1 What are drugs?

1.2 Tabers Cyclopedic Medical Dictionary under the word drug

1.3 NIDA Research Reports.

2 Physical effects of drugs in the body

2.1 Toxic effects of drugs: Tabor's Cyclopedic Medical Dictionary, in its essay defining the word "drug", compares "toxic" and allergic reactions of all drugs, stating that the toxic reaction time may occur with the first dose, or may be due to cumulative effects.

The 2004 Physician's Desk Reference provides a list of over 4000 drugs. EVERY entry includes side effects and adverse interactions with other drugs that are toxic in nature.

Further, comparative drug education materials describe the toxic effects of drugs: "Tips for Teens" flyers on tobacco, inhalants, club drugs, cocaine, steroids, heroin, etc. all describe these drubs as being toxic and "can kill you."

Sequence of effects:

The science behind the cellular response to drug dosage is quite complex. Every drug submitted for regulatory approval through the FDA is studied within a well-defined "pharmacological dose response curve" that defines the small, tightly controlled range of clinical or therapeutic dosages. It is also known that either within or outside this range that the first low-dose effect is stimulation followed by a high-dose inhibition. This also happens to be true of heavy metals and other poisons and of antibiotics.

This phenomenon was identified as early as 1888, and was called the Arndt-Schultz Law. A paper published in Science (Vol 302, 17, October 2003) states "The [cellular] receptor for a specific compound tends to come in two flavors: stimulatory or inhibitory. When the concentration of the drug is low, the stimulatory type of receptor is more likely to be activated; at higher levels, inhibition takes over. Opiates work this way, for example.

Standard literature on drugs reports repetitively this similar sequence with major drugs of abuse and alcohol. As example from the NIDA Research Report Series:

Cocaine: "Short Term Effects of Cocaine: Increased energy, decreased appetite, mental alertness, increased heart rate and blood pressure, constricted blood vessels, increased temperature, dilated pupils: "Long Term Consequences: Addiction, irritability and mood disturbances, restlessness, paranoia, auditory hallucinations: "Medical Consequences: Cardiovascular - disturbances in heart rhythm, heart attacks; respiratory - chest pain, respiratory failure; neurological - strokes, seizures and headaches..." etc. (pg 5)

Inhalant Abuse: "Short and Long-Term Effects: Although the chemical substances found in inhalants may produce various pharmacological effects, most inhalants produce a rapid high that resembles alcohol intoxication with initial excitation, then drowsiness, disinhibition, lightheadedness, and agitation. If sufficient amounts are inhaled, nearly all solvents and gases produce anesthesia, a loss of sensation and even unconsciousness."... "Dizziness, drowsiness, slurred speech, lethargy, depressed reflexes, general muscle weakness, and stupor are other possible effects." (pg 5)

Heroin Abuse and Addiction: "Immediate (short-term) effects:...Abusers typically report feeling a surge of pleasurable sensation, a 'rush.' The intensity of the rush is a function of how much drug is taken and how rapidly the drug enters the brain and binds to the natural opioid receptors....After the initial effects, abusers usually will be drowsy for several hours. Mental function is clouded by heroin's effect on the central nervous system. Cardiac function slows. Breathing is also severely slowed, sometimes to the point of death."

2.2 Drug Metabolism: The Merck Manual Chapter 11 states:

"Drug distribution refers to the movement of drug to and from the blood and various tissues of the body (for example, fat, muscle, and brain tissue) and the relative proportions of drug in the tissues.

"After a drug is absorbed into the bloodstream, it rapidly circulates through the body; the average circulation time of blood is 1 minute. As the blood recirculates, the drug moves from the bloodstream into the body's tissues.

"Once absorbed, most drugs do not spread evenly throughout the body. Drugs that dissolve in water (water-soluble drugs), such as the antihypertensive drug atenolol, tend to stay within the blood and the fluid that surrounds cells (interstitial space). Drugs that dissolve in fat (fat-soluble drugs), such as the anesthetic drug halothane, tend to concentrate in fatty tissues. Other drugs concentrate mainly in only one small part of the body (for example, iodine concentrates mainly in the thyroid gland), because the tissues there have a special attraction for and ability to retain (affinity) the drug....

"Some drugs accumulate in certain tissues, which can also act as reservoirs of extra drug. These tissues slowly release the drug into the bloodstream, keeping blood levels of the drug from decreasing rapidly and thereby prolonging the effect of the drug. Some drugs, such as those that accumulate in fatty tissues, leave the tissues so slowly that they circulate in the bloodstream for days after a person has stopped taking the drug.

"Distribution of a given drug may also vary from person to person. For instance, obese people may store large amounts of fat-soluble drugs, whereas very thin people may store relatively little. Older people, even when thin, may store large amounts of fat-soluble drugs because the proportion of body fat increases with age."

(www.merck.com/mrkshared/mmanual_home2/sec02/ch011/ch011d.jsp)

Many scientific studies exist that describe the redistribution of specific drugs to adipose. The following are a selection of these studies that provide data on illicit drugs:

Levisky JA, Bowerman DL, Jenkins WW, Karch SB Drug Deposition in adipose tissue and skin: evidence for an alternative source of positive sweat patch tests. Forensic Sci Int. 2000 May 8;110(1):35-46.

Kidwell DA, Holland JC, Athanaselis S. Testing for drugs of abuse in saliva and sweat. J Chromatogr B Biomed Sci Appl 1998 Aug;713(1):111-35.
Axelrod J, Brady RO, Witkop B and Evarts EV The distribution and metabolism of lysergic acid diethylamide. Ann NY Acad Sci 1957 66: 435-444.

Stoman A The absorption, distribution, and excretion of drugs and poisons and their metabolites. Progress in Chem Tox Academic Press 1974 pp 1 -99.

James SH and Schnoll SH Phencyclidine: tissue distribution in the rat. Clin Tox 1976 9: 573-582.

Nayak PK, Misra AL and Mule SJ Physiological disposition and biotransformation of [3H] cocaine in acutely and chronically treated rats. J Pharmacol & Exper Ther 1976 196: 556 - 569.

Dackis CA, Pottash ALC, Annitto W and Gold MS Persistence of urinary marijuana levels after supervised abstinence. Am J Psychiatry 1982 139: 1196-1198.

Friedman H, Ochs HR, Greenblatt DJ and Shader RI Tissue distribution of diazepam and its metabolite desmethyldiazepam: A human autopsy study. J Clin Pharmacol 1985 25: 613-615.

M Shields MD, S Beckmann PhD, F Tennant MD, RM Wisner, Reduction of drug residues: Applications in drug rehabilitation, Presentation at 123rd Annual Meeting of the American Public Health Association, San Diego, 1995.

3. Mental Effects

3.1 Mind as mental pictures: (www.gis.net/~tbirch/mi5a.htm) "According to Kosslyn, mental images really should be understood in two ways: First, from the scientific standpoint, mental images are UNCONSCIOUS SPECIFIC DATA STRUCTURES THAT PLAY THE ROLE OF 'IMAGES' IN MENTAL COMPUTATIONS... etc.

Additional References: "Images of Mind," MI Posner, ME Raichle; and "An Introduction to the Science and Philosophy of Mental Imagery," JTN Thomas, PhD (www.calstatela.edu/faculty/nthomas/home.htm)

3.2 Hallucinogens: www.nida.nigh.gov/MOM/HALL/MOMHALL1.html "Hallucinogens powerfully affect the brain, distorting the way our five senses work and changing our impressions of time and space. People who use these drugs a lot may have a hard time concentrating, communicating, or telling the difference between reality and illusion." Etc.

3.3 (See 3.2)

4 Drug Addiction

4.1 The World Health Organization definition of addiction is "Addiction means using a substance repeatedly despite knowing and experiencing its harmful effects. The person using the substance cannot control the urge to use it and needs increasing amounts to achieve the effect he craves." http://www.emro.who.int/mnh/whd/PublicInformation-Part3.htm

4.1.1 Additional references: (http://teens.drugabuse.gov/facts/facts_brain2.asp)
4.1.2 "How Many Times Does Someone Have to Take a Drug to become an Addict?" "No one know how many times a person can use a drug without changing his or her brain and becoming addicted...

4.2 Depletion of vitamin and minerals: Extant science has shown that alcoholics, for example, are seriously deficient in vitamins A, E, C, B1 (thiamine), and B6. These deficiencies then impede cognition and further "can produce confusion and psychotic symptoms" (as stated by Petrie and Ban in the 1985 issue of the journal Drugs.) Dosages of thiamine plus B12 and folate have been shown to prevent alcohol-induced psychosis, or Wernicke-Korsakoff Syndrome. Depressant abuse addicts have been helped with a basic vitamin package plus amino acids phenylalanine and glutamine. Stimulant abuse patients have been helped with phenylalanine, tyrosine, and glutamine. Notes indicate that taurine calms down addicts coming off drugs and reduces their upset. Other work with simple orthomolecular treatment, including Calcium and Magnesium as well as other vitamins for the first week of withdrawal and amino acids later, showed rapid improvement in psychological test scores. Many experiments have shown the calming effects of Tryptophan with addicts in withdrawal.

The following references describe the above:

Mechanisms of vitamin deficiencies in alcoholism, Hoyumpa AM, Alcohol Clin Exp Res 1986 Dec 10:573-81.d

Bjornboe & Bjornboe, 1993, Alcohol and Alcoholism Vol 28: 111-116.

Odeleye et al, 1991, Alcohol Vol 8: 273-277.

Adult scurvy, Hirschmann JV, Raugi GJ, J Am Acad Dermatol 1999 Dec 41:895-906; quiz 907-10.

Merck Manual of Diagnosis & Therapy, Chptr 195 - Drug Use & Dependence: Alcoholism, 2002

Cognitive effects of nutritional deficiency, Rosenthal MJ, Goodwin JS, Adv Nutr Res 1985 7:71-100.
Vitamins in psychiatry. Do they have a role?, Petrie WM, Ban TA, Drugs 1985 Jul 30:58-65.

Mechanisms of vitamin deficiency in chronic alcohol misusers and the development of the Wernicke-Korsakoff syndrome, Thomson AD, Alcohol Alcohol Suppl 35 Suppl 1:2-7.

Methodology: Use of Orthomolecular Techniques for Alcohol and Drug Abuse in a Post-Detox Setting. Libby et al, 1982, Orthomolecular Psychiatry Vol 11: 277-288.

4.3 See 4.2

7. Drugs and Emotions

7.3 http://www.nida.hih.gov/MOM/METH/MOMMETH2.html
"Usually neurons recycle dopamine. But methamphetamine is able to fool neurons into taking it up just like they would dopamine. Once inside a neuron, methamphetamine causes that neuron to release lots of dopamine. All this dopamine causes the person to feel an extra sense of pleasure that can last all day. But eventually these pleasurable effects stop. They are followed by unpleasant feelings called a 'crash' that often lead a person to use more of the drug. If a person continues to use methamphetamine, they will have a difficult time feeling pleasure from anything. Imagine no longer enjoying your favorite food or an afternoon with your friends."