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48. DRUG ABUSE AND DEPENDENCE: PSYCHOMOTOR

STIMULANTS, PSYCHEDELICS, CANNABIS

PSYCHOMOTOR STIMULANTS

Overview - psychomotor stimulants are abuse-drugs that exhibit both physical- and psychological effects

in the subject of interest

Relevant Drugs

- 3 categories

1) AMPHETAMINE ANALOGUES

- amphetamines are abuse-drugs that fascilitate secretion of monoamines

(dopamine, noradrenaline and serotonin) into the synaptic cleft

- they are taken up by the neuron by way of the uptake 1 monoamine transporter

in exchange for cytoplasmic monoamines, thus facilitating the release of

monoamines

- further, they are taken up by the cytoplasmic neurotransmitter vesicles by the

way of VMAT in exchange for monoamines, thus displacing monoamines

from the neurotransmitter vesicles and into the cytoplasm

- the effects of amphetamines are classified according to the monoamines

released

MONOAMINE EFFECT

DOPAMINE Abuse dose

- euphoria

- pleasure

- excitement

- increased confidence

- increased sex drive

- increased mental performance

- increased physical performance

- insomnia

Overdose

- hallucinations

- paranoia

- aggression

NORADRENALINE - increased motor activity

SEROTONIN - anorexia

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- like any other abuse-drug they have 4 mechanisms by which they cause

dependence (see 47)

MECHANISM CAUSE

POSITIVE REINFORCEMENT - release of dopamine, and following

stimulation of the mesolimbic-

mesocortical dopaminergic pathway

CONDITIONING - see 47

TOLERANCE - depletion of dopamine

- depletion on noradrenaline

(- depletion of serotonin)

NEGATIVE REINFORCEMENT - apathy

- axiety

- depression

- suicidality

- consequences of amphetamine consumption include

ORGAN EFFECT

HEART - tachycardia

- cardiac arrhythmias

BLOOD VESSELS - vasoconstriction

- hypertension

SKELETAL MUSCLE - tremor

- hyperthermia

ENDOCRINE SYSTEM - increased ADH secretion by the

pituitary gland

- hypotonic hypervolemia

UPON OVERDOSE - sudden death (even from just a

single moderate dose (!))

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- they are used orally or nasally and absorbed from the nasal- and/or small

intestinal mucosa

- 6 types

DRUG NAME DESCRIPTION

AMPHETAMINE General information

- abuse-drug

Medical uses

- treatment of narcolepsy

- treatment of obesity

METHAMPHETAMINE General information

- “speed”

- abuse-drug

METHYLENEDIOXY-

METHAMPHETAMINE

General information

- “ecstasy”

- abuse-drug

MESACAINE General information

- abuse-drug

METHYLPHENIDATE Medical uses

- treatment of ADHD (paradoxically

(!))

FENFLURAMINE General information

- has a stronger action of serotonin

release, thus producing more

pronounced anorexia

2) COCAINE ANALOGUES

- cocaine is an abuse-drug found in coca leaves

- it inhibits presynaptic reuptake of monoamines uptake 1, thus increasing

monoamine concentration (dopamine and noradrenaline) in the synaptic cleft

- it also blocks sodium channels, thus is clinically used as a local surface

anaesthetic (see 22)

- the effects of cocaine are classified according to the monoamines increased in

the synaptic cleft

MONOAMINE EFFECT

DOPAMINE - euphoria

- pleasure

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- garrulity

NORADRENALINE Abuse Dose

- increased motor activity

- hyperthermia

- tachycardia

- vasoconstriction

- hypertension

Overdose

- tremor

- convulsions

- respiratory depression

- vasomotor depression

- like any other abuse-drug it has 4 mechanisms by which it causes dependence

(see 47)

MECHANISM CAUSE

POSITIVE REINFORCEMENT - inhibition of presynaptic dopamine

reuptake, and following stimulation

of the mesolimbic-mesocortical

dopaminergic pathway

CONDITIONING - see 47

TOLERANCE - downregulation of dopaminergic

receptors

- downregulation of adrenergic

receptors

NEGATIVE REINFORCEMENT - dysphoria

- depression

- decreased mental performance

- decreased physical performance

- consequences of cocaine consumption include

ORGAN EFFECT

HEART - tachycardia

- cardiac arrhythmias

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- myocardial damage

BLOOD VESSELS - vasoconstriction

- hypertension

- coronary- and/or cerebral artery

thrombosis

SKELETAL MUSCLE - tremor

- hyperthermia

UPON OVERDOSE - convulsions

- vasomotor depression

- respiratory depression

- death

- 2 types

DRUG NAME DESCRIPTION

HYDROCHLORIDE SALT

COCAINE

General information

- “snow”

- abuse-drug

- used nasally or IV

FREE BASE COCAINE General information

- “crack”

- abuse-drug

- used by inhalation, nasally or IV

3) NICOTINE

- nicotine is an abuse-drug found in nicotiana (“tobacco”)

- tobacco is a compound substance consisting of several pharmacologically

active components

- the pharmacologically active components of tobacco are divided in 2 groups

according to the chemical phase of the components

A) SOLID PHASE COMPONENTS

- “particular phase components”

- include

TYPE DESCRIPTION

NICOTINE

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POLYCYCLIC

AROMATIC

HYDROCARBONS

(TAR)

B) GASSEOUS PHASE COMPONENTS

- include

TYPE DESCRIPTION

CARBON MONOXIDE

NITROGEN DIOXIDE

HYDROGEN CYANIDE

AMMONIA

FORMALDEHYDE

NITROSAMIDES

- of these, nicotine is the most pharmacologically active component causing

both ALL the immediate effects and the ALL the mechanisms of dependence

of tobacco (see below)

- nicotine is a nicotinergic receptor agonist, thus causing excitation of

nicotinergic cholinergic receptors (see 14)

- the effects of nicotine are classified according to the nicotinergic receptor it

acts on

TYPE EFFECT

CNS TYPE - satiety

- analgesia

- sedation

- alertness

- increased mental performance

- increased physical performance

- decreased skeletal muscle tone

GANGLION TYPE - positive chronotropic effect

(increased heart rate)

- positive ionotropic effect

(increased force of heart contraction)

- vasoconstriction

- increased circulating free fatty

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acids

- decreased glomerular filtration

- decreased peristalsis

- sweating

MUSCLE TYPE - increased skeletal muscle tone

(completely overridden by the

decreased skeletal muscle tone of the

CNS type nicotinergic receptors (see

above))

- like any other abuse-drug it has 4 mechanisms by which it causes dependence

(see 47)

MECHANISM CAUSE

POSITIVE REINFORCEMENT - stimulation of the mesolimbic-

mesocortical dopaminergic pathway

CONDITIONING - see 47

TOLERANCE - desensitization of nicotinic

receptors (partly opposed by a

simultaneous upregulation of the

same nicotinic receptors (!))

NEGATIVE REINFORCEMENT - irritability

- insomnia

- decreased mental performance

- decreased physical performance

- consequences of tobacco consumption may be divided in 2 groups according

to the causative agents

A) CONSEQUENCES OF NICOTINE AND CARBON MONOXIDE

- include

TYPE CONSEQUENCE

CARDIOVASCULAR

DISORDERS

- hypertension

- hyperlipoproteinemia

- coronary- and/or cerebral artery

thrombosis

- gangrene

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FETAL DISORDERS - spontaneous abortion

- placenta praevia (obstruction of the

cervical canal by the placenta)

- premature delivery

- increased perinatal death

- decreased birth weight

B) CONSEQUENCES OF TAR AND ALL OTHER GASSEOUS STATE

COMPONENTS

- include

TYPE CONSEQUENCE

PULMONARY

DISORDERS

- chronic obstructive pulmonary

disorders (COPD)

CANCERS - respiratory tract cancers

- oesophageal cancers

- pancreatic cancers

- urinary bladder cancers

4) CANNABIS

- cannabis is an abuse drug found in cannabis sativa (“hemp”)

- the pharmacologically active components of cannabis are cannabinoids

- there are 3 main types of cannabinoids

TYPE DESCRIPTION

THC - “delta-9 tetrahydrocannabinol”

- the only pharmacologically active

cannabinoid

CANNABIDOL - THC precursor

CANNABINOL - THC metabolite

- cannabinoids are cannabinoid receptor agonists

- there are 2 types of cannabinoid receptors

RECEPTOR TYPE LOCATION

CB1 RECEPTOR - mesolimbic-mesocortical pathway

- hippocampus

- substantia nigra

- crebellum

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CB2 RECEPTOR - lymphoid system

- cannabinoid receptors inhibit adenylyl cyclase, thus leading to decreased

formation of cAMP

- cannabinoid receptors also activate potassium channels and inhibit calcium

channels, thus inhibiting neuronal depolarization and inhibiting release of

neurotransmitters respectively and following inhibition of neuronal

transmission

- the effects of cannabinoids include

ORGAN EFFECT

CNS - euphoria

- sensory amplification (visual-,

auditory- and tactile-)

- sedation

- decreased mental performance

(with subjective perception of

increased mental performance)

- decreased motor coordination

- catalepsy

- analgesia

- antiemesis

- increased appetite

HEART - tachycardia

BLOOD VESSELS - vasodilation

EYES - decreased intraocular pressure

- blood-shot eyes (conjunctival

blood vessel vasodilation)

BRONCHI - bronchoconstriction

LYMPHOID SYSTEM - decreased immune function

GENITO-URINARY TRACT - teratogenesis

- decreased testosterone production

- decreased sperm production

- it causes little or no dependence

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- it is used by inhalation, orally or IV

- it is lipophilic, thus will accumulate in adipose tissue over time

- 2 types

TYPE DESCRIPTION

MARIJUANA General information

- dried leaves and flowers of

cannabis sativa

HASHISH - resin of cannabis sativa

5) METHYLXANTHINES

- methylxanthines inhibit adenylyl cyclase, thus leading to decreased formation

of cAMP - effects of xanthines include

ORGAN EFFECT

CNS - CNS excitation

- insomnia

- increased mental performance

- nervousness

- increased motor activity

- tremor

- increased respiration

HEART - increased heart rate

- increased force of contraction

BLOOD VESSELS - systemic vasodilation

- cerebral vasoconstricion

BRONCHI - bronchodilation

KIDNEYS - increased glomerular filtration

- decreased reabsorption

- increased diuresis

- they cause little or no dependence

- 4 types

DRUG NAME DESCRIPTION

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THEOPHYLLINE General information

- found in tea (and coffee)

- administered orally

Medical uses

- treatment of asthma

Side effects

- any other effect of xanthines (see

above)

AMINOPHYLLINE General information

- administered IV

- same as theophylline

CAFFEINE General information

- found in coffee (and tea) and cola

nuts (coca cola)

THEOBROMINE General information

- found in cocoa

PSYCHEDELICS (PSYCHOMIMETIC DRUGS)

Overview - psychedelics are abuse-drugs that exhibit only psychological effects in the subject of interest

Relevant Drugs

- 3 categories

1) LSD ANALOGUES

- LSD is an extremely potent abuse-drug

- it is a 5-HT 2 receptor agonist in the CNS and –antagonist in the periphery

- the CNS effects of LSD are classified according to dose

DOSE EFFECT

ABUSE DOSE - hallucinations (visual-, auditory-,

olfactory-, tactile-, and cross-

connections (eg. auditory stimuli

are perceived as visual stimuli (!)))

- illogical mental performance

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OVERDOSE - “bad trip”

- horrific halucinations

- paranoia

- suicide

- homicide

- it causes little or no dependence (!)

- consequences of LSD, see 34

- 2 types

DRUG NAME DESCRIPTION

LSD General information

- “lysergic acid diethylamide”

- abuse-drug

- semisynthetic compound

synthesized from ergot alkaloids

(found in fungus)

PSILOCYBIN General information

- found in fungus

2) PHENCYCLIDINE

- phencyclidine is an abuse-drug with 2 effects in the CNS

EFFECT CONSEQUENCE

FACILITATION OF SIGMA NON-

OPIOID RECEPTORS

INHIBITION OF NMDA

RECEPTORS

- inhibition of glutamate-mediated

neuronal excitation

- it causes little or no dependence

- the effects of phencyclidine are divided according to dose

MONOAMINE EFFECT

ABUSE DOSE - analgesia

- same as LSD

OVERDOSE - same as LSD