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206 American Scientist, Volume 94
Macroscope
© 2006 Sigma Xi, The Scientific Research Society. Reproduction
with permission only. Contact perms@amsci.org.
The Toxicity of Recreational Drugs
Robert S. Gable
T
he Shuar tribes in Ecuador have
for centuries used native plants to
induce religious intoxication and to dis
-
cipline recalcitrant children. By compari
-
son, most North Americans know little
about the mood-altering potential of the
wild vegetation around them. And those
who think they know something on this
subject are often dangerously ignorant.
Over a three-week period in 1983, for
example, 22 Marines wanting to get high
were hospitalized because they ate too
many seeds of the jimsonweed plant
(Datura stramonium), which they found
growing wild near their base, Camp
Pendleton in southern California.
A dozen seeds of jimsonweed contain
about 1 gram of atropine, 10 grams of
which can cause nausea, severe agita-
tion, dilation of pupils, hallucinations,
headache and delirium. Tribal groups in
South America refer to datura plants as
the “evil eagles.” Of approximately 150
hallucinogenic plants that are routinely
consumed around the world, those with
atropine have the most pernicious repu
-
tation—something these Marines dis
-
covered the hard way.
Toxicity Profiles
The easier way to learn about the rela-
tion between the quantity of a substance
taken and the resulting level of physi
-
ological impairment is through careful
laboratory study. The first example of
such an exercise, in 1927, used rodents.
Research toxicologist John Trevan pub
-
lished an influential paper that reported
the use of more than 900 mice to as
-
sess the lethality of, among other things,
cocaine. As he and others have since
found, a substance that is tolerated or
even beneficial in small quantities often
has harmful effects at higher levels. The
amount of a substance that produces a
beneficial effect in 50 percent of a group
of animals is called the median effective
dose. The quantity that produces mortal-
ity in 50 percent of a group of animals is
termed the median lethal dose
.
Laboratory tests with animals can
give a general picture of the potency of a
substance, but generalizing experimen
-
tal results from, say, mice to humans
is always suspect. Thus toxicologists
also use two other sources of informa
-
tion. The first is survey data collected
from poison-control centers, hospital
emergency departments and coroners’
offices. Another consists of published
clinical and forensic reports of fatalities
or near-fatalities.
But these sources, like animal studies,
have their limitations. Simply tallying
the number of people who die or who
show up at emergency rooms is, by it
-
self, meaningless because the number of
such incidents will be influenced by the
total number of people using a particular
substance, something that is impossible
to know. For example, atropine is more
toxic than alcohol, but more deaths will
be reported for alcohol than for atropine
because so many more people get drunk
than ingest jimsonweed. Furthermore,
most overdose fatalities involve the use
of two or more substances (usually in
-
cluding alcohol), situations for which the
overall toxicity is largely unknown. In
short: When psychoactive substances are
combined, all bets are off.
How then does one gauge the relative
risks of different recreational drugs? One
way is to consider the ratio of effective
dose to lethal dose. For example, a nor
-
mally healthy 70-kilogram (154-pound)
adult can achieve a relaxed affability
from approximately 33 grams of ethyl
alcohol. This effective dose can come
from two 12-ounce beers, two 5-ounce
glasses of wine or two 1.5-ounce shots
of 80-proof vodka. The median lethal
dose for such an adult is approximately
330 grams, the quantity contained in
about 20 shots of vodka. A person who
consumes that much (10 times the me
-
dian effective dose), taken within a few
minutes on an empty stomach, risks a
lethal reaction. And plenty of people
have died this way.
As far as toxicity goes, such deaths
are quite telling. Indeed, autopsy reports
from cases of fatal overdose (whether
from alcohol or some other substance)
provide key information linking death
and drug consumption. But coroners
are generally hard-pressed to determine
the size of the dose because significant
redistribution of a drug often occurs af
-
ter death, typically from tissues of solid
organs (such as the liver) into associ
-
ated blood vessels. As a result, blood
samples may show different concen
-
trations at different times after death.
Even if investigators had a valid way
to measure the concentration of a lethal
drug in a decedent’s blood, they would
still need to work backward to make a
retrospective estimate of the quantity of
the drug consumed. Although the ap
-
proximate time of death is often known,
the time the drug was taken and the rate
at which it was metabolized are not so
easily established. Lots of guesswork is
typically involved. Obviously, people
who want clean answers should not
seek information from corpses.
Alcohol is more lethal
than many other
commonly abused
substances
Robert S. Gable is an emeritus professor of psychol-
ogy at Claremont Graduate University. He received
both a doctorate in education from Harvard and a
doctorate in experimental psychology from Brandeis
in 1964. Much of his professional work has centered
on developing behavioral therapy for juvenile delin-
quents, including remote radio-frequency monitor-
ing of physiological responses. Address: Department
of Psychology, Claremont Graduate University, 150
E. 10th St., Claremont, CA 91711. Internet: Robert.
Gable@cgu.edu
2006 May–June 207
www.americanscientist.org
© 2006 Sigma Xi, The Scientific Research Society. Reproduction
with permission only. Contact perms@amsci.org.
Safety Comparison
Despite these difficulties, it is evident that
there are striking differences among psy
-
choactive substances with respect to the
lethality of a given quantity. The way a
substance is absorbed is also a critical fac
-
tor. The common routes of consumption,
from the least toxic to the most toxic (in
general), are: eating or drinking a sub
-
stance, depositing it inside the nostril,
breathing or smoking it, and injecting it
into a vein with a hypodermic syringe.
So, for example, smoking methamphet
-
amine (as is done with the increasingly
popular illicit drug “crystal meth”) is
more dangerous than ingesting it.
Once a drug enters the body, physi
-
ological reactions are determined by
many factors, such as absorption into
various tissues and the rates of elimina
-
tion and metabolism. Individuals vary
enormously in how they metabolize dif
-
ferent substances. One persons sedative
can be another person’s poison. This
variability alone introduces unavoidable
ambiguities in estimating effective and
lethal doses. Still, the wide range be-
tween different substances suggests that
they can be rank-ordered with reason
-
able confidence. One can be quite cer
-
tain, for example, that the risk of death
from ingesting psilocybin mushrooms is
less than from injecting heroin.
The most toxic recreational drugs,
such as GHB (gamma-hydroxybutyr-
ate) and heroin, have a lethal dose less
than 10 times their typical effective dose.
The largest cluster of substances has a
lethal dose that is 10 to 20 times the effec
-
tive dose: These include cocaine, MDMA
(methylenedioxymethamphetamine, of
-
ten called “ecstasy”) and alcohol. A less
toxic group of substances, requiring 20
to 80 times the effective dose to cause
death, include Rohypnol (flunitrazepam
or “roofies”) and mescaline (peyote
cactus). The least physiologically toxic
substances, those requiring 100 to 1,000
times the effective dose to cause death,
include psilocybin mushrooms and
marijuana, when ingested. I’ve found no
published cases in the English language
that document deaths from smoked mari
-
juana, so the actual lethal dose is a mys
-
tery. My surmise is that smoking mari
-
juana is more risky than eating it but still
safer than getting drunk.
Alcohol thus ranks at the danger
-
ous end of the toxicity spectrum. So
despite the fact that about 75 percent
of all adults in the United States enjoy
an occasional drink, it must be remem
-
bered that alcohol is quite toxic. Indeed,
A worshipper smokes marijuana for meditation at the Pashupatinath Hindu temple complex
in Kathmandu, Nepal (top). The authors studies of relative toxicity suggest that although this
custom is probably more dangerous than ingesting marijuana, it is far less likely than drinking
alcohol (a practice demonstrated here by actor David Niven in the 1957 remake of My Man God-
frey) to cause a sudden lethal reaction. Drinking a mere 10 times the normal amount of alcohol
within 5 or 10 minutes can prove fatal, whereas smoking or eating marijuana might require
something like 1,000 times the usual dose to cause death.
Universal/The Kobal Collection David Longstreath/AP Photo
208 American Scientist, Volume 94
© 2006 Sigma Xi, The Scientific Research Society. Reproduction
with permission only. Contact perms@amsci.org.
if alcohol were a newly formulated bev-
erage, its high toxicity and addiction
potential would surely prevent it from
being marketed as a food or drug. This
conclusion runs counter to the common
view that one’s own use of alcohol is
harmless. That mistaken impression
arises for several reasons.
First, the more frequently we experi
-
ence an event without a negative out
-
come, the lower our level of perceived
danger. For example, most of us have
not had a life-threatening traffic acci
-
dent; thus, we feel safer in a car than
in an airplane, although we are 10 to
15 times more likely to die in an auto
-
mobile accident than in a plane crash.
Similarly, most of us have not had a life-
threatening experience with alcohol, yet
statistics show that every year about 300
people die in the United States from an
alcohol overdose, and for at least twice
that number of overdose deaths, alco
-
hol is considered a contributing cause.
Second, having a sense of control
over a risky situation reduces fear. Peo
-
ple drinking alcoholic beverages believe
that they have reasonably good control
of the quantity they intend to consume.
Control of the dose of alcohol is indeed
easier than with many natural or illicit
substances where the active ingredients
are not commercially standardized. Fur
-
thermore, alcohol is often consumed in
a beverage that dilutes the alcohol to a
known degree.
Consider the following: The stomach
capacity of an average adult is about 1
liter; therefore, a person is unlikely to
overdose after drinking beer containing
5 percent alcohol. Compare this situation
to GHB (a depressant originally market-
ed in health food stores as a sleep aid),
where stomach capacity does not place
much of a limit on consumption because
the effective dose is only one or two tea
-
spoonfuls. No wonder that more than
50 percent of novice users of GHB have
experienced an overdose that included
involuntary loss of consciousness.
Another reason that alcohol is of-
ten thought to be safe is that popular
media do not routinely report fatali
-
ties from alcohol overdoses. Deaths are
usually considered newsworthy when
they involve a degree of novelty. Thus
a fatality caused by LSD or MDMA is
thought to be more interesting than
one caused by alcohol.
Other Ways to Invite Death
A simpleminded look at the ratio of
effective to lethal doses ignores many
complications, some of which are well
recognized, some rather subtle. Take,
for example, the fact that danger gen
-
erally increases with repetitive con
-
sumption. High blood levels of a drug,
without rest periods between use, tend
to heighten risk, because the affected
organs do not have sufficient time to
recover. Studies of MDMA use, for
example, show that relatively small
repeated doses result in dispropor
-
tionately large increases of MDMA in
blood plasma. Cocaine is the substance
that induces the highest rate of repeti
-
tive consumption as a result of mood
change. Heroin and alcohol come in
second and third. Also, the tendency of
a user to take a “boosterdose prema
-
turely is greater with substances that
require an hour or more to provide the
full psychological effect—during the
interim the user often assumes that
the original dose was not sufficiently
potent. This phenomenon routinely oc
-
curs with dextromethorphan (found in
cough medicines), GHB and MDMA.
Overdose quantities that are based on
acute toxicity also do not take into ac
-
count the probability that an individual
will become addicted. This probability
can be cast as a drug’s capture ratio: Of
the people who sample a particular sub
-
stance, what portion will become physi
-
ologically or psychologically dependent
on the drug for some period of time?
Heroin and methamphetamine are the
most addictive by this measure. Cocaine,
pentobarbital (a fast-acting sedative), nic
-
otine and alcohol are next, followed by
marijuana and possibly caffeine. Some
hallucinogensnotably LSD, mescaline
and psilocybin—have little or no poten
-
tial for creating dependence.
Finally, a comparison of overdose fa
-
talities does not take into account cogni
-
tive impairments and risky or aggressive
behaviors that sometimes follow drug
use. And as most people are well aware,
a substantial proportion of violent con
-
frontations, rapes, suicides, automobile
accidents and AIDS-related illnesses are
linked to alcohol intoxication.
Despite the health risks and social
costs, consciousness-altering chemi-
cals have been used for centuries in
almost all cultures. So it would be
unrealistic to expect that all types of
recreational drug use will sudden
-
ly cease. Self-management of these
substances is extremely difficult, yet
modern Western societies have not, in
general, developed positive, socially
sanctioned rituals as a means of regu-
lating the use of some of the less haz
-
ardous recreational drugs. I would
argue that we need to do that.
The
science of toxicology may provide one
step in that direction, by helping to
teach members of our society what a
lot of tribal people already know.
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Ranking psychoactive substances by their ratios of lethal dose to effective dose gives a general
picture of how likely each is to precipitate an acute fatal reaction. By this measure, many illicit
drugs are considerably safer than alcohol.
... 4 Conversely, psychedelics display no tendency for dependence or addiction. 1,5,8,13 Psychedelics have even been touted for their ability to ameliorate addiction of drugs such as tobacco and alcohol. 1 Daily use of hallucinogenic substances is not habit forming due to rapid 5-HT2A receptor downregulation, a phenomenon deemed tachyphylaxis. 1 Persistent alcoholism and nicotine addiction are linked to altered serotonergic activity in the brain and an increased 5-HT2A receptor density. 14,15 Ostensibly, psychedelic-mediated 5-HT2A receptor activation facilitates drug rehabilitation by exerting "mystical" subjective effects that promote acute enhancement in therapeutic suggestibility. ...
... They have an extremely low risk of overdose, and a lethal administration is between 100-to-1000 times an effective quantity. 13 Most undesired effects following acute administration are transient, including increases in (systolic and diastolic) blood pressure, as well as altered spatial working memory, delayed temporal perception, and slowed reaction time. 11,17 Opponents of psychedelics are often concerned with hallucinogenic effects and subsequent alterations in behavior. ...
... While there is no clinical literature investigating the effects of psychedelics on enhanced cognitive function, there is a mechanistic basis to suggest 5-HT2A receptor agonist (or partial agonist) activity plays a beneficial role in working memory. 1 Furthermore, rodents administered mescaline demonstrated robust increases in the neurotransmitter, acetylcholine. 1 It is important to emphasize that these drugs not only lack addictive potential, but also impart several qualitative effects valued amongst athletes. 8,13,27 A wealth of survey-based subjective descriptions claim enhanced focus, vitality, and productivity, lending the potential to facilitate greater training quality across all exercise modalities. 8,19,20 Lastly, psychedelics may find a supplementary role to caffeine. ...
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... rely knows what to call the bio-mechanic parts of fungi, often borrowing terms from botanical physiology, such as "stem" for the vertical fruiting body, but mushroom "stems" have no phloem, xylem, cork, cambium, or meristem cells. Yet, we fear a naturally occurring mushroom that exhibits effects on our bodies 1,000 times less harmful than alcohol. (Gable. 2006) The Iroquois have a term for the energy needed for a mushroom to push through the vegetative layer of forest floor and rise to broadcast spores, "Puhpowee". As an offering of gratefulness, any new plant or fungi therapy should be made available to any interested Native Americans. Colonization stole their pantry long ago, but we can shar ...
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As Terra Vetus Therapeutics, a not-for-profit researcher, I am seeking laboratory space and funding opportunities to develop my patents, and assist with beneficial therapeutic case studies, for review by NY State licensing, FDA, NIH, NHC, etc. #psilocybin #cannabis #honey #therapy #mushroooms # fungi #mycology
... MC has been suggested as a less harmful alternative to prescription opioids in the treatment of chronic neuropathic pain, and as a tactic to help alleviate the nationwide opioid overdose epidemic ( Collen, 2012 ). Indeed, cannabis is far less immediately dangerous to health, ratios of lethal to effective doses being > 1,0 0 0:1, which pale in comparison to alcohol (10:1) and opioids ( < 10:1) ( Gable, 2006 ). Cannabis-based products concentrated with CBD have greater (although still overall weak) evidence of efficacy for chronic, neuropathic and other noncancer pain symptoms, and may be further beneficial by exerting no psychoactive effects and counteracting those when combined with -9-THC ( Chang et al., 2021 ;Pertwee, 2014 ;Stockings et al., 2018 ). ...
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... This transition is more likely to occur with some drugs than with others, and for all drugs, it is the minority that initiates problematic use, with most individuals remaining casual, responsible users. 5,6 What leads some to transition to problematic use, whereas most others do not, is a crucial question in addiction research, and one that the medical paradigm aims to resolve by discovering the neural deficits that drive problematic use. The advent of addiction involves the development of various vulnerabilities that work to intensify and complicate drug consumption and ultimately perpetuate a seemingly intractable pattern of problematic use. ...
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... For example, according to Gable's scale the use of cannabis is over 100 times safer if overdosed than alcohol, and over 200 times safer if overdosed than heroin. Fatal cases of cannabis overdose are extremely rare, and their occurrence is often linked to using cannabis together with other psychoactive substances and/or alcohol, or sometimes linked to creating physical symptoms that interact tragically with a pre-existing medical condition = (Caulkins et al., 2012; Gable, 2006). As a result, it is often disputed that these rare cases of fatal overdosing should be attributed to cannabis, if it was not the sole cause of death. ...
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... In addition, psilocybin reportedly does not induce longterm memory impairment, delirium, or addiction (Halberstadt, 2015;Tyls et al., 2014)-on the contrary, it has actually been reported to have beneficial effects on human well-being (Griffiths, Richards, McCann, & Jesse, 2006). Finally, the ratio of lethal dose to psychoactive dose for psilocybin was estimated to be 1000:1 (Gable, 2006). ...
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This chapter focuses on the potential use of serotonergic hallucinogen psilocybin in clinical as well as experimental psychiatry, addictology, and neurology. It presents the results of recent clinical studies with psilocybin and summarizes the psychological and neurobiological aspects of its effect in specific therapeutic indications. In addition, it discusses the association between the psychotomimetic and therapeutic effects of this drug within the framework of the "entropic brain" theory.
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Över en miljon människor i Sverige har ett riskbruk, missbruk eller beroende av alkohol eller narkotika. Alkohol- och narkotikaproblem berör ofta även anhöriga, vänner och arbetskamrater. För att kunna förstå, förebygga och behandla sådana problem krävs kunskap. I denna grundläggande lärobok presenteras aktuell, forskningsbaserad kunskap på ett pedagogiskt och lättillgängligt sätt. Boken är unik i den bemärkelsen att den tar ett helhetsgrepp på alkohol- och narkotikaområdet. Författarna belyser och problematiserar drogernas effekter och skadeverkningar, tar upp hur drogproblem kan förklaras med hjälp av teorier och begrepp från olika vetenskapsområden samt beskriver de sociala och hälsomässiga konsekvenser som problematisk droganvändning kan innebära för den enskilde. Boken innehåller även en gedigen redogörelse för samhällets olika insatser på området – alkohol- och narkotikakontroll, prevention, utredning, vård- och behandling samt skadebegränsning. Ett viktigt inslag i boken är intervjuer med yrkesutövare och en brukarföreträdare, som berättar om sina egna erfarenheter av att arbeta med frågor som rör bruk, missbruk och beroende. Alkohol- och narkotikaproblem vänder sig till personer som studerar till socionom, psykolog, sjuksköterska, läkare, polis eller behandlingsassistent samt till dem som redan arbetar inom något av dessa yrken. Personer som själva har eller har haft drogproblem är också en viktig målgrupp, liksom deras anhöriga. Men boken kan även läsas av personer med ett mer allmänt intresse av alkohol- och narkotikafrågor.
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U.S. America's aggressive drug enforcement policy, costing over US$1 trillion and putting millions of people in prison for casual drug use, is an abject failure. By regulating drug use rather than criminalizing it, per capita recreational drug use in the United States would be the same or even lower than it currently is, safer for consumers, and far less costly to society in terms of socioeconomic harm. This failed policy has not only affected U.S. society in such a harmful way that it almost cannot be overstated, but it has also resulted in quite needless drug cartel violence in Mexico and other countries. Included here is a pragmatic suggestion for reform of U.S. drug policy.
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Many countries across the world are interested in natural healing products. They are less toxic products. The genus Myristica fragrans belongs to the family Myristicaceae. The various parts of the plant have been used in traditional medicine for the treatment of inflammation, vomiting, asthma, hypertension, diarrhea, polyarthritis and gout etc. In the present study, the pericarp of Myristica fragrans is extracted successfully with solvents methanol, ethanol and hexane using Soxhlet apparatus. Phytochemical screenings were performed as per the standard procedures. Alkaloids, Saponins, Phytosterols, tannins, flavonoids and proteins were identified as the major compounds. The antibacterial activities of extracts were studied for various microorganisms by broth dilution method using streptomycin as the standard drug. The methanolic and ethanolic extract of M.fragrans pericarp showed remarkable activity against Staphylococcus aurous and Salmonella typhi respectively. Based on this TLC and Column chromatography were performed on the more bioactive methanol extract. Further investigation on the structure elucidation of the bioactive compound was done using UV, IR, and GC-MS analysis. The results of the present study suggest that the extracts of M.fragrans pericarp contains compounds with antibacterial properties that can be used as antimicrobial agents for the therapy of infectious diseases caused by pathogens.
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