Marijuana - Understanding Addiction

• Marijuana is a leafy material from the cannabis plant that is smoked.

• You can make rope and other materials from C. sativa because it is cultivated into hemp.

• Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive agent in cannabis. Most of the THC is present in the flowering tops of the plant. The leaves and stock have some but much less.

• Hashish is the most potent. It is not found in the US very often.

• Sinsemilla is the high potency marijuana made from female plant.

• Chinese emperor Shen Nung made the first reference to cannabis in a pharmacy book in 2737 BC. He recommended it for many small medical uses.

• Social use spread in 1000 AD to the Muslim world and North Africa.

• During the 1840’s many writers and artists used hashish and expressed it in their writings.

• As the end of the 19th century approached, the use of psychoactive drugs increased and hashish held little interest in middle America.

• In 1926 a series of articles associating marijuana and crime appeared in a New Orleans newspaper.

• Thirty-six states had laws regulating the use, sale and/or possession of marijuana by 1935.

• Many laws were based on, and developed, because of popular literature linking marijuana to crime, and not because of the effect of the drug.

• Scientific American reported in 1939 that marijuana, when combined with intoxicants, makes the user have a desire to fight and kill.

• Many newspaper reports were similar and blamed marijuana for killing and fighting.

• The problem was that there was no medical evidence to support the relationship between marijuana and crime.

• The Marijuana Tax Act of 1937 was passed without much debate. It was a tax law so it did not outlaw marijuana – just taxed it.

• One medical doctor testified against the bill because he felt the states anti-marijuana laws were adequate and that the social-menace case against cannabis had not been proven.

• In the 1950’s and 60’s scientific research on cannabis declined but use went up.

• There are more then 400 chemicals in marijuana but only 66 of them are unique to cannabis.

• THC was isolated and synthesized in 1964 and is clearly the most pharmacologically active.

• THC is rapidly absorbed into the blood and distributed first to the brain. Peak psychological and cardiovascular effects occur within 5 to 10 minutes but have a half-life of 19 hours.

• THC can be found in the body for over one week. The longer and more regular the usage, the longer THC can be found in the body.

• THC is known to bind to two receptors located in the cerebellum, the hippocampus, the cerebral cortex and the nucleus accumbens. Others are located throughout the body.

• A consistent, acute, physiological effect of smoking marijuana and oral THC is an increase in heart rate.

• Recent studies demonstrate that animals will consistently self-administer Cannabinoid in laboratory experiments.

• Epidemiological data shows us that marijuana is the most widely used illicit drug in the world and that Americans have sought treatment for marijuana abuse and dependence more than any other illicit drug.

• Cannabis never attained the medical status of opium.

• One problem with medical research is the variability of cannabis.

• In 1941 cannabis was dropped from The National Formulary and The US Pharmacopoeia.

• The development of better drugs, the variability of the available medicinal cannabis, the insolubility of it in water, thus not amenable to be injectable, and if the unusually long latency of effect if taken orally all lead to the decline inmedical use of cannabis.

• In 1972 a new report showed that marijuana smoking was effective in reducing the fluid pressure in the eyes of glaucoma patients.

• Another medical use was reported in 1975. THC was found to help with severe nausea suffered by those taking certain cancer treating drugs.

• The FDA licensed a drug company to make a pill form of THC for treatment of the nausea in cancer patients in 1985 and extended the use to AIDS patients in 1993.

• The National Organization for the Reform of Marijuana Laws (NORML) pushed to have marijuana moved from a Schedule I to Schedule II so it can be prescribed to patients.

• In 1992 the DEA said that there was “insufficient evidence” to justify rescheduling marijuana because THC pills were available.

• According to the DSM-IVTR marijuana does not have withdrawal effects. There are some studies that show that there is such a thing.

• The acute physiological effects of marijuana have not been seen to be life threatening. There have been no reported deaths from overdose of THC.

• There is no clear decision on if marijuana impairs driving. Studies done in a lab, with non-regular marijuana users, show there are significant impairments. Studies done on drivers involved in car accidents show there is not an over-representation of marijuana use.

• A panic reaction is another problem with marijuana intoxication. This reaction is most common among less experienced marijuana users.

• Total tar levels, carbon monoxide, hydrogen cyanide and nirosamines are found in similar amounts in tobacco cigarettes and marijuana cigarettes. Benzopyrene is found in greater amounts in marijuana but few users smoke 20 marijuana cigarettes at one time.

• Heavy marijuana smoking can decrease testosterone levels and diminish sperm counts. Sperm structure also can be altered.

• Lower birth weight and shorter length at birth are reported in mothers who smoked during pregnancy. The problem is that most women who are smoking marijuana are also drinking and smoking tobacco during the pregnancy.

• Chronic, heavy marijuana smokers have been seen to be have diminished motivation, impaired ability to learn and experience family problems. If they stop smoking and remain in counseling, the condition can improve. This would seam to indicate a constant state of intoxication rather than changes in the brain.

• In 1970 the National Organization for the Reform of Marijuana Laws (NORML) was established with a grant from the Playboy Foundation.

• Many groups came out for the decriminalization of marijuana, not to make it legal, but to take away the jail time for having small amounts

• Many states give small amounts of marijuana a civil fine, while others legalized marijuana for medical reason. The Federal government still has marijuana as a schedule I drug with federal consequences. Federal law supersedes state law.

Hallucinogens - Understanding Addiction

Animism is the belief that plants, animals, rocks, streams, puddles and more have characteristics from a spirit contained within the object. Plants that can alter perception when eaten are said to do this by transferring the spirit of the plant to the person who is eating it.

• Phantastica drugs are able to alter the users’ perceptions while being able to not detach from the real world, they are hallucinogenic and they do not produce acute physiological toxicity.

• Lysergic Acid Diethylamide (LSD) is the most potent and notorious hallucinogen.

• LSD was originally synthesized from fungus that when ingested made people sick.

• In 1938 Dr. Albert Hoffmann synthesized LSD for its chemical similarity to a known stimulant, nikethamide.

• Not until 1943, was Dr. Hoffmann aware of the biochemical psychiatry when he accidentally absorbed some LSD through the skin of his fingers and got a small reaction. He experimented with a larger dose and had a much different experience.

• In 1953 biochemical and animal behavior research was done with LSD.

• Scientific study of hallucinogens declined in the 1970’s.

• The CIA and military did many studies using LSD. In 1953 the suicide of Frank Olson brought it into the news. The military had been studying mind-bending drugs as weapons as well as other uses of LSD. In doing so the military broke many ethical codes by not letting the person know they were in an experiment or not letting them out.

• Recreational use of LSD came to the forefront with Timothy Leary and Dr. Aldous

PHOTOGRAPH TAKEN BETWEEN SUMMER-FALL 1989, IN LOS ANGELES, CALIFORNIA, AT THE HOME OF TIMOTHY LEARY (PHOTO CREDIT: WIKIPEDIA)

Huxley.

• Leary performed experiments on Harvard graduate students in true scientific studies.

• This changed when Leary started to use LSD with the students and had no physician present when the drug was administered. His studies ended without scientific value.

• The League for Spiritual Discovery was founded in 1966 by Leary with LSD as a sacrament.

• Hallucinogen use increased during the mid-1960’s.

• Its main effects are described as new sensations, aphrodisiac effects, feelings of kinship with a peer group, as well as other hallucinogen feelings.

• Usage peaked in 1967 and 1968.

• With more news of bad trips, “flashbacks” and self-injurious behavior usage tapered off.

• LSD is odorless, colorless, tasteless and potent.

• LSD is quickly absorbed in the GI tract. Most take LSD orally.

• Typical symptoms of taking LSD are dilated pupils, elevated temperatures and blood pressure as well as an increase in salivation.

• A tolerance develops rapidly but physical dependence is not seen.

• The LSD experience is based on the modification of perception and particularly visual images. Even at low doses illusions and distortions appear when in fact, the object is present but distorted by colors and brightness.

• Depictured in movies and writings, synesthesia is what LSD is known for.

• Autonomic response happens within the first 20 minutes of taking LSD.

• Adverse reactions include panic reactions and flashbacks.

• Flashbacks are reactions that happen weeks or months after an individual has taken LSD.

• Beliefs about LSD include that they make the user more creative and that they have therapeutic uses.

• Psilocybin is the active agent in many of the mushrooms in Mexico that have hallucinogenic effects.

• Seeds of Morning Glory plants have several active alkaloids that are about one-tenth as active as LSD.

• Hawaiian Baby Woodrose seeds have higher levels of lysergic acid than Morning Glory seeds.

• Catechol hallucinogens are the second group of phantastica next to indole types.

• Peyote is a spineless, carrot-shaped cactus that for the most part is subterranean. Mescaline is the active chemical in peyote.

• Amphetamine Derivatives is a large group of synthetic hallucinogens.

• DOM 2,5-dimethoxy-4-methyl-amphetamine called STP in the 1960’s and 70’s. Only 1/13th as potent as LSD.

• MDMA or Ecstasy differs from most other hallucinogens because it can promote empathy. The other big difference is that studies have shown that MDMA can cause brain damage. Currently in the category of “club drug”.

• Deliriants produce mental confusion and a loss of touch with reality.

• PCP was looked at as a good analgesic but it did not produce good muscle relaxation or sleep. With more research PCP was linked to angry and uncooperative reactions. Recreational use of PCP was seen as a “garbage” drug. Sometimes it was sprinkled onto oregano and sold to unsuspecting youngsters as marijuana. In this way it is called angle dust.

• Ketamine is chemically similar to PCP, producing a mixture of stimulant and depressive effects. It currently is in the category of “club drug”.

• Atropine was used as a poison. Belladonna uses the extract of atropine to dilate the pupils. The sensation of flying is also reported by belladonna users.

• Mandrake contains all three alkaloids. Its ties go back to Genesis in the Bible.

• Henbane is the poison used to kill Hamlet.

• Datura contains all three alkaloids. It is associated with Buddha in the Chinese culture.

• Synthetic Anticholinergics were once used to treat Parkinson’s disease and are still used to treatPseudoparkinsonism produced by antipsychotic drugs.

• Amanita Muscari is a mushroom that is also called “fly agaric”.

Opioids and Opiates - Understanding Addiction

• Opioids are naturally occurring substances derived from the opium poppy.  They have a long history of medicinal use.
• Opium delivers pleasure and relieves pain and anxiety. This is what makes it so popular in medical and recreational use.
• Papaver somniferum produces opium for only 7 to 10 days a year. All opioids are derived from this.
• As far back as 1500BC the medical use of opium is on record.  Galen, a Greek physician, emphasized caution in the use of opium but felt it was a cure all.
• Because of the dark ages the Arabic world is credited for bringing opioids to the world.  The Arabian world started to trade with India and China.
• Arabic civilization prospered and made grand contributions to medicine and history of opium.
• Biruni, an Arabic physician, wrote about opioid dependence in 1000AD.  At the same time Avicenna, an Arabic physician as well, used opium extensively in medical practice.  His work, along with Galen’s work set the base for medical education in Europe.
• By the 10^th century opium was integrated into Chinese medicine.
• In Europe a phenomenon named Paracelsus was a successful doctor who praised what he labeled the “stone of immortality”.
• Dr. Thomas Sydenham, who was called the English Hippocrates, believed that without opium medicine would not be.
• In 1805 writer Tomas De Quincey had a toothache and was given laudanum.  From that point he continued to take it and did not try to hide his opium use.  He wrote “The Confessions of an English Opium-Eater,” and gave insight into opium.  He enjoyed it so much he continued to use opium until his dependence on it made him unable to write.
• China was introduced to opium before 1000 AD but it did not come into favor except for the elite.
• When there was a ban on tobacco, opium use went up in China.
• The first law against opium smoking, called for opium shop owners to be strangled.
• Once opium was outlawed it was smuggled in from India. This started the road to the Opium wars.
• Many countries wanted to trade with China but China did not want to.  Under pressure, the port of Canton was opened but with very strict rules for foreigners.  While tea was the major export opium, thou illegal, was the primary import.  In 1839, the emperor of China sent a representative to deal with the opium problem.  He did and destroyed 20,000 British chests of opium, about $6 million worth, and sent the British merchants free.   Then drunken American and British sailors killed a Chinese citizen starting the Opium Wars in 1839.
• The British army arrived 10 months later and won within two years.  China lost Hong Kong to Great Britain and had to reimburse the merchants the $6 million whose opium was destroyed as well as give the British broader trading rights.
• In 1805, Frederich Serturner isolated the primary active ingredient in opium.  He named it morphium.
• Use of this new opioid, that is 10 times stronger then opium, did not happen until 1831 when the medical use of morphine had become so powerful.
• In 1832 another alkaloid was isolated named codeine.
• The hypodermic syringe and war helped morphine.  With the hypodermic syringe, morphine was delivered into the blood stream or tissue getting a faster reaction from the drug.  Military medicine is about fast reactions.  The American Civil War, the Prussian-American War and the Franco-Prussian War put morphine into many soldiers.
• Many came back dependent on morphine and the illness was called “soldier’s disease” or the “army disease”.
• In 1874, heroin was developed by adding two acetyl groups to morphine.
• This chemical change made heroin easier to pass through the brain barrier, making it three times stronger then morphine.
• Heroin and morphine effects are the same except that the reaction comes faster with heroin and it is more potent.
• Heroin was marketed as a non-habit-forming substitute for codeine.  Heroin was later found to be habit forming
• There were three types of opioid dependence developing at the end of the 19^th century: oral intake of opium, opium smoking and injection morphine.
• By the start of the 20^th century, more Americans were dependent on one or more of the opioids.  No real statistics are available but it is thought that 1% of the population was dependent.
• In 1880 the typical opioid user was a white woman between 30-50 years old.  She would buy opium or morphine at the local store.
• After the 1914 Harrison Act, many laws were passed that effecedt people dependent on opioids.
• In 1915 possession of smuggled opioids became a crime.  Users could still get their supply from their doctor until 1919 when that was outlawed.
• Even when a new law opened the avenue back up in 1925, most doctors chose not to prescribe opioids.
• For this and other reasons opioids became expensive on the black market.
• More and more people chose to injected morphine so they could get the most for their money.
• After World War II fewer stay-at-home moms were using, as were more entertainers and musicians, thieves and pickpockets, and pimps.
• In the 1960’s the use of heroin increased as did the use of other drugs.
• Heroin was very cheep and easy to get in Vietnam.  Some estimates are that 10 to 15 % of American troops in Vietnam were dependent on heroin.
• Operation Golden Flow was used to test solders for use.   What they found was that when the solders got back to the US few went back to using.  This exemplified the belief that if drugs were cheap and readily available and people were bored, then the chance that a person will use is high.
• The US spent $35 million in 1972 on Turkey to make up for destroyed crops and helped develop new cash crops. This and a cooperative effort with France helped take a large percentage of heroin off the streets.
• By 1975 the shortage of heroin was over because Mexican black tar was plentiful and cheap.
• Currently it is estimated that the majority of illicit heroin comes from South America.  The purity of the street product is better from South America (46%) then from Mexico (27%) and there is not much of a price difference.
• Opioids have long been used for there pain killing effects.
• Opioid antagonists were being developed to help block the action of morphine, heroin and other drugs.  In the early 1970’s, opioid receptors (that were long believed to be there) were found in the synapses of the brain.
• Enkephalins are naturally found in the brain.  They act like morphine but are more potent.  Endorphins were also detected to have opioid-like effects.
• Pain relief is the most common medical use of opioids.
• Morphine reduces the emotional response to pain and diminishes the patient’s awareness of and response to the aversive stimulus.
• Opioids also help with intestinal disorders.  They counteract diarrhea and help with colic.
• As a cough suppressants codeine is very helpful.  In the form of Dextromethorphan it is available over the counter.  At high doses hallucinogenic effects are seen.
• Opioids have a large dependence potential.
• Tolerance comes on relatively quick so an increased amount of the drug is needed for both medical and recreational results once tolerance is reached.
• There is a high-cross tolerance potential within all opioids.
• Physical dependence is also seen with opioids.
• The time needed to become dependent on opioids depends on the amount used and for how long.
• Psychological Dependence is easy to see through opioids positive reinforcement interaction.
• Once physical dependence is set negative reinforcement is seen in not using; thus making it had to stop using.
• There is a high toxicity potential of opioids.
• Acute toxicity leads to depressed respiratory action.  This is a very deadly reaction.
• Chronic toxicity was believed to make the user weak but there has been no scientific evidence of harm to the organ systems.  The largest chronic effect is that it takes more and more drug to get the effect and with that, overdose becomes more common.
• Due to the short-lived reaction of the drug, many people dependant on opioids must take the drug many times a day.  For this, the sheer time needed to find and take the drug is great.
• Not to mention the cost on the addiction.  Not only to you have to consider the cost of the drug but also the cost of the paraphernalia needed to use the drug.
• There are many misconceptions and preconceptions in opioid use.  Many believe that each time a person mainlines they get a feeling of a whole body orgasm.  This is not the case for most.  While they might have that feeling the first time they use, all subsequent uses are not as intense.  Others only feel nausea and discomfort the first time.
• Another misconception is that if you try heroin once, you are hooked for life.  No drug fits that mold.  All dependence takes time to develop.
• Remember: No drug can have an effect until it enters the body. Don’t take that first step. 

Tobacco - Understanding Addiction

• Tobacco was one of the main things that Europe got from the New World, along with chocolate, sweet potatoes and corn.
• Tobacco was used in two forms: snuff and smoked.
• Tobacco had many early medical uses: from treating headaches to the common cold and other ailments of the time.
• There are two main different types of Nicotiana: Nicotiana tobacum and Nicotiana rustica.  In Virginia, tobacum was found to grow well and became the colony’s main product in 1612.
• Tobacco played a large role in the war.  From money to trade, tobacco was the turning point.
• The method for administering nicotine also changed.  It went from snuff to smoking and chewing.
• The regulation of tobacco happened as early as 1604 by King James of England.  While he published anti-tobacco information, he supported the growth of tobacco in Virginia.
• In 1908 New York made it illegal for women to smoke in public.
• In the 1930’s and 40’s reports of health risks came out. A 1952 Readers Digest printed “Cancer by the Carton”.
• Filtered cigarettes were starting to be looked at as alternatives and marketed to make sure that everyone knew original cigarettes were “safe”.
• “Safer” cigarettes were filtered and lower in tar.  They were looked at as safer but not safe cigarettes.
• Cigarettes makers looked at delivery devices that were even safer.  The problem became that if they went in a particular direction cigarettes were no longer a food and then would be regulated as a drug.  The companies stopped looking at the devices and looked toward less-smoke or smokeless cigarettes.
• Smokeless tobacco became a popular alternative in the 1970’s due to the rising risks of lung cancer.
• Once thought of as something just cowboys did, chewing tobacco grew until it became a public concern.  There are two different types of chew: loose-leaf and moist snuff.
• Though chewing tobacco was not as unhealthy as smoking it, chewing tobacco still had risks.  An increased risk of cancer of the mouth, pharynx, and esophagus as well as leukoplakia and other dental problems came with chewing tobacco.
• There are a lot of causes for concern with the adverse health effects of tobacco. There are effects of tobacco without smoking the tobacco itself such as environmental tobacco smoke, sidestream smoke, passive smoke and even mainstream smoke.
• There are effects on children of people who smoke.  They include low birth weight and Sudden Infant Death syndrome.
• Nicotine is a liquid alkaloid that is colorless and volatile.  Tolerance develops quickly as dose-dependence on nicotine.
• When smoked, 90% of inhaled nicotine is absorbed.
• A lethal dose of nicotine is 60mg; death would follow quickly.
• Enzymes in the liver help with the deactivation of nicotine in the body.
• The elimination of deactivated nicotine is slowed by nicotine itself because of its affects on thehypothalamus.
• Effects on the central nervous system by nicotine mimics acetylcholine.
• With the continued occupation of receptors, nicotine blocks the transmission of information at the synapse while stimulating it.
• Some of these receptors are found in the skin, tongue and large arteries.  Nausea, dizziness and feeling of illness are all the feeling of a person’s first smoke.  These are also the symptoms of low-level nicotine poisoning.
• With acute poisoning, the cause of death is suffocation from paralysis of the respiratory muscles.  Another negative effect of nicotine is that it increases the tendency of the blood to clot.
• Monotonous of the taste buds and a slight increase in blood sugar might be the basis for a decrease in hunger after smoking.
• Regular smokers will have high levels of carboxyhemoglobin in their blood decreasing the oxygen-carrying ability of blood.
• Nicotine is the driving force in tobacco that reinforces behavior.  Nicotine dependence was reinforced by the 1988 surgeon general’s report that stated that:

1. Cigarettes and other forms of tobacco are addicting.
2. Nicotine is the drug in tobacco that causes the addiction.
3. The pharmacological and behavioral processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine.

• Most new research is focused on the fact that nicotine affects dopamine.
• There is a large reduction in one type of MAO in the brains of chronic nicotine smokers.  This slows the breakdown of dopamine henceforth enhancing the effect of the dopamine released by each nicotine dose.
• Smoking is extremely hard to quit.  One reason might be the pure number of hits a pack-a-day smoker gets;annually hits total over 50,000.
• Most can quit smoking for a few days but 70 to 80 percent will be smoking again in six months.
• There are also drugs to help people quit.  Gum, and skin patches as well as pills are now available to help someone quit smoking.

Medications for Mental Disorders - Understanding Addiction

• The look and treatment of mental illness has changed over the years.  Currently the main method of therapy is drug therapy.
• Using this approach: the patient shows symptoms, they are diagnosed, and then treated with drugs.  Others believe that this just covers the problem.
• The Diagnostic and Statistical Manual of Mental Disorders provides criteria for classifying mental disorders to hundreds of specific diagnostics. The DSM V is expected in 2013.
• Many insurance companies use these definitions. DSM sets the standards for health
  
  

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  professionals.
• Anxiety disorders include:
  • panic disorders
  • specific phobias
  • generalized anxiety disorder
• They are commonly treated with benzodiazepines and otherdepressants.
• Psychosis is a major loss of contact with reality.  People suffering from a long-term psychotic condition with no known cause are diagnosed with Schizophrenia.
• “Malaria therapy” was used to treat general paresis when they say that the fever produced helped.  The introduction of antibiotics eliminated this treatment.
• Thiopental sodium, “truth serum”, was used to help patients express repressed thoughts.
• Insulin was used to shock schizophrenics but was seen to be not effective.
• Electronvulsive therapy, ECT, was also used on schizophrenics but was found to only work in half the people and there was a high relapse rate.
• Phenothiazines have special properties that did not by itself induce drowsiness or loss of consciousness.   First used to calm patients before surgery, it was then used to help calm mentally ill patients.Chlorpromazine was the first tranquilizer.
• Phenothiazines are still used to treat acute schizophrenics.  It is understood that this is not a cure but it is better then the placebo treatments.
• Pseudoparkinsonism is sometimes a side effect of those treated with Phenothiazines.
• Antipsychotic drugs block D2 dopamine receptors.
• Clozapine blocks D2 dopamine and 5HT2A serotonin receptors.
• Clozapine produces less Pseudoparkinsonism then other antipsychotics. Another advantage is that some patients show improvement that did not on the other drugs.  The major negative side effect is that in some it suppresses white blood cell production.
• With antipsychotic drugs, few are addictive.
• Monoamine Oxidase Inhibitors (MAO) are limited due to side effects.
• Tricyclic antidepressant had little effect on psychotic symptoms but improved the mood of depressed patients.
• Selective Serotonin Reuptake Inhibitors changed how the class of drug was looked at and marketed.  Prozac, and other SSRIs drugs, are safer than tricyclic antidepressants because they are less likely to lead to overdose deaths.
• Most antidepressants work by increasing the availability of norepinephrine or serotonin at the respective synapses.
• Electroconvulsive therapy is the most effective treatment for depression.
• If there is possibility of suicide then ECT is the best choice due to the fast results as compared to drug therapy.
• Mood Stabilizers like Lithium show good results with manic individuals while showing little to no improvement in depressed individuals.
• Valproic, Carbamazepine and lamotrigine are not as effective on bipolar disorder but do help with patients that are susceptible to epileptic seizures.
• One consequence of these drugs is the number of people in mental hospitals went down greatly.
• The number of outpatient programs has increased dramatically as has the number of people onantidepressant drugs.
• Psychiatrists are more likely to prescribe drug than do psychotherapy.

Depressants and Inhalants (Downers) - Understanding Addiction

Depressants

• Most widely used and abused drugs in the U.S.
• Popular for its stress and anxiety relieving properties as well as acceptably.

Before Barbiturates

• Chloral Hydrate was first synthesized in 1832 but not used clinically until 1870.
• Chloral Hydrate has a short onset (30 minutes) and 1g can induce sleep.
• Chloral Hydrate abuse causes massive stomach pain.
• Paraldehyde was first synthesized in 1829 but not used clinically until 1882.
• Paraldehyde has a very large margin of safety and is a very effective CNS depressant.
• Its negative point is that it has an awful taste and a bad smell that permeates the breath of the user.
• Bromides salts were used to induce sleep in the 19^th century and used until the 1960’s in OTC meds.
• Bromides have serious toxic effects.

Barbiturates

• Barbiturates were first used clinically in 1903.
• Barbiturates are very dangerous when combined with alcohol, however, they are still used for sleep.
• Barbiturates are grouped into time of onset and duration of action.
• Meprobamate was the first antianxiety agent, known as The Happy Pill of 1953.
• Meprobamate can cause physical dependence with as little as twice the normal daily dose.
• Methaqualone was mass marketed as a safe downer.
• Physicians over prescribed Methaqualone and many problems, from suicides to overdoses, were seen.
• Methaqualone is now listed as a schedule I drug.

Benzodiazepines

• Librium was the first benzodiazepines marketed as an anxiety reducer with a large safety margin. Others followed as did reports of psychological dependence.
• Rohypnol is one version. It is legal in places other then the US. Here it is known as the “date rape” drug.
• Benzodiazepines work by bonding with receptors. They enhance the normally inhibitory effects of GABA.

Sedatives and Hypnotics (Nonbenzodiazepines)

• Nonbenzodiazepine hypnotics are the newest additions to the depressant drug class.
• Nonbenzodiazepine are more selective for the GABA-A type of receptor
• Sedatives cause mild depression of the CNS and are used to treat extreme anxiety referred to as anxiolytic.
• Four top selling prescribed medications in the US are anxiolytic. They are the most widely prescribed drug class.
• Many types of anxieties are treated with these antianxiety drugs.
• Hypnotics are used to encourage sleep because of their amnesiac effects. They have, in the past, been liked to very harsh side effects.
• Anticonvulsants are given at very low doses, chronically. For this reason a tolerance tends to develop. This lowers or stopping the desired effects.
• Short-acting barbiturates are the benzodiazepines that are most likely to cause psychological dependence.
• Chronic use of large doses can lead to withdraw syndromes from barbiturates that are similar to alcohol but longer lasting and more unpleasant.
• Barbiturates can produce alcohol-like intoxication with impaired judgment and coordination. This can make it easier to cause harm to oneself while under the influence.
• Depressed rate of respiration is the largest physiological concern. Especially when mixed with alcohol.

Inhalants

• Gaseous anesthetics have been used for many years, with people misusing them for just as long. Nitrous oxide, laughing gas, is still used today as a light anesthesia.
• Butyl nitrites cause rapid delegation of the arteries and can cause faintness or unconsciousness. It can help with high blood pressure. Sold as “Poppers” , they usual have a very unpleasant stench.
• There are many types of volatile solvents. Most “huffers” are children that use household items to get high. Aerosols, toluene, gasoline, freon, butane and propane can all be used.

• GHB – gamma hydroxybutyric acid is a CNS depressant that occurs natural in the body.
• It has been taken as a dietary supplement to stimulate muscle growth.
• It is listed as a schedule I drug except in one form that is used to help with cataplexy. In the form of Xyrem it is a schedule II.

Stimulants (Uppers) - Understanding Addiction

• Stimulants are substances that cause the user to feel pleasant effects such as an increase in energy, due to the ability of the drug’s release of dopamine.
  • Stimulants increase alertness, excitation, and euphoria, and are referred to as uppers.
• Cocaine
  • Cocaine can be traced back to coca, which has been used as a stimulant for thousands of years.
  • Natives of the Andes mountains chewed coca leafs into balls and held them in their mouths.  This gave them energy to run and carry large weights long  istances over hard terrain.
    
    

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  • The coca leaf is an important part of the culture and civilization in 16^th Century Peru.  Coca was treated as money even by invaders of the country.
  • Angelo Mariani was a French chemist who used extracts from coca in multiple products.  It was wine that made him rich.
  • Then Dr. W.S. Halsted experimented with cocaine as a local anesthesia.   He became known as “the father of modern surgery”.
  • Sigmund Freud saw cocaine’s potential for treatment of a variety of complaints.  For many years he sang the praises of cocaine.  He helped one of his friends through a cocaine psychosis that Freud had prescribed him into.
  • Even with so much positive force behind cocaine from 1887 to 1914, 46 states passed laws to regulate cocaine.
  • With unverified facts, articles were written stating that cocaine was used at very high rates by blacks in the south, and that they had “homicidal” tendency because of this.  It explained that cocaine made black men unaffected by .32 caliber guns.  Many of these articles in the press and in medical journals were a major influence on the passage of the Harrison Act.
  • Coca paste is coca leaves that have been mixed with an organic solvent, soaked, mixed, mashed and had all the excess liquid filtered out.  The paste is made into cocaine hydrochloride that is snorted or injected.
  • Freebase is cocaine that is converted into a volatile organic solvent, heated and then the vapors inhaled.  This is very dangerous and flammable.
  • Crack
  • Crack is cocaine mixed with baking soda and water, then dried.
  • At the end of the 1960’s cocaine use began to increase again due to the cost of amphetamines.
  • Psychiatrist Peter Bourne sounded like Sigmund Freud when he made a case for legalizing cocaine.  Many plugged the benefits of cocaine, from doctors to celebrities.   It was these doctors and celebrities, along with others with auxiliary income, who could afford the drug due to its high cost.
  • Then an inexpensive ($5 to $10 a hit) form of cocaine that could be smoked became available.  Again, history repeated itself with the media and politicians going after a certain race of urbanites who used the drug.
  • The Anti-drug Abuse act of 1986 targeted high-level crack dealers.
  • It lowered the amount of drug you need to be caught due to the potency of crack.
  • The Anti-drug abuse act of 1988 added tougher penalties for first time users.  After these two laws passed, there was an increase in the number of black Americans in jail and thus concerns about racial profiling was raised.
  • The chemical structure of cocaine does not tell us how or why it works.
  • Cocaine blocks reuptake many neurotransmitters at one time.
  • Chewing or sucking on the leaves allows small amounts to slowly enter the system.
  • With snorting the absorption is fast as is the effect on the body.
  • Intravenous offers a fast, but short, lasting effect.
  • Smoking crack is becoming the preferred way to use cocaine due to the fact that no needles are needed and the high happens fast as well.
  • In 1860 the anesthetic properties of cocaine were developed but not used medically until 1884.
  • It is stilled used in surgery in the nasal and laryngeal regions.
  • Acute toxicity of cocaine or the lethal dose is hard to estimate.
  • The route of admission can change the LD as can the form of the drug.
  • Chronic toxicity of cocaine is found in problems with the nasal septum and the heart.
  • Dependence of cocaine is most likely in those who inject or smoke the drug.
  • Lab animals, when given the chance, will administer the drug to themselves until the die.  This shows that even without deadly withdraw symptoms, cocaine is additive.
  • Cocaine is easy to obtain in most major cities and is around 75% pure.  Most of it comes in from South America countries; the majority of that from Peru.
  • Due to pressure on the water/land routes, more then half of cocaine is smuggled in at the US- Mexico border.
• Amphetamines
  • Amphetamines, patented in 1932, are potent synthetic stimulant capable of causing dependence.
  • They were first used as replacement for ephedrine to treat asthma.
  • Then it was used as a treatment for narcolepsy due to it being a stimulant.
  • American soldiers in WWII used amphetamines to fight fatigue.
  • Truck drivers and students use amphetamines to help them stay awake for long periods of time.
  • One of several side effects was that people taking amphetamines were not hungry.  This became a major use for amphetamines.
  • Speed, which is an illegal methamphetamine, is a common and highly used amphetamine.
  • Until the 1960 the problems with amphetamines were with legally manufactured and prescribed ones.
  • Amphetamines are often used with other combinations of drugs called speedballs.
  • An approach to using amphetamines is smoking ice or crystal meth, which induces a rush, followed by a 4-16 hour high.
  • Synthesized drugs that mimic the psychoactive effects of amphetamines are called “designer” amphetamines.  MDMA (Ecstacy) is the most popular designer amphetamine.
  • Amphetamines are consumed in a verity of ways including orally, intranasally, intravenously and smoked.
  • When taking amphetamines orally, effects are felt about 1.5 hours after ingesting them.  This differs from intranasal peak effects that come 15 to 30 minutes after taking the drug.
  • During intoxication, behavioral toxicity can cause the user harm.  With large doses over long periods of time paranoia and panic can be problems, as can violence and aggression.
  • Compulsive and repetitive actions are yet another development of chronic toxicity of amphetamines.
  • Withdraw effects are small and more annoying then dangerous.
  • Psychological dependence is a concern with amphetamines.

Drugs and The Brain - Understanding Addiction

• Drugs come from plants either as by-products of them or developed chemically.
• In the US, $150 billion is spent on legal pharmaceutical drugs.
• All pharmaceutical drugs have at least three names.
  • chemical name of a drug is the organic chemistry chemical description of the molecule.  Most will never know or understand this name of a drug they are taking.
  • generic name of a drug is the official name of the drug.  It is still a detailed chemical name but much simpler.
  • brand name is for a specific formulation and manufacturer.
• The big difference between the generic name and the brand name is that a generic name is public domain while a brand name is trademarked by the company that developed the drug.  The developing company gets to name the drug but it must be FDA approved.
• One drug can be a painkiller, a controlled substance, a schedule II substance or just morphine.
• Categories of psychoactive drugs are:
  • stimulants
  • hallucinogens
  • marijuana
  • depressants
  • opioids
  • psychotherapeutics
  • nicotine.
• All drugs have defining characteristics.
• The Physician’s Desk Reference has color photographs of most legally manufactured drugs; it also includes information like dose and potency.
• The placebo effect is usually thought of in terms of a sugar or fake pill.
• Many drugs effects are influenced by the users experiences, mood, how tired they are, in addition to other substances in the system, such as food to other drugs.
• Dose-response refers to the correlation between the response and the quantity of drug administered.
  • The response may vary due to factors such as tolerance.
  • With a dose-response curve we hope to be able to answer a verity of questions; from what is an effective dose or a lethal dose.
• Toxicity, in early animal studies, is measured in how many animals die as a result of taking the drug.  After more studies, the therapeutic index is set as LD50 / ED50.
• The margin of safety is the difference between doses necessary for an intended effect and toxic unintended effects.
• Potency refers to the amount of drug necessary to cause an effect, while toxicity is the capacity of a drug to upset or destroy normal body functions.
• The forms and methods of taking drugs greatly effect how the drugs will interact with the users system.
  • Oral ingestion is the simplest way the drugs enter the body, but also the most complicated way to enter the bloodstream. Oral ingestion must make it through the acid in the stomach while avoiding neutralization by food and drink.  When the drug gets past the stomach it still has to go through the liver, as well as other organs.
  • Inhalation is when the drug is smoked or “huffed”.  Nicotine, marijuana, crack are most effective when delivered this way.   It is also rapidly absorbed due to all the capillaries in the lungs consequently moving quickly into the blood.  This is the fastest way to get psychoactive drugs into the system.
  • Injection put the drug into the system as well.
    • Intravenous injection puts the drugs right in the vein, so the onset of the effect of the drug is fast.  You can so put a high concentration of drugs in because it does not have to pass through a membrane.
    • Intramuscular injection puts the drug into the muscle and subcutaneous goes just under the skin.
  • Topical application is not used as often because many drugs are not absorbed effectively through the skin.
• After drug administration, the body eliminates the drug through metabolism and excretion.
• The drug will either leave the system or be changed so much that it will no longer have an effect on the body.
• Prodrugs have been developed to start working only after they have been altered by the body.
• The body has adaptive processes such as tolerance and dependence to protect against potential harm.
• With drug disposition tolerance the more the drug is used the faster the metabolism or excretion.
• Behavioral tolerance (conditioned tolerance) is when the behavior of the user changes even if the bio-chemical reaction in the body does not. There is strong evidence that tolerance effects are maximized when the drug-taking behavior occurs consistently in the same surroundings or under the same circumstances.

Today's Society &

Drug USe

• Drug use is taking an aspirin for a headache, or a single dose of cough syrup for a cough or a hit of acid.
• How the drug is taken has an effect on how the body reacts.
• How much and how often are points that make the difference between normal use and abuse.
• Four principles of psychoactive drugs:

1. Drugs are not bad or good; they are not evil, they are a substance. By itself a drug cannot do anything until it enters a body. Some drugs help the body function when taken correctly but can cause harm when misused or abused.
2. Every drug has multiple effects. No part of the body works independently from the rest; all systems are connected. When a drug is taken it affects all parts of the body it passes through.
3. Both size and the quality of the drug affect the effects of the drug. The better the quality, or the larger the dose the larger the response or the more severe the response.
4. The effects of a drug depend on the person. Not only personality, but age, race, weight… all  of them influence how the body takes in and responds to the drug.

• History tells us that humans have used, misused and abused some plants or substances for as long as humans have been around.
• Four pharmacological revolutions

1. 19th century – vaccines. This is the first time drugs were used to help stop the number one killers at the time: communicable diseases. For the first time there were drugs that were powerful and have selective beneficial effects. This helped people have faith in medicine stopping illness.
2. WWII – antibiotics. Not only did they help cure diseases but also helped prevent infection. This got us to the point that we are now; we expect to take something to fix everything.
3. 1950’s – anti-psychotic drugs. This was the first time that drugs were used to treat psychotic disorders. This changed the way people saw and treated mental illness. We have new drugs that effect how we think, our emotions, and perceptions.
4. Oral contraception – now we have control of our body through chemicals. Some drugs are not meant to treat anything but to control and change the way the body was meant to work.

• Then there were many social changes in the US: The Beatles, civil rights, Vietnam, LSD, etc. Drugs became more common and accepted.
• In 1971 Nixon declared the first “War on drugs”; yet during this time the legal drinking age was lowered and penalties for having marijuana were eased.
• In the 80’s tolerance lessened. The legal drinking age was raised to 21 again and penalties were stiffened on all drugs, including marijuana.
• Perception of the risk – when the perception of the risk is low the use is high and vice versa. This differs from perception of availability.
• Longitudinal studies are one way we have looked for antecedents of drug use.
• Evidence tells us not to do things but we do them anyways; from eating too much, driving too fast,drinking too much, texting while driving, and driving while intoxicated
• Cultural trends influence what drugs are being used.

Alcohol - Understanding Addiction

• Mead, made from honey dates back to about 8000 BC.  Beer and wine followed close behind.
• Fermentation is the basis to all alcohol.  Depending on what fruits, grains and yeast is used gives you different types of alcohol fewer than 15 percent concentration; above 15% distillation in needed.
•  In the US large scale distillation started at the end of the 18^th century.
•  It was more profitable to ship a barrel of whiskey than it was to ship 100 bails of corn.
• The percent of alcohol content is indicated by proof in the United States.  The percent alcohol is half the proof = 90 proof whiskey is 45 percent alcohol.
• Beer is about 4 percent alcohol.  It is made by adding barley malt to other grains.  Then hops are added with the yeast.  From there, different techniques give the variety of tastes of beer.
• In the US Anheuser-Busch , Coors, and Miller make up a majority of beer sales.  Imported and independent (microbreweries) beers are growing in popularity.
• Wine is one of the oldest alcoholic beverages that is still drunk today.
• There are two main types of American wine, generics and Varietals.  Generic is made to taste like a region in Europe.  Varietal is made from a specific type of grape.  There are more Varietal wines and they are normally more expensive the Generic wine.
• Other wines add sugar, brandy or are fortified making sherry, port, Madeira or Muscatel.
• Distilled spirits were first known to Europeans as fermented malted barley.   Whiskey made in the US began to grow in popularly in 1789.  Today many commercial distilleries produce 95 percent pure alcohol.  The proof influences the taste and other properties of liquor.
• In the 1700’s most Americans drank more alcoholic beverages than water because water was not always clean.
•  Alcoholic drinks were seen as good while drunkenness was seen as bad. The problem was the “weak” person not the alcohol.
• Things soon changed and alcohol became “evil” and demonized.  In 1784 Dr. Benjamin Rush documented the problems of heavy drinking such as jaundice, delirium, and seizures.
• Today these are all proven disadvantages of long term heavy drinking.  Dr. Rush was the first to call theaddiction to alcohol a disease.  Other doctors saw the same symptoms in others, which led to thetemperance movement.
•  In the temperance movement, people were to use beer and wine in moderation and no distilled spirits at all.  Soon beer became a problem as well and the temperance movement started to include abstaining from all alcohol beverages, including beer and wine.
• In 1851 Maine became the first state to have a prohibition law.  13 states fallowed but by 1868 9 states had rescind them.  After that many states and counties became “wet” or “dry”.
• Then on January 16^th, 1920, one year after the 36^th state ratified the law, the 18^th Amendment was national law.  This made the sale, manufacture and transport of intoxicating liquors illegal.
• As a result organized crime became profitable and speakeasies and bathtub gin became common words.
• Another effect was that alcohol consumption went down and deaths from alcohol went down.
• On February 20^th, 1933 the 18^th Amendment was repealed by the 21^st Amendment.  One of the main reasons was tax revenue the government was missing and the beginning of the great depression.
•  By the end of the “noble experiment” alcohol dependence and alcohol-related deaths were lower then before Prohibition.
• Some state and local governments remained completely dry or allowed just the sell of beer and wine.  This is still true today.
• The age at which someone can drink was 18 or 21, depending on the state, until 1988 when all states had to have a minimum age of 21 or lose federal transportation money.
• Today the federal government gets 1% or $8.5 billion of all taxes collected from alcohol tax.  Then the states tax collect $4 billion each year in taxes from alcohol.   With all of these taxes added up, more than half the cost of the average bottle comes from taxes.
• Ethnic and social factors lead to differences in patterns of use.  The Irish are associated with drinking hard liquor while the French are associated with wine.  Russian and Irish are associated with heavy drinking and drinking problems from hard liquor while Germany is associated with beer.  In reality the Czechs are the world’s leaders in beer and the French have the highest rate of alcohol dependence, suicide and death from cirrhosis of the liver.
• About one-third of adults in the United States said they abstain from alcohol.
• Half the alcohol that is consumed in the US is done by 10% of the drinkers.  Aspects that effect if and how much someone drinks is race, gender, religion, urban vs rural, and education level.
• College students are still associated with heavy drinking.  They are more likely to binge drink than drink every day.
• Many schools have banned alcohol at school related activities and have stiffer penalties for groups that break school rules.  This has not changed how many college aged drinkers drink.
• The absorption of alcohol in the body is not only dependent on the type of alcohol but the gender, their weight, what they ate and how often they work out among other things.
• When alcohol is taken in, it is distributed throughout the body in the blood in addition to other body fluids.
•  Until the alcohol is metabolized it remains in the body.  Only about 2% escapes the body in its original form.
• The enzyme alcohol dehydrogenase converts alcohol to acetaldehyde and that gets converted to acetic acid.  Until that happens nothing will “sober”  a person up; not coffee, exercise, a pill or a sports drink.
• Some people have a higher amount of the enzyme than others. Heavy drinkers will start to have higher levels of this enzyme because the liver will adjust.
• Until the 19^th century alcohol was used as an anesthetic because of it’s affect on the CNS.
• It had many disadvantages in comparison to nitrous oxide and ether so it was not used once there was an alternative.
•  Alcohol enhances the inhibitory effects of GABA as well as effects on other neurons in the brain.  Even at low levels there are adverse effects on behavior; euphoria sets in, there is a reduction in anxieties, inhibitions go away and simple behaviors become hard.
• While a heavy drinker’s blood-alcohol-concentration (BAC) will continue to go up, the behavioral effects will not be provoked as fast as in a novice drinker.
•  In the early 1980’s attention was given to driving while drunk.  Dose has a large effect on the ability to drive safely.  With a  BAC of .08 a driver is three times more likely to be involved in a crash than those who have not had anything to drink.  If the driver has little experience with driving in the first place, it is up to five times than a sober adult with training.  The risk goes up from there, if the BAC goes up.  Drinking and driving is still a problem today.
• No other psychoactive drug has been linked to sexual behavior as alcohol has. Shakespeare knew how alcohol affects sex drive and sexual performances.  Today alcohol is linked to risky sexual behavior.  This is an example of how alcohol affects the brain and decreases inhibitions.  Many times we are willing to have unprotected sex while we are under the influence of alcohol, something that we would not normally do; and even just have sex with someone we would not normally do it.
• Alcohol is also associated with many sexual assaults.  Alcohol impairs information processing so that the user concentrates on the action and not the outcome.
• Blackout can affect the user of alcohol as well.
• There is a correlation between alcohol and homicides. About 50% of all the murders are accounted with alcohol.
•  Even suicide is associated with drinking; with 1/3 of all suicides involving alcohol.
• Dilation of the peripheral blood vessel make a user of alcohol feels warm when in reality their body temperature is going down.
•  Fluid balance becomes a problem as the brain decreases the output of antidiuretic hormone ADH.  The diuretic effect is what makes a user increase in urine flow and can lower blood pressure in others.
• Hormonal balance becomes a problem because with each dose of alcohol the adrenal corticosteroid are released and testosterone is suppressed.
• Behavior toxicity comes from the belief that you can do something on alcohol when in reality you cannot, such as operating heavy equipment, swimming, or driving.
• Acute toxicity can come from drinking too much in one sitting.
• There is not a cure for the “hangover”.  Other counties call it different things but a hangover is the effect on the body after high or very fast intake of alcohol.  Rest and time is what it will take to feel better.
• You can treat some of the symptoms of a hangover but the only cure is not to over indulge in any alcohol.
• Chronic toxicity comes from repeated damage to organs that are directly or indirectly affected by the intake of alcohol.   From the brain (Wernicke-Korsakoff syndrome) the heart (heart disease) and the liver (cirrhosis) many areas of the body are effected by heavy drinking.  Cancer and immune deficiency are related to many parts of the body affected by alcohol as well as the increased likelihood of getting other diseases.
• When a pregnant woman drinks, she not only puts herself at risk but the baby as well.  Fetal alcohol syndrome and fetal alcohol effect impair the baby before and after birth.