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To Alyssa, Jacob, Nicholas, James, Jillian, Sarah, Aiden, and Petra
and
Darron and Cole
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CONTENTS
Preface xvii
Chapter 1 SOME BASIC PHARMACOLOGY 1

What Is a Drug? 1
Names of Drugs 1
Describing Dosages 4
Potency and Effectiveness 6
Primary Effects and Side Effects 6
Drug Interactions 7
Pharmacokinetics 7
Routes of Administration 8
Absorption from Parenteral Sites 10
Inhalation 12
Oral Administration 13
Transdermal Administration 16
Distribution of Drugs 16
Elimination 18
Factors that Alter Drug Metabolism 21
Combining Absorption and Excretion Functions 23
The Therapeutic Window 23
Chapter 2 BEHAVIORAL ANALYSIS OF DRUG EFFECTS 25

History of Behavioral Pharmacology 25
Research Design 27
Measuring Unconditioned Behavior of Nonhumans 30
Measuring Conditioned Behavior of Nonhumans 31
Stimulus Properties of Drugs 33
Reinforcing Properties of Drugs—Abuse Liability 34
Measuring Behavior of Humans 35
Development and Testing of Psychotherapeutic Drugs 38
Chapter 3 HOW WE ADAPT TO DRUGS—TOLERANCE, SENSITIZATION,

AND EXPECTATION 40
Tolerance 40
Mechanisms of Tolerance 42
Withdrawal 43
ix
x Contents
Conditioning of Drug Effects 46

Sensitization 52
Expectancy and Context 53
Chapter 4 NEUROPHYSIOLOGY, NEUROTRANSMITTERS,

AND THE NERVOUS SYSTEM 56
The Neuron 56
The Synapse 63
The Nervous System 67
Development of The Nervous System and Potential for Disruption 78
Neurotransmitters 79
Brain Imaging of Drug Effects 91
Chapter 5 SUBSTANCE USE AND ADDICTIVE DISORDERS 96

Defining Addiction 97
History of Research on Drug Use and Addiction 100
Addiction as Physical Dependence 102
Modern Behavioral Explanations of Drug Use 104
The Neuroanatomy of Motivation and Reinforcement 114
Incentive Sensitization Theory 121
Hedonic Dysregulation and Adaptation 123
Disruption of Brain Control Circuits 125
Treating Drug Addiction 126
Chapter 6 ALCOHOL 132

Source of Alcohol 132
Origin and History 133
Measuring Alcohol Levels in the Body 135
Route of Administration and Pharmacokinetics 136
Absorption 136
Distribution 137
Elimination 139
Neuropharmacology 139
Alcohol Antagonists 142
Effects of Alcohol 142
Effects on Human Behavior and Performance 143
Effects on the Behavior of Nonhumans 146
Discriminative Stimulus Properties 146
Tolerance 147
Contents xi
Withdrawal 148
Self-Administration in Nonhumans 148
Self-Administration in Humans 149
Alcoholism 150
Harmful Effects of an Acute Administration 152
Harmful Effects of Chronic Consumption 154
Benefits of Alcohol Consumption 156
Treatments 159
Chapter 7 ANXIOLYTICS AND SEDATIVE-HYPNOTICS 162

The Nature and Neurophysiology of Anxiety 162
Introduction to Anxiolytics and Sedative-Hypnotics 163
History of Anxiolytic and Sedative-Hypnotic Drug Development 164
Neurophysiology 167
Route of Administration and Absorption 169
Distribution and Excretion 170
Effects on the Body 170
Effects on the Behavior and Performance of Humans 171
Tolerance 174
Withdrawal 175
Harmful Effects 180
Treatment 181
Chapter 8 TOBACCO AND NICOTINE 182

Preparations 182
History 183
Route of Administration 186
Distribution 189
Excretion 189
Neurophysiology 189
Effects of Nicotine 191
Drug State Discrimination 195
xii Contents
Withdrawal Symptoms 196

Harmful Effects 202
Treatments 205
Chapter 9 CAFFEINE AND THE METHYLXANTHINES 209

Sources of Methylxanthines 209
History of Methylxanthine Use 213
Extent of Methylxanthine Use 214
Route of Administration 215
Absorption 215
Distribution 215
Excretion 216
Neurophysiology 216
Effects of Caffeine and the Methylxanthines 217
Withdrawal 221
Harmful Effects 225
Beneficial Effects 227
Epilogue 227
Chapter 10 PSYCHOMOTOR STIMULANTS 228

Sources 228
History 229
Routes of Administration and Absorption 231
Distribution 232
Excretion 232
Neurophysiology 232
Effects of Psychomotor Stimulants 235
Dissociation and Drug State Discrimination 242
Tolerance 242
Withdrawal 243
Contents xiii
Harmful Effects 249

Treatment 251
Chapter 11 OPIOIDS 254

Origins and Sources of Opioids 254
History 256
Distribution 258
Excretion 259
Neurophysiology 259
Effects of Opioids 262
Effects on Human Behavior and Performance 262
Tolerance 265
Laboratory Studies 268
Self-Administration in NonHumans 269
Harmful Effects 270
Pharmacological Treatment of Opioid Addiction 273
Chapter 12 ANTIPSYCHOTIC DRUGS 277

The Nature of Schizophrenia 277
Theories of Schizophrenia 280
Discovery of Antipsychotic Medications 285
Comparing Typical and Atypical Antipsychotics 286
Absorption and Distribution 289
Excretion 289
Effects of Antipsychotics 290
Effects on the Behavior and Performance
of Humans 291
Drug State Discrimination and Dissociation 292
Tolerance 292
Withdrawal 292
Self-Administration in Humans and Nonhumans 292
xiv Contents
Harmful Effects 293

Other Therapeutic Effects of Antipsychotic Drugs 293
Chapter 13 ANTIDEPRESSANTS 294

The Nature of Depression 294
Theories of Depression 296
History of Antidepressant Medications 300
Neurophysiology 302
Absorption 303
Distribution 303
Excretion 303
Effects of Antidepressants 304
Tolerance 308
Withdrawal 308
Harmful Effects 309
Other Treatments for Depression 310
Chapter 14 CANNABIS 312

History 312
The Cannabinoids 314
Absorption 315
Distribution 316
Excretion 317
Neuropharmacology 317
Effects of Cannabis 319
Dissociation 324
Tolerance 325
Withdrawal 325
Epidemiology 326
Harmful Effects 327
Contents xv
Chapter 15 HALLUCINOGENS, PHANTASTICANTS, AND CLUB DRUGS 332

LSD and the Monoamine-Like Drugs 332
Ecstasy and Synthetic Mescaline-Like Drugs 339
Salvia 342
Dissociative Anesthetics: Phencyclidine and Ketamine 343
Dextromethorphan 346
GHB 347
Mephedrone 349
References 350
Credits 392
Index 396
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PREFACE
Like most modern scientific endeavors, the field of behavioral pharmacology is ever changing. Each day brings
exciting new developments and insights, and a great many discoveries have been made since the first edition of this
book in 1987. These discoveries intrigue people who use drugs both as medicines and for recreation. It is an ongoing
challenge to keep current with these new developments and decide what to include in each succeeding edition. At the
same time, we believe that it is important to tell the stories of the pioneers, to describe their groundbreaking research
and insights, and to provide the context in which these new discoveries were made. In addition, new drugs and new
fashions in drug use, both recreational and medicinal, come on the scene as others go out of style. As students ask new
and different questions, it is important to be able to provide answers. While every edition of this book has attempted
to keep up with these rapid changes, it is sometimes difficult to keep pace, and any book in the field is apt to be a bit
behind the times. As such, we count on course instructors to supplement the text content with up-to-date material
on new trends and developments, with the text providing background in which the significance of new developments
can be understood.
NEW TO THIS EDITION

The following changes have been made to the seventh edition.
• This edition welcomes a coauthor, Dr. Stephanie Hancock. Stephanie is an experienced teacher and researcher.
In the sixth edition, she contributed to the chapter on neurophysiology. Now, she has brought her energy,
enthusiasm, and fresh new insights to the seventh edition, making it a completely revised text.
• We have expanded the discussion of the neuroscience behind each class of drugs, the area of research in which
the most new developments are taking place.
• We have also expanded the chapters covering psychotherapeutic drugs—anxiolytics, antipsychotics, and
antidepressants—and updated the descriptions of the related disorders.
• We have updated the chapter on addictions, detailing the most recent theoretical and neurophysiological
developments.
• We have also increased the amount of visual material–graphs, tables, drawings, and figures–in order to make
the information more accessible to students.
• MySearchLab: Included with this edition, MySearchLab provides engaging experiences that personalize,
stimulate, and measure student learning. Pearson’s MyLabs deliver proven results from a trusted partner in
helping students succeed. Features available with this text include: A complete eText—just like the printed
text, you can highlight and add notes, listen to audio files, and more. Assessment—chapter quizzes, topic-
specific assessment, and flashcards offer and report directly to your grade book. Chapter-specific learning
applications—ranging from videos to case studies, and more. Writing and Research Assistance—a wide
range of writing, grammar, and research topics including access to a variety of databases that contain academic
journals, census data, Associated Press newsfeeds, and discipline-specific readings. MySearchLab can be
packaged with this text at no additional cost—just order using the ISBN on the back cover. Instructors can also
request access to preview MySearchLab by contacting your local Pearson sales representative or visiting www.
mysearchlab.com.
xvii
xviii Preface
SUPPLEMENTS
The following supplements are available to qualified instructors.
Instructor’s Manual with test materials (0205913571): Written by Dr. Anna Hicks, the instructor’s manual is a
wonderful tool for classroom preparation and management. The manual contains a brief overview of each chapter
of the text with suggestions on how to present the material, sample lecture outlines, classroom activities and discus-
sion topics, ideas for in-class and out-of-class projects, and recommended outside readings. The test bank contains
multiple-choice, short-answer, and essay questions, each referencing the relevant content pages in the text.
PowerPoint Presentation (0205920926): Created by Dr. Anna Hicks, the PowerPoint Presentation is an exciting
interactive tool for use in the classroom. Each chapter pairs key concepts with images from the textbook to reinforce
student learning.
MySearchLab (0205924824): MySearchLab provides engaging experiences that personalize learning and comes
from a trusted partner with educational expertise and a deep commitment to helping students and instructors achieve
their goals. Features include the ability to highlight and add notes to the eText online, or download changes straight
to the iPad. Chapter quizzes and flashcards offer immediate feedback and report directly to the grade book.
ACKNOWLEDGMENTS
This book would not have been possible without the assistance of many people. These include all of the individuals
acknowledged in the earlier editions whose contributions are still reflected in the text. In this edition, we would like
to further acknowledge the help of our spouses, Edna McKim and Darron Kelly, who tolerated our frequent and pro-
longed absences, both physical and mental, while the manuscript was being revised.
We would also like to acknowledge the contribution of many of our colleagues at Memorial University and at other
institutions around the world who have made helpful suggestions, read drafts, and corrected our errors. We also want
to acknowledge the many students who have used earlier editions and contributed helpful suggestions and criticisms
that have helped shape this most recent edition. We acknowledge the help of Brent Turner and Cam Rempel, two
young men with very bright futures, who researched and contributed particularly to the chapters on alcohol, cannabis,
and hallucinogens.
We would like to acknowledge the helpful comments of the reviewers of the seventh edition and thank the people
at Pearson for their excellent professional help with the editing and production. These include, but are not limited to,
Susan Hartman, Jessica Mosher, Shivangi Ramachandran, Wendy Albert, Shelly Kupperman, Revathi Viswanathan,
and Sathya Dalton.
Apart from taking credit where it is due, none of these people can be held responsible for errors or problems in the
book. Please direct all complaints to us so we can make the eighth edition even better.
William A. McKim
Brighton, Ontario
Stephanie D. Hancock
Medicine Hat, Alberta
C H A P T E R
1
Some Basic Pharmacology
WHAT IS A DRUG? best to think of it as a drug, but if it is consumed for

taste or sustenance, it may not be useful to think of it
Most people understand what is meant by the term as a drug. Such a debate has been waged about caffeine.
drug, but, surprisingly, coming up with a precise defini- As you will see in Chapter 9, caffeine clearly alters hu-
tion is not all that easy. The traditional way is to define man physiology, but it also has been used as a flavor-
a drug as any substance that alters the physiology of ing agent in products such as soft drinks. If consumers
the body. This definition, however, includes food and prefer a soft drink that contains caffeine because they
nutrients, which are not usually thought of as drugs. like the drink’s taste, perhaps caffeine should not be
Consequently, a drug is sometimes defined as a sub- thought of as a drug in that context. If the soft drink
stance that alters the physiology of the body but is is consumed because of the effect caffeine has on the
not a food or nutrient. This definition usually works, nervous system, then it is appropriate to think of it as
but it still leaves a lot to be desired. To begin with, the a drug. A similar debate has been waged about the role
distinction between a drug and a nutrient is not at all of nicotine in tobacco (see Chapter 8). In these cases,
clear. Vitamin C, for example, alters physiology, but is the consequences are important to government regula-
it a drug? If it is consumed in the form of an orange, it tory agencies and various manufacturers. Fortunately,
is clearly food, but if taken as a tablet to remedy a cold, it is not necessary for us to form a precise definition
it could be thought of as a drug. of the term drug. An intuitive definition will serve our
Similarly, some substances that alter the physiology purposes. However, we should never lose sight of the
of the body may best be thought of as toxins or poi- fact that any one definition may not be appropriate in
sons rather than as drugs and may not be deliberately all circumstances.
consumed. Gasoline and solvent vapors are examples.
If they are consumed deliberately to get high, they
NAMES OF DRUGS
might be drugs, but when inhaled unintentionally in
the workplace, they may be called environmental tox- One of the more confusing things about studying drugs
ins. The exact distinction between a toxin and a drug is their names. Most drugs have at least three names—a
is not clear. chemical name, a generic name, and a trade name—and
One element that complicates the definition appears it may not always be apparent which name is being used
to be the intention of the drug user. If a substance is at any given time. In addition, recreational drugs have an
consumed to get high or to treat a disorder, it is clearly assortment of street names.
1
2 Chapter 1 ● Some Basic Pharmacology
Chemical Name generic name is used throughout the world. In spite of

these attempts, there are still a few cases where differ-
All drugs have a chemical name stated in formal chemi-
ent names are used for the same drug. For example, the
cal jargon. A chemist can usually tell by looking at the
USAN amphetamine is still widely used in Britain and
name what the molecule of the drug looks like. Here is
the United States, but many other parts of the world are
the chemical name of a drug:
now using amfetamine, the INN. Most scientific journals
and textbooks published in North America (including
7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,
this book) use USANC generic names.
4-benzodiazepin-2-one
There is a type of unofficial generic name you might
also encounter. Because establishing a generic name is
As you can see, it is full of chemical terminology, letters,
a costly and time-consuming process, new drugs cre-
and numbers. The numbers refer to places where dif-
ated by drug companies may be used extensively before
ferent parts of the drug molecule are joined. To make
generic names are officially awarded by the official nam-
things more complicated, there are different conventions
ing agencies. But instead of using their clumsy chemical
for numbering these parts of molecules. As a result, the
names, these drugs are sometimes referred to by a code
same drug will have different chemical names if different
using letters and numbers established by the company.
conventions are used.
For example, you may see a name like SKF 10,047. The
letters refer to the drug company (in this case, Smith,
Generic Name Kline, and French), and the numbers are a unique code
for the drug. SKF 10,047 has now been assigned the
When a drug becomes established, its chemical name
generic name alazocine.
is too clumsy to be useful, so a new, shorter name is
made up for it—a generic name or nonproprietary name.
Trade Name
The generic name for the drug whose chemical name
we just struggled through is diazepam. A drug’s generic When a drug company discovers and develops a new
name bears some resemblance to its chemical name. The drug, often at a cost of millions of dollars, it can patent
conventions for making up generic names are handy to the drug for a number of years so that no other company
know because they are clues to the nature of the drug. can sell it. Even though it must use the generic name
Initially, the generic name was derived by combining somewhere in its advertising and documentation, the
parts of the chemical name, and these names are still in drug company does not sell the drug under its generic
use, but more recently, a system has been adopted that name. Instead, it makes up a new name called the trade
uses a stem to indicate the class or function of the drug. name, proprietary name, or brand name. The trade name
The stem is usually the last part of the generic name, al- is the property of the company that sells the drug, and
though it could be at the beginning or in the middle. For no other company can use that name (hence, the name
example, oxetine is a stem that indicates an antidepres- is proprietary). Generic names, on the other hand,
sant drug. Thus, if you see the name fluoxetine or dulox- are nonproprietary and can be used by anyone. The trade
etine, you know what type of drug it is, even though you name for diazepam is Valium. After the patent expires,
may never have heard of it before. Table 1-1 shows stems which typically occurs in 5 to 7 years, other companies
for some behaviorally active drugs you may come across. can sell the drug or they can make it under license from
Generic names are established in the United States by the owner of the patent, but they frequently sell it un-
the United States Adopted Names Council (USANC) der a different trade name. Therefore, one drug can have
and are called United States Adopted Names (USAN). many different trade names.
Similarly, the British Approved Name (BAN) is estab- Because drug companies sell their products under
lished by the British Pharmacopoeia (2012). Interna- trade names, people in the medical profession are most
tionally, the World Health Organization establishes the familiar with trade names and are most likely to use
International Nonproprietary Name (INN). Attempts those names. If a physician gives you a prescription for a
are made to harmonize all these names so that the same drug and you are told the name of the drug, you may not
Chapter 1 ● Some Basic Pharmacology 3
TABLE 1-1 Generic Name Stems of Behaviorally Active Drugs
Generic Drug
Name Stem Definition Examples
-adol or -adol- Analgesics (mixed opiate receptor agonists/ tazadolene; spiradolene; levonantradol
antagonists)
-anserin Serotonin 5-HT2 receptor antagonists altanserin; tropanserin; adatanserin
-axine Antianxiety, antidepressant inhibitor radafaxine
of norepinephrine and dopamine reuptake
-azenil Benzodiazepine receptor agonists/antagonists bretazenil; flumazenil
-azepam Antianxiety agents (diazepam type) lorazepam
-azocine Narcotic antagonists/agonists quadazocine; ketazocine
(6,7-benzomorphan derivatives)
-barb or -barb- Barbituric acid derivatives phenobarbital; secobarbital; eterobarb
-caine Local anaesthetics dibucaine
-caserin Serotonin receptor agonists, primarily 5-HT2 lorcaserin; vabicaserin
-clone Hypnotics/tranquilizers (zopiclone type) pagoclone
-dopa Dopamine receptor agonists levodopa
-erg- Ergot alkaloid derivatives pergolide
-fenine Analgesics (fenamic acid subgroup) floctafenine
-fylline Theophylline derivatives enprofylline; bamifylline; cipamfylline
nab- or -nab- Cannabinol derivatives nabazenil; dronabinol
nal- Narcotic agonists/antagonists nalmefene
(normorphine type)
-nicline Nicotinic acetylcholine receptor partial altinicline
agonists/agonists
-orphan Narcotic antagonists/agonists dextro-methorphan; dextrorphan
(morphinan derivatives)
-peridol Antipsychotics (haloperidol type) haloperidol
-peridone Antipsychotics (risperidone type) risperidone; iloperidone; ocaperidone
-perone Antianxiety agents/neuroleptics (4’-fluoro-4- duoperone
piperidinobutyrophenone derivatives)
-serod Serotonin receptor antagonists piboserod
and partial agonists
-spirone Anxiolytics (buspirone type) zalospirone; tiospirone
-stigmine Cholinesterase inhibitors (physostigmine type) quilostigmine; teserstigmine
Prefixes are shown as “stem-,” middle syllable as “-stem-,” and suffixes as “-stem.”
Source: Adapted from United States National Library of Medicine, National Institutes of Health (2011), http://druginfo.nlm.nih.gov/
drugportal/jsp/drugportal/DrugNameGenericStems.jsp, accessed December 7, 2011.
be able to find it listed in this or any other text that uses individual. To ensure that the drug is present in the
generic names. Trade names can be distinguished from same concentration in the brains of all experimental
generic names because the first letter is capitalized. participants or patients, different doses are frequently
Strictly speaking, the trade name refers to more than given according to body weight. For this reason, in
just the active ingredient in the medicine; it refers to the research papers, doses are usually reported in terms
drug’s formulation. The active ingredient is marketed of milligrams per kilogram (kg) of body weight—for
in the form of a pill, tablet, capsule, or liquid that may example, 6.5 mg/kg (a kilogram is equal to 2.2 pounds).
contain a number of other ingredients—fillers, coloring Reporting doses in this manner also helps when com-
agents, binding agents, and coatings, collectively referred paring research on different species. If you account for
to as excipients. The excipients and the active ingredient such other factors as metabolic rate and body composi-
are combined in a particular way, and this is known as the tion, a dose of 1 mg/kg in a monkey will be roughly com-
formulation. Different pharmaceutical companies may parable to a dose of 1 mg/kg in a human. Interspecies
market the same drug but in different formulations that comparisons, however, can be tricky. Generally, smaller
are given different trade names. It cannot be assumed organisms have higher metabolic rates than larger ani-
that all formulations with the same active ingredient are mals. As we shall see later, many drugs are destroyed by
equal. For example, different formulations may dissolve the body’s metabolism. What this means is that drugs are
at different rates in different parts of the digestive system metabolized faster in smaller animals, and so it is often
and, consequently, may not be equally effective. necessary to give them a higher dose if they are to reach
an exposure equivalent to that of a human. Thus, a dose
of 1.0 mg/kg in a human may be equivalent to a dose of
Street Name
10.0 mg/kg in a mouse or a rat. For this reason, research
Drugs that are sold on the street for recreational pur- done on rats and mice often uses doses that seem ridicu-
poses usually have a street name, which can change lously high in human terms.
with time and differ geographically; however, a
particular drug usually has one street name that is
Dose–Response Curves
widely recognized. For example, the club drug MDMA
(3,4-methylenedioxymethamphetamine) is widely known To establish a true picture of the physiological and be-
by most people by the street name ecstasy, even though it havioral effects of a drug, it is usually necessary to give
has had many other names at different times and in dif- a wide range of drug doses. The range should include a
ferent places. A quick search of the Internet can turn up dose so low that there is no detectable effect, a dose so
names such as X, E, XTC, Disco Biscuit, Go, Crystal, high that increases in dose have no further effect, and a
Adam, Hug Drug, Love Drug, Lover’s Speed, Clarity, and number of doses in between. It is usual to plot the effect
Speed. Some street names for Valium include Downers, of this range of doses on a graph, with the dose indicated
Tranks, Vs, Foofoo, Dead Flower Powers, and Sleep Away. on the horizontal axis and the effect on the vertical axis.
This type of figure is called a dose–response curve or a
dose–effect curve. Some make a distinction between these
DESCRIBING DOSAGES
terms, but such distinctions are not widely used and
All of modern science uses the metric system, and these terms are often used interchangeably. The term
drug doses are nearly always stated in milligrams (mg). dose–response curve (DRC) will be used here.
A milligram is 1/1,000 of a gram (there are a little over Figure 1-1 shows a typical DRC. It indicates the ef-
28 grams in an ounce). fect of caffeine on a mouse’s rate of pressing a lever on an
It is generally true that the behavioral and physi- FI (fixed interval) schedule (schedules will be explained
ological effects of a drug are related to its concentra- in Chapter 2). Note that the scale on the horizontal
tion in the body rather than the absolute amount of axis is graduated logarithmically. It is generally found
drug administered. If the same amount of a drug is that a small change in low doses can have a big effect,
given to individuals of different sizes, the drug will but an equally small change in a large dose has no effect.
reach a different concentration in the body of each Plotting doses on a log scale allows a wide range of doses
200
180
160
PERCENT CONTROL
140
120
100
80
60
40
20
0
SAL 1· 8 5·6 18·0 56·0 180·0 560·0
μM/kg
FIGURE 1-1 The dose–response curve for the effect of caffeine
on the rate of responding of a mouse on an FI schedule with
food reinforcement. Note that the dose is given in S.I. units.
(Adapted from McKim, 1980)
to be reported and permits greater precision at the low ED50 AND LD50. A common way of describing these
end of the dosage range. curves and comparing the effectiveness of different drugs
In the example just used, the drug effect was a mea- is by using the ED50, the median effective dose, or the
sure of response rate, but there are other types of DRCs dose that is effective in 50% of the individuals tested.
in which the effect is a discrete binary variable rather than The ED 50 for losing consciousness from endital in
a continuous one. For example, we could not use this Figure 1-2 is 35 mg/kg. By checking the next curve, you
type of curve if we wanted to report a DRC for the can see that the dose of endital that killed 50% of the
effectiveness of a drug as an anesthetic. Either sub- rats was 84 mg/kg. This is known as the median lethal
jects are anesthetized or they are not. If the vertical dose, or the LD50.
axis simply read Yes or No, we would not have any sort It is also common to use this shorthand to refer to
of a curve. When a binary variable is used, DRCs are lethal and effective doses that are not at the median. For
constructed differently. example, the LD50 is the dose at which 50% of subjects
Binary drug effects are handled by working with die, the LD1 is the dose that kills 1% of subjects, and the
groups of subjects. Each group is given a different dose ED99 is the dose that is effective in 99% of all cases.
of the drug, and the percentage of subjects in each group In DRCs constructed from continuous rather than
that shows the effect is then plotted. An example of this binary measures, the ED50 is also used, but in this case,
type of DRC is given in Figure 1-2. This hypothetical it refers to a dose that produces an effect that is 50%
experiment is designed to establish the DRC for loss of of the maximum effect that the drug causes at its most
consciousness and the lethal effects (another clearly bi- effective dose.
nary variable) of a fictitious new drug Endital. In this
experiment, there are 12 groups of rats. Each group is
Drug Safety
given a different dose of endital—from 0 mg/kg, a pla-
cebo, to 110 mg/kg. The vertical axis of the graph shows When new drugs are being developed and tested, it
the percentage of rats in each group that showed the is common to establish the LD 50 and the ED 50 to
effect. The curve on the left shows how many rats lost give an idea of the safety of a drug. Obviously, the far-
consciousness, and the curve on the right shows the per- ther the lethal dose is from the effective dose, the safer
centage of rats in each group that died. the drug. The therapeutic index (TI; also known as
100
PERCENT OF ANIMALS SHOWING EFFECT

90
80 loss of
consciousness death
70
60
50
40
30
20
10 ED50 LD50
0
0 10 20 30 40 50 60 70 80 90 100 110
DOSE mg/kg
FIGURE 1-2 Results of a hypothetical experiment using
12 groups of rats. Each group was given a different dose
of enditol, ranging from 0.0 (a placebo) to 110 mg/kg. One
curve shows the percentage of animals in each group that
lost consciousness; the other curve shows the percentage that
died at each dose. The ED50 and the LD50 are also indicated.
the therapeutic ratio) is sometimes used to describe the would be the same as that of LSD if you increased the
safety of a drug. This is the ratio of the LD50 to the dose of lysergic acid amide by a factor of 10—LSD is
ED50; TI = LD50/ED50. The higher the TI, the safer 10 times more potent than lysergic acid amide.
the drug. The TI of endital calculated from Figure 1-2 Effectiveness refers to differences in the maximum
would be 84/35 = 2.4. effect that drugs will produce at any dose. Both aspirin
Drug safety may also be described as a ratio of the and morphine are analgesics or painkillers. When dealing
ED99 and the LD1. with severe pain, aspirin at its most effective dose is not
as effective as morphine. To compare these two drugs in
terms of potency would not be appropriate. They both
POTENCY AND EFFECTIVENESS might produce analgesia at the same dose and, thus, be
equally potent, but the extent of the analgesia would
Potency and effectiveness (or efficacy) are terms that are
be vastly different. The difference between potency and
sometimes used to describe the extent of a drug’s effect.
effectiveness is shown in Figure 1-3.
The two terms do not mean the same thing. When you
are comparing two drugs that have the same effect, po-
tency refers to differences in the ED50 of the two drugs.
PRIMARY EFFECTS AND SIDE EFFECTS
The drug with the lower ED50 is more potent. For ex-
ample, if you constructed two DRCs for LSD and lyser- It is generally accepted that no drug has only one effect.
gic acid amide (a related hallucinogen found in morning In most cases, however, only one effect of a drug is
glory seeds) for the ability to cause hallucinations, you wanted, and other effects are not wanted. It is common
would find that the ED50 of lysergic acid amide is 10 to call the effect for which a drug is taken the primary
times higher than that of LSD. In other words, the or main effect and any other effect a side effect. If a drug
nature and extent of the effect of lysergic acid amide is taken to treat a disease symptom, that is its primary
100% 100%
Drug A Drug B Drug C
Drug D
Response
Response
0 5 10 15 0 5 10 15
Dose Dose
FIGURE 1-3 Left: Drugs A and B are equally effective, but the potency of Drug
A is greater than that of Drug B. Right: Drugs C and D are equally potent, but the
effectiveness of Drug C is greater than that of Drug D.
effect. Anything else it might do, harmful or otherwise, is established by plotting two DRCs: one DRC for the drug
is a side effect. alone and a second DRC for the drug in the presence of the
Very often, the distinction between the two is ar- other drug. If the DRC for the first drug is shifted to the
bitrary. Aspirin, for example, has several physiological right (i.e., the ED50 increases) by adding the new drug, this
effects: It brings down fever, it reduces swelling and in- result indicates antagonism between the drugs.
flammation, and it slows the blood’s ability to clot. If you If adding the new drug shifts the DRC to the left (i.e.,
take aspirin because you have a high temperature, the the ED50 decreases), the drugs are said to have an addi-
temperature-reducing effect is the primary effect, and the tive effect. If drugs have an effect together that is greater
other two are side effects. The inhibition of blood clot- than might be expected simply by combining their ef-
ting is a potentially harmful effect because it can cause fects, a superadditive effect, or potentiation, exists. This
bleeding into the stomach, which can have serious conse- can be particularly dangerous if the drugs’ effects include
quences for some people. But this anticlotting effect can respiratory depression, as is the case with alcohol and
be useful. Strokes are caused by a clot of blood getting tranquilizing drugs (barbiturates). It is not always obvi-
caught in the brain. It has been shown that taking low- ous whether a drug interaction is additive or superaddi-
dose aspirin every day can reduce the chances of stroke tive, but in one situation the distinction is clear: If one
in people at risk. In this case, the anticlotting effect would drug has no effect alone but increases the effect of a sec-
be the primary effect, and any other effects that the aspi- ond drug, potentiation is clearly occurring.
rin might be having would be the side effects. In these examples, drug interaction is defined in
When new behaviorally active drugs are developed to terms of shifts in the DRC indicated by changes in the
treat diseases, the ability of a drug to be abused or to create ED50, that is, changes in potency, but interactions may
an addiction is considered a dangerous side effect. To a drug also change the effectiveness of drugs. That is, the ED50
user, however, this psychological effect of the drug is vitally may not change, but the maximum effect may increase or
important, and any other effects the drug may have on the decrease (see Figure 1-4).
body are considered unimportant or undesirable side effects.
PHARMACOKINETICS
DRUG INTERACTIONS
The study of how drugs move into, get around in, and
When two drugs are mixed together, their effects can inter- are eliminated from the body is called pharmacokinet-
act in several ways. If one drug diminishes the effect of an- ics. The pharmacokinetics of a drug can be described
other, this interaction is called antagonism. Drug antagonism in three processes: absorption, how a drug gets into
Potentiation Antagonism
B A C
Response 50%
Dose
FIGURE 1-4 Drug interactions. The curve labeled A is the dose–
response curve (DRC) for a drug, against which the effects of the
addition of other drugs will be compared. The curve labeled B shows
the DRC after the administration of a second drug. Note that the
DRC has been shifted to the left and the ED50 has decreased. This
indicates potentiation or an additive effect. Curve C is the DRC after
another drug has been given. This drug has shifted the DRC to the
right, increasing the ED50. This indicates antagonism. Curve D shows
the effect of another drug on the DRC. In this case the DRC has been
shifted to the right, showing a decrease of potency, and the maximum
effect has also been reduced showing a decrease in effectiveness.
the blood; distribution, where it goes in the body; and A route of administration refers to the method used
elimination, how the drug leaves the body. to get a drug from outside the body to some place un-
Drugs do not have an effect on all body tissues. As der the skin. Some substances can be directly absorbed
a matter of fact, most drugs influence the operation through the skin, but most are not. Getting drugs
of the body only at specific and limited places, called into the body can be accomplished by taking advantage
sites of action. A drug may get into the body, but it of the body’s natural mechanisms for taking substances
will have no effect unless it gets to its site of action inside itself (such as digestion, breathing, or absorption
where it will interact with the cell to change the through mucous membranes), or the drug can be artifi-
cell’s biochemical processes. It is, therefore, impor- cially placed under the skin by means of injection.
tant to understand how drugs get from their place
of administration to the place where they act (i.e., Parenteral Routes of Administration
pharmacokinetics).
Parenteral routes of administration involve injection
through the skin into various parts of the body, using a
ROUTES OF ADMINISTRATION hollow needle and syringe. Parenteral routes are further
Some foods and medications may contain large amounts subdivided, depending on the specific point in the body
of valuable nourishment and medicine, but simply where the drug is to be left by the needle.
swallowing them or otherwise putting them into the
body is no guarantee that they will get to their site of VEHICLE. Before a drug can be injected, it must be in
action and have the desired effect. It is also true that the a form that can pass through a syringe and needle—
way a substance is administered can determine not only that is, it must be liquid. Because most drugs are in
whether it gets to its site of action but also how fast it a dry powder or crystalline form (the word drug is de-
gets there and how much of it gets there. rived from the French drogue, meaning dry powder), it is
necessary to dissolve or suspend a drug in some liquid injection, the muscle must be fairly large, so i.m. injec-
before it can be injected. This liquid is called a vehicle. tions are seldom given to rats and mice. They are more
Most behaviorally active drugs tend to dissolve well in frequently given to monkeys. This route of administra-
water and remain stable for long periods of time in wa- tion is common for pigeons as well; the injection is given
ter solution. Pure water is not totally inert with respect into the large breast muscle. Drugs administered i.m.
to the physiology of the body, so a weak salt solution is are typically absorbed through the muscle’s capillaries
used instead. Because body fluids contain dissolved salts, within about an hour.
the most common vehicle is normal or physiological saline,
a solution of 0.9% sodium chloride (ordinary table salt), INTRAPERITONEAL. The abbreviation for the
which matches body fluids in concentration and does intraperitoneal route is i.p., and, as the name suggests, the
not irritate the tissues when it is injected as pure water needle is inserted directly into the peritoneal cavity. The
would. peritoneum is the sack containing the visceral organs,
In some cases, the drug to be injected does not dis- such as the intestines, liver, and spleen. The aim of an
solve in water. The primary active ingredient in mari- i.p. injection is to insert the needle through the stomach
juana, tetrahydrocannabinol (THC), is an example of muscle and inject the drug into the cavity that surrounds
such a drug; it requires a different vehicle, such as veg- the viscera. It is not desirable to inject the drug directly
etable oil (see Chapter 14). Administering lipid-soluble into the stomach or any of the other organs. Doing so
drugs in an oil vehicle slows the rate of absorption, pro- could be harmful and cause hemorrhaging and death. At
longing the drug’s effects over several days. the very least, injection into an organ is likely to alter the
When a drug is in liquid form and the syringe is reaction to the drug.
filled, the needle can be inserted into various places in Intraperitoneal injections are commonly used with
the body, and the drug and vehicle are then injected to rats and mice because they are easy and safe and cause the
form a small bubble, or bolus. There are four common animals very little discomfort. They are much less conve-
parenteral routes, depending on the site where the bolus nient in larger animals and are almost never given to hu-
containing the drug is to be placed: (a) subcutaneous, mans. At one time, rabies vaccine was commonly given to
(b) intramuscular, (c) intraperitoneal, and (d) intravenous. humans via this route, but this is no longer the case.
SUBCUTANEOUS. In published material, the term INTRAVENOUS. In an intravenous (i.v.) injection, the
subcutaneous is frequently abbreviated s.c. In jargon, it is needle is inserted into a vein, and the drug is injected di-
called sub-q. As the name suggests, in this route of ad- rectly into the bloodstream. This procedure is more pop-
ministration, the drug is injected to form a bolus just ularly known as mainlining. Before an i.v. injection can
under the skin or cutaneous tissue. In most laboratory be given, it is necessary to find a vein that comes close
animals, the injection is usually made into the loose enough to the surface of the skin that it can be pierced
skin on the back, between the shoulders. For medical with a needle. In humans, this is usually the vein on the
purposes in humans, s.c. injections are usually done un- inside of the elbow. The most common procedure is to
der the skin of the arm or thigh, but the hand or wrist wrap a tourniquet around the upper arm between the
is sometimes used to self-administer recreational drugs injection site and the heart. Because veins carry blood to-
such as heroin, a procedure referred to as skin popping. ward the heart, the tourniquet will dilate or enlarge the
Some drugs, including contraceptives, may be manufac- vein at the injection site and make injection easier.
tured as pellets for s.c. implantation, which prolongs ab- When the end of the needle is inserted into the vein,
sorption, sometimes for years. the tourniquet is removed, and the drug is injected when
normal blood flow has resumed. This is essentially the
INTRAMUSCULAR. In the intramuscular (i.m.) route, reverse of the procedure used when blood is removed for
the needle is inserted into a muscle, and a bolus is left a blood test. When a drug is administered i.v., it gets dis-
there. In humans, the most common muscle used for this tributed throughout the body very quickly, reaching the
purpose is the deltoid muscle of the upper arm or the glu- brain in a matter of seconds and producing rapid effects.
teus maximus muscle of the buttock. To receive such an One difficulty with i.v. injections, however, is that a vein
cannot be used too frequently or it will collapse and sim- cannula. A cannula is like a catheter, except it is a rigid
ply stop carrying blood. When veins have collapsed in tube resembling a hypodermic needle. Cannulae are of-
the arms, other veins in the wrists, hands, and feet may ten attached to the animal’s skull using dental cement
be used, but they are more difficult to strike accurately and can remain permanently implanted.
with a needle. Another problem is that recreational
drugs may contain contaminants that are insoluble (do ABSORPTION FROM
not dissolve) and, once in the bloodstream, become
PARENTERAL SITES
lodged in and cause damage to small blood vessels in or-
gans such as the lungs or eyes. With intravenous injections, the drug is put directly
In laboratory animals, i.v. injections are not com- into the blood, but when other sites are used, the drug
monly used by behavioral pharmacologists because must be absorbed into the circulatory system. The rate
veins close to the surface of the skin are unusual in rats, at which a drug gets into the blood from an injection site
mice, and pigeons, and the procedure is not easy in unre- is determined by a number of factors associated with
strained animals. Fur and feathers also make the location blood flow to the area. Generally, the volume of blood
of such veins difficult to find. When i.v. injections are flow is greater to the peritoneal cavity than to the mus-
necessary, they are usually accomplished by means of a cles, and it is greater to the muscles than under the skin.
permanently implanted catheter. A catheter is a tube that As a result, absorption is fastest from an i.p. injection
is surgically implanted into the body. One end of the tube and slowest from an s.c. injection.
is at a site inside the body, and the other end is outside. Heat and exercise can speed absorption from i.m.
In rodents and monkeys, venous (in a vein) catheters and s.c. sites because such factors increase blood flow
are usually inserted in the jugular vein in the neck, and to muscles and skin. Thus, an i.m. injection will be ab-
the free end of the tube emerges from the animal’s back. sorbed faster if the muscle is exercised after the injection,
When an intravenous injection is required, the syringe is and the drug from a subcutaneous site will get into the
attached to the end of the catheter outside the body, and blood faster if heat is applied to the area and more slowly
the drug is injected. Researchers frequently use this type if the area is chilled.
of preparation to study self-administration of drugs by To be absorbed into the bloodstream, a drug must
animals (the catheter may be attached to a motor-driven pass through the walls of the capillaries. A capillary is a
pump that the animal can control by pressing a lever; see tiny vessel through which blood flows. Capillaries per-
Chapter 5). Intravenous catheters are fairly permanent meate most body tissues. They are so small in diameter
and may last for months before they have to be replaced. that red blood cells can barely pass through. It is through
the walls of capillaries that nutrients and oxygen pass
OTHER PARENTERAL ROUTES. Experimental re- out of the blood into body tissues, and it is also through
search with laboratory animals sometimes involves these capillary walls that waste products and carbon di-
injections directly into the central nervous system oxide pass into the blood and are removed. Blood leaves
(the brain and spinal cord; see Chapter 4). In intrathe- the heart and is distributed around the body in arteries.
cal injections, for example, the needle is inserted into The arteries divide into smaller and smaller branches
the nervous system between the base of the skull and until they become capillaries. The blood in capillaries is
the first vertebra. The drug is left in the cerebrospinal eventually collected in veins, which carry the blood back
fluid (CSF; the fluid that bathes the nervous system) to the heart and the lungs (see Figure 1-5).
and quickly diffuses throughout the nervous system. The walls of the capillaries are made up of a single
A drug may also reach the CSF through an intracere- layer of cells. Between these cells are small openings,
broventricular injection directly into one of the brain’s or pores, through which nutrients, waste products, and
ventricles, which are chambers filled with CSF. To more drugs may pass freely. The only substances in the blood
precisely determine drug effects on specific areas of the that cannot move in and out of the capillaries through
brain, intracerebral injections may be used in which a these pores are red blood cells and large protein mol-
drug is administered directly into brain tissue. These ecules, which are trapped inside because they are larger
forms of drug administration are often done through a than the pores.
Capillaries of
Anterior
head and
vena cava
forelimbs
Pulmonary
artery Pulmonary
artery
Aorta
Capillaries Capillaries
of right lung of left lung
Pulmonary Pulmonary
vein vein
Right atrium Left atrium
Left ventricle
Right ventricle
Posterior Aorta
vena cava
Capillaries of
abdominal organs
and hind limbs
FIGURE 1-5 Circulatory system.
Injected drugs pass into capillaries and the blood- evenly throughout the tub of water. The same prin-
stream through these pores by simple diffusion. Diffu- ciple determines that a drug injected into a muscle or
sion is the process by which a substance tends to move under the skin will move from the area of high con-
from an area of high concentration to an area of low centration (the bolus at the site of the injection) into
concentration until the concentrations are equal in the blood, an area of low concentration, until the con-
both areas. If a drop of food coloring is placed in the centrations in the two places are equal. The drug from
corner of a tub of still water, it will remain as a highly an injection site will move through the pores into the
colored drop for only a short period of time. The blood in the capillaries surrounding the injection site.
force of diffusion will soon distribute the coloring Because this blood is constantly circulating and being
replaced by new blood with a low concentration of INHALATION

drug, more will be absorbed as the blood circulates
through the area. Gases
Areas that are serviced by many capillaries will absorb Every cell in the body requires oxygen and gives off carbon
drugs faster than areas that have few capillaries. Because dioxide as a waste product. The body has developed a very
muscles use more oxygen, they have a richer capillary efficient system for absorbing gases from the air (that is,
supply than the skin; for this reason, absorption into the the lungs) and distributing them quickly and completely
blood is faster from i.m. injections than from s.c. injec- throughout the body (that is, the circulatory system).
tions. Drugs injected into the peritoneum have access to When drugs in the form of gases, vapors, or fine mists
an even greater number of capillaries; consequently, i.p. are breathed into the lungs, this system gets them into the
injections are absorbed even more rapidly. blood very rapidly.
Absorption through capillary walls is not a factor The lungs are an extremely efficient gas exchange
in intravenous injections because the drug is placed di-
system. Their inside surface is convoluted and contains
rectly into the blood. Blood in the veins is transported to
many pockets of air so that the total surface area exposed
the heart and then redistributed around the body after
to the air is very large. This entire area is richly supplied
a short detour through the lungs (see Figure 1-5). The
with blood by capillaries, which are close to the surface.
body has about 6 liters of blood, and the heart pumps
When a gas or fumes of volatile substances (substances
these 6 liters once a minute, so the drug in most i.v. in-
jections is distributed around the body about a minute that evaporate rapidly, such as solvents) are inhaled, they
after injection. are very quickly absorbed through the capillary walls and
enter the circulating blood.
Depot Injections Figure 1-5 shows the circulation to and from the
lungs. After blood returns to the heart through the veins,
Some drugs need to be taken continuously or chroni- it is pumped directly to the lungs. Here the carbon di-
cally to prevent the symptoms of a disease or disor- oxide is released from the blood into the air, and oxygen
der from reappearing. The antipsychotic drugs (see in the lungs is absorbed into the blood. The blood then
Chapter 12) are examples of drugs that sometimes returns directly to the heart and is pumped around the
need to be taken continuously for many years. Often body. One of the main arteries from the heart goes di-
people do not like to take these drugs and do not con-
rectly to the brain. Consequently, drugs dissolved in the
tinue to use them after release from a hospital. As a
blood in the lungs are delivered very quickly to the brain
result, they are readmitted regularly with recurring
without having to pass through the liver first, where
psychotic symptoms. It is possible to give these people
some metabolism takes place.
depot injections—the drug is dissolved in a high con-
The principle that governs the movement of gases
centration in a viscous oil (often sesame oil), which
from inhaled air into the blood and from the blood
is then injected into a muscle, usually in the buttock.
The drug then slowly diffuses from the oil into the into the air within the lungs is diffusion. Gases move
body fluids over a long period of time. A single de- from areas of high concentration to areas of low
pot injection of an antipsychotic drug can be effec- concentration. If the concentration of drug in the
tive as long as 4 weeks. This technique usually works inhaled air is higher than that in the blood, the drug
only with drugs that are highly lipid soluble (to be will move from the air into the blood, but the reverse
discussed shortly); otherwise, they would be released is also true; the drug passes out of the blood into the
too quickly. Fortunately, antipsychotic drugs have this air and is exhaled so that the concentration of the gas
property (Lemberger, Schildcrout, & Cuff, 1987). in the blood reflects the concentration in the gas that is
Newer formulations use more advanced techniques to breathed. Thus, the inhalation of gases provides a means
generate synthetic polymer beads that have no physi- of controlling drug levels in the blood with considerable
ological effect, but degrade slowly in the body and re- precision. This ability is one reason gases are used widely
lease constant levels of a drug over an extended period as general anesthetics, and inhalation is the favored route
of time (Fleischhacker, 2009). of administration for anesthesia. Volatile substances
can also be exhaled from the lungs, although the rate is technical problems of administration make this a cum-
determined by how rapidly the substance evaporates. bersome and unpopular route of administration in be-
havioral pharmacology. However, some researchers have
Smoke and Solids had some success in training monkeys to suck smoke or
vaporized drugs from a spout inserted into their cage.
Gases and solvent vapors are not the only substances ad-
Powdered drugs such as cocaine, heroin, and tobacco
ministered through the lungs. Drugs that occur naturally
snuff are sometimes sniffed into the nostrils. This prac-
in some plants may be administered by burning the dried
tice is known as intranasal administration or insufflation.
plant material and inhaling the smoke. Tobacco, opium,
On the street it is called snorting. What happens to the
and marijuana are traditionally ingested in this manner.
drug when given in this manner is unclear. It appears
When the dried plant material is burned, the active in-
that most of the drug sniffed in the nose is dissolved
gredient remains either in the smoke as a vapor or in tiny
in the moist mucous membranes of the nasal cavities
particles of ash that are inhaled into the lungs. When con-
and is absorbed into the blood from there. Some drug
tact is made with the moist surface of the lungs, the drug
enters the lungs, while more runs down the throat into
dissolves and diffuses into the blood. The major difference
the stomach and digestive system and may be absorbed
between smoke and gases is that the drug in the smoke par-
there. Although the nasal cavity is not as richly supplied
ticles will not revaporize after it is dissolved in the blood,
with blood as the lungs and although the area is not de-
and, consequently, it cannot be exhaled. These drugs must
signed to transport substances into the blood, it is a rea-
stay in the body until they are eliminated by other means.
sonably efficient system for getting drugs into the blood.
The problem with administration of solids and smoke
by inhalation is the susceptibility to damage of all the tis-
sues in the respiratory system. Smoke from burning mari- ORAL ADMINISTRATION
juana and tobacco contains many substances in addition
to the active drug; there are tars, hydrocarbons, and other Drugs absorbed into the body through the digestive
chemicals created by the burning process. In time, these system are taken into the mouth and swallowed—hence
substances may cause respiratory diseases such as emphy- the term per oral or per os (p.o.). Sometimes substances
sema, asthma, and lung cancer, and they may decrease the can get into the digestive system by other means. As
ability of the lungs to absorb oxygen and eliminate carbon just explained, snuff from the nostrils can get down the
dioxide from the blood. Other forms of the drug with un- throat and be swallowed.
known toxicity may also be created by the burning process. A drug may be taken into the mouth and not swal-
In addition, when most substances burn in air, carbon mon- lowed, as with chewing tobacco. Although this is tech-
oxide gas is given off. Carbon monoxide is a very toxic gas nically an oral administration, the absorption into the
because it blocks the ability of the blood to carry oxygen. body is through the buccal membranes, or mucous mem-
Sometimes, refined drugs like cocaine, heroin, meth- branes of the mouth, not the digestive system.
amphetamine, and oxycodone are administered by heat- The digestive system may also be entered via its other
ing them till they vaporize and inhaling the vapors. This end (intrarectal administration). Suppositories placed in
works the same way as inhaling smoke, but has the the rectum also cause the drug to be absorbed into the
advantage that there is no smoke involved and conse- blood. Such absorption is not as reliable as oral admin-
quently no hydrocarbons or carbon monoxide. istration, but it can be a useful method of administering
In the experimental laboratory, drugs are seldom ad- a medication when it is impossible to give it orally (e.g.,
ministered by inhalation to laboratory animals. This is when a patient or animal is unconscious or vomiting).
unfortunate because inhalation is a common method
used by humans to administer abused drugs. The major The Digestive System
difficulty is that in order to make an animal inhale After a drug is swallowed, it goes directly to the stom-
a gas or smoke, it is usually necessary to confine it in ach. The stomach churns and secretes strong acids and
a closed environment filled with gas or smoke, or the digestive enzymes to break down food pieces and turn
experimenter must make it wear some kind of helmet them into a liquid that is then released slowly into the
or face mask. The uncertainty about total dose and the intestines, where nutrients are absorbed. Drugs that are
soluble in gastric fluids and resistant to destruction by preventing the passage of water-soluble substances
digestive enzymes may be absorbed from the stomach, through the membrane. Therefore, the extent to which
but absorption is most efficient in the intestines. The a drug can get through the lining of the intestine to the
rate at which a swallowed drug will be absorbed may be blood will depend on its ability to dissolve in lipids.
determined by the speed with which it gets through the Large molecules of protein are embedded in the lipid
stomach to the intestines. Because solid food tends to be bilayer, and they have specific functions that will be de-
held in the stomach, taking a drug with a meal generally scribed in this chapter and in Chapter 4.
slows its absorption. When a drug is taken on an empty
stomach, it passes quickly into the intestines and is ab-
Lipid Solubility
sorbed rapidly.
The walls of the intestines are lined with capillaries Different drugs have different degrees of lipid solubility
to absorb nutrients from food, and these capillaries also that are usually expressed in terms of the olive oil
absorb drugs. To get to the capillaries and be absorbed partition coefficient. To test lipid solubility, equal amounts
into the blood through the pores in the capillary walls, of olive oil and water are placed in a beaker, and a fixed
the drug must first pass through the membrane of the amount of drug is mixed in. Later the oil and water are
intestinal wall, which does not have any pores. separated, and the amount of drug dissolved in each one
All body tissue is made of cells that form membranes. is measured. Drugs that are highly lipid soluble are more
Figure 1-6 shows the cross section of a typical mem- highly concentrated in the oil. Poorly lipid-soluble drugs
brane in the body, made up primarily of what is called a mostly end up in the water. This test, although not per-
lipid bilayer. Lipid is another name for fat, and the mem- fectly accurate, predicts reasonably well the degree to
brane consists of two layers of fat molecules held tightly which a drug will dissolve in fat tissue in the body.
together. Each lipid molecule has a clump of atoms at All drug molecules vary in their degree of lipid sol-
one end (the head region) and two chains of atoms at the ubility in their normal state, but when a molecule of a
other (the tail region). The lipid molecules in a mem- drug carries an electric charge, it loses its ability to dis-
brane are organized so that, in each of the two layers, the solve in lipids. Such a charged molecule is called an ion.
heads point outward, toward the intracellular fluid for Ions are unable to pass through membranes. When a
one layer and toward the extracellular fluid for the other, drug is dissolved in a liquid, some or all of its molecules
and the tails of each layer point inward, toward each become ionized. The percentage of ionized molecules
other. The heads are hydrophilic (water loving) whereas in a solution is determined by (a) whether the drug is a
the tails are hydrophobic (water repelling), thereby weak acid or a weak base, (b) whether it is dissolved in
Extracellular space
Protein
channel
Cell membrane
Carrier
proteins
Intracellular space
FIGURE 1-6 A cross section of a typical membrane. It is made up of two layers of lipid
molecules with their hydrophilic heads pointing out and their lipophilic tails pointing
inward. Embedded in this lipid bilayer are large molecules of protein that serve special
functions such as protein channels, ion pumps, and transporters.
an acid or a base, and (c) its pKa. The pKa of a drug is ionization increases as it moves toward the base end.
the pH at which half its molecules are ionized. Just the opposite is true for endital, the base. It starts
The easiest way to understand pKa is to imagine the with 100% ionization in the acids, but its percentage
following experiment with a fictional drug called dam- of ionization decreases as the solution gets more basic.
ital. A fixed amount of damital is dissolved in each of The pKa for endital is calculated in the same way as
15 bottles; each bottle contains a liquid with a different that for damital. In this case, the pKa for endital is 8.
pH, ranging from 0 to 14. A solution’s pH is a number By knowing whether a drug is an acid or a base and by
that describes the degree to which it is either an acid or a knowing its pKa, it is possible to predict the degree to
base. On this scale, 7 is completely neutral. Numbers less which it is likely to be ionized in a solution of known
than 7 indicate increasing acidity, and numbers greater pH. The pH at the lining of the intestine is about 3.5.
than 7 indicate increasing alkalinity. In Figure 1-7, we can see that damital is about 5% ion-
After we dissolve the damital in each bottle, we de- ized at this pH, and endital is completely ionized. Be-
termine the percentage of damital molecules that are cause ionized molecules are not lipid soluble and do
ionized and plot the results. As shown in Figure 1-7, the not pass through membranes, we can conclude that
pH at which half the damital molecules are ionized is 5. endital will not be very effective when taken orally,
Most drugs are either weak acids or weak bases. whereas damital will be readily absorbed.
Damital is a weak acid. If we do this experiment again Morphine is a base; its pKa is about 8. Bases are
with a drug that is a weak base, we see something dif- highly ionized in solutions with a low pH (acids), and
ferent. One line in Figure 1-7 is a plot for an imagi- the curve drops in solutions with higher pHs, so we
nary base, endital. The curve for the acid damital starts can predict (correctly) that morphine will be poorly ab-
with 0% ionization at the acid end of the scale, and sorbed from the digestive system.
100
90 pH of
intestinal damital (acid)
80
lining
PERCENT IONIZATION
endital (base)
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
pH OF SOLUTION
FIGURE 1-7 The percentage of ionized molecules in two
fictional drugs dissolved in solutions with different pHs.
Damital, a weak acid, becomes more highly ionized as the pH
becomes more basic (higher numbers). Endital is a weak base,
and it becomes more highly ionized at acid pHs. By drawing a
horizontal line at the 50% ionization level, we can determine
the pKa of each drug: damital, 5.0, and endital, 8.0. Caffeine
is a weak base with a pKa of 0.5. Try to envision what its curve
would look like on the graph. There is no significant ionization
of caffeine at any of the physiological pHs in the body.
In general, most bases like morphine are poorly ab- rate of absorption, or the drug may be fixed in a special
sorbed when taken orally, but their absorption depends substance that releases it slowly for absorption.
on their pKa. For example, caffeine is a base, but it has a The technology of transdermal administration has
pKa of 0.5. Its ionization curve drops off quickly at very greatly improved with the development of the patch tech-
low pHs; consequently, it is almost entirely nonionized nology where the drug is separated from the skin by a
at pHs encountered in the digestive system. Caffeine, special membrane that limits the rate of absorption. Using
therefore, is readily absorbed when taken orally. systems such as this, it is possible to administer a drug at
It should be pointed out that significant absorption will a constant rate and maintain a constant blood level for an
take place even if only a small percentage of molecules is not extended period of time. Nicotine patches were first de-
ionized. For example, if 97% of a drug is ionized at diges- veloped in the 1980s for the treatment of tobacco addic-
tive system pHs, only 3% will be lipid soluble, but as soon tion (see Chapter 8), but now skin patches are used for
as that percentage diffuses through the membrane and is the controlled delivery of many drugs including opioid
removed by the blood, 3% of the remaining drug loses its analgesics such as fentanyl (see Chapter 11), methylpheni-
charge, so the 97% ionization figure will stay constant for date for treating symptoms of Attention Deficit Hyperac-
the drug remaining in the digestive system. The newly non- tivity Disorder (ADHD; see Chapter 10), and hormones
ionized 3% now diffuses into the blood, and 3% more can including the contraceptive patch Ortho Evra.
lose its ionization. This process will continue until equilib-
rium is reached—that is, the concentration of nonionized
DISTRIBUTION OF DRUGS
molecules is the same on either side of the membrane. For
this reason, it is not appropriate to think that the percentage Even though most drugs get transported widely around
of nonionized drug is all that is absorbed. Rather, the per- the body by the blood, they tend to become concentrated
centage of nonionized molecules determines the number in particular places and segregated from others. This
of molecules available for absorption at any period of time process is called the distribution of a drug.
and, therefore, determines the rate of absorption. If 50% of
the molecules are not ionized, absorption will be rapid, but Lipid Solubility
if 3% are not ionized, absorption will be much slower.
It has been stressed that lipid-soluble substances can get
through membranes easily, but as the olive oil partition
TRANSDERMAL ADMINISTRATION coefficient experiment shows, this capacity also means that
highly lipid-soluble drugs tend to stay in lipids wherever
Some drugs can be absorbed through the skin. This is
they encounter them. Consequently, highly lipid-soluble
called transdermal administration. The skin is composed
drugs tend to concentrate in body fat outside the central
of several layers, but the main barrier to absorption is the
nervous system. Because few drugs have any effect in body
epidermis, the outer layer of skin. It is made up of a con-
fat, all of a drug dissolved in fat is, in effect, inactive. Very
tinuous sheet of flattened cells that are densely packed
often, the body fat acts like a sponge, absorbing a lipid-
with keratin. This layer is virtually impermeable to water
soluble drug, preventing it from reaching its site of action,
and can be penetrated only by lipid-soluble substances.
and diminishing its effect. Later, the drug is slowly released
Even then, absorption is very slow. The layer just under
back into the blood from the fat over a long period of time.
the epidermis, however, is made up of connective tissue
and serviced by capillaries; therefore, drugs applied to
Ion Trapping
areas where there is a break in the epidermis (as occurs
when there is a cut or a wound) can be absorbed. The pKa of a drug can also influence where a drug ends
Considerable research has been aimed at developing up in the body. As pointed out earlier, drugs that are
ways to make transdermal administration more effective. weak bases tend to ionize in acidic solutions, and drugs
Traditionally, a drug has been applied in ointments or that are weak acids tend to ionize in basic solutions.
salves. In this form, absorption of the drug is determined Since ionized molecules are not lipid soluble, the pKa of
entirely by the lipid solubility of the drug. In some cases, a drug can hasten or retard its absorption and excretion.
an absorption enhancer may be added to increase the This process was described earlier in the discussion of
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DANCE ON STILTS AT THE GIRLS’ UNYAGO, NIUCHI
Newala, too, suffers from the distance of its water-supply—at least

the Newala of to-day does; there was once another Newala in a lovely
valley at the foot of the plateau. I visited it and found scarcely a trace
of houses, only a Christian cemetery, with the graves of several
missionaries and their converts, remaining as a monument of its
former glories. But the surroundings are wonderfully beautiful. A
thick grove of splendid mango-trees closes in the weather-worn
crosses and headstones; behind them, combining the useful and the
agreeable, is a whole plantation of lemon-trees covered with ripe
fruit; not the small African kind, but a much larger and also juicier
imported variety, which drops into the hands of the passing traveller,
without calling for any exertion on his part. Old Newala is now under
the jurisdiction of the native pastor, Daudi, at Chingulungulu, who,
as I am on very friendly terms with him, allows me, as a matter of
course, the use of this lemon-grove during my stay at Newala.
FEET MUTILATED BY THE RAVAGES OF THE “JIGGER”
(Sarcopsylla penetrans)
The water-supply of New Newala is in the bottom of the valley,

some 1,600 feet lower down. The way is not only long and fatiguing,
but the water, when we get it, is thoroughly bad. We are suffering not
only from this, but from the fact that the arrangements at Newala are
nothing short of luxurious. We have a separate kitchen—a hut built
against the boma palisade on the right of the baraza, the interior of
which is not visible from our usual position. Our two cooks were not
long in finding this out, and they consequently do—or rather neglect
to do—what they please. In any case they do not seem to be very
particular about the boiling of our drinking-water—at least I can
attribute to no other cause certain attacks of a dysenteric nature,
from which both Knudsen and I have suffered for some time. If a
man like Omari has to be left unwatched for a moment, he is capable
of anything. Besides this complaint, we are inconvenienced by the
state of our nails, which have become as hard as glass, and crack on
the slightest provocation, and I have the additional infliction of
pimples all over me. As if all this were not enough, we have also, for
the last week been waging war against the jigger, who has found his
Eldorado in the hot sand of the Makonde plateau. Our men are seen
all day long—whenever their chronic colds and the dysentery likewise
raging among them permit—occupied in removing this scourge of
Africa from their feet and trying to prevent the disastrous
consequences of its presence. It is quite common to see natives of
this place with one or two toes missing; many have lost all their toes,
or even the whole front part of the foot, so that a well-formed leg
ends in a shapeless stump. These ravages are caused by the female of
Sarcopsylla penetrans, which bores its way under the skin and there
develops an egg-sac the size of a pea. In all books on the subject, it is
stated that one’s attention is called to the presence of this parasite by
an intolerable itching. This agrees very well with my experience, so
far as the softer parts of the sole, the spaces between and under the
toes, and the side of the foot are concerned, but if the creature
penetrates through the harder parts of the heel or ball of the foot, it
may escape even the most careful search till it has reached maturity.
Then there is no time to be lost, if the horrible ulceration, of which
we see cases by the dozen every day, is to be prevented. It is much
easier, by the way, to discover the insect on the white skin of a
European than on that of a native, on which the dark speck scarcely
shows. The four or five jiggers which, in spite of the fact that I
constantly wore high laced boots, chose my feet to settle in, were
taken out for me by the all-accomplished Knudsen, after which I
thought it advisable to wash out the cavities with corrosive
sublimate. The natives have a different sort of disinfectant—they fill
the hole with scraped roots. In a tiny Makua village on the slope of
the plateau south of Newala, we saw an old woman who had filled all
the spaces under her toe-nails with powdered roots by way of
prophylactic treatment. What will be the result, if any, who can say?
The rest of the many trifling ills which trouble our existence are
really more comic than serious. In the absence of anything else to
smoke, Knudsen and I at last opened a box of cigars procured from
the Indian store-keeper at Lindi, and tried them, with the most
distressing results. Whether they contain opium or some other
narcotic, neither of us can say, but after the tenth puff we were both
“off,” three-quarters stupefied and unspeakably wretched. Slowly we
recovered—and what happened next? Half-an-hour later we were
once more smoking these poisonous concoctions—so insatiable is the
craving for tobacco in the tropics.
Even my present attacks of fever scarcely deserve to be taken
seriously. I have had no less than three here at Newala, all of which
have run their course in an incredibly short time. In the early
afternoon, I am busy with my old natives, asking questions and
making notes. The strong midday coffee has stimulated my spirits to
an extraordinary degree, the brain is active and vigorous, and work
progresses rapidly, while a pleasant warmth pervades the whole
body. Suddenly this gives place to a violent chill, forcing me to put on
my overcoat, though it is only half-past three and the afternoon sun
is at its hottest. Now the brain no longer works with such acuteness
and logical precision; more especially does it fail me in trying to
establish the syntax of the difficult Makua language on which I have
ventured, as if I had not enough to do without it. Under the
circumstances it seems advisable to take my temperature, and I do
so, to save trouble, without leaving my seat, and while going on with
my work. On examination, I find it to be 101·48°. My tutors are
abruptly dismissed and my bed set up in the baraza; a few minutes
later I am in it and treating myself internally with hot water and
lemon-juice.
Three hours later, the thermometer marks nearly 104°, and I make
them carry me back into the tent, bed and all, as I am now perspiring
heavily, and exposure to the cold wind just beginning to blow might
mean a fatal chill. I lie still for a little while, and then find, to my
great relief, that the temperature is not rising, but rather falling. This
is about 7.30 p.m. At 8 p.m. I find, to my unbounded astonishment,
that it has fallen below 98·6°, and I feel perfectly well. I read for an
hour or two, and could very well enjoy a smoke, if I had the
wherewithal—Indian cigars being out of the question.
Having no medical training, I am at a loss to account for this state
of things. It is impossible that these transitory attacks of high fever
should be malarial; it seems more probable that they are due to a
kind of sunstroke. On consulting my note-book, I become more and
more inclined to think this is the case, for these attacks regularly
follow extreme fatigue and long exposure to strong sunshine. They at
least have the advantage of being only short interruptions to my
work, as on the following morning I am always quite fresh and fit.
My treasure of a cook is suffering from an enormous hydrocele which
makes it difficult for him to get up, and Moritz is obliged to keep in
the dark on account of his inflamed eyes. Knudsen’s cook, a raw boy
from somewhere in the bush, knows still less of cooking than Omari;
consequently Nils Knudsen himself has been promoted to the vacant
post. Finding that we had come to the end of our supplies, he began
by sending to Chingulungulu for the four sucking-pigs which we had
bought from Matola and temporarily left in his charge; and when
they came up, neatly packed in a large crate, he callously slaughtered
the biggest of them. The first joint we were thoughtless enough to
entrust for roasting to Knudsen’s mshenzi cook, and it was
consequently uneatable; but we made the rest of the animal into a
jelly which we ate with great relish after weeks of underfeeding,
consuming incredible helpings of it at both midday and evening
meals. The only drawback is a certain want of variety in the tinned
vegetables. Dr. Jäger, to whom the Geographical Commission
entrusted the provisioning of the expeditions—mine as well as his
own—because he had more time on his hands than the rest of us,
seems to have laid in a huge stock of Teltow turnips,[46] an article of
food which is all very well for occasional use, but which quickly palls
when set before one every day; and we seem to have no other tins
left. There is no help for it—we must put up with the turnips; but I
am certain that, once I am home again, I shall not touch them for ten
years to come.
Amid all these minor evils, which, after all, go to make up the
genuine flavour of Africa, there is at least one cheering touch:
Knudsen has, with the dexterity of a skilled mechanic, repaired my 9
× 12 cm. camera, at least so far that I can use it with a little care.
How, in the absence of finger-nails, he was able to accomplish such a
ticklish piece of work, having no tool but a clumsy screw-driver for
taking to pieces and putting together again the complicated
mechanism of the instantaneous shutter, is still a mystery to me; but
he did it successfully. The loss of his finger-nails shows him in a light
contrasting curiously enough with the intelligence evinced by the
above operation; though, after all, it is scarcely surprising after his
ten years’ residence in the bush. One day, at Lindi, he had occasion
to wash a dog, which must have been in need of very thorough
cleansing, for the bottle handed to our friend for the purpose had an
extremely strong smell. Having performed his task in the most
conscientious manner, he perceived with some surprise that the dog
did not appear much the better for it, and was further surprised by
finding his own nails ulcerating away in the course of the next few
days. “How was I to know that carbolic acid has to be diluted?” he
mutters indignantly, from time to time, with a troubled gaze at his
mutilated finger-tips.
Since we came to Newala we have been making excursions in all
directions through the surrounding country, in accordance with old
habit, and also because the akida Sefu did not get together the tribal
elders from whom I wanted information so speedily as he had
promised. There is, however, no harm done, as, even if seen only
from the outside, the country and people are interesting enough.
The Makonde plateau is like a large rectangular table rounded off
at the corners. Measured from the Indian Ocean to Newala, it is
about seventy-five miles long, and between the Rovuma and the
Lukuledi it averages fifty miles in breadth, so that its superficial area
is about two-thirds of that of the kingdom of Saxony. The surface,
however, is not level, but uniformly inclined from its south-western
edge to the ocean. From the upper edge, on which Newala lies, the
eye ranges for many miles east and north-east, without encountering
any obstacle, over the Makonde bush. It is a green sea, from which
here and there thick clouds of smoke rise, to show that it, too, is
inhabited by men who carry on their tillage like so many other
primitive peoples, by cutting down and burning the bush, and
manuring with the ashes. Even in the radiant light of a tropical day
such a fire is a grand sight.
Much less effective is the impression produced just now by the
great western plain as seen from the edge of the plateau. As often as
time permits, I stroll along this edge, sometimes in one direction,
sometimes in another, in the hope of finding the air clear enough to
let me enjoy the view; but I have always been disappointed.
Wherever one looks, clouds of smoke rise from the burning bush,
and the air is full of smoke and vapour. It is a pity, for under more
favourable circumstances the panorama of the whole country up to
the distant Majeje hills must be truly magnificent. It is of little use
taking photographs now, and an outline sketch gives a very poor idea
of the scenery. In one of these excursions I went out of my way to
make a personal attempt on the Makonde bush. The present edge of
the plateau is the result of a far-reaching process of destruction
through erosion and denudation. The Makonde strata are
everywhere cut into by ravines, which, though short, are hundreds of
yards in depth. In consequence of the loose stratification of these
beds, not only are the walls of these ravines nearly vertical, but their
upper end is closed by an equally steep escarpment, so that the
western edge of the Makonde plateau is hemmed in by a series of
deep, basin-like valleys. In order to get from one side of such a ravine
to the other, I cut my way through the bush with a dozen of my men.
It was a very open part, with more grass than scrub, but even so the
short stretch of less than two hundred yards was very hard work; at
the end of it the men’s calicoes were in rags and they themselves
bleeding from hundreds of scratches, while even our strong khaki
suits had not escaped scatheless.
NATIVE PATH THROUGH THE MAKONDE BUSH, NEAR

MAHUTA
I see increasing reason to believe that the view formed some time
back as to the origin of the Makonde bush is the correct one. I have
no doubt that it is not a natural product, but the result of human
occupation. Those parts of the high country where man—as a very
slight amount of practice enables the eye to perceive at once—has not
yet penetrated with axe and hoe, are still occupied by a splendid
timber forest quite able to sustain a comparison with our mixed
forests in Germany. But wherever man has once built his hut or tilled
his field, this horrible bush springs up. Every phase of this process
may be seen in the course of a couple of hours’ walk along the main
road. From the bush to right or left, one hears the sound of the axe—
not from one spot only, but from several directions at once. A few
steps further on, we can see what is taking place. The brush has been
cut down and piled up in heaps to the height of a yard or more,
between which the trunks of the large trees stand up like the last
pillars of a magnificent ruined building. These, too, present a
melancholy spectacle: the destructive Makonde have ringed them—
cut a broad strip of bark all round to ensure their dying off—and also
piled up pyramids of brush round them. Father and son, mother and
son-in-law, are chopping away perseveringly in the background—too
busy, almost, to look round at the white stranger, who usually excites
so much interest. If you pass by the same place a week later, the piles
of brushwood have disappeared and a thick layer of ashes has taken
the place of the green forest. The large trees stretch their
smouldering trunks and branches in dumb accusation to heaven—if
they have not already fallen and been more or less reduced to ashes,
perhaps only showing as a white stripe on the dark ground.
This work of destruction is carried out by the Makonde alike on the
virgin forest and on the bush which has sprung up on sites already
cultivated and deserted. In the second case they are saved the trouble
of burning the large trees, these being entirely absent in the
secondary bush.
After burning this piece of forest ground and loosening it with the
hoe, the native sows his corn and plants his vegetables. All over the
country, he goes in for bed-culture, which requires, and, in fact,
receives, the most careful attention. Weeds are nowhere tolerated in
the south of German East Africa. The crops may fail on the plains,
where droughts are frequent, but never on the plateau with its
abundant rains and heavy dews. Its fortunate inhabitants even have
the satisfaction of seeing the proud Wayao and Wamakua working
for them as labourers, driven by hunger to serve where they were
accustomed to rule.
But the light, sandy soil is soon exhausted, and would yield no
harvest the second year if cultivated twice running. This fact has
been familiar to the native for ages; consequently he provides in
time, and, while his crop is growing, prepares the next plot with axe
and firebrand. Next year he plants this with his various crops and
lets the first piece lie fallow. For a short time it remains waste and
desolate; then nature steps in to repair the destruction wrought by
man; a thousand new growths spring out of the exhausted soil, and
even the old stumps put forth fresh shoots. Next year the new growth
is up to one’s knees, and in a few years more it is that terrible,
impenetrable bush, which maintains its position till the black
occupier of the land has made the round of all the available sites and
come back to his starting point.
The Makonde are, body and soul, so to speak, one with this bush.
According to my Yao informants, indeed, their name means nothing
else but “bush people.” Their own tradition says that they have been
settled up here for a very long time, but to my surprise they laid great
stress on an original immigration. Their old homes were in the
south-east, near Mikindani and the mouth of the Rovuma, whence
their peaceful forefathers were driven by the continual raids of the
Sakalavas from Madagascar and the warlike Shirazis[47] of the coast,
to take refuge on the almost inaccessible plateau. I have studied
African ethnology for twenty years, but the fact that changes of
population in this apparently quiet and peaceable corner of the earth
could have been occasioned by outside enterprises taking place on
the high seas, was completely new to me. It is, no doubt, however,
correct.
The charming tribal legend of the Makonde—besides informing us
of other interesting matters—explains why they have to live in the
thickest of the bush and a long way from the edge of the plateau,
instead of making their permanent homes beside the purling brooks
and springs of the low country.
“The place where the tribe originated is Mahuta, on the southern
side of the plateau towards the Rovuma, where of old time there was
nothing but thick bush. Out of this bush came a man who never
washed himself or shaved his head, and who ate and drank but little.
He went out and made a human figure from the wood of a tree
growing in the open country, which he took home to his abode in the
bush and there set it upright. In the night this image came to life and
was a woman. The man and woman went down together to the
Rovuma to wash themselves. Here the woman gave birth to a still-
born child. They left that place and passed over the high land into the
valley of the Mbemkuru, where the woman had another child, which
was also born dead. Then they returned to the high bush country of
Mahuta, where the third child was born, which lived and grew up. In
course of time, the couple had many more children, and called
themselves Wamatanda. These were the ancestral stock of the
Makonde, also called Wamakonde,[48] i.e., aborigines. Their
forefather, the man from the bush, gave his children the command to
bury their dead upright, in memory of the mother of their race who
was cut out of wood and awoke to life when standing upright. He also
warned them against settling in the valleys and near large streams,
for sickness and death dwelt there. They were to make it a rule to
have their huts at least an hour’s walk from the nearest watering-
place; then their children would thrive and escape illness.”
The explanation of the name Makonde given by my informants is
somewhat different from that contained in the above legend, which I
extract from a little book (small, but packed with information), by
Pater Adams, entitled Lindi und sein Hinterland. Otherwise, my
results agree exactly with the statements of the legend. Washing?
Hapana—there is no such thing. Why should they do so? As it is, the
supply of water scarcely suffices for cooking and drinking; other
people do not wash, so why should the Makonde distinguish himself
by such needless eccentricity? As for shaving the head, the short,
woolly crop scarcely needs it,[49] so the second ancestral precept is
likewise easy enough to follow. Beyond this, however, there is
nothing ridiculous in the ancestor’s advice. I have obtained from
various local artists a fairly large number of figures carved in wood,
ranging from fifteen to twenty-three inches in height, and
representing women belonging to the great group of the Mavia,
Makonde, and Matambwe tribes. The carving is remarkably well
done and renders the female type with great accuracy, especially the
keloid ornamentation, to be described later on. As to the object and
meaning of their works the sculptors either could or (more probably)
would tell me nothing, and I was forced to content myself with the
scanty information vouchsafed by one man, who said that the figures
were merely intended to represent the nembo—the artificial
deformations of pelele, ear-discs, and keloids. The legend recorded
by Pater Adams places these figures in a new light. They must surely
be more than mere dolls; and we may even venture to assume that
they are—though the majority of present-day Makonde are probably
unaware of the fact—representations of the tribal ancestress.
The references in the legend to the descent from Mahuta to the
Rovuma, and to a journey across the highlands into the Mbekuru
valley, undoubtedly indicate the previous history of the tribe, the
travels of the ancestral pair typifying the migrations of their
descendants. The descent to the neighbouring Rovuma valley, with
its extraordinary fertility and great abundance of game, is intelligible
at a glance—but the crossing of the Lukuledi depression, the ascent
to the Rondo Plateau and the descent to the Mbemkuru, also lie
within the bounds of probability, for all these districts have exactly
the same character as the extreme south. Now, however, comes a
point of especial interest for our bacteriological age. The primitive
Makonde did not enjoy their lives in the marshy river-valleys.
Disease raged among them, and many died. It was only after they
had returned to their original home near Mahuta, that the health
conditions of these people improved. We are very apt to think of the
African as a stupid person whose ignorance of nature is only equalled
by his fear of it, and who looks on all mishaps as caused by evil
spirits and malignant natural powers. It is much more correct to
assume in this case that the people very early learnt to distinguish
districts infested with malaria from those where it is absent.
This knowledge is crystallized in the
ancestral warning against settling in the
valleys and near the great waters, the
dwelling-places of disease and death. At the
same time, for security against the hostile
Mavia south of the Rovuma, it was enacted
that every settlement must be not less than a
certain distance from the southern edge of the
plateau. Such in fact is their mode of life at the
present day. It is not such a bad one, and
certainly they are both safer and more
comfortable than the Makua, the recent
intruders from the south, who have made USUAL METHOD OF
good their footing on the western edge of the CLOSING HUT-DOOR
plateau, extending over a fairly wide belt of
country. Neither Makua nor Makonde show in their dwellings
anything of the size and comeliness of the Yao houses in the plain,
especially at Masasi, Chingulungulu and Zuza’s. Jumbe Chauro, a
Makonde hamlet not far from Newala, on the road to Mahuta, is the
most important settlement of the tribe I have yet seen, and has fairly
spacious huts. But how slovenly is their construction compared with
the palatial residences of the elephant-hunters living in the plain.
The roofs are still more untidy than in the general run of huts during
the dry season, the walls show here and there the scanty beginnings
or the lamentable remains of the mud plastering, and the interior is a
veritable dog-kennel; dirt, dust and disorder everywhere. A few huts
only show any attempt at division into rooms, and this consists
merely of very roughly-made bamboo partitions. In one point alone
have I noticed any indication of progress—in the method of fastening
the door. Houses all over the south are secured in a simple but
ingenious manner. The door consists of a set of stout pieces of wood
or bamboo, tied with bark-string to two cross-pieces, and moving in
two grooves round one of the door-posts, so as to open inwards. If
the owner wishes to leave home, he takes two logs as thick as a man’s
upper arm and about a yard long. One of these is placed obliquely
against the middle of the door from the inside, so as to form an angle
of from 60° to 75° with the ground. He then places the second piece
horizontally across the first, pressing it downward with all his might.
It is kept in place by two strong posts planted in the ground a few
inches inside the door. This fastening is absolutely safe, but of course
cannot be applied to both doors at once, otherwise how could the
owner leave or enter his house? I have not yet succeeded in finding
out how the back door is fastened.
MAKONDE LOCK AND KEY AT JUMBE CHAURO

This is the general way of closing a house. The Makonde at Jumbe
Chauro, however, have a much more complicated, solid and original
one. Here, too, the door is as already described, except that there is
only one post on the inside, standing by itself about six inches from
one side of the doorway. Opposite this post is a hole in the wall just
large enough to admit a man’s arm. The door is closed inside by a
large wooden bolt passing through a hole in this post and pressing
with its free end against the door. The other end has three holes into
which fit three pegs running in vertical grooves inside the post. The
door is opened with a wooden key about a foot long, somewhat
curved and sloped off at the butt; the other end has three pegs
corresponding to the holes, in the bolt, so that, when it is thrust
through the hole in the wall and inserted into the rectangular
opening in the post, the pegs can be lifted and the bolt drawn out.[50]
MODE OF INSERTING THE KEY
With no small pride first one householder and then a second

showed me on the spot the action of this greatest invention of the
Makonde Highlands. To both with an admiring exclamation of
“Vizuri sana!” (“Very fine!”). I expressed the wish to take back these
marvels with me to Ulaya, to show the Wazungu what clever fellows
the Makonde are. Scarcely five minutes after my return to camp at
Newala, the two men came up sweating under the weight of two
heavy logs which they laid down at my feet, handing over at the same
time the keys of the fallen fortress. Arguing, logically enough, that if
the key was wanted, the lock would be wanted with it, they had taken
their axes and chopped down the posts—as it never occurred to them
to dig them out of the ground and so bring them intact. Thus I have
two badly damaged specimens, and the owners, instead of praise,
come in for a blowing-up.
The Makua huts in the environs of Newala are especially
miserable; their more than slovenly construction reminds one of the
temporary erections of the Makua at Hatia’s, though the people here
have not been concerned in a war. It must therefore be due to
congenital idleness, or else to the absence of a powerful chief. Even
the baraza at Mlipa’s, a short hour’s walk south-east of Newala,
shares in this general neglect. While public buildings in this country
are usually looked after more or less carefully, this is in evident
danger of being blown over by the first strong easterly gale. The only
attractive object in this whole district is the grave of the late chief
Mlipa. I visited it in the morning, while the sun was still trying with
partial success to break through the rolling mists, and the circular
grove of tall euphorbias, which, with a broken pot, is all that marks
the old king’s resting-place, impressed one with a touch of pathos.
Even my very materially-minded carriers seemed to feel something
of the sort, for instead of their usual ribald songs, they chanted
solemnly, as we marched on through the dense green of the Makonde
bush:—
“We shall arrive with the great master; we stand in a row and have
no fear about getting our food and our money from the Serkali (the
Government). We are not afraid; we are going along with the great
master, the lion; we are going down to the coast and back.”
With regard to the characteristic features of the various tribes here
on the western edge of the plateau, I can arrive at no other
conclusion than the one already come to in the plain, viz., that it is
impossible for anyone but a trained anthropologist to assign any
given individual at once to his proper tribe. In fact, I think that even
an anthropological specialist, after the most careful examination,
might find it a difficult task to decide. The whole congeries of peoples
collected in the region bounded on the west by the great Central
African rift, Tanganyika and Nyasa, and on the east by the Indian
Ocean, are closely related to each other—some of their languages are
only distinguished from one another as dialects of the same speech,
and no doubt all the tribes present the same shape of skull and
structure of skeleton. Thus, surely, there can be no very striking
differences in outward appearance.
Even did such exist, I should have no time
to concern myself with them, for day after day,
I have to see or hear, as the case may be—in
any case to grasp and record—an
extraordinary number of ethnographic
phenomena. I am almost disposed to think it
fortunate that some departments of inquiry, at
least, are barred by external circumstances.
Chief among these is the subject of iron-
working. We are apt to think of Africa as a
country where iron ore is everywhere, so to
speak, to be picked up by the roadside, and
where it would be quite surprising if the
inhabitants had not learnt to smelt the
material ready to their hand. In fact, the
knowledge of this art ranges all over the
continent, from the Kabyles in the north to the
Kafirs in the south. Here between the Rovuma
and the Lukuledi the conditions are not so
favourable. According to the statements of the
Makonde, neither ironstone nor any other
form of iron ore is known to them. They have
not therefore advanced to the art of smelting
the metal, but have hitherto bought all their
THE ANCESTRESS OF
THE MAKONDE
iron implements from neighbouring tribes.
Even in the plain the inhabitants are not much
better off. Only one man now living is said to
understand the art of smelting iron. This old fundi lives close to
Huwe, that isolated, steep-sided block of granite which rises out of
the green solitude between Masasi and Chingulungulu, and whose
jagged and splintered top meets the traveller’s eye everywhere. While
still at Masasi I wished to see this man at work, but was told that,
frightened by the rising, he had retired across the Rovuma, though
he would soon return. All subsequent inquiries as to whether the
fundi had come back met with the genuine African answer, “Bado”
(“Not yet”).
BRAZIER
Some consolation was afforded me by a brassfounder, whom I

came across in the bush near Akundonde’s. This man is the favourite
of women, and therefore no doubt of the gods; he welds the glittering
brass rods purchased at the coast into those massive, heavy rings
which, on the wrists and ankles of the local fair ones, continually give
me fresh food for admiration. Like every decent master-craftsman he
had all his tools with him, consisting of a pair of bellows, three
crucibles and a hammer—nothing more, apparently. He was quite
willing to show his skill, and in a twinkling had fixed his bellows on
the ground. They are simply two goat-skins, taken off whole, the four
legs being closed by knots, while the upper opening, intended to
admit the air, is kept stretched by two pieces of wood. At the lower
end of the skin a smaller opening is left into which a wooden tube is
stuck. The fundi has quickly borrowed a heap of wood-embers from
the nearest hut; he then fixes the free ends of the two tubes into an
earthen pipe, and clamps them to the ground by means of a bent
piece of wood. Now he fills one of his small clay crucibles, the dross
on which shows that they have been long in use, with the yellow
material, places it in the midst of the embers, which, at present are
only faintly glimmering, and begins his work. In quick alternation
the smith’s two hands move up and down with the open ends of the
bellows; as he raises his hand he holds the slit wide open, so as to let
the air enter the skin bag unhindered. In pressing it down he closes
the bag, and the air puffs through the bamboo tube and clay pipe into
the fire, which quickly burns up. The smith, however, does not keep
on with this work, but beckons to another man, who relieves him at
the bellows, while he takes some more tools out of a large skin pouch
carried on his back. I look on in wonder as, with a smooth round
stick about the thickness of a finger, he bores a few vertical holes into
the clean sand of the soil. This should not be difficult, yet the man
seems to be taking great pains over it. Then he fastens down to the
ground, with a couple of wooden clamps, a neat little trough made by
splitting a joint of bamboo in half, so that the ends are closed by the
two knots. At last the yellow metal has attained the right consistency,
and the fundi lifts the crucible from the fire by means of two sticks
split at the end to serve as tongs. A short swift turn to the left—a
tilting of the crucible—and the molten brass, hissing and giving forth
clouds of smoke, flows first into the bamboo mould and then into the
holes in the ground.
The technique of this backwoods craftsman may not be very far
advanced, but it cannot be denied that he knows how to obtain an
adequate result by the simplest means. The ladies of highest rank in
this country—that is to say, those who can afford it, wear two kinds
of these massive brass rings, one cylindrical, the other semicircular
in section. The latter are cast in the most ingenious way in the
bamboo mould, the former in the circular hole in the sand. It is quite
a simple matter for the fundi to fit these bars to the limbs of his fair
customers; with a few light strokes of his hammer he bends the
pliable brass round arm or ankle without further inconvenience to
the wearer.
SHAPING THE POT
SMOOTHING WITH MAIZE-COB
CUTTING THE EDGE

FINISHING THE BOTTOM
LAST SMOOTHING BEFORE

BURNING
FIRING THE BRUSH-PILE

LIGHTING THE FARTHER SIDE OF
THE PILE
TURNING THE RED-HOT VESSEL
NYASA WOMAN MAKING POTS AT MASASI

Pottery is an art which must always and everywhere excite the
interest of the student, just because it is so intimately connected with
the development of human culture, and because its relics are one of
the principal factors in the reconstruction of our own condition in
prehistoric times. I shall always remember with pleasure the two or
three afternoons at Masasi when Salim Matola’s mother, a slightly-
built, graceful, pleasant-looking woman, explained to me with
touching patience, by means of concrete illustrations, the ceramic art
of her people. The only implements for this primitive process were a
lump of clay in her left hand, and in the right a calabash containing
the following valuables: the fragment of a maize-cob stripped of all
its grains, a smooth, oval pebble, about the size of a pigeon’s egg, a
few chips of gourd-shell, a bamboo splinter about the length of one’s
hand, a small shell, and a bunch of some herb resembling spinach.
Nothing more. The woman scraped with the
shell a round, shallow hole in the soft, fine
sand of the soil, and, when an active young
girl had filled the calabash with water for her,
she began to knead the clay. As if by magic it
gradually assumed the shape of a rough but
already well-shaped vessel, which only wanted
a little touching up with the instruments
before mentioned. I looked out with the
MAKUA WOMAN closest attention for any indication of the use
MAKING A POT. of the potter’s wheel, in however rudimentary
SHOWS THE a form, but no—hapana (there is none). The
BEGINNINGS OF THE embryo pot stood firmly in its little
POTTER’S WHEEL
depression, and the woman walked round it in
a stooping posture, whether she was removing
small stones or similar foreign bodies with the maize-cob, smoothing
the inner or outer surface with the splinter of bamboo, or later, after
letting it dry for a day, pricking in the ornamentation with a pointed
bit of gourd-shell, or working out the bottom, or cutting the edge
with a sharp bamboo knife, or giving the last touches to the finished
vessel. This occupation of the women is infinitely toilsome, but it is
without doubt an accurate reproduction of the process in use among
our ancestors of the Neolithic and Bronze ages.
There is no doubt that the invention of pottery, an item in human
progress whose importance cannot be over-estimated, is due to
women. Rough, coarse and unfeeling, the men of the horde range
over the countryside. When the united cunning of the hunters has
succeeded in killing the game; not one of them thinks of carrying
home the spoil. A bright fire, kindled by a vigorous wielding of the
drill, is crackling beside them; the animal has been cleaned and cut
up secundum artem, and, after a slight singeing, will soon disappear
under their sharp teeth; no one all this time giving a single thought
to wife or child.
To what shifts, on the other hand, the primitive wife, and still more
the primitive mother, was put! Not even prehistoric stomachs could
endure an unvarying diet of raw food. Something or other suggested
the beneficial effect of hot water on the majority of approved but
indigestible dishes. Perhaps a neighbour had tried holding the hard
roots or tubers over the fire in a calabash filled with water—or maybe
an ostrich-egg-shell, or a hastily improvised vessel of bark. They
became much softer and more palatable than they had previously
been; but, unfortunately, the vessel could not stand the fire and got
charred on the outside. That can be remedied, thought our
ancestress, and plastered a layer of wet clay round a similar vessel.
This is an improvement; the cooking utensil remains uninjured, but
the heat of the fire has shrunk it, so that it is loose in its shell. The
next step is to detach it, so, with a firm grip and a jerk, shell and
kernel are separated, and pottery is invented. Perhaps, however, the
discovery which led to an intelligent use of the burnt-clay shell, was
made in a slightly different way. Ostrich-eggs and calabashes are not
to be found in every part of the world, but everywhere mankind has
arrived at the art of making baskets out of pliant materials, such as
bark, bast, strips of palm-leaf, supple twigs, etc. Our inventor has no
water-tight vessel provided by nature. “Never mind, let us line the
basket with clay.” This answers the purpose, but alas! the basket gets
burnt over the blazing fire, the woman watches the process of
cooking with increasing uneasiness, fearing a leak, but no leak
appears. The food, done to a turn, is eaten with peculiar relish; and
the cooking-vessel is examined, half in curiosity, half in satisfaction
at the result. The plastic clay is now hard as stone, and at the same
time looks exceedingly well, for the neat plaiting of the burnt basket
is traced all over it in a pretty pattern. Thus, simultaneously with
pottery, its ornamentation was invented.
Primitive woman has another claim to respect. It was the man,
roving abroad, who invented the art of producing fire at will, but the
woman, unable to imitate him in this, has been a Vestal from the
earliest times. Nothing gives so much trouble as the keeping alight of
the smouldering brand, and, above all, when all the men are absent
from the camp. Heavy rain-clouds gather, already the first large
drops are falling, the first gusts of the storm rage over the plain. The
little flame, a greater anxiety to the woman than her own children,
flickers unsteadily in the blast. What is to be done? A sudden thought
occurs to her, and in an instant she has constructed a primitive hut
out of strips of bark, to protect the flame against rain and wind.
This, or something very like it, was the way in which the principle
of the house was discovered; and even the most hardened misogynist
cannot fairly refuse a woman the credit of it. The protection of the
hearth-fire from the weather is the germ from which the human
dwelling was evolved. Men had little, if any share, in this forward
step, and that only at a late stage. Even at the present day, the
plastering of the housewall with clay and the manufacture of pottery
are exclusively the women’s business. These are two very significant
survivals. Our European kitchen-garden, too, is originally a woman’s
invention, and the hoe, the primitive instrument of agriculture, is,
characteristically enough, still used in this department. But the
noblest achievement which we owe to the other sex is unquestionably
the art of cookery. Roasting alone—the oldest process—is one for
which men took the hint (a very obvious one) from nature. It must
have been suggested by the scorched carcase of some animal
overtaken by the destructive forest-fires. But boiling—the process of
improving organic substances by the help of water heated to boiling-
point—is a much later discovery. It is so recent that it has not even
yet penetrated to all parts of the world. The Polynesians understand
how to steam food, that is, to cook it, neatly wrapped in leaves, in a
hole in the earth between hot stones, the air being excluded, and
(sometimes) a few drops of water sprinkled on the stones; but they
do not understand boiling.
To come back from this digression, we find that the slender Nyasa
woman has, after once more carefully examining the finished pot,
put it aside in the shade to dry. On the following day she sends me
word by her son, Salim Matola, who is always on hand, that she is
going to do the burning, and, on coming out of my house, I find her
already hard at work. She has spread on the ground a layer of very
dry sticks, about as thick as one’s thumb, has laid the pot (now of a
yellowish-grey colour) on them, and is piling brushwood round it.
My faithful Pesa mbili, the mnyampara, who has been standing by,
most obligingly, with a lighted stick, now hands it to her. Both of
them, blowing steadily, light the pile on the lee side, and, when the
flame begins to catch, on the weather side also. Soon the whole is in a
blaze, but the dry fuel is quickly consumed and the fire dies down, so
that we see the red-hot vessel rising from the ashes. The woman
turns it continually with a long stick, sometimes one way and
sometimes another, so that it may be evenly heated all over. In
twenty minutes she rolls it out of the ash-heap, takes up the bundle
of spinach, which has been lying for two days in a jar of water, and
sprinkles the red-hot clay with it. The places where the drops fall are
marked by black spots on the uniform reddish-brown surface. With a
sigh of relief, and with visible satisfaction, the woman rises to an
erect position; she is standing just in a line between me and the fire,
from which a cloud of smoke is just rising: I press the ball of my
camera, the shutter clicks—the apotheosis is achieved! Like a
priestess, representative of her inventive sex, the graceful woman
stands: at her feet the hearth-fire she has given us beside her the
invention she has devised for us, in the background the home she has
built for us.
At Newala, also, I have had the manufacture of pottery carried on
in my presence. Technically the process is better than that already
described, for here we find the beginnings of the potter’s wheel,
which does not seem to exist in the plains; at least I have seen
nothing of the sort. The artist, a frightfully stupid Makua woman, did
not make a depression in the ground to receive the pot she was about
to shape, but used instead a large potsherd. Otherwise, she went to
work in much the same way as Salim’s mother, except that she saved
herself the trouble of walking round and round her work by squatting
at her ease and letting the pot and potsherd rotate round her; this is
surely the first step towards a machine. But it does not follow that
the pot was improved by the process. It is true that it was beautifully
rounded and presented a very creditable appearance when finished,
but the numerous large and small vessels which I have seen, and, in
part, collected, in the “less advanced” districts, are no less so. We
moderns imagine that instruments of precision are necessary to
produce excellent results. Go to the prehistoric collections of our
museums and look at the pots, urns and bowls of our ancestors in the
dim ages of the past, and you will at once perceive your error.
MAKING LONGITUDINAL CUT IN
BARK
DRAWING THE BARK OFF THE LOG
REMOVING THE OUTER BARK

BEATING THE BARK
WORKING THE BARK-CLOTH AFTER BEATING, TO MAKE IT

SOFT
MANUFACTURE OF BARK-CLOTH AT NEWALA

To-day, nearly the whole population of German East Africa is
clothed in imported calico. This was not always the case; even now in
some parts of the north dressed skins are still the prevailing wear,
and in the north-western districts—east and north of Lake
Tanganyika—lies a zone where bark-cloth has not yet been
superseded. Probably not many generations have passed since such
bark fabrics and kilts of skins were the only clothing even in the
south. Even to-day, large quantities of this bright-red or drab
material are still to be found; but if we wish to see it, we must look in
the granaries and on the drying stages inside the native huts, where
it serves less ambitious uses as wrappings for those seeds and fruits
which require to be packed with special care. The salt produced at
Masasi, too, is packed for transport to a distance in large sheets of
bark-cloth. Wherever I found it in any degree possible, I studied the
process of making this cloth. The native requisitioned for the
purpose arrived, carrying a log between two and three yards long and
as thick as his thigh, and nothing else except a curiously-shaped
mallet and the usual long, sharp and pointed knife which all men and
boys wear in a belt at their backs without a sheath—horribile dictu!
[51]
Silently he squats down before me, and with two rapid cuts has
drawn a couple of circles round the log some two yards apart, and
slits the bark lengthwise between them with the point of his knife.
With evident care, he then scrapes off the outer rind all round the
log, so that in a quarter of an hour the inner red layer of the bark
shows up brightly-coloured between the two untouched ends. With
some trouble and much caution, he now loosens the bark at one end,
and opens the cylinder. He then stands up, takes hold of the free
edge with both hands, and turning it inside out, slowly but steadily
pulls it off in one piece. Now comes the troublesome work of
scraping all superfluous particles of outer bark from the outside of
the long, narrow piece of material, while the inner side is carefully
scrutinised for defective spots. At last it is ready for beating. Having
signalled to a friend, who immediately places a bowl of water beside
him, the artificer damps his sheet of bark all over, seizes his mallet,
lays one end of the stuff on the smoothest spot of the log, and
hammers away slowly but continuously. “Very simple!” I think to
myself. “Why, I could do that, too!”—but I am forced to change my
opinions a little later on; for the beating is quite an art, if the fabric is
not to be beaten to pieces. To prevent the breaking of the fibres, the
stuff is several times folded across, so as to interpose several
thicknesses between the mallet and the block. At last the required
state is reached, and the fundi seizes the sheet, still folded, by both
ends, and wrings it out, or calls an assistant to take one end while he
holds the other. The cloth produced in this way is not nearly so fine
and uniform in texture as the famous Uganda bark-cloth, but it is
quite soft, and, above all, cheap.
Now, too, I examine the mallet. My craftsman has been using the
simpler but better form of this implement, a conical block of some
hard wood, its base—the striking surface—being scored across and
across with more or less deeply-cut grooves, and the handle stuck
into a hole in the middle. The other and earlier form of mallet is
shaped in the same way, but the head is fastened by an ingenious
network of bark strips into the split bamboo serving as a handle. The
observation so often made, that ancient customs persist longest in
connection with religious ceremonies and in the life of children, here
finds confirmation. As we shall soon see, bark-cloth is still worn
during the unyago,[52] having been prepared with special solemn
ceremonies; and many a mother, if she has no other garment handy,
will still put her little one into a kilt of bark-cloth, which, after all,
looks better, besides being more in keeping with its African
surroundings, than the ridiculous bit of print from Ulaya.
MAKUA WOMEN

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Drugs & Behavior 7th Edition, (Ebook

Chapter 1 SOME BASIC PHARMACOLOGY 1

Chapter 2 BEHAVIORAL ANALYSIS OF DRUG EFFECTS 25

Chapter 3 HOW WE ADAPT TO DRUGS—TOLERANCE, SENSITIZATION,

Conditioning of Drug Effects 46

Chapter 4 NEUROPHYSIOLOGY, NEUROTRANSMITTERS,

Chapter 5 SUBSTANCE USE AND ADDICTIVE DISORDERS 96

Chapter 6 ALCOHOL 132

Chapter 7 ANXIOLYTICS AND SEDATIVE-HYPNOTICS 162

Chapter 8 TOBACCO AND NICOTINE 182

Withdrawal Symptoms 196

Chapter 9 CAFFEINE AND THE METHYLXANTHINES 209

Chapter 10 PSYCHOMOTOR STIMULANTS 228

Harmful Effects 249

Chapter 11 OPIOIDS 254

Chapter 12 ANTIPSYCHOTIC DRUGS 277

Harmful Effects 293

Chapter 13 ANTIDEPRESSANTS 294

Chapter 14 CANNABIS 312

Chapter 15 HALLUCINOGENS, PHANTASTICANTS, AND CLUB DRUGS 332

NEW TO THIS EDITION

WHAT IS A DRUG? best to think of it as a drug, but if it is consumed for

Chemical Name generic name is used throughout the world. In spite of

TABLE 1-1 Generic Name Stems of Behaviorally Active Drugs

PERCENT OF ANIMALS SHOWING EFFECT

Right atrium Left atrium

FIGURE 1-5 Circulatory system.

replaced by new blood with a low concentration of INHALATION

Newala, too, suffers from the distance of its water-supply—at least

The water-supply of New Newala is in the bottom of the valley,

NATIVE PATH THROUGH THE MAKONDE BUSH, NEAR

MAKONDE LOCK AND KEY AT JUMBE CHAURO

MODE OF INSERTING THE KEY

With no small pride first one householder and then a second

Some consolation was afforded me by a brassfounder, whom I

SMOOTHING WITH MAIZE-COB

CUTTING THE EDGE

LAST SMOOTHING BEFORE

FIRING THE BRUSH-PILE

TURNING THE RED-HOT VESSEL

NYASA WOMAN MAKING POTS AT MASASI

DRAWING THE BARK OFF THE LOG

REMOVING THE OUTER BARK

WORKING THE BARK-CLOTH AFTER BEATING, TO MAKE IT

MANUFACTURE OF BARK-CLOTH AT NEWALA

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