Drugs of abuse are broadly classified by their CNS effects. Stimulants (uppers): increase CNS activity. Examples: cocaine, amphetamines, nicotine, caffeine. Effects: increased heart rate, BP, alertness, decreased appetite. Depressants (downers): decrease CNS activity. Examples: alcohol, barbiturates, benzodiazepines, heroin (at high doses), morphine. Effects: sedation, anxiolysis, respiratory depression. Hallucinogens: alter perception, mood, consciousness. Examples: LSD, mescaline, psilocybin (magic mushrooms), cannabis (THC). Opioids/Narcotics: morphine, heroin, codeine, fentanyl — analgesic and euphoric. Inhalants: volatile solvents — glue, paint thinner (especially abused by street children). Tobacco: nicotine (stimulant) + multiple carcinogens.

Nicotine: primary addictive component of tobacco. Source: tobacco (Nicotiana tabacum). Chemical: alkaloid. Mechanism: binds nicotinic acetylcholine receptors (nAChRs) — ligand-gated ion channels found in: CNS (mesolimbic dopamine pathway — reward circuit), autonomic ganglia, neuromuscular junction. Stimulates mesolimbic dopamine release → pleasure/reward → addiction. Stimulates adrenal medulla → releases adrenaline (epinephrine) and noradrenaline → increased heart rate, blood pressure, cardiac output, blood glucose. Immediate effects: alertness, concentration, appetite suppression. Short-term withdrawal: anxiety, irritability, difficulty concentrating, strong craving. Health effects of tobacco: lung cancer, COPD, cardiovascular disease, oral cancer, throat cancer. Passive smoking also harmful. India: tobacco is leading cause of preventable death.

Opioids are derived from or act on opiate receptors. Source: Papaver somniferum (opium poppy). Natural opioids in poppy: morphine, codeine, thebaine, papaverine. Morphine: the major active component of opium. Mechanism: binds mu-opioid receptors in brain (periaqueductal grey, limbic system) and spinal cord → inhibits pain signal transmission → analgesia. Also: euphoria (mesolimbic dopamine), respiratory depression (brainstem), miosis (pupil constriction), constipation (peripheral gut), nausea. Medical use: cancer pain, post-surgical pain, acute severe pain. Addiction: tolerance develops rapidly → need higher doses. Dependence. Withdrawal (cold turkey): anxiety, sweating, diarrhoea, vomiting, insomnia. Heroin (diacetylmorphine): produced by acetylation of morphine. More lipophilic → crosses blood-brain barrier 100x faster than morphine → more intense euphoric rush. Converted back to morphine in brain. Most addictive opioid. Injected, snorted, or smoked.

Cocaine: alkaloid from Erythroxylum coca leaves (South America). Mechanism: blocks reuptake of monoamine neurotransmitters (dopamine, noradrenaline, serotonin) from the synapse. Dopamine accumulates in nucleus accumbens (reward centre) → intense euphoria. Noradrenaline accumulation → sympathomimetic effects (increased HR, BP, temperature). Medical use: only topical local anaesthetic (ENT surgery, ophthalmic). Blocks sodium channels → local anaesthesia. Routes: intranasal (snorting), intravenous injection, smoked as crack cocaine (freebase, faster absorption). Effects: euphoria, increased energy, decreased fatigue, talkativeness, decreased appetite, increased confidence. Adverse: paranoia, anxiety, cardiac arrhythmia, myocardial infarction (even in young healthy individuals — coronary vasospasm), stroke, nasal septum perforation (from snorting). Crack cocaine: highly addictive, cheaper, smoked form → very rapid intense high.

Cannabis (marijuana, ganja, hashish, bhang): from Cannabis sativa plant. Active component: THC (tetrahydrocannabinol). Mechanism: binds CB1 cannabinoid receptors in brain (basal ganglia, hippocampus, cerebellum, cortex) and CB2 receptors in immune system. Endogenous cannabinoids (endocannabinoids): anandamide and 2-AG. Forms: marijuana/ganja (dried leaves/flowers), hashish (resin), bhang (leaves/seeds preparation in India). Effects: relaxation, altered time perception, increased appetite (munchies), short-term memory impairment, altered sensory perception. Adverse: impairs driving, precipitation of psychosis in vulnerable individuals, chronic use associated with motivational syndrome. Medical use: emerging evidence for pain, nausea in chemotherapy, epilepsy (CBD — cannabidiol). In India: cannabis is classified as a narcotic substance under NDPS Act, except traditional preparations like bhang in some states.

Alcohol (ethanol) is the most widely consumed psychoactive substance globally. Mechanism: enhances GABA (inhibitory) receptor activity → CNS depression. Also inhibits NMDA glutamate receptors. Effects at different blood alcohol levels: 0.05%: relaxation, judgment impaired. 0.08%: legal limit for driving in most countries. 0.10%: slurred speech, incoordination. 0.30%: stupor. 0.40%+: coma, death possible. Organ effects: liver (fatty liver → alcoholic hepatitis → cirrhosis), brain (Wernicke encephalopathy — thiamine deficiency, Korsakoff psychosis), heart (cardiomyopathy), pancreas (pancreatitis), increased cancer risk (oral, oesophageal, liver, breast). Foetal alcohol syndrome (FAS): alcohol consumption in pregnancy → intellectual disability, facial abnormalities, growth retardation in child. Alcohol metabolism: ethanol → acetaldehyde (toxic) → acetic acid, by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). ALDH2 deficiency (common in East Asians) → acetaldehyde accumulation → flushing reaction.

Addiction is a chronic brain disorder characterised by compulsive drug seeking despite negative consequences. Key brain region: mesolimbic dopamine system (nucleus accumbens — reward centre). Natural rewards (food, sex, social interaction) → moderate dopamine release → normal reward learning. Addictive drugs → massive dopamine release (5-10x normal) → intense reward signal → compulsive drug seeking. Neuroadaptation: brain adapts to chronic drug exposure. Tolerance: same dose produces less effect (receptors downregulate). Dependence: drug needed to maintain normal function (withdrawal if stopped). Craving: intense desire for drug triggered by cues (people, places, paraphernalia associated with drug use). Relapse triggers: stress, drug-associated cues (due to conditioned learning). Treatment approaches: behavioural therapies (cognitive behavioural therapy), pharmacotherapy (methadone/buprenorphine for opioid addiction, naltrexone, disulfiram), support groups (NA, AA), rehabilitation centres.

Prevention strategies: Education: school-based drug awareness programmes. Life skills training (refusing peer pressure, decision-making). Delay of initiation: later the first use, lower the risk of addiction. Family involvement: strong parental supervision and communication. Community programmes: NACO (National AIDS Control Organisation), NDPS Act enforcement. Warning signs of drug abuse: changes in behaviour, academic decline, withdrawal from family/friends, neglect of appearance, secretive behaviour, new peer group, unexplained financial needs, drug paraphernalia found. Role of media: responsible portrayal of drugs in entertainment. Social factors: poverty, unemployment, peer pressure, family dysfunction, mental health issues are risk factors. Treatment resources in India: National Institute of Mental Health and Neurosciences (NIMHANS), AIIMS psychiatry departments, de-addiction centres under MSJE (Ministry of Social Justice and Empowerment).