tachycardia
Jitteriness, anxiety, paranoia, panic Systolic hypertension & postural
Depersonalization, subjective time- hypotension
slowing Bradycardia, hypotension
Dizziness, sensation of floating Increased appetite & thirst
Impaired coordination & balance Decreased intraocular pressure
Impaired memory & judgment Analgesia
Conjunctival injection, decreased Auditory and visual illusions or
salivation hallucinations
Urinary frequency Psychosis
HALLUCINOGENS

Phenylalkylamine mescaline

Idolealkylamines psilocin & psilocybin

Synthetic ergot D-lysergic acid diethylamide (LSD)

Salvia divanorum

Numerous designer hallucinogens are available, with such

street names as “Fly” and “Bromodragonfly”
HALLUCINOGENS
Acute Effects

Perceptual Paranoia or panic

Psychological "Flashbacks"
Somatic Seizures or stupor

Treatment of overdose

Calm reassurance
No withdrawal syndrome
 INHALANTS
Products Contents

Aerosols Fluorinated hydrocarbons, propane, isobutane

Cleaning fluids, furniture polish Chlorinated hydrocarbons, naphtha

Glues, cements Toluene, acetone, benzene, trichloroethylene, n-hexane, xylene

Paints, enamels, paint thinners Toluene, methylene chloride, aliphatic acetates

Lighter fluid Aliphatic and aromatic hydrocarbons

Fire extinguishing agents Bromochlorodifluoromethane

Natural gas Methane, ethane, propane, butane

Petroleum Many aliphatic and aromatic hydrocarbons

Anesthetics Nitrous oxide, diethyl ether, halothane, chloroform, trichloroethylene

Room odorizers Amyl, butyl, and isobutyl nitrite

INHALANTS
Treatment of overdose
Respiratory & cardiac monitoring
No withdrawal syndrome other
than craving

Effects are similar to ethanol intoxication

Symptoms usually last only 30 minutes or so, leading to repeated use
over many hours
Overdose can cause respiratory depression, hallucinations, psychosis,
seizures, and coma
PHENCYCLIDINE

"Angel dust" is easily manufactured by kitchen

chemists & usually smoked
Low dose : relaxation & euphoria
High dose : agitation, violent behavior,
hallucinations, psychosis, myoclonus, seizures,
coma, respiratory depression & shock
PCP reproduces both positive & negative
symptoms of schizophrenia
Treatment

Calm environment, benzodiazepine sedation & restraints

Withdrawal symptoms are usually limited to nervousness & tremor
 ANTICHOLINERGICS
Datura stramonium ("jimson weed')
Less often used recreationally are
antiparkinsonian anticholinergics & the
tricyclic antidepressant amitriptyline
The result is a predictable intoxication :
Delirium, fever, and dilated unreactive
Treatment pupils

Physostigmine, gastric lavage, anticonvulsants

Neuroleptics, which have anticholinergic properties, are contraindicated
Sedatives should be used cautiously
No withdrawal syndrome
Neurologica COMPLICATIONS
l
Trauma
Infection
Seizures
Stroke
Cognitive Effects
Fetal Effects
Miscellaneous Effects
TRAUMA
Drug intoxication can result in trauma
Driving accidents with marijuana
Acts of violence with psychostimulants
Self-mutilation with hallucinogens
Among users of illicit drugs, trauma is most
often related to the illegal activities necessary
to distribute and procure them
INFECTION
Parenteral drug abusers are subject to local &
systemic infections that affect the nervous system
Hepatitis
Cellulitis & pyogenic myositis
Tatanus
Botulism
Endocarditis
Drug injection is a major risk factor for HIV
infection
 SEIZURES
Amphetamine-like psychostimulants seizure are usually accompanied by
other symptoms of intoxication such as
Fever, hypertension, or delirium
Cocaine-related seizures have a "kindling" effect—repeated use
progressively reduces seizure threshold
Opioids lower seizure threshold
Meperidine more often causes seizures or myoclonus
Ethanol cause seizures as a withdrawal phenomenon
Marijuana use was protective against the development of incident seizures
 STROKE
Illicit drug users often smoke tobacco or abuse ethanol, increasing their
risk for ischemic or hemorrhagic stroke
Parenteral drug abusers are additionally at risk for stroke related to
endocarditis, hepatitis, and AIDS
Heroin nephropathy carries risk for stroke
Amphetamine-like psychostimulants; hemorrhagic stroke has occurred in
the setting of overdose
Ischemic stroke attributed to large & small vessel vasculitis
Amphetamine/methamphetamine users
Based on angiographic "beading", a nonspecific sign
 STROKE
Cocaine users, roughly half ischemic and half hemorrhagic stroke
Cocaine is a significant stroke risk factor
Hemorrhagic stroke is probably most often caused by hypertensive
surges
Ischemic stroke is most often associated with direct cerebrovascular
constriction
Cerebral vasculitis is rare
Marijuana, stroke temporally without other vascular risk factors
Also at risk for myocardial infarction & Buerger-like peripheral
vascular disease
COGNITIVE EFFECTS

Chronically altered mentation in drug users might related

to ethanol, infection, malnutrition, or trauma
Determining whether the drugs themselves cause lasting
cognitive or behavioral abnormality has been difficult;
intoxication or withdrawal effects can persist for uncertain
durations, and baseline cognitive performance prior to
drug use is seldom available
COGNITIVE EFFECTS
Meta-analysis of studies addressing "neuropsychological
consequences of chronic opioid use"
Identified significant impairments in verbal working memory,
verbal fluency, and cognitive impulsivity
Structural & functional imaging studies have demonstrated
reduced cerebral gray matter density & decreased white matter
fractional anistotropy in heroin users
Abnormal connectivity patterns are described in both heroin
users and recreational users of oxycodone & hydrocodone
 FETAL EFFECTS
Adverse effects of in utero exposure to drugs are difficult to disentangle
Opioids is associated with decreased gestational size, respiratory distress, and
later, cognitive impairment
Methamphetamine is significantly associated with restricted fetal growth,
depressed arousal in neonates, and in older children, lower verbal memory,
spatial memory, working memory, attention, and visual-motor integration
Cocaine's fetal effects are conflicting
Neuropsychological testing has shown subtle abnormalities in executive
functioning, and diffusion tensor imaging shows frontal white matter
abnormalities
 FETAL EFFECTS
Human and animal studies offer evidence that in utero exposure to
marijuana carries risk for later cognitive impairment
Long-term cohort studies have demonstrated impaired performance on
tasks of attention and visual memory as well as greater impulsivity and
smaller head size, persisting into adolescence
In animals, prenatal exposure disrupts cortical development by interfering
with cytoskeletal dynamics critical for axonal connectivity between neurons
 MISCELLANEOUS EFFECTS
Heroin users : Guillan-Barré polyneuropathy &
brachial or lumbosacral plexopathy
Glue containing n-hexane : severe axonal
sensorimotor polyneuropathy
Rhabdomyolysis, myoglobinuria, and renal failure
have followed use of heroin, psychostimulants, and
phencyclidine

Cocaine users develop extrapyramidal symptoms progressing from

repetitive stereotypic behavior to choreoathetosis and dystonia
Precipitate or aggravate symptoms of Tourette syndrome
 MISCELLANEOUS EFFECTS
Marijuana inhibits FSH & LH, causing reversible
erectile dysfunction in men & menstrual irregularity in
women
Hallucinogen users not only experience flashbacks,
but the visual phenomena—geometric shapes, objects
in the peripheral field, flashes of color, enhanced color
sensitivity, trailing & stroboscopic perception of
moving objects,

after images, halos, and macro/micropsia—can persist for years

(“hallucinogen-persisting perception disorder”)