CNS PHARMACOLOGY

The CNS [brain and spinal cord (SC)] can be divided into its anatomical areas or
its physiological functions, both of which our knowledge base of the entire system
is not
complete. The study of the drugs that can affect the brain and their varied
mechanisms of action (MOA) compounds the complexity of this system.

CENTRAL NEUROTRANSMITTERS

Neurotransmitters are chemical mediators which are released from nerve endings
into the synaptic cleft once an action potential has been reached eliciting an
influx of Ca++ ions (a voltage dependent action). The neurotransmitter then reaches
it target postsynaptic receptor site with the result being either direct excitation
or inhibition or enhancing excitation or inhibition.

1. Biogenic amines:
a. dopamine-precursor of norepinephrine. Approximately � of CNS content of
catecholamines is dopamine with large amounts in the basal ganglia (esp. caudate
nucleus), olfactory tubercle, central nucleus of the amygdala, limbic system, and
certain areas of the frontal cortex. There are 5 dopamine receptor subtypes: D1
(and D5) activate adenylyl cylclase, D2 (and D3 & D4) inhibit adenylyl cyclase.
Some D2 receptors may also suppress Ca++ currents and activate K+ currents.

b.norepinephrine-relatively large amounts are located in hypothalamus and in

certain zones of the limbic system (parts of amygdale & hippocampus) but is present
in most brain regions (cerebral cortex, brain stem, cerebellum, and spinal cord)
but in lower amounts. It is primarily an excitatory neurotransmitter but in
selected areas in the CNS & PNS it has inhibitory effects.

c. epinephrine-epi containing neurons are found in medullary reticular formation

with some connections to the pontine region, diencephalic nuclei, and
paraventricular nucleus of the dorsal thalamus. Also found in periaqueductal gray
area and spinal cord.

d. serotonin (5-hydroxytryptamine or 5-HT)-is primarily an inhibitory

neurotransmitter. Is found in hypothalamus, limbic system, cerebellum, piriform
cortex, cerebral cortex, choroids plexus, and retina. It is found in the highest
concentration in platelets and the GI tract. There are 14 receptor subtypes each of
which is composed of a further set of sybtypes.

e. histamine-most of histamine receptors are found in ventral posterior

hypothalamus and extends to ascending and descending tracts in the brain. The
histamine system is thought to function in regulating arousal, body temperature,
vascular dynamics, the reticular activating system. There are 3 histamine receptor
subtypes.

2. acetylcholine-seems to be an excitatory transmitter in the CNS vs. its

inhibitory effects in the PNS.

3. amino acids-most common inhibitory and excitatory neurotransmitters in CNS.

a. gamma-aminobutyric acid (GABA)-is major inhibitory mediator in brain with cells
containing GABA are some neurons in basal ganglia, cerebellar Purkinje, cerebral
cortex, and certain interneurons in spinal cord. There are two subtypes of GABA:
GABA-A (a
ligand-gated Cl- channel) and GABA-B (a G-protein coupled receptor).
b. glycine-inhibitory transmitter released by brainstem and interneurons in spinal
cord.

c. glutamate-major excitatory neurotransmitter found in cerebral cortex and brain

stem.

d. aspartate-an excitatory neurotransmitter found in the visual cortex.

4. neuropeptides (polypeptides)
a. substance P
b. vasopressin
c. oxytocin
d. somatostatin
e. glucagons
f. angiotensin II
g. atrial natriuretic peptide
h. enkephalins
i. endorphins

5. purine nucleotides
a. adenosine
b. ATP

ACTIONS OF DRUGS IN THE CNS

A. The structural and functional properties of neurons and their specific receptors
provides a means to modify CNS function, either specifically or generally, by
administering drugs that can act at defined receptor sites, either causing
inhibition or excitation at the receptor. Drugs that act within the CNS include
anticonvulsants, antiparkinsonian agents, opiod & nonopiod analgesics, antiemetics,
antipyretics, antidepressants, anypsychotic & antimanic agents, and sedatives &
hypnotics.

The drugs that selectively modify CNS function act either specifically or
nonspecifically according to its effect or response. For example, the effect of the
drug is specific when it binds to a target cell�s receptors and affects an
identifiable intracellular mechanism and imparts a specific therapeutic action.
(These include all the drug categories listed above.) A drug is considered
nonspecific if it produces effects on many different target cells and results in
diverse molecular mechanisms. The nonspecific drugs are classified according to
whether they produce behavioral depression or stimulation.

Examples of nonspecific CNS depressants include the anesthetic gases, ethanol, and
some hypnoticssedatives.

Example of nonspecific CNS stimulants are caffeine and amphetamines.

The specific drugs affecting the CNS include the psychotropic drugs which are
utilized to correct the �pathological�aspects of the CNS. The four primary
categories include the antidepressants, antipsychotics (neuroleptic), antimanic
drugs, and antianxiety
drugs.
It was previously recommended to discontinue certain classes of these drugs, i.e.
TCAs and MAOIs, approximately two weeks before surgery; however it is now
recommended to continue these medications as the discontinuation of these
medications before surgery could possibly increases the risk of the patient
developing suicidal ideation or psychotic disturbances. As well, it has been
determined that the patient can safely undergo anesthesia and surgery while
currently taking these medications.

CNS Stimulants

Central Nervous System Stimulation -primary action of a diverse group of

pharmacological agents -adverse effect associated with many drugs.

Behavioral Manifestations of CNS Stimulation

-mild elevation in alertness, decrease in drowsiness and lessening of fatigue
(Analeptic Effect)
-increased nervousness and anxiety -convulsions.

Molecular Basis of CNS Stimulation

Imbalance between inhibitory and excitatory processes as in the brain. This hyper-
excitability of neurons results from:
* potentiation or enhancement of excitatory neurotransmission(e.g. amphetamine)

* depression or antagonism of inhibitory transmission (e.g. Strychnine)

presynaptic control of neurotransmitter release (e.g. picrotoxin)

Classification of CNS Stimulants

1-Analeptic Stimulants
2-Respiratory Stimulants
3-Convulsants
4-Psychomotor Stimulant
5-Sympathomimetics or Adrenergic CNS Stimulants
6-Methylxanthines

Analeptic Stimulants
diverse chemical class of agents
majority can be absorbed orally
have a short duration of action �
primary expression of pharmacological effect is convulsions (tonic-clonic)
uncoordinated
pharmacological effect is terminated through hepatic metabolism
Possible Common Mechanism of Action -ability to alter movement of chloride ions
across neuronal membranes
Therapeutic Uses Group as a whole has limited therapeutic use.

Doxapram and Nikithamide - used to counteract postanesthetic respiratory depression

and for acute hypercapnia in chronic pulmonary disease.
Pentylenetetrazole - used clinically as a tool for screening latent epileptics and
experimentally to screen compounds for anti-epileptic activity.
Picrotoxin - used to study CNS mechanisms; it interferes with pathways that are
strychnine resistant.

Strychnine is a source of accidental poisoning. Also used to study CNS mechanism

because of its relatively specific action as a glycine antagonist.
Adverse Reactions:
Convulsion is characterized by opisthotonos, i.e., tonic extension of body
and all limbs. Back is arched and only the back of the head and the heels are
touching the touching the surface. All sensory stimuli produce exaggerated response
and slight sensory stimulation may trigger convulsion.

Treatment of Strychnine Poisoning

(1) Remove/reduce external sensory stimuli
(2) Diazepam or Clonazepam I.V. or nitrous oxide by inhalation to depress CNS and
stop convulsions which can be fatal

PSYCHOMOTOR STIMULANTS
Drugs of Primary Importance
Amphetamine - prototype Methamphetamine
Methylphenidate
CHARACTERISTICS
all compounds are absorbed well orally
large portion of untransformed amphetamine is excreted unchanged
in the urine. Consequently, acidifying the urine with ammonium chloride hastens its
clearance, and thus reduces its reabsorption in the renal tubules.
Overdose: hyperreflexia, tremors and convulsions
Fatalities: hyperthermia rather than cardiovascular effects

Pharmacological Actions
The primary effects of an oral dose are wakefulness, alertness, decrease fatigue;
mood elevation, increased ability to concentrate; an increase in motor and speech
activity. Amphetamines also diminish the awareness of fatigue; person may push
exertion to the point of severe damage or even death.

Stimulate the respiratory center, especially when respiration is depressed by

centrally acting drugs, (barbiturates and alcohol).
Amphetamine can reverse the marked sedation and behavioral retardation resulting
from reserpine-like drug.
Depresses appetite by their action on the lateral hypothalamus rather than an
effect on metabolic rate.

Mechanisms of Action
Releases monoamines at synapses in the brain and spinal cord.
Inhibits neuronal uptake of monoamine
Direct agonist of DA and 5-HT receptors
Antagonist at certain adrenreceptors
May inhibit monoamine oxidase.

Therapeutic Uses
Hyperkinesias - Methylphenidate
Narcolepsy - Amphetamine or methylphenidate
Obesity - Fenfluramine

Adverse Effects
CNS: Euphoria, dizziness, tremor, irritability, insomnia, Convulsion (at higher
doses), hyperthermia and coma
C.V. Cardiac stimulation leads to headache, palpitations, cardiac arrhythmias,
anginal pain
Other: Weight loss, Psychotic Reaction which are often misdiagnosed as
schizophrenia.
Addiction - including psychic dependence, tolerance and physical dependence.

Drug Interactions:
Tricyclic antidepressant
Antihypertensive Agents
Foods high in tyramine content

METHYLXANTINES
Caffeine:
Coffee (100-150 mg/cup)
Tea (30-40 mg/cups)
Cocoa (15-18mg/cup)
Theophylline: Tea and cocoa
Theobromine: Cocoa

Mechanisms of Action
Increase cyclic nucleotide concentration
Blocks adenosine receptors
Alters intracellular calcium distribution

Caffeine, the most widely used drug in the world, is a stimulant. Commonly found in
coffee, tea, soft drinks, chocolate and a wide variety of over-the-counter
medications, it is legal to buy and easily accessible.
Caffeine is a physically addictive drug
Pharmacological Activity/
Adverse Effects
Low Doses: 50-250mg/Caffeine (Oral Doses) Increase mental alertness, decrease
drowsiness Lessen fatigue
Larger Doses: 250-600mg/Caffeine Irritability, restlessness, tremor, insomnia,
headache, palpitations and hyperesthesia GIT upset
Large Doses: > 1000 mg Overt excitement, delirium and clonic seizures

Cardiovascular System: Increase rate and force of the heart by directly stimulating
myocardium (low doses) Tachycardia and arrhythmias at higher doses. Peripheral
vasodilation decease in blood pressure (acute administration) Hypotension and
cardiac arrest (rapid i.v. theophyline)

Smooth Muscles: Relaxes vascular smooth muscle (Theophylline �Caffeine)

Kidney: All xanthines are capable of producing some degree of diuresis in humans
(Theophylline > Caffeine)
Miscellaneous: Xanthines shorten clotting time by increasing tissue prothrombin and
factor V.

Adverse effects
Stimulate gastric secretions in patients with ulcer
Dehydration in children due to vomiting and transient diuretic action (theophyline)

Allergic reaction (aminophylline)

Psychic Dependence (Caffeine)
Therapeutic Uses
Caffeine + plus ergot alkaloid (Ergotamine): used to treat migraine headaches
OTC preparations: Theophylline: Prophylaxis for chronic asthma
Respiratory Stimulant Bronchodilator for relief of asthmatic symptoms
NICOTINE
CNS Effects:
Powerful CNS stimulant at lower doses; Large doses produce clonic convulsion, then
depress CNS, compounding postictal depression
Stimulates respiration
Produces emesis
Tolerance to central actions with chronic use

Cardiovascular Effects
Tachycardia
Increased blood pressure
Pupillary constriction
Cardiovascular collapse - due to CNS depression
Ganglionic blockade and arrhythmias Fatalities: Due to respiratory failure

COCAINE
Psychomotor stimulant
local anesthetic

Chemistry- alkaloid from coca plant alkaloid is highly lipid-soluble hydrochloride

salt is water soluble
Routes of Administration
Chewing: with an-alkaloid material (South America)
Sniffing: hydrochloride salt -absorption: nasal mucous membranes -local
vasoconstriction slows absorption and prolongs effect
Oral: large doses are needed for effect rapid onset
Smoking: cocaine is converted to alkaloid (freebase or "crack") which is readily
volatilized undegraded at lower temperature. I.V. and smoking: reaches CNS in
seconds in high concentration produces more immediate and intense effects
Pharmacokinetics
large vol. of distribution
quickly metabolized: half-life 30-90 minutes
principal metabolites: a) Ecogonine methylester - inactive b) Benzoylecogonine -
inactive c) norcocaine - active
half lives of metabolites: 4 to 6 hrs. - metabolites: Excreted in urine
Drug Testing: BE - detectable for 1-3 days Cocaine - detectable for a few
hours

Drug addiction
Drug addiction is widely considered a pathological state. The disorder of addiction
involves the progression of acute drug use to the development of drug-seeking
behavior, the vulnerability to relapse, and the decreased, slowed ability to
respond to naturally rewarding stimuli. The Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition (DSM-IV) has categorized three stages of
addiction: preoccupation/anticipation, binge/intoxication, and withdrawal/negative
affect. These stages are characterized, respectively, everywhere by constant
cravings and preoccupation with obtaining the substance; using more of the
substance than necessary to experience the intoxicating effects; and experiencing
tolerance, withdrawal symptoms, and decreased motivation for normal life
activities. By the American Society of Addiction Medicine definition, drug
addiction differs from drug dependence and drug tolerance.
Drugs causing addiction
Drugs known to cause addiction include illegal drugs as well as prescription or
over-the-counter drugs, according to the definition of the American Society of
Addiction Medicine.
� Stimulants:
o Amphetamine and Methamphetamine
o Caffeine
o Cocaine
o Nicotine
� Sedatives and Hypnotics:
o Alcohol
o Barbiturates
o Benzodiazepines, particularly alprazolam, clonazepam, temazepam, and
nimetazepam
o Methaqualone and the related quinazolinone sedative-hypnotics
� Opiate and Opioid analgesics
o Morphine and Codeine, the two naturally-occurring opiate analgesics
o Semi-synthetic opiates, such as Heroin (Diacetylmorphine), Oxycodone, and
Hydromorphone
o Fully synthetic opioids, such as Fentanyl and its analogs,
Meperidine/Pethidine, and Methadone

Addictive drugs also include a large number of substrates that are currently
considered to have no medical value and are not available over the counter or by
prescription.
An article in the Lancet compared the harm and addiction of 20 drugs, using a scale
from 0 to 3 for physical addiction, psychological addiction, and pleasure to create
a mean score for addiction. Caffeine was not included in the study. The results can
be seen in the chart above.
Addictive potency
The addictive potency of drugs varies from substance to substance, and from
individual to individual
Drugs such as codeine or alcohol, for instance, typically require many more
exposures to addict their users than drugs such as heroin or cocaine. Likewise, a
person who is psychologically or genetically predisposed to addiction is much more
likely to suffer from it.
Although dependency on hallucinogens like LSD ("acid") and psilocybin (key
hallucinogen in "magic mushrooms") is listed as Substance-Related Disorder in the
DSM-IV, most psychologists do not classify them as addictive drugs.
The most common drug addictions are to legal substances such as:
� Caffeine
� Nicotine in the form of tobacco, particularly cigarettes
� Alcohol
Individual mechanisms of effect
The basic mechanisms by which different substances activate the reward system are
as described above, but vary slightly among drug classes.
Depressants
Depressants such as alcohol and benzodiazepines work by increasing the affinity of
the GABA receptor for its ligand; GABA. Narcotics such as morphine and methadone,
work by mimicking endorphins�chemicals produced naturally by the body which have
effects similar to dopamine�or by disabling the neurons that normally inhibit the
release of dopamine in the reward system. These substances (sometimes called
"downers") typically facilitate relaxation and pain-relief.
Stimulants
Stimulants such as amphetamines, nicotine, and cocaine, increase dopamine signaling
in the reward system either by directly stimulating its release, or by blocking its
absorption (see "reuptake"). These substances (sometimes called "uppers") typically
cause heightened alertness and energy. They cause a pleasant feeling in the body,
and euphoria, known as a high. This high wears off leaving the user feeling
depressed. This sometimes makes them want more of the drug, and can worsen the
addiction
Treatment
Treatments for drug addiction vary widely according to the types of drugs involved,
amount of drugs used, duration of the drug addiction, medical complications and the
social needs of the individual.
Determining the best type of recovery program for an addicted person depends on a
number of factors, including: personality, drug(s) of addiction, concept of
spirituality or religion, mental or physical illness, and local availability and
affordability of programs.
Many different ideas circulate regarding what is considered a "successful" outcome
in the recovery from addiction. It has widely been established that abstinence from
addictive substances is generally accepted as a "successful" outcome, however
differences of opinion exist as to the extent of abstinence required.
In the USA and in many other countries, the goal of treatment for drug dependence
is generally total abstinence from all drugs, which while theoretically the ideal
outcome, is in practice often very difficult to achieve. Other countries
particularly in Europe argue the aims of treatment for drug dependence to be more
complex, with treatment aims including reduction in use to the point that drug use
no longer interferes with normal activities such as work and family commitments,
shifts away from more dangerous routes of drug administration such as injecting to
safer routes such as oral administration, reduction in crime committed by drug
addicts, and treatment of other comorbid conditions such as AIDS, hepatitis and
mental health disorders. These kind of outcomes can often be achieved without
necessarily eliminating drug use completely, and so drug treatment programs in
Europe often report more favourable outcomes than those in the USA because the
criteria for measuring success can be met even though drug users on the programme
may still be using drugs to some extent. The supporters of programs with total
abstinence from drugs as a goal stress that enabling further drug use mean
prolonged drug use and a risk for an increase of total number of addicts; the
participants in the program can introduce new users in the habit.

Drug addiction is a complex but treatable brain disease. It is characterized by

compulsive drug craving, seeking, and use that persist even in the face of severe
adverse consequences. For many people, drug addiction becomes chronic, with
relapses possible even after long periods of abstinence. In fact, relapse to drug
abuse occurs at rates similar to those for other well-characterized, chronic
medical illnesses such as diabetes, hypertension, and asthma. As a chronic,
recurring illness, addiction may require repeated treatments to increase the
intervals between relapses and diminish their intensity, until abstinence is
achieved. Through treatment tailored to individual needs, people with drug
addiction can recover and lead productive lives. The ultimate goal of drug
addiction treatment is to enable an individual to achieve lasting abstinence, but
the immediate goals are to reduce drug abuse, improve the patient's ability to
function, and minimize the medical and social complications of drug abuse and
addiction. Like people with diabetes or heart disease, people in treatment for drug
addiction will need to change behavior to adopt a more healthful lifestyle.
Anti-addictive drugs
Other forms of treatment include replacement drugs such as methadone or
buprenorphine, used as a substitute for illicit opiate drugs Although these drugs
are themselves addictive, opioid dependency is often so strong that a way to
stabilize levels of opioid needed and a way to gradually reduce the levels of
opioid needed are required. In some countries, other opioid derivatives such as
levomethadyl acetate, dihydrocodeine, dihydroetorphine and even heroin are used as
substitute drugs for illegal street opiates, with different drugs being used
depending on the needs of the individual patient.
Substitute drugs for other forms of drug dependence have historically been less
successful than opioid substitute treatment, but some limited success has been seen
with drugs such as dexamphetamine to treat stimulant addiction, and clomethiazole
to treat alcohol addictionBromocriptine and desipramine have been reported to be
effective for treatment of cocaine but not amphetamine addiction.
Other pharmacological treatments for alcohol addiction include drugs like
disulfiram, acamprosate and topiramate, but rather than substituting for alcohol,
these drugs are intended to reduce the desire to drink, either by directly reducing
cravings as with acamprosate and topiramate, or by producing unpleasant effects
when alcohol is consumed, as with disulfiram. These drugs can be effective if
treatment is maintained, but compliance can be an issue as alcoholic patients often
forget to take their medication, or discontinue use because of excessive side
effects.[36][37] Additional drugs acting on glutamate neurotransmission such as
modafinil, lamotrigine, gabapentin and memantine have also been proposed for use in
treating addiction to alcohol and other drugs.
Opioid antagonists such as naltrexone and nalmefene have also been used
successfully in the treatment of alcohol addiction, which is often particularly
challenging to treat. These drugs have also been used to a lesser extent for long-
term maintenance treatment of former opiate addicts, but cannot be started until
the patient has been abstinent for an extended period, otherwise they can trigger
acute opioid withdrawal symptoms.
Treatment of stimulant addiction can often be difficult, with substitute drugs
often being ineffective, although newer drugs such as nocaine, vanoxerine and
modafinil may have more promise in this area, as well as the GABAB agonist
baclofen. Another strategy that has recently been successfully trialled used a
combination of the benzodiazepine antagonist flumazenil with hydroxyzine and
gabapentin for the treatment of methamphetamine addiction.
Another area in which drug treatment has been widely used is in the treatment of
nicotine addiction. Various drugs have been used for this purpose such as
bupropion, mecamylamine and the more recently developed varenicline. The
cannaboinoid antagonist rimonabant has also been trialled for treatment of nicotine
addiction but has not been widely adopted for this purpose.
Ibogaine is a psychoactive drug that specifically interrupts the addictive
response, and is currently being studied for its effects upon cocaine, heroin,
nicotine, and SSRI addicts. Alternative medicine clinics offering ibogaine
treatment have appeared along the U.S. border. Ibogaine treatment for drug
addiction can be reasonably effective, but potentially dangerous side effects which
have been linked to several deaths have limited its adoption by conventional
medical practice. A synthetic analogue of ibogaine, 18-methoxycoronaridine has also
been developed which has similar efficacy but less side effects, however this drug
is still being tested in animals and human trials have not yet been carried out.
[edit] Alternative therapies
Alternative therapies, such as acupuncture, are used by some practitioners to
alleviate the symptoms of drug addiction. In 1997, the American Medical Association
(AMA) was adopted as policy following statement after a report on a number of
alternative therapies including acupuncture:
There is little evidence to confirm the safety or efficacy of most alternative
therapies. Much of the information currently known about these therapies makes it
clear that many have not been shown to be efficacious. Well-designed, stringently
controlled research should be done to evaluate the efficacy of alternative
therapies.
Accupuncture has been shown to be no more effective than control treatments in the
treatment of opiate dependence. Acupuncture, acupressure, laser therapy and
electrostimulation have no demonstrated efficacy for smoking cessation.

Medical definitions
The terms abuse and addiction have been defined and re-defined over the years. The
1957 World Health Organization (WHO) Expert Committee on Addiction-Producing Drugs
defined addiction and habituation as components of drug abuse:
Drug addiction is a state of periodic or chronic intoxication produced by the
repeated consumption of a drug (natural or synthetic). Its characteristics include:
(i) an overpowering desire or need (compulsion) to continue taking the drug and to
obtain it by any means; (ii) a tendency to increase the dose; (iii) a psychic
(psychological) and generally a physical dependence on the effects of the drug; and
(iv) detrimental effects on the individual and on society.
Drug habituation (habit) is a condition resulting from the repeated consumption of
a drug. Its characteristics include (i) a desire (but not a compulsion) to continue
taking the drug for the sense of improved well-being which it engenders; (ii)
little or no tendency to increase the dose; (iii) some degree of psychic dependence
on the effect of the drug, but absence of physical dependence and hence of an
abstinence syndrome [withdrawal], and (iv) detrimental effects, if any, primarily
on the individual.
In 1964, a new WHO committee found these definitions to be inadequate, and
suggested using the blanket term "drug dependence":
The definition of addiction gained some acceptance, but confusion in the use of the
terms addiction and habituation and misuse of the former continued. Further, the
list of drugs abused increased in number and diversity. These difficulties have
become increasingly apparent and various attempts have been made to find a term
that could be applied to drug abuse generally. The component in common appears to
be dependence, whether psychic or physical or both. Hence, use of the term 'drug
dependence', with a modifying phase linking it to a particular drug type in order
to differentiate one class of drugs from another, had been given most careful
consideration. The Expert Committee recommends substitution of the term 'drug
dependence' for the terms 'drug addiction' and 'drug habituation'.
The committee did not clearly define dependence, but did go on to clarify that
there was a distinction between physical and psychological ("psychic") dependence.
It said that drug abuse was "a state of psychic dependence or physical dependence,
or both, on a drug, arising in a person following administration of that drug on a
periodic or continued basis." Psychic dependence was defined as a state in which
"there is a feeling of satisfaction and psychic drive that requires periodic or
continuous administration of the drug to produce pleasure or to avoid discomfort"
and all drugs were said to be capable of producing this state:
There is scarcely any agent which can be taken into the body to which some
individuals will not get a reaction satisfactory or pleasurable to them, persuading
them to continue its use even to the point of abuse � that is, to excessive or
persistent use beyond medical need.
The 1957 and 1964 definitions of addiction, dependence and abuse persist to the
present day in medical literature. It should be noted that at this time (2006) the
Diagnostic Statistical Manual (DSM IVR) now spells out specific criteria for
defining abuse and dependence. (DSM IVR) uses the term substance dependence instead
of addiction; a maladaptive pattern of substance abuse, leading to clinically
significant impairment or distress, as manifested by three (or more) specified
criteria, occurring at any time in the same 12-month period. This definition is
also applicable on drugs with smaller or nonexistent physical signs of withdrawal,
for ex. cannabis.
In 2001, the American Academy of Pain Medicine, the American Pain Society, and the
American Society of Addiction Medicine jointly issued "Definitions Related to the
Use of Opioids for the Treatment of Pain," which defined the following terms:[3]
Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial,
and environmental factors influencing its development and manifestations. It is
characterized by behaviors that include one or more of the following: impaired
control over drug use, compulsive use, continued use despite harm, and craving.
Physical dependence is a state of adaptation that is manifested by a drug class
specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose
reduction, decreasing blood level of the drug, and/or administration of an
antagonist.
Tolerance is the body's physical adaptation to a drug: greater amounts of the drug
are required over time to achieve the initial effect as the body "gets used to" and
adapts to the intake.
Pseudo addiction is a term which has been used to describe patient behaviors that
may occur when pain is undertreated. Patients with unrelieved pain may become
focused on obtaining medications, may �clock watch,� and may otherwise seem
inappropriately �drug seeking.� Even such behaviors as illicit drug use and
deception can occur in the patient's efforts to obtain relief. Pseudoaddiction can
be distinguished from true addiction in that the behaviors resolve when pain is
effectively treated.
The Diagnostic and Statistical Manual of Mental Disorders, DSM-IV-TR doesn�t use
the word addiction at all. Instead it has a section about Substance dependence
"When an individual persists in use of alcohol or other drugs despite problems
related to use of the substance, substance dependence may be diagnosed. Compulsive
and repetitive use may result in tolerance to the effect of the drug and withdrawal
symptoms when use is reduced or stopped. This, along with Substance Abuse are
considered Substance Use Disorders...." [54]
A definition of addiction proposed by professor Nils Bejerot:
"An emotional fixation (sentiment) acquired through learning, which intermittently
or continually expresses itself in purposeful, stereotyped behavior with the
character and force of a natural drive, aiming at a specific pleasure or the
avoidance of a specific discomfort."[55]
[edit] Addiction and drug control legislation
Depending on the jurisdiction, addictive drugs may be legal only as part of a
government sponsored study, illegal to use for any purpose, illegal to sell, or
even illegal to merely possess.
Most countries have legislation which brings various drugs and drug-like substances
under the control of licensing systems. Typically this legislation covers any or
all of the opiates, amphetamines, cannabinoids, cocaine, barbiturates,
hallucinogenics and a variety of more modern synthetic drugs, and unlicensed
production, supply or possession is a criminal offence.
Usually, however, drug classification under such legislation is not related simply
to addictiveness. The substances covered often have very different addictive
properties. Some are highly prone to cause physical dependency, whilst others
rarely cause any form of compulsive need whatsoever. Also, under legislation
specifically about drugs, alcohol is not usually included.
Although the legislation may be justifiable on moral or public health grounds, it
can make addiction or dependency a much more serious issue for the individual:
reliable supplies of a drug become difficult to secure, and the individual becomes
vulnerable to both criminal abuse and legal punishment.
It is unclear whether laws against drugs do anything to stem usage and dependency.
In jurisdictions where addictive drugs are illegal, they are generally supplied by
drug dealers, who are often involved with organized crime. Even though the cost of
producing most illegal addictive substances is very low, their illegality combined
with the addict's need permits the seller to command a premium price, often
hundreds of times the production cost. As a result, the addict sometimes turns to
crime to support their habit.