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. DrugText information on the 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

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.

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)-

Methaqualone

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
• 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

• 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

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

A Word about Ritalin (methylphenidate)

(www.erowid.org)

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