• Legal Instrumental Use: Physiological and Psychological Medicine
• Used to ease lives
• Wide range: common-unusual, non-problematic-severe
• Sedatives and Tranquilizers, Anti-depressants, and Anti-psychotics
• The DASIS Report: Prescription and Over-the-Counter Drug Abuse Admissions
• 1997 NHS: "The estimated prevalence rate of non-medical use of psychotherapeutics (tranquilizers, sedatives, analgesics, or stimulants) in the past month for those 12 and older was 1.4 percent in 1996 and 1.2 percent in 1997, not a statistically significant change. There
  was some variation in rates of use by specific drug category and by age group."(1)
• 1998 NHS: "The estimated prevalence rate of nonmedical use of psychotherapeutics (tranquilizers, sedatives, analgesics, or stimulants) in
  the past month for those 12 and older was 1.2 percent in 1997 and 1.1 percent in 1998, not a statistically significant change." (2)
• Shopping for Drugs: http://www.ncpa.org/pub/st/st262/
• Current MTF (all ages) Data Tables (2011)
• 2007: Spending on Psychotherapeutic Drugs Soars

Sedatives

• General depressants
• Low doses reduce anxiety
• Higher doses sedate
• Alcohol
• Sedatives: Hypnotics (sleep aids)
• Tranquilizers: Old designation- Major/Minor

Major: Serious psychological problems

1. Anti-psychotics
2. Phenothiazines
3. No high
4. Rarely used recreationally
5. Defining Neuroleptica

Minor: Less serious problems

1. Benzodiazepines
2. Reduce anxiety
3. Calmatives

Sedatives vs. Tranquilizers: Sedatives can do the same thing as tranquilizers, but therapeutic doses tend to produce clouding, intoxication, dis-coordination and dependence. Experience with tranquilizers showed later that dependence was a reality with them, too.

Types of Sedatives

Chloral hydrate

• Knock out drops, "Mickey Finn"
• Synthesized in 1832, first used clinically: 1870
• By 1871- 'recreational use' noted
• Short onset: 30 minutes; sleep within 1 hour
• Not as problematic as the barbiturates: not as much depression of respiration, CVS, and fewer after effects
• But addictive, coupled with gastric irritant, and other side effects

Paraldehyde

• Synthesized in 1829; first used clinically in 1882
• Very effective
• Wide margin of safety
• Widespread use in the 1950's
• Problem: Horrible taste and odor that effects the breath of the user.
• Use as part of alcoholism cure

Bromides

• Widely used in 19th Century: Sleeping salts
• Patent Medicines
• A "bromide" was a tiresome, boring person
• Dangerous: accumulate in the body, depression develops, toxicity with repeated doses, dermatitis, and constipation
• Low (ineffective) doses were part of OTC preparations up to 1960's
• "Bromo-Seltzer"

Barbiturates

• 2500 types
• First: Barbital (Veronal), 1903-- A. Bayer
• Barbituratic Acid: Named after a girl named Barbara or celebration of discovery on St. Barbara's Day in a tavern with artillery officers
• Practice, still today: All end in al
• 1912: Phenobarbital (Luminal)- long acting
• 1923: Amobarbital (Amytal)- short acting; street name- "Ammies"
• 1930: Pentobarbital (Nembutal)- short acting; street name- "Yellow Jackets"
• 1930: Secobarbital (Seconal)- short acting; street name- "Reds" or "Sekkies"
• Also: Tuinal- short acting; street name- "Tooies" or "Christmas Trees"

• Long acting: 1 hour for onset, effects last 6-10 hours. Low doses (50 mg) as daytime calmative. Rarely used recreationally
• Short acting: 15-30 minute onset, effects last 2-6 hours. High dose (200 mg) as sleeping pill. Higher doses: 400-600 mg used recreationally

• Widely prescribed during the 1950's and 1960's
• Metabolized in the liver: stimulates the activity of the microsomal enzymes (alcohol); tolerance develops and impacts the metabolism of other drugs.
• Problems: Tolerance, Psychological and Physiological dependence (severe- 5% death on withdrawal), depress respiration, and in combination with alcohol- synergy-- OD. Drug of choice for suicide. LD50=> 10x ED50. Cross-tolerance, Interferes with REM sleep, cumulative toxic effect, and amnesiac effect.
• 800-1000 mg per day over a period of 4-6 weeks: severe dependence
• Prescription use of short acting barbiturates- down ~90%
• Street use down, DAWN reports down ~65%, deaths from OD, etc. down 46%
• Use during the 1960's
  1. Hundreds of thousands addicted
  2. The "Hidden Addiction"
  3. Older, Respectable, Middle-class individuals
  4. Legal supply- quasi-therapeutic
  5. Social tolerance- use was not viewed as problematic

Recreational use significant too.

1. The "Downer Freak"
2. Obliteration of Awareness
3. Juveniles and VIOLENCE especially with alcohol; 78% rank SECONAL as producing assaultiveness (11% rank alcohol): Not all barbiturates equal. Potentiation vs. Causation.

Meprobamate

• First of the modern anti-anxiety agents. Developed from muscle relaxant called mephenesin in the 1950's.
• Brand names: Miltown, also Equanil.
• Drug revolution of the 1950's (1955): Sales in May- $7500; by December- $500,000.
• "Happy Pills"
• Concern about over-prescribing grew; gradually awareness developed that psychological and physiological dependence did occur within two months at twice the typical dose.
• Placed on Schedule IV in 1970, still available- but replaced by Benzodiazepines

Benzodiazepines

• 1957: First clinical use=> Librium.
• "Breakthrough" in behavioral research: Give mouse barbiturate=> it falls asleep; Give mouse Librium-> it loosens its grip on inclined wire screen, fall to floor and walk around, acting "normal"
• Marketed as a selective ant-anxiety agent, with fewer problems than all of the above. Quickly became #1 seller.
• Originally thought to have a high margin of safety, but: OOPS
• Tolerance (although little escalation of use or "craving"), and physical and psychological dependence. Therapeutic dose=> 25 mg; @ 300 dependency
• 1970: Diazepam (Valium). More rapid onset, metabolized slower, longer acting. Therapeutic dose=> 2-10 mg @ 120 dependency. Became #1 and stayed there through 1978. Current Top 200 Drugs-- not there!
• For the most part, most users do not use in sufficient quantities to produce serious problems
• Frequently used, yet few DAWN reports
• Doctors began to limit prescriptions: Street users, multiple "scripts," and diverted production. Recreational use at much larger doses.
• Placidyl another brand name
• Now Xanax (Alprazolam) (see also) (early 1990s)-

1. Thought to be less problematic.
2. Concern: Rushed through testing without adequate controls or review in order to get to the market-- Profit potential very high.
3. Problems: dependency, memory loss, rage?

• Another: Rohypnol (see also)(late 1990s)- Date rape........
• And coming up: Ativan (Lorazepam), Serax (Oxazepam), and a variety of others.
• Sedative-hypnotic: Halcion (triazolam) (see below)

(www.erowid.org)

Methaqualone

• Early ad
• After introduction of "tranks," barbiturates were still used for sleep: Market- Open
• Everything seems to have gone wrong with this drug: FDA, DEA, Press, and Doctors
• Developed in India as an anti-malaria medication, but found ineffective
• After Thalidomide disaster, Europeans were looking for a safe sleeping pill.
• England- 1965: Mass Advertising, "Mandrax," by 1971, 2 million prescriptions being written
• Long before that: Hits the streets. Quickly becomes "drug of choice" for downer freaks. Stiffer controls, gradually replaced by other drugs
• Introduced in Germany in 1960, non-prescription. First OD- 1962, discovered that ~15% drug OD's related. 1963- prescription
• 1960-1964: Japan; 40% of all OD's
• USA: No one paid attention??? After 3 years of tests, introduced in 1965: Quaalude and Sopor brand names: "Addiction potential not established"
• Not Scheduled, monitored, or refill limitations. "No evidence of abuse potential"
• By 1970: "Ludes" and "Sopors" were the Drug of Choice on the streets. "Love Drug" and/or "Wallbanger"
• Prescriptions continued to soar, production diverted to streets, Sales increased
• Finally in 1973 (4 years after it was recognized as addicting: dependency as easy as with barbiturates) Methaqualone was placed on Schedule II. By 1985: No longer available. Now: Schedule I

All of the above drugs apparently enhance the inhibitory effects of GABA . Seems there are GABA-Receptor Complexes which attract the variety of drugs described. Now work is on to develop new drugs that work on this complex: Xanax

Pattern: Conventional-Deviant Behavior

• Drive for profit-Capitalism
  • Costs of developing a drug==> $800 million to $2 billion (for 2008: see, "The Cost of Developing a New Drug: New wonder medicines come from years of research, high costs," US Department of State)
  • Patent lasts==> around 20 years
  • Then==> Generics
  • When patents expire--profits decline. (NY Times, March 6, 2011, in print page A1 March 7, 2011)
• Competition: Advertising
• Even with FDA review: often little known about potential problems in large user population, or street level use.
• Instrumental use==> Street use, as properties become known
• Widespread recreational use:
  1. Scare stories
  2. Government investigations
  3. Tightening controls
  4. Illicit/deviant use=> Impetus: Profit
  5. Search for the next drug

Crime and deviance as converted form of Conventional behavior

PCP

• Morgan and Kagan: Media myths and realities. Dangerous, yes- But: with each "new" drug explosion of negative publicity feed itself to create overblown vision of danger. Use and "morbidity of PCP declining. Culture has "adjusted."
• Parke, Davis and Co. In the 1950's: New intravenous anesthetic-- Phencyclidine.
• Not a very good product, but animals did seem to become "disassociated"
• Use in humans: unpredictable psychological effects-- feelings of unreality, depersonalization, persecution, depression, and intense anxiety.
• By 1960: seen as useful as anesthetic for animals; medically safe, but problematic for humans; and a hallucinogen of a "different sort."
• Used in veterinary medicine to "stun" animals (not a tranquilizer)
• Similar drug marketed: Ketamine

• Appears on the streets- late 1960's-1970's: "Hog," "garbage," "Angel Dust."
• Use to "beef" up poor quality marijuana, sold as a substitute for just about everything
• Linked to violence (especially with alcohol)
• Little used today, typical user- Older than late 1970's

Anti-Psychotics

• Major Tranquilizers
• No "high" associated with use.
• Little to no recreational use
• Phenothiazines: Thorazine, Compazine, Mellaril
• Psychotherapeutic Revolution: Depopulation of Mental Hospitals

1946: 525,000 patients (220,000 admit/year)

1955: 680,000 patients (350,00 admit/year) (Chlorpromazine: Thorazine introduced)

1993: 120,000 patients (750,000 admit/year)

1998: 90,000 patients (no data available)

Admissions up steadily, census peaks in 1955 and then steady, dramatic decline

Stay earlier: 6 or more months, Now: 2-3 weeks

• 85% of patients receive some type of pharmacological therapy
• Produces significant improvement in behavior and manageability
• No addiction, OD rare, side effects: "ticks," shuffle, etc.
• Relapse if therapy terminated: 75-95%, ~15% can go back to normalcy

Antidepressants

• Psychotics: Bizarre and delusional behavior vs. Mood and Affective Disorder- Depression. Extreme sadness and/or despair. 15% suicidal
• Uni/bipolar.
• Stimulants don't seem to help
• ECT: effective, yet negative image. Used more frequently in England, etc. Today, more precise, lower voltage; Yet still viewed in negative light.
• Research on depression: neurochemical, inherited
• Drugs: SSRIs: Prozac, Tofranil, Elavil and Lithium (bipolar), MAOIs
• No euphoria; for non-depressed: unpleasant effect
• 2-3 week onset
• Most seem to be helped; ~5% problems
• Starting to produce a fair showing in DAWN reports

Focus: Prozac

1. Introduced in 1987, by 1990 prescriptions up 500%. Now in the top 10
2. One million prescriptions filled per month. More than one-half by non-psychiatrists.
3. Psychologist James Goodwin of Wenatchee, WA, has used himself since 1989, and virtually demands that all his clients be prescribed the drug!
4. Big $$$$$'s for Eli Lilly.
5. Questions: Testing. By 1990 reports of bizarre, violent and self-destructive behavior.
6. "Prozac-Generated Syndrome."
7. Prozac Survivors: legal action.
8. 1991: FDA rejected request by above groups to remove Prozac.
9. Continues to be one of the most popular antidepressants (Zoloft and Paxil outsell now).
10. Now "Sarafem."

Another Horror Story (Pattern Continues): Halcion (triazolam) (1997 IOM Report)

• Introduced in 1982 (Upjohn--Pharmacia)
• "Safe and Effective"
• Rapidly became the best selling sedative/hypnotic. 1991 profits ~$220 million.
• George Bush: Used to combat jet lag--Vomits in lap of Japanese Prime Minister
• Utah: women shoots mother 8 times, places birthday card on deceased's head. Drug defense-- Charges dropped, case dismissed; Upjohn settles civil suit.
• Reports of all sorts of craziness begin to surface
• Researcher reanalyze test: Falsified, Cover-up, Problems at three times the level reported
• Upjohn claims there were "mistakes," not intentional misrepresentation.  Justice Department Review (1994-96)
• ?????: Profit motive????
• Some suggest that Upjohn railroaded the drug through the FDA, Pharmacological-Industrial Complex: FDA and Psychiatrist dependent on the drug companies?? Drug companies interest==> Profit. Lying is means to an end.
• Taken off the market in Holland and Great Britain, other countries: small doses
• USA: Still under consideration, warning insert. Sales down.
• Now: Ambien (Zolpidem)
  • More specific action at one benzodiazapine site.
  • Clinically: similar to Halcion, rapid onset, short duration.

The "new" drug: Ambien

A Word about Ritalin (methylphenidate)

(www.erowid.org)

• AKA: Concerta
• Mild stimulant (schedule II)?
• Drug of choice for treatment of ADHD
• Cause(s) of ADHD not known, nor is how Ritalin works fully understood: sensory deprivation, food additives, social context, environment?   Whatever, Ritalin seems to help (assumption-- since drug "fixes" cause must be neuro-chemical).  Alternatives? Recent (2004) research on how stimulants work in the treatment of ADHD: NIDA NewScan for July 19, 2004. (local copy)
• Question: Who has the problem?  Child (now adults, too) or control agents?  For adults, who decides "normal?"
• Problem: Indiscriminate use.  Estimate--750,000 to 1,000,000 school children being treated. (198th out of top 200 drug in 1997)
• Non-Medical Use.
• ADD Resources (www.addresources.org) (a medicalized perspective)
NOW: Strattera (see also: Atomoxetine) (FDA information). Strattera is a norepinephrine re-uptake inhibitor. See, Wikipedia on norepinephrine.
• FDA publishes warning on ADHD Drugs, June 29, 2005
• Drugs to Treat A.D.H.D. Reach the Preschool Set, NY Times, Health, The Consumer, Octoger 24, 2011 (Page D5 in the October 25, 2011 print edition)

The Next Drug=>????????????????

Drugs and Crime

URL: http://www.umsl.edu/~keelr/180/prescrip.html
Owner: Robert O. Keel rok@umsl.edu
References and Credits for this Page of Notes
Last Updated: Thursday, April 12, 2012 8:33 AM