Addiction Predicament and Augmentations in the field of Pharmacology

Addiction is when “wanting” becomes “craving”.It can be delineated as Persistent, retrogressing disorder attributed by irresistible use of drugs despite its detrimental effects on the body and mind of an individual, taking one into hell disguised as heaven. This crisis exerts corrosive effects on families and societies leading into bigger Narco-politics and Narco -economics muddle. It provokes loss of productivity, agitation, impulsivity, euphoria, troubles in interpersonal relationships, periods of hyperactivity etc.

Today’s society has been deceived by drug euphemism that is becoming customary especially among teenagers.According to the World Health Organisation (WHO) report, about 5.5 million people on the globe use psychoactive substances and among them almost 12.9% users suffer from drug disorders. Nearly 0.5 million deaths are caused due to drug overdose annually. With such a Colossal number of victims, scientists are obliged to ameliorate pharmacodynamics and annihilate this problem from its root.

Drugs can be classified based on their chemical makeup as : Alcohol(Most widely abused substance that creates Euphoria),Opioids( interacts with neurotransmitters in the brain),Benzodiazepines(interacts with gamma-aminobutyric acid-A (GABA-A). ),Cannabinoids(creates a feeling of elation) and Barbiturates( acts on CNS and slows down it’s functioning).

They can also be classified on the basis of their effects : Depressants,Stimulants, Hallucinogens and Inhalants. Compartmentalizing drugs can expedite the treatment discovery.

Finding treatment can be onerous(example cocaine(a stimulant)) owing to the extortionate relapsing rate. A possible elucidation of this can be that the region of the brain involved engendering cocaine elation is different from the region in the brain integrated with the yearning of cocaine.

There are customarily three modus operandi to treat addiction: First: Expeditiously stopping the use of these substances. This is completely arduous and can espouse grave withdrawal symptoms and even death.

Another approach could be using proxy drugs(example: methadone(for opioid) or levo-alpha-acetyl-methadol (LAAM)).

Lastly, dwindling the use of these substances, essentially by replacement therapy (eg. nicotine patches) or Psychosocial therapy.

These methods work for only those who can fight tooth and nail to get rid of the anathema(or in case of caffeine addiction) and are not tenable for extreme addiction cases and some anodynes. Ergo, enters pharmacotherapy.

Firstly, one has to ascertain the site of action of different drugs. Furthermore, the mechanism of their action and their effect on the body should be validated. Subsequently, plausible pharmacotherapies of discrete drug categories can be established.

Alkaloids are preponderantly being used to diminish the detrimental biphasic effects of alcohol, cocaine and Morphine by plummeting the exigency of self-administration. They possess the therapeutic attributes of anti-addiction and anti-craving.For example, Ibogaine can rub shoulders with various neurotransmitters(including serotonin (5-HT), kappa-opioid, sigma-2 (σ-2), nicotinic sites ) and also sway the release of dopamine. Ibogaine and related compounds (noribogaine) can fasten up with opioid, nicotine and sigma receptors(involved in vital brain functions encompassing memory and drug dependence). Moreover, it can also act as a competitive inhibitor of MK-801 that binds to N-Methyl-D-aspartic acid(NMDA), thereby hampering the mediation of substance abuse triggered by the latter. It is the complex of the Pharmacology of Iboganine that makes it inimitable.

Another drug detoxifier is MEMANTINE that impedes withdrawal symptoms and truncates vulnerability to Morphine addiction. It blocks the NMDA ion channels and thus possess anti-craving and anti-addiction properties. Minute doses of these are a medicament for Alzheimer’s disease.

Methadone, LAAM(levo-α-acetylmethadol) and dolophine are synthetic drugs that induce minuscule euphoria and hence help in curing heroin addiction.Less opioid use is an upshot of the decreased longing for heroin. BUPRENORPHINE,a potent analgesic, is a semisynthetic drug that also treats opioid disorder by partially activating opiate receptors (agonist).

Psychotic disorders such as schizophrenia( caused by hallucinogens like cannabis, LSD, PCP and cocaine) are associated with a D3 receptor which instigates positive prodrome and obstructs the normal functioning of the brain.The contingency of the D3 receptor is being studied and it is found that its partial antagonism can dampen the guerdoning effects of drug seeking, like cocaine may fail to produce doldrums which is one of its withdrawal symptoms. The idea that no “the medicament does not beget reward feelings” has drawn a lot of attention. A partial agonist of D3 receptor- BP 897 has shown to assuage cocaine seeking behaviour.

Another remedy for cocaine addiction is VANOXERINE (GBR12909). It is a non competitive inhibitor of dopamine active transporter (DAT). It antagonises the capability of cocaine to hoist extracellular dopamine by 50%. Pretreatment with GBR12909 results in unprompted need for self-administration of cocaine.

To abate opium withdrawal symptoms, LOFEXIDINE (BRITLOFEX) -an α2 adrenergic receptor (localised in several regions of central nervous system) agonist is being used parallelly in place of Clonidine without provoking hypotension. ClonidineIs is further used to treat withdrawal symptoms of alcohol and opium. Nowadays, brain implants are also being used in case of opium addiction, but only in severe cases because it involves ethical issues.

Phenylcyclohexyl piperidine or PCP utilizes monoclonal antibody, who’s addiction can be treated with small doses of monoclonal anti-phencyclidine antibody which dwindles the amount of PCP in the brain despite its ceaseless use.

Synthesizing haptens and reagents is an immunological approach that produces catalytic monoclonal antibodies that bind to cocaine and degrade it. Active immunization approach of administration of conjugates of ester and amide cocaine acts as a vaccine and produces anti-cocaine antibodies.

Human Genome Projects are being accentuated as genetics has a major role to play in addiction. More addictive substances are more likely to be inherited. Cocaine and opioids are one of the most addictive substances and are inherited the most. Hallucinogens are the least addictive and hence, not much inherited. Heritability is also higher for addiction than for substance use and initiation.

Pharmacology requires a great deal of diligence and research because addiction is a chronic disorder that entails a lot of physical, mental and psychological effects. Each drug category and a particular drug of the same category producing different effects may require unique techniques to tackle. As we still lack explicit agents, research in this field will continue to burgeon.