Drug dependence

Drug dependence

Repeated administration of certain drugs may induce a habit and dependence.

If the habit-forming agent is not made available to the habitué, he develops withdrawal symptoms characterized by psychic/physical disturbances like headache, restlessness & emotional upset and/or convulsions & vasomotor collapse.

WHO definition à, ‘A state, psychic & sometimes also physical, resulting from the interaction between a living organism & a drug, characterized by behavioral & other responses that always include a compulsion to take the drug on a continuous or periodic basis in order to experience its psychic effects & sometimes to avoid the discomfort of its absence.

Tolerance may or may not be present. A person may be dependent on more than one drug’. Withdrawal of a drug can precipitate a drug withdrawal syndrome.

Drug dependence is of 3 type:

1. Psychic: A condition in which a drug produces ‘a feeling of satisfaction & a psychic drive that require periodic or continuous administration of the drug to produce pleasure or to avoid discomfort’, is called psychic dependence.
2. Physical: In the case of physical dependence, the body achieves an adaptive state that manifests itself by intense physical disturbances when the drug is withdrawn (withdrawal syndrome).
3. Combined.

Drugs causing dependence include

• Opioids: Morphine, Heroin, Pethidine (Psychological + Physical)
• CNS Stimulants: Amphetamjines, Methylphenidate, Caffeine, Nicotine, Cocaine
• CNS Depressants: Ethyl alcohol,  Barbiturates, Benzodiazepines, Methaqualone
• Hallucinogens: Lysergic acid diethylamide (Only Psychological), Phencyclidine, Cannabinoids,

             Psilocybine, Psilocin, Dimethyl tryptamine,

Role of Dopamine

• Primary neurotransmitter of the reward circuit in the brain.
• It regulates movement, emotion, cognition, motivation, and feelings of pleasure.
• Natural Rewards like food, water, coitus, nurturing etc. cause a release of dopamine, and are associated with the reinforcing nature of these stimuli.
• Nearly all addictive drugs, directly or indirectly, act upon the brain’s reward system by flooding the circuit with dopamine.
• On drug abuse, dopamine secretion can increase from 2 to 10 folds. Thus, addictive drugs are perceived by the brain as being very rewarding, this can lead to repetitive behavior (reinforcement).

1. Opioids

Overdose à Accidental, suicidal or seen in drug abusers

S/S: respiratory depression, cyanosis, fall in BP and shock, miosis, flaccidity, stupor, coma, death due to respiratory failure

Treatment:

Respiratory support, maintenance of BP, gastric lavage

Specific antidote: Naloxone 0.4-0.8 mg i.v.

Opioid Dependence

Most individuals with Opioid Dependence have significant levels of tolerance.

Withdrawal is associated with marked drug seeking behaviour

Physical manifestations à lacrimation, sweating, yawning, anxiety, fear, restlessness, mydriasis, tremor, insomnia, abdominal colic, diarrhoea, rise in BP, palpitation, rapid weight loss

Treatment:

1. Substitution therapy with methadone
2. Clonidine: α₂ agonist acts on presynaptic receptors & inhibit release of NE
3. Naltrexone + Clonidine: naltrexone induces withdrawal which is overcome by clonidine, then naltrexone is used for maintenance
4. Cannabinoids

Obtained from Cannabis indica (marijuana)

Various forms in which it is used:

1. Bhang derived from dried leaves, taken orally
2. Ganja derived from dried female inflorescence, smoked
3. Charas resinous extract from flowering tops and leaves, smoked with tobacco (hashish)

• Most important active principle isΔ⁹ tetrahydrocannabinol (Δ⁹ THC)

Cannabis Dependence

• Individuals with dependence have compulsive use & generally do not develop physiological dependence.
• Chronic use leads to tolerance
• Withdrawl symptoms – mild
• Interferes with family, school, work or recreational activities. (amotivational syndrome)
• Persistent use despite physical (e.g chronic cough d/t smoking) or psychological (e.g excess sedation d/t repeated use of high doses)
• Supportive treatment suffice in withdrawal state.

• Hallucinogens

Affect thought, perception and mood at low doses with minimal effects on memory & orientation

Produce shape and color distortion, depersonalization, hallucination, slowing of time perception, sense that colors are heard & sounds are seen

• Hallucinogens may continue to be used despite the knowledge of adverse effects (e.g., memory impairment while intoxicated; “bad trips,“ which are usually panic reactions; or flashbacks)
• Bad trips require medical attention in form of talking down/reassurance.
• Severe agitation may respond to diazepam (20 mg orally)
• Nicotine and tobacco

Spending a great deal of time in using the substance is best exemplified by chain-smoking. (time to procure is minimal)

Giving up important social, occupational, or recreational activities (in searching smoking-restricted areas)

Continued usage despite medical problems like bronchitis, COPD d/t smoking.

• Combination of psychological and pharmacological treatment
• Nicotine replacement therapy: transdermal patch, chewing gum, inhalers, nasal spray, lozenges
• Bupropion, Clonidine
• Rimonabant : CB1receptor inverse agonist improves abstinence rates and reduces the weight gain but high frequency of depressive and neurologic symptoms
• Varenicline : partially stimulates nicotinic receptors – reducing craving and preventing most withdrawal symptoms.

• Alcohol (ethanol)
• Acts through several cellular mechanisms
• Ionotropic receptors:

       GABA_A – enhances GABA mediated inhibition,

            NMDA (glutaminergic) – inhibition

       5-HT₃ – activation

• Ion channel: Kir3/GIRK
• Transporter: (equilibrative nucleoside transporter, ENT1, related to adenosine uptake)
• Not known which target is responsible for DA release

• Anti-craving agents
• Naltrexone: interferes with alcohol induced reinforcement by blocking opioid receptors
• Acamprosate : NMDA receptor antagonist –  normalize the dysregulated neurotransmission associated with chronic ethanol intake
• Fluoxetine: used occasionally

• Amphetamines dependence treatment
  • Behaviour therapy: aversion therapies like sub threshold electric shock or emetic like apomorphine
  • Psychotherapy
  • Group therapy e.g. alcoholics anonymous, narcotic anonymous
  • Detoxification: Gradual tapering of drug that has caused dependence or sudden withdrawal of drug followed by substitution therapy
  • Specific drug therapy e.g. Disulfiram
  • Correction of nutritional deficiencies
  • Community treatment and rehabilitation