Friday, December 19, 2014

Drug Addiction: Current Perspectives and the Neurological Basis - by Dr. M.S. Menon Medical Director Kripa Foundation

Drug Addiction: Current Perspectives and the Neurological Basis

Introduction :
Current Perspectives of the Problem
Drug Addiction is a global socio-cultural problem at all ages and involves both sexes of human populations. While the origins of drug use practices lies in antiquity, the world is faced today with a bewildering range of modern day variability in drug practices associated with socioeconomic inequalities and an increasingly hedonistic lifestyle. The impact of drug abuse is almost never a ‘single person’ issue and is often the cause of breakdown in family systems and economic integrity. The consequences of risk behaviour related to drug abuse is linked to a plethora of co morbidities apart from that due to the drug effects.
Worldwide, the business of drug production and illegal trafficking is a multibillion dollar annual enterprise. All countries make efforts through suitable legislation for the control and management of drug production, medicinal and sanctioned use and also prevention and control of illicit production, sale and trafficking. However, the balance between Supply Reduction through enforcement and Demand Reduction through social reconstructive efforts yet remains in favour of the former.
Extent of the problem:
  • Estimates indicate 14 million people in India are dependent drinkers requiring ‘help’
  • Over 2.09 million people are living with HIV in India, (National AIDS Control Organization, Annual Report, 2012-2013).
  • The percentage of the drinking population aged under 21 years has increased from 2% to more than 14% in the past 15 years according to studies by Alcohol and Drugs Information Centre India, a non-governmental organization (NGO)
  • Up to 18% of the total work force may have serious personal problems; one of the main problems being Chemical Dependency
  • Children whose parents have a drug/alcohol problem are more likely to develop a chemical dependency problem themselves, apart from other psychosocial disabilities
  • The Central Ministries recognize the deficiency of adequate and accurate data on the situation of chemical dependency in rural areas and those below the poverty line. More specific information is expected from the concurrent Household Survey
  • The Narcotics Control Bureau (India), National Drug Abuse Treatment Centre and the United Nations Office on Drugs and Crime-Regional Office for South Asia report 26 Jun 2013 indicate.
  • 5% of the global population aged 15-64 use drugs.
  • 0.7% (500 million) of world population are problem drug users.
  • Around 27 million problem drug users have significant health problems.
  • 18% of Injecting Drug Users are HIV positive.
  • 2,63,000 deaths each year are caused by drugs and nearly half of them are due to drug overdose.
  • Around 122 Drug Deaddiction Centres under the Central Government can cater to only around 30% of the total admissions for treatment. The remaining are in the private sector and may provide non standardized care.
General considerations : 
Some important aspects of the drug abuse epidemic are:
  • Newer user populations & newer drugs of abuse, especially combinations of Amphetamine Type
  • Substances (ATS) with other Stimulants and Depressants available on the streets
  • Hidden user population especially among younger age group (<18 li="" years="">
  • Limited understanding and therapeutic measures in the public sector
  • Sizeable numbers of drug users
  • Strong link between Injecting Drug Use (IDU) and HIV, Hepatitis B & C infection
  • Widespread use due to weak law enforcement and regulatory controls
  • Inadequate control over human trafficking and other related crimes
  • Poor reporting and monitoring of the situation
Drugs of Abuse and Addiction include the following Groups:
  • Cannabis- ganja, hashish,
  • Opiates- Natural-Opium, Brown Sugar, Heroin & synthetic opoid compounds.
  • Depressants/ Sedatives- Benzodiazepines.
  • Amphetamine Type Stimulants- amphetamine, MDMA, Ketamine, other precursor chemicals .
  • Cocaine
  • Hallucinogens-LSD, PCP, Mescalin, Psilocybin, newer synthetic compounds.
  • Volatile substances-solvents, aerosol, gases, nitrites.
Classifying the Psychoactive drugs:
Drug Classifications
Any classification of drugs that have psychoactive properties, that is, licit and illicit drugs that affect mood, thought, and behaviour, should include specifically:
  • drugs that are used in a recreational or social manner
  • drugs that have the potential for creating physical or psychological dependence
  • drugs that may result in drug-related harms
  • volatile substances, some prescription medications, ethanol products & nicotine.
Drugs are generally classified as Depressants, Stimulants and Hallucinogens.
BarbituratesNicotineCannabis (high doses)
Cannabis (low doses)CaffeineMagic Mushroom
Other natural substancesOther precursor/ ATS compoundsOther synthetic compounds
Drug Addiction: Current Perspectives and the Neurological Basis
Common drugs of abuse:
  • Alcohol remains the commonest drug of Abuse in India followed by Cannabis, Heroin, Opium, Sedatives and Pharmaceuticals, Amphetamine Type Substances (ATS) & some chemical often referred to as ‘date rape drugs’.
  • In a National Household survey in India of 40,697 Males (12-60yrs), the prevalence of ‘current’ use (i.e. during last month) were-
  • Alcohol 21%
  • Cannabis 3%
  • Opiates 0.7%
  • IDUs (ever) 0.1%
  • The prevalence of opiate use in India is 0.7% and particularly alarming as the Asian and Global average is 0.3%.
Legality in India:
The applicable legislation is the ‘Narcotic Drugs and Psychotropic Substances Act, 1985. Act No 61 of 1985’. Published in 1997, Government of India Press. Amended in 2002 & 2008. (141 pages, 6 Chapters, 6 Annexures).
Some important definitions:
  • Drug addiction is a complex illness characterized by compulsive, and at times, uncontrollable drug craving, seeking, and use that persist even in the face of extremely negative consequences.
Substance Use Disorder
  • Refers to an inappropriate or excessive and extra prescription or illicit use of mood altering substances
  • Patterns of use of the substance and resultant phenomena fit the criteria of Dependence, Abuse and other associated diagnoses given in the American Psychiatric Association’s Diagnostic and Statistical Manual IV (DSM-IV revised) and WHO-International Classification of Diseases (ICD-10).
Substance Abuse
  • A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period:
  • Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (e.g., repeated absences or poor work performance, related to substance use, substance- related absences, suspensions, or expulsions from school; neglect of children or household)
  • Recurrent substance use in situations in which it is physically hazardous (e.g., driving an automobile or operating a machine when impaired by substance use)
  • Recurrent substance related legal problems (e.g., arrests for substance-related disorderly conduct)
  • Continued substance use despite having persistent or recurrent social or interpersonal problems caused by or exacerbated by the effects of substances (e.g., arguments with spouse about consequences of intoxication, physical fights)
Substance Dependence
  • A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12 month period.
  • Tolerance.
  • Withdrawal.
  • The substance is often taken in larger amounts or over a longer period than intended
  • There is persistent desire or unsuccessful efforts to cut down or control substance use
  • A great deal of time is spent in activities necessary to obtain the substance
  • Important social, occupational, or recreational activities are given up or reduced because of substance use
  • The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance (e.g., current cocaine use despite recognition of cocaine induced depression, or continued drinking despite recognition that an ulcer was made worse by alcohol consumption)
  • (Note: the above are abbreviated and detailed definitive criteria are available in DSM-IV).
Health providers should look for the following indications of substance use problems:
  • housing instability, difficulty budgeting funds, symptom relapses apparently unrelated to life stressors, treatment non-compliance
  • prostitution, sexual deviance, social isolation, violent behaviour or threats of violence
  • pervasive, repeated social difficulties, sudden unexplained mood shift , suicidal ideation or attempts
  • employment difficulties, legal problems
  • hygiene and health problems, cognitive impairments
  • avoidance of disclosure (of likely concurrent disorders) for fear of being admitted to an inpatient psychiatry unit
  • repeated self-harm in the absence of clear situational relevant stressors
  • cyclical history of substitute or replacement addictions.
In addition to alcohol or illicit drugs, these problems often arise from inappropriate use of prescription medications in a therapeutic or quasi therapeutic setting.
The Addicts State of Mind
  • Pre contemplative (Addict? Who-me?)
  • Contemplative (maybe I have a problem)
  • Action (I do have a problem / I should do something about it)
  • Maintenance (Abstinence is the best option for me; then I can really change my life).
Cannabis/alcohol/ ATS / Cocaine are notorious. Anxiety, panic, depression, Delirium, Alcohol/drug induced psychosis, Alcohol hallucinations, Alcohol/drug induced delusional disorder, Schizophrenia and Amotivational syndrome. Acute intoxication phenomena may include mania and at times even uncontrollable aggression, rape and homicidal behaviour (detailed descriptions are beyond the scope of this article).
Accidents & injuries, Cardio-vascular complications, Gastro-Intestinal complication, Haematopoietic complications, Hepatic complications, Neuro-muscular complications, Pulmonary complications, Reproductive system complications, Risk Behaviour related infections, Skin complications, Special Senses complications and Sexual dysfunctions.
The core consideration in management of addiction is abstinence from the chemical, followed by rehabilitation programmes. This programme of care would optimally contain the following component, Outreach, Awareness and intake: Community level activity to identify, motivate and induct users into treatment.
Detoxification short duration abstinence in a quasi- controlled environment or hospital setting (5-7 days), with medicines and other support to minimize withdrawal phenomena.
Deaddiction-care in a quasi- controlled environment with counselling and psychological / medical support and group activities, to educate and sustain motivation for rehabilitation intentions, in the recent relatively unstable mental state due to the absence of the regularly used psycho-active substance. This may last 3-4 weeks and include contact / discussions with significant others who themselves would be included in the programme.
Rehabilitation- longer duration of a quasi- controlled environment and structured programme that allows the individual to introspect, learn and practice issues related to social relationships, responsibilities, identification and managing potential stressors and other circumstances that could lead to a relapse in addictive behaviour. The programme duration may last 1-3 months.
Whole Person Recovery would include reintegration into society and sustaining a drug free life while efforts continue towards personal growth. Self Help Groups (such as alcoholics Anonymous, Narcotics Anonymous, Al-Anon for Family Members) are extremely useful in providing support. There isways a need for a continuum of care within the community to facilitate change in community to address issues of stigma and discrimination as well as early identification of relapse and provision of care for it.
The following ‘Continuum of Care’ model would be extremely useful method.
Continuum of Care

The Neurological basis of Addiction
Natural Rewards:
Natural Rewards
Food & Water, Shelter, Sex, Nurturing.
  • Natural pleasures in life establish habits which dominate our behavior
  • All 5 senses provide input
  • Hunger, thirst, sexual activity: appetites
  • In humans: interpersonal relationships, religion, exercise, art, music, beauty
The neurological reward pathway
Nucleus Accumbens - Ventral Tegmental Area (VTA) - Pre Frontal Cortex. The VTA is connected to both the nucleus accumbens and the prefrontal cortex via this pathway and it sends information to these structures via its neurons. The neurons of the VTA contain the neurotransmitter dopamine which is released in the nucleus accumbens and in the prefrontal cortex. This pathway is activated by a rewarding stimulus. This is not the only pathway activated by rewards, other structures are involved too.
A major reason people take a drug is they like what it does to their brains Why can’t people just stop drug use?
When people first try drugs, it is usually a voluntary decision, but after using the drug for a while, it is no longer voluntary.
Their Brains…Get Rewired by Drug Use!
Brain regions and neuronal pathways
Certain parts of the brain govern specific functions, such as the sensory, motor and visual cortex, the cerebellum for coordination and the hippocampus for memory. Nerve cells or neurons connect one area to another via pathways to send and integrate information. The distances that neurons extend can be short or long, for example, as in the reward pathway. This pathway is activated when a person receives positive reinforcement for certain behaviors ("reward").
This happens when a person takes an addictive drug. The thalamus receives information about pain coming from the body (through the spinal cord pathways and nuclei), and passes the information up to the cortex.
Dopamine Pathways
(Substantia Nigra to Nucleus Accumbens and activating Hippocampus and Striatum to Frontal Cortex).
Functions affected
  • reward (motivation), pleasure, euphoria, motor function (fine tuning), compulsion, perseveration, decision making.
 Neurochems Dopamine Serotonin
Serotonin Pathways
(Raphe to Nucleus Accumbens and activating Hippocampus and Striatum and Superior and inferior Frontal Cortex).
Functions affected
  • mood, memory processing, sleep, cognition.
How some drugs of abuse cause dopamine release:
  • opioids narcotics (activate opioid receptors)
  • nicotine (activate nicotine receptors)
  • marijuana (activate cannabinoid receptors)
  • caffeine
  • alcohol (activate GABA receptors; an inhibitory transmitter) Drug like cocaine & Ritalin affect Neuronal Terminal Transport. Drugs like Amphetamines –methamphetamine -MDMA (Ecstasy) release DA from vesicles and reverse Transporter.
    • Brain Area Involvement:
      For Amphetamines, Opiates, Cocaine, Cannabinoids, Phencyclidine, Ketamine- Peri Basal Ganglionic areas affected.
      For Opiates, Ethanol, Cannabinoids, Barbiturates, Benzothiazepines, Nicotine- Midbrain and supero hypothalamic areas affected.
      Effects of Drugs on Dopamine Release
      Amphetamines cause much greater activity than Nicotine, Cocaine and Ethanol—they all cause Neurotoxicity.
      There is decrease in metabolism in the Orbito Frontal Cortex (OFC)-seen on Positron Emission Tomography analysis. Dopamine Transporter Loss is seen after heavy Methamphetamine use.
      Motor Function is affected to cause
      • Slowed gait
      • Impaired balance.
      Impairment correlates with damage to the dopamine system.
      Brain changes resulting from prolonged use of psycho stimulants such as methamphetamine, maybe reflected in compromised cognitive and motor functioning.
      Is There Recovery?
      • Good News: After 2 years, some of the dopamine deficits are recovering
      • Bad News: Functional deficits persist
      What does this mean???
      The ability to experience Reward is damaged.
      (A comparatively decreasing order of reward sensation is experienced: from cocaine -to methamphetamines -to alcohol, with Cocaine being the least. Food, sex and nurturing provide comparatively only about 20% efficacy).
      Addictive drugs activate the reward system via increasing dopamine neurotransmission. The reward pathway is associated with several drugs that have addictive potential.
      Just as heroin (morphine) and cocaine activate the reward pathway in the VTA and nucleus accumbens, other drugs such as nicotine and alcohol activate this pathway as well, although sometimes indirectly (through the globus pallidus, an area activated by alcohol that connects to the reward pathway).
      While each drug has a different mechanism of action, each drug increases the activity of the reward pathway by increasing dopamine transmission.
      Because of the way our brains are designed, and because these drugs activate this particular brain pathway for reward, they have the ability to be abused. Thus, addiction is truly a disease of the brain.
      This knowledge will in time help to find an effective treatment strategy for the recovering addict.

      Dr M. S. Menon,
      MD., Major (Retd) AMC.,
      Director, Kripa Foundation. 
      01 December 2014