Misused Substances

• 1970: Nixon signed the controlled substances act (CSA) which would evaluate and regulate thousands of drugs. Interestingly, neither tobacco nor alcohol is under this bill
• CSA ranking criteria:

  • Impact on health (addictiveness, toxicity)
  • Potential applications in the medical field
• CSA ranked drugs from Schedule I to Schedule V. Drugs like Heroin are Schedule 1 (harmful, addictive, useless in medicine), while Lyrica, an antiepileptic, is 1 because of its uses, low risk, and low addictiveness
• Psychoactive substances


  Substances which have an impact on the nervous system that can have impacts on behavior or mind state
• Alcohol


  Most widely used drug that is misused (85% of adults have had it)
• Alcohol


  Usually consumed in ethanol (ethyl) whose use is overwhelmingly recreational. Leading risk factor for premature death in males 15-59 globally
• At low concentrations, alcohol leads to decreased anxiety, impaired judgement, slower reflexes, and an elevation of mood. At high concentrations, it leads to areflexia, anaglesia, memory deficits, and loss of consciousness. It can also lead to death if the respiratory system gets too relaxed
• Chronic exposure to low levels of alcohol can lead to liver cirrhosis, liver cancer, and related violence or injuries. It can also decrease risk of cardiovascular disease but it's generally outweighed by the risks
• Ethanol is synthesized by yeast as a byproduct of making sugar, and is chemically very similar to water, so it easily slips through membranes and activates a bunch of receptors (GABA, glutamate, serotonin, K+ channels) and is usually inhibitory, except for when it activates dopamine receptors in the ventral tegmental area
• Nicotine


  Alkaloid compound synthesized by a lot of plants in the nightshade family, but mainly by tobacco. Leading cause of premature death in the US (1 in 5). As addictive as cocaine or heroin. Usually consumed through inhalation or transbuccal
• Nicotine is an agonist for nicotinic acetylcholine receptors (all throughout the body), which releases norepinepherine and by activating the sympathetic nervous system it gives you a high within seconds
• Main psychoactive ingredient in cannabis is delta-9-tetrahydrocannabinol (THC) which is capable of activating endocannabinoid receptors within seconds. CB1 receptors are the ones which give people most of the psychoactive effects and CB2 is mostly within the immune system
• Endorphin


  Most well-known opioid produced by the human body
• Opioids are the current gold standard in pain relief, causing feelings of sedation and euphoria in addition to the analgesia. Drugs like heroin and morphine are taken IV, but prescription drugs for long-term conditions are generally taken orally
• Crack = inhalation, powder = insufflation
• Sympathomimetic

  Activates the sympathetic nervous system
• Cocaine


  Psychostimulant derived from the leaves of the coca plant that activates the sympathetic nervous system and is a dopamine reuptake inhibitor, causing transporters to be unable to put dopamine back at the terminals
• Transporter


  Proteins that take molecules from the extracellular space back into the presynaptic terminal
• Cocaine is a schedule 2 drug because it has potent local anaesthetic purposes in addition to its many many harms
• Psychedelics


  Synthetic or natural, they activate serotonin receptors and can lead to ego death, hallucinations, synesthesia, or connection to nature or god. Got a lot of bad press because of US 70s counterculture but we're seeing they have medicinal benefits to people with mental issues
• Tolerance


  Decrease in action of a drug due to repeat exposure
• Metabolic tolerance


  When the body becomes more efficient at eliminating a substance because it has more of the enzymes to get rid of it, so less of the drug reaches the receptors.
• Functional tolerance


  When receptors get dragged into a cell after repeated drug exposure so that the drug can interact with them less
• Conditional tolerance


  When the body gets signals it's about to get a drug so it develops compensatory opposite responses (like hyperglesia as a heroin injection site is prepared. It can be lethal if these conditions change but the dose remains the same because you are unprepared for what's going to happen
• Sensitization


  When a person experiences increased effects of a drug the longer they take it, like nicotine or amphetamines
• Withdrawal


  When you experience the opposite effects of a drug after abstaining from it because your body has reached a homeostasis that assumed the drug would always be there and had to overcompensate with the reverse to keep you alive