Recreational drugs.docx

**Recreational drugs** **History and modern use** **Pharmacological effects** **Mechanism of action** **Side effects** Heroin -- Diacetylmorphine (opioid) replaces 2 OH in morphine with 2 acetyl groups Opiates are naturally occurring alkaloids such as morphine and codeine Heroine is the diac...

**Recreational drugs** **History and modern use** **Pharmacological effects** **Mechanism of action** **Side effects** Heroin -- Diacetylmorphine (opioid) replaces 2 OH in morphine with 2 acetyl groups Opiates are naturally occurring alkaloids such as morphine and codeine Heroine is the diacetyl derivative of morphine In the body, it is rapidly deacetylated into morphine Morphine metabolites: M3G and M6G (morphine glucuronide) Heroin and its metabolites 6-monoacetylmorphine are more lipophilic more brain penetrant Analgesia (main use) Euphoria (addiction) Impaired cough reflex (anti-tussive) Constipation (anti-diarrhoea) Nausea and vomiting Tolerance and dependence (addiction) Respiratory depression Bind and activate mu-opioid receptors Decrease the release of neurotransmitters such as GABA (which normally inhibits the release of dopamine) Increase release of dopamine Cocaine (psychostimulant) Derived from Erythroxylum coca plant Life time use 11% Acute effects: - Euphoria - Loss of appetite - Increased alertness, self-confidence, sense of well-being, energy, motor activity, sexuality and social activities - Increased HR and BP - Local anaesthetic Binges and severe crash Inhibit dopamine reuptake transporters Also inhibit NAd and serotonin transporters Repeated use: eating and sleeping disorders, impaired sexual performance, respiratory problems, convulsions, kidney failure, stroke Acute side effects: damage to nasal membranes and septum if snorted, tissue damage due to vasoconstriction if injected Chronic use: psychosis, heart failure Excessive dosage: tremor, convulsions followed by respiratory depression and cardiac arrythmias Methamphetamine (psychostimulant) a synthetic homologue of amphetamine First use in WWII Life time use 5.8% Initial effects: - Euphoria - Increased alertness and concentration - Increased energy - Increased libido - Loss of appetite **Binge and crash** pattern of euphoria effect Release of dopamine and blockade of monoamine transporters Long half-life (8 -- 30h) compared to cocaine (2h) effects can last for several hours Very highly addictive due to the intense rush caused by dopamine release Side effects: increased HR, breathing, BP and irregular body temp. Long-lasting cognitive and emotional changes: paranoia, anxiety, depression, irritability, hallucinations, violence Long-term side effects: meth mouth, cardiac failure, overdose, neurotoxicity due to neurodegenerative damage to DA and 5HT neurons and transporters, loss of gray matter and alteration of the BBB integrity Ecstasy -- MDMA (psychostimulant) First used as an appetite suppressant Lifetime use: 12% Tolerance Serotonin syndrome Bind to the serotonin transporters and cause serotonin release via transporter-mediated exchange Block the reuptake of serotonin Inhibit vesicular monoamine transporter (VMAT) Inhibit monoamine oxidase (MAO) Increased brain and plasma oxytocin concentrations Acute psychosis, panic attacks, insomnia, involuntary teeth clenching, seizures Long term serotoninergic neurotoxicity dose-dependent reduction in 5HT receptors and transport proteins, axonal damage in the striatum, hippocampus and prefrontal cortex Elevated body temperature accelerates the neuronal damage 5HT depletion in heavy use impulsivity, depression, memory loss Cannabis Life time use 36% Has increased among older people Mainly used for pain THC -- the main intoxicant -- CB1 and CB2 receptor partial agonist with moderate affinity CBD (cannabidiol) -- non-intoxicating Endocannabinoids (Anandamide and 2-AG) -- naturally occurring cannabis found in the brain and body (natural breastmilk) Good: euphoria, increase appetite, analgesia Bad: anxiety, memory impairment, sedation Long-term: schizophrenia, addiction CB1 receptors in CNS and periphery CB2 receptors in periphery -- largely immune cells In CNS mainly presynaptic Gi/o coupled receptors that inhibits Ca2+ channels and adenylate cyclase Endocannabinoids -- endogenous ligands that act as retrograde messengers in CNS undergo enzymatic degradation and reuptake LSD (hallucinogenic) -- Lysergic acid diethylamide 1% AU uses in the last 12 months Distorted sensory perception of a fantastic and hallucinatory nature Synaesthesia -- overflow from one sensory modality to another (hearing colours, seeing sounds) Loss of boundaries and fear of fragmentation (cultogenic drug) Distortion of subjective time Feelings of a greater sensitivity for art, music, Altered mood that can be labile and shift to extremes Psychosis symptoms: difficulty thinking, depersonalisation, visual hallucinations Extremely potent Long lasting up to 10 -- 22 hours Binds to 5-HT 1, 2A, 2C, dopamine receptors and alpha adrenergic receptors and modulate GABA and glutamate release Partial agonist at 5HT2A hallucination Higher affinity but less intrinsic activity than serotonin Strong tolerance Flashbacks Fatal accidents by belief of having superpower Bad trips Unpredictability and unexpected thoughts and memories Precipitation of psychosis Somatic symptoms: dizziness, weakness, tremors, nausea, drowsiness, paraesthesia, blurred vision Alcohol (CNS depressant) Product of fermentation of sugars and starches in fruits and grains 77% use in the last 12 months Slurred speech Motor incoordination Increased self-confidence Euphoria/dysphoria Aggressivity Impairment in intellectual, sensory and motor performance Diuresis Vasodilation Benefits from moderate drinking: - Reduce 30% mortality related to heart diseases - Increasing level of HDL - Inhibit platelet aggregation Inhibit action of glutamate at NMDA receptors and kainate receptors Inhibition of voltage-sensitive Ca2+ channels Enhance GABA action at GABA A receptors Enhance serotonin action at 5-HT3 receptors Enhance action of ACh at nicotinic acetylcholine receptors Adverse drug interactions Neurological degenerations causing dementia and peripheral neuropathy (Korsakoff's syndrome -- vitamin B deficiency) Chronic gastritis Pseudo-Cushing syndrome Liver damage cirrhosis and liver failure Impotence and feminisation in males Malnutrition Birth defects Increased risk of cancer in the mouth Tobacco (psychostimulant) Biggest drug-related killer 11% of the population Highly addictive Increased alertness when drowsy Calming when stressed Improve general sensory and motor performance Relaxation of skeletal muscle Increased HR and BP Decreased GI motility Nicotinic acetylcholine receptors agonists Cancer of the lung, oesophagus, pancreas, bladder Coronary heart disease and vascular disease Chronic bronchitis Harmful in pregnancy Caffeine (psychostimulant) Most widely used psychoactive drug in the world Decreased fatigue leading to insomnia Increased alertness Performance enhancement Low doses -- pleasant and stimulatory High doses -- dysphoria (anxiety, irritability, restlessness) Diuresis Stimulation of cardiac muscle Relaxation of smooth muscle Small tolerance, no withdrawal Caffeine is a methylxanthine Antagonise adenosine A2A receptors release of dopamine, NAd, 5-HT, Ach, glutamate and GABA At very high concentration inhibit phosphodiesterase build-up of cAMP Few side effects, relatively safe A table with numbers and symbols Description automatically generated