Psychostimulants

Not a pharmacologically similar group like the CNS depressants

Psychostimulants

u Cocaine and amphetamines

u Caffeine & its relatives

u OTC and herbal stimulants

u Nicotine

Stimulants That Affect
DA, NE, And 5HT

Cocaine

u Naturally occurring in leaves of coca bush (2% concentration)

u Available as powdered salt (cocaine hydrochloride) (~25-30 mg per “line”) – if snorted, effect peaks 30-60 minutes, if injected, rush is faster, stronger but shorter (30 min. total)

u Crystallized chunks of crack cocaine (doses average 250-1000mg for this or older version of freebase)- intense rush, but again short-lived

u In South America 60-80% pure coca paste

Street Names

u Cocaine – coke, C, snow, blow, toot, Peruvian lady, white girl

u Crack cocaine – base, black rock, Roxanne, gravel

u Amphetamine – speed, crystal, bennies, uppers, jolly beans, copilots, hearts, white crosses, dexies, pep pills

u Meth – crystal meth, ice, crank

Cocaine’s Actions

u Local anesthetic

u Sympathomimetic- stimulates body

u Vasoconstrictor

u Psychostimulant – stimulates behavior

u Blocks reuptake of Da, NE and 5HT

u DA is key neurotransmitter in reward system; NE is involved in arousal of body and brain; 5HT related to mood

Side Effects

u Depression

u Weight loss, malnutrition and signs of ill health

u Poor sleep

u Bruxism (grinding of teeth)

u Sexual dysfunction as use increases

Adverse Effects Besides Dependency

u depression, anxiety, paranoia, risk of “cocaine psychosis” and repetitive, stereotyped behavior

u stroke, arrhythmias, heart attack, seizures

u respiratory arrest

u risk to fetus

u often used with downers, alcohol, heroin – may lead to dual dependency

u Use with alcohol produces cocaethylene which increases coke’s toxic effects

Amphetamines

u originally developed as a synthetic substitute for ephedrine

u was sold as OTC asthma inhaler/decongestant Benzedrine (1932)

u amphetamine pills used world-wide during WWII

u became a controlled drug in 1965 because of growing abuse

Basic Amphetamines

u molecules come in right (dextro)& left (levo) -handed varieties or stereoisomers

u Benzedrine is a mix (d,l amphetamine)(5-50 mg.)

u Dexedrine is d-amphetamine & is more psychoactive (2-20 mg.)

u Methamphetamine crosses BBB even better.

u “Freebase” dextromethamphetamine (“ice”) is smokable like crack, but much longer acting.

Best Known
Amphetamine-like Drugs

u methylphenidate (Ritalin) (half-life 2-4 hrs)

u pemoline (Cylert) (half-life 11-13 hrs)

u fenfluramine & phentermine *(phen-fen)

u dexfenfluramine *(Redux)

– *Removed from market for health reasons

u sibutramine (Meridia)

u Less psychoactive OTC drugs phenylephrine, phenylpropanolamine, ephedrine

Effects

u Amphetamines release DA & NE; may also be able to activate receptors

u Sympathetic NS stimulation

u Wakefulness, energy, less hunger

u Elevated confidence, mood

u Increased movement & speech

u May be jumpy, short-tempered

u Longer acting than cocaine (hrs vs mins)

Possible Side-Effects

u Excess stimulation (jittery, agitated, palpitations, tremors & twitches, dizziness, headache, insomnia)

u Dry mouth, hi BP, stomach ache, bruxism, eventual malnutrition & ill health

u Hallucinations, delusions, paranoia (“amphetamine psychosis”), violence, obsessive-compulsive-like behaviors (amphetamine stereotypy- repetitive behaviors) with high doses

u Irritability and aggression

Withdrawal After Regular Use

u Depression, apathy, irritability, anhedonia

u Fatigue, lethargy, no energy, increased sleep

u Rebound hunger, binging

u Crave positive drug effects

u Some evidence that methamphetamine is followed by a persisting shortage of DA & 5HT

Medical Uses

u Treatment of narcolepsy

u Treatment of attention-deficit hyperactivity disorder (ADHD).

u Medical uses more limited than when amphetamines were first marketed (not used for asthma, depression, most not recommended for weight-loss)

Ritalin Risks

u Appetite-suppression, reduced growth

u Sleep disturbance possible

u Stomach ache, headache, motor tics

u Kids may not receive adequate assessment and follow-up

u Best if combined with behavioral strategies

Treatment of Stimulant Abuse

u Many treatments tried but none stand out

u Drugs to relieve depression of withdrawal- antidepressants

u Drugs to relieve craving or prevent rewarding effects have been tried with no outstanding successes

u All types of inpatient, outpatient, counseling & support approaches (Cocaine Anonymous; 1-800-cocaine hotline), behavior therapy to avoid or extinguish responses to stimuli associated with drug use, etc.

Class Use (out of 41 F and 13 M)

u Caffeine

– Use 39F +10M; Used in past 2F & 3M

u Tobacco

– Cigarettes 15F + 5M; In past 12F + 6M

– Cigars 2M; In past 9F + 7 M

– Chew 1F + 3M; In past 7F + 3M

Class Use

u Amphetamine

– Use 1F + 1 M; Tried 3F + 1M

u Methamphetamine

– Use 1M; Tried 4F + 1M

u Cocaine

– Use 1M; Tried 5F + 2M

u Ecstacy

– Use 1M; Tried 1F + 2M

Other Stimulants of Interest

u Methcathinone (cat, Khat)

– Another synthetic amphetamine-like stimulant used by any route of administration with all the effects and risks of the other major stimulants.Similar to natural African stimulant from Khat shrub.

Diet Pill Risks

u FDA has removed the best-selling drugs because of a unacceptably high rate of cardiac valve problems

u ~25-50 X increased risk of deadly primary pulmonary hypertension (PPH)

u may aggravate bipolar disorder & use with antidepressants should be avoided

u Tolerance develops & rebound weight return after stopping is common