CNS STIMULANTS AND

PSYCHOTOMIMETICS
Group 1
ADEBOLA ADEBIMPE (160702705) ADERIYE TOLULOPE (140705067)
ADENOWO JOHNSON (150702018) ADETUNJI ADEBAYO(150702035)
ADEOSUN ADEBUSAYO (150702029) AKAME JOHN-PAUL (160702708)
AREMU ADEJOKE (150702007) ANDREW MERCY
 CNS STIMULANTS AND
PSYCHOTOMIMETICS
Drugs that have a stimulant effect on the CNS are divided into:
 Psychomotor Stimulants e.g. amphetamine, modafinil, cocaine etc.
Drugs in this category have a marked effect on mental function and behavior,
producing excitement and euphoria, reduced sensation of fatigue, and an
increase in motor activity. Some enhance cognitive function.

 Psychotomimetic (hallucinogenic) drugs e.g. lysergic acid diethylamide

(LSD), psilocybin and mescaline
Drugs in this category mainly affect thought patterns and perception,
distorting cognition in a complex way.
 CNS STIMULANTS AND
PSYCHOTOMIMETICS
 Central nervous system (CNS) stimulants are medicines that speed up physical
and mental processes.
 Central nervous system stimulants are used to treat conditions characterized 
by lack of adrenergic stimulation, including narcolepsy and neonatal apnea.
 A drug with psychotomimetic actions mimics the symptoms of psychosis,
including delusions and/or delirium, as opposed to just hallucinations
AMPHETAMINE

 Their mode of action is basically release and inhibition of uptake of

catecholamines
 They are substrates for the monoamine uptake transporters DAT and NET but
not SERT , and thus act as competitive inhibitors, reducing the reuptake of
dopamine and noradrenaline
 At high concentrations amphetamines can inhibit monoamine oxidase.
 In animals, prolonged administration results in degeneration of monoamine-
containing nerve terminals and eventually cell death.
AMPHETAMINES

 The main central effects of amphetamine-like drugs are:

• locomotor stimulation
• euphoria and excitement
• insomnia
• increased stamina
• anorexia
• long-term psychological effects: psychotic symptoms, anxiety, depression and cognitive
impairment.
 Amphetamines have peripheral sympathomimetic actions, producing a rise in blood
pressure and inhibition of gastrointestinal motility.
 The locomotor and rewarding effects of amphetamine are due mainly to release of
dopamine rather than noradrenaline
Dependence and Tolerance

 Repeated usage of amphetamine over a few days induces a state of

‘amphetamine psychosis’.
 This state resembles an acute schizophrenic attack, with hallucinations,
paranoia and aggressive behavior.
 Tolerance develops rapidly to euphoric and anorexic effects of amphetamines,
but more slowly to the other effects.
 Dependence on amphetamines appears to be a consequence of the insistent
memory of euphoria.
 It is estimated that about 10–15% of users progress to full dependence
 There currently is no clear-cut withdrawal syndrome of amphetamines
 Experimental animals, given unlimited access to amphetamine, take it in such
large amounts that they die from the cardiovascular effects within a few days.
Pharmacokinetics

  
Amphetamines are readily absorbed from the gastrointestinal tract. When
administered orally, they have bioavailability of 75-100%
 Amphetamines freely penetrate the blood–brain barrier, more readily than
ephedrine and tyramine
 They are metabolized by CYP2D6, Dopamine β-hydroxylase and (Flavin-
containing monooxygenase 3)
 Amphetamines are mainly excreted unchanged in the urine, and the rate of
excretion is increased when the urine is made more acidic.
 The plasma half-life of amphetamines varies from 5 to 30 hours,
Cocaine

 It binds to and inhibits NET, DAT & SERT.

 It produces euphoria, garrulousness and an increased magnification of pleasure.
 Its peripheral sympathomimetic actions lead to tachycardia, vasoconstriction
and increase in blood pressure.
 Cocaine causes strong psychological dependence
 Increase of cocaine intake by users is more based on their desire for more than
tolerance
 They also like amphetamine have no clear-cut withdrawal syndrome
 Studies have shown that cocaethylene (which is formed when alcohol combines
with cocaine in the liver when they are both consumed together) is more
euphoric and has a higher cardiovascular toxicity than cocaine
Pharmacokinetics

 Cocaine is rapidly absorbed by many routes.

 Inhaling cocaine causes atrophy & necrosis of nasal mucosa & septum
 It’s duration of action is 5 to 90 minutes
 It is rapidly metabolized in the liver by CYP3A4
 Its onset of action is within seconds to minutes based the route of
administration
 It has a biological half-life of 1 hour
Dependence and Tolerance

 Cocaine causes strong psychological dependence

 Users may increase their intake of the drug but this may reflect a desire for
an increased effect rather than the development of tolerance.
 Cocaine produces no clear-cut withdrawal syndrome
 The pattern of dependence, evolving from occasional use through escalating
dosage to compulsive binges, is similar to that seen with amphetamines.
Adverse Effects

 Toxic effects occur commonly in cocaine abusers.

 The main acute dangers are serious cardiovascular events.
 Progressive myocardial damage can lead to heart failure, even in the absence
of a history of acute cardiac effects.
 Cocaine can severely impair brain development in utero
Clinical Significance

 CNS stimulants have few legitimate therapeutic indications

 Amphetamines and methylphenidate are used in the treatment of Attention
deficit/hyperactivity disorder (ADHD)
 Amphetamine is helpful but not completely effective in the treatment of
narcolepsy
 Modafinil is effective in reducing the need for sleep in narcolepsy
CNS Stimulants

 Other CNS stimulants include: methylphenidate, modafinil, methylxanthines

etc.
Delphic analysis of recreational drugs
Psychotomimetic Drugs

 Psychotomimetic drugs affect thought, perception and mood, without causing

marked psychomotor stimulation or depression
 Psychotomimetic drugs do not cause dependence
 Psychotomimetic drugs include the following:
• Drugs that act on 5-hydroxytryptamine (5-HT) receptors and transporters.
E.g. lysergic acid diethylamide (LSD), psilocybin and mescaline, MDMA
(ecstasy)
• Ketamine and phencyclidine
• Δ9-Tetrahydrocannabinol
• Salvinorin A
LSD

 LSD is an exceptionally potent psychotomimetic drug capable of producing

strong effects in humans in doses less than 1 μg/kg
 The main effects of these drugs are on mental function
 It causes hallucinations – visual, auditory, tactile or olfactory
 Thought processes tend to become illogical and disconnected
 Occasionally it causes ‘bad trips’ in which the hallucination is accompanied
by paranoid delusions.
 It has a duration of action of 8-12 hours, with an onset of action ranging from
30-40 minutes. Its plasma half-life is 3.6 hours
 It has no medicinal use and is not addictive
LSD

 Some sensory effects of LSD include an altered sense of time, strong metallic
taste, surfaces appearing to ripple.
 Users usually report that inanimate objects become animate
 Some users experience “flashbacks”
 Tolerance to LSD builds up over consistent use
MDMA (ECSTASY)

 MDMA (3,4-methylenedioxymethamphetamine) is widely used as a ‘party

drug’ because of the euphoria, loss of inhibitions and energy surge that it
induces.
 It is a stimulant drug that also has mild hallucinogenic effects.
 It causes loss of appetite, insomnia, impulsiveness, restlessness etc.
Pharmacologic Effect

 It inhibits monoamine transporters, principally the 5-HT transporter, and also

releases 5-HT
 MDMA is addictive
 Sudden illness and death can occur even after small doses of MDMA.
 The after-effects of MDMA persist for a few days and comprise depression,
anxiety, irritability and increased aggression – the ‘mid-week blues’.
 Illicit ‘ecstasy’ tablets and powder are sometimes contaminated or entirely
substituted with para-methoxyamphetamine, which produces similar
behavioural effects but which may be more dangerous to the user.
 The most serious short-term physical health risks of MDMA are hyperthermia
and dehydration
Pharmacological effects

 MDMA use at high doses produces brain lesion in the serotonergic pathways.
 Long-term exposure produces marked neurodegeneration in striatal,
hippocampal, prefrontal and occipital serotonergic axon terminals
 There are adverse neuroplastic changes to brain white mater even in people
using low doses of MDMA
 It has no medicinal use
Pharmacokinetics

 It is metabolized in the liver by CYP2D6 & CYP3A4

 It is commonly administered orally
 Its onset of action is 30-45 minutes
 It has a duration of action of 4-6 hours
 It is excreted by the kidney
Effects of Ecstasy
APPRECIATION