Drugs and the Brain Sooren Moosavy and Vanessa Travieso
What are drugs? DRUG: any substance which, when ingested in relatively small amounts, induces a physiological change LD50 lethal dose 50% = dose of drug that kills 50% of subjects EC50 effective concentration 50% = dose of drug that induces 50% of maximum effects Therapeutic index (TI) = LD50 / EC50
Receptors and Neurotransmitters (NTs) Lock and Key analogy: Endogenous, or homemade NT s what do these keys do when they get in the lock?: Dopamine motor control, motivation, reward, arousal, etc. GABA the main inhibitory NT, slows down neurons communication Anandamide (CB receptor) food intake/appetite + Hundreds more
Receptors and Neurotransmitters (NTs) Drugs often act as impostors for endogenous NT s drug molecule structurally similar to NT molecule fits same lock (receptor), but activates it somewhat differently, for example: Amphetamine Dopamine
Receptors and Neurotransmitters (NTs) What is Agonism? Drugs and other chemical keys can fit into the lock in different ways: 1. Partial Agonism: molecule stimulates the receptor, but with a ceiling 2. Full Agonism: molecule stimulates the receptor however much it can! 3. Reverse Agonism: molecule actually does the opposite of normal receptor function 4. Antagonism: molecule does nothing but block a chemical bouncer
Alcohol Receptor: GABA (mainly) Sociability, talkativeness Euphoria Sense of relaxation and calm Loss of motor control Disinhibition Impaired judgment Health Overall quite toxic to the body, hence liver Dangerous interactions with many common prescription medications Increased risks of certain cancers, with heavy use Lifelong liver problems Withdrawal (CT) can be fatal for this drug
Tobacco Receptors: nachr (nicotinic acetylcholine receptor) Examples: cigars, cigarettes, hookah, dip, dokha Shortterm anxiety relief Short term memory recall improvement Feeling of groundedness Loss of appetite Health Running a serious risk of cancer, no matter what kind of tobacco is used, w/ or w/o additives Myriad of heart problems Sense of taste is diminished Respiratory diseases Notoriously difficult addiction to fight MUCH more
Routes of Administrations ROA s Bloodstream is what brings drugs from the body to the brain ROA has effects on: 1. How fast the substance enters bloodstream, and thus the brain 2. How much of it gets there all at once ( peak plasma concentration ) 3. The user s body, depending on RoA Some common ROAs in increasing order of (1) and (2): 1. Oral ingestion 2. Insufflation 3. Rectal 4. Intramuscular injection 5. Inhalation 6. Intravenous injection
Psychedelics Receptor: 5HT partial agonists ( 5HT = serotonin) Examples: LSD, Mushrooms (psilocybin), Ayahuasca (DMT), Peyote (mescaline) 1. 2. 3. 4. 5. 6. 7. 8. 9. Health effects: unique not physically or neurologically toxic, but dangers manifest in other ways: Laughter Giddiness/euphoria 1. Hallucinations*** 2. Increased creativity 3. Sedation Stimulation 4. Paranoia 5. Thought acceleration Other perceptual changes Latent mental illness Suppressed trauma Paranoia, delusions, hallucinations Worst case: psychotic episode All above are amplified with combinations Fun fact! 5HT = 5hydroxytryptamine
Nitrous Oxide (N2O, laughing gas, whippets) Receptor: NMDA antagonist 1. 2. 3. 4. 5. 6. Laughter Euphoria Loss of coordination Dissociation Anaesthesia Unconsciousness Health effects: 1. 2. 3. 4. Poor motor function > injury Canisters get extremely cold O2 deprivation Vitamin B12 deficiency (IMPORTANT)
Stimulants Receptor: wide range: Dopamine (DA), (Nor)Adrenaline (NA), Serotonin (5HT) Examples: MDMA, Amphetamine (Adderall), Methamphetamine, Cocaine/Crack Euphoria Talkativeness Sociability Focus Energy Loss of appetite Arousal Paranoia Delusions Health effects: Increased heart rate and blood pressure, Stimulant psychosis (repeated use), Neurotoxicity (Meth and esp. MDMA), Cardiotoxicity (cocaine/crack, and any other excessive stimulant use), Addiction (esp. cocaine/crack and meth), And any of the myriad health effects that result from lack of sleep and no food
Opioids Receptor: μopioid, modulates pain (physical & mental), nausea Example: Heroin, Codeine ( Lean ), Oxycodone (Oxycontin, Percocet), Hydrocodone (Vicodin), Fentanyl Euphoria Analgesia (reduced pain) Contentedness Strong sedation Itchiness Loss of inhibition Health effects: Many consider opioids to be #1 most addictive Very strong depressants alone, possible OD Even stronger when combined w/other depressants Respiratory depression Arterial damage (if injected) Often cut with fentanyl, etc. > very easy death Fun fact: endorphins = endogenous morphine
Benzodiazepines ( Benzos, BZD s) Receptor: enhance action of GABA in the brain. Example: Alprazolam (Xanax), Diazepam (Valium), Clonazepam (Klonopin) Health Anxiolysis (reduces anxiety) Sedation (sleepiness) Muscle relaxation Though deceleration Anterograde amnesia Powerful potentiation w/other depressants ( 1+1=3 ) Loss of coordination > injury/death Paradoxical anger fits Loss of inhibition Combining w/depressants > death Long periods of total memory loss Fun Fact #1: >30% of OD s involving opioids also involve BZDs Fun Fact #2: BZDs are one of few drugs whose WDs can be fatal
Inhalants DO. NOT. DO. THESE. Don t even think about it. Receptor: UNKNOWN Examples: Gasoline, Glue, Computer Duster Note: does not include N2O or poppers (amyl nitrites) Extreme hallucinations, often unpleasant Powerful delusions Anterograde amnesia Severe urge to redose Vomiting Health effects: Severely neurotoxic: severe brain damage, hypoxia, postuse depression, suicidal ideation, cognitive decline all possibly permanent Neurotoxicity not solely from hypoxia these chemicals are acutely toxic Severely cardiotoxic: cardiac arrest, failure, arrhythmia Toxic to liver and kidneys Fun fact: Sudden Sniffing Death Syndrome