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Psychoactive drug A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. ...
s, such as
caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine t ...
,
amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
,
mescaline Mescaline or mescalin (3,4,5-trimethoxyphenethylamine) is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine class, known for its hallucinogenic effects comparable to those of LSD and psilocybin. Biological sou ...
,
lysergic acid diethylamide Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
(LSD),
marijuana Cannabis, also known as marijuana among other names, is a psychoactive drug from the cannabis plant. Native to Central or South Asia, the cannabis plant has been used as a drug for both recreational and entheogenic purposes and in various tra ...
,
chloral hydrate Chloral hydrate is a geminal diol with the formula . It is a colorless solid. It has limited use as a sedative and hypnotic pharmaceutical drug. It is also a useful laboratory chemical reagent and precursor. It is derived from chloral (trichl ...
,
theophylline Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
,
IBMX IBMX (3-isobutyl-1-methylxanthine), like other methylated xanthine, xanthine derivatives, is both a: # competitive non-selective phosphodiesterase inhibitor which raises intracellular Cyclic adenosine monophosphate, cAMP, activates cAMP-dependent ...
and others, can have strong effects on certain animals. It is believed that plants developed caffeine as a chemical defense against insects.


Invertebrates


Spiders

In 1948, Swiss pharmacologist Peter N. Witt started his research on the effect of drugs on spiders. The initial motivation for the study was a request from his colleague, zoologist H. M. Peters, to shift the time when garden spiders build their webs between 2 a.m. and 5 a.m., which apparently annoyed Peters, to earlier hours. Witt tested spiders with a range of psychoactive drugs, including amphetamine, mescaline, strychnine, LSD, and caffeine, and found that the drugs affect the size and shape of the web rather than the time when it is built. At small doses of caffeine (10 µg/spider), the webs were smaller; the radii were uneven, but the regularity of the circles was unaffected. At higher doses (100 µg/spider), the shape changed more, and the web design became irregular. All the drugs tested reduced web regularity except for small doses (0.1–0.3 µg) of LSD, which increased web regularity. The drugs were administered by dissolving them in sugar water, and a drop of solution was touched to the spider's mouth. In some later studies, spiders were fed with drugged flies. For qualitative studies, a well-defined volume of solution was administered through a fine syringe. The webs were photographed for the same spider before and after drugging. Witt's research was discontinued, but it became reinvigorated in 1984 after a paper by J.A. Nathanson in the journal ''
Science Science is a systematic endeavor that builds and organizes knowledge in the form of testable explanations and predictions about the universe. Science may be as old as the human species, and some of the earliest archeological evidence for ...
'', which is discussed below. In 1995, a
NASA The National Aeronautics and Space Administration (NASA ) is an independent agency of the US federal government responsible for the civil space program, aeronautics research, and space research. NASA was established in 1958, succeeding t ...
research group repeated Witt's experiments on the effect of caffeine,
benzedrine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used a ...
,
marijuana Cannabis, also known as marijuana among other names, is a psychoactive drug from the cannabis plant. Native to Central or South Asia, the cannabis plant has been used as a drug for both recreational and entheogenic purposes and in various tra ...
and
chloral hydrate Chloral hydrate is a geminal diol with the formula . It is a colorless solid. It has limited use as a sedative and hypnotic pharmaceutical drug. It is also a useful laboratory chemical reagent and precursor. It is derived from chloral (trichl ...
on
European garden spider The spider species ''Araneus diadematus'' is commonly called the European garden spider, diadem spider, orangie, cross spider, and crowned orb weaver. It is sometimes called the pumpkin spider, although this name is also used for a different spec ...
s. NASA's results were qualitatively similar to those of Witt, but the novelty was that the pattern of the spider web was quantitatively analyzed with modern statistical tools, and proposed as a sensitive method of drug detection. Also published i
''New Scientist magazine''
, on 29 April 1995


Other arthropods and molluscs

In 1984, Nathanson reported an effect of
methylxanthine Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, including caffeine, ...
s on
larvae A larva (; plural larvae ) is a distinct juvenile form many animals undergo before metamorphosis into adults. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle. The ...
of the
tobacco hornworm ''Manduca sexta'' is a moth of the family Sphingidae present through much of the Americas. The species was first described by Carl Linnaeus in his 1763 '' Centuria Insectorum''. Commonly known as the Carolina sphinx moth and the tobacco hawk m ...
. He administered solutions of finely powdered tea leaves or coffee beans to the larvae and observed, at concentrations between 0.3 and 10% for coffee and 0.1 to 3% for tea, inhibition of feeding, associated with
hyperactivity Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
and
tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...
. At higher concentrations, larvae were killed within 24 hours. He repeated the experiments with purified caffeine and concluded that the drug was responsible for the effect, and the concentration differences between coffee beans and tea leaves originated from 2–3 times higher caffeine content in the latter. Similar action was observed for
IBMX IBMX (3-isobutyl-1-methylxanthine), like other methylated xanthine, xanthine derivatives, is both a: # competitive non-selective phosphodiesterase inhibitor which raises intracellular Cyclic adenosine monophosphate, cAMP, activates cAMP-dependent ...
on mosquito larvae,
mealworm Mealworms are the larval form of the yellow mealworm beetle, ''Tenebrio molitor'', a species of darkling beetle. Like all holometabolic insects, they go through four life stages: egg, larva, pupa, and adult. Larvae typically measure about or ...
larvae,
butterfly Butterflies are insects in the macrolepidopteran clade Rhopalocera from the Order (biology), order Lepidoptera, which also includes moths. Adult butterflies have large, often brightly coloured wings, and conspicuous, fluttering flight. The ...
larvae and milkweed bug nymphs, that is, inhibition of feeding and death at higher doses.
Flour beetle Flour beetles are members of the darkling beetle genus, genera ''Tribolium (beetle), Tribolium'' or ''Tenebrio''. They are pests of cereal silos and are widely used as laboratory animals, as they are easy to keep. The flour beetles consume wheat ...
s were unaffected by IBMX up to 3% concentrations, but
long-term experiment A long-term experiment is an experimental procedure that runs through a long period of time, in order to test a hypothesis or observe a phenomenon that takes place at an extremely slow rate. What duration is considered "long" depends on the academ ...
s revealed suppression of reproductive activity. Further, Nathanson fed tobacco hornworm larvae with leaves sprayed with such psychoactive drugs as caffeine, formamidine pesticide didemethylchlordimeform (DDCDM), IBMX or
theophylline Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
. He observed a similar effect, namely inhibition of feeding followed by death. Nathanson concluded that caffeine and related methylxanthines could be natural
pesticide Pesticides are substances that are meant to control pests. This includes herbicide, insecticide, nematicide, molluscicide, piscicide, avicide, rodenticide, bactericide, insect repellent, animal repellent, microbicide, fungicide, and lampri ...
s developed by plants as protection against worms: Caffeine is found in many
plant Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...
species, with high levels in seedlings that are still developing foliage, but are lacking mechanical protection; caffeine paralyzes and kills certain
insect Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body ( head, thorax and abdomen), three pairs ...
s feeding upon the plant. High caffeine levels have also been found in the soil surrounding coffee bean seedlings. It is therefore understood that caffeine has a natural function, both as a natural pesticide and as an inhibitor of seed germination of other nearby coffee seedlings, thus giving it a better chance of survival. Coffee berry borers seem to be unaffected by caffeine, in that their feeding rate did not change when they were given leaves sprayed with caffeine solution. It was concluded that those beetles have adapted to caffeine. This study was further developed by changing the solvent for caffeine. Although aqueous caffeine solutions had indeed no effect on the beetles,
oleate Oleic acid is a fatty acid that occurs naturally in various animal and vegetable fats and oils. It is an odorless, colorless oil, although commercial samples may be yellowish. In chemical terms, oleic acid is classified as a monounsaturated omega ...
emulsions An emulsion is a mixture of two or more liquids that are normally immiscible (unmixable or unblendable) owing to liquid-liquid phase separation. Emulsions are part of a more general class of two-phase systems of matter called colloids. Althoug ...
of caffeine ''did'' inhibit their feeding, suggesting that even if certain insects have adjusted to some caffeine forms, they can be tricked by changing minor details, such as the drug solvent. These results and conclusions were confirmed by a similar study on
slug Slug, or land slug, is a common name for any apparently shell-less terrestrial gastropod mollusc. The word ''slug'' is also often used as part of the common name of any gastropod mollusc that has no shell, a very reduced shell, or only a smal ...
s and
snail A snail is, in loose terms, a shelled gastropod. The name is most often applied to land snails, terrestrial pulmonate gastropod molluscs. However, the common name ''snail'' is also used for most of the members of the molluscan class Gastro ...
s. Cabbage leaves were sprayed with caffeine solutions and fed to ''
Veronicella cubensis ''Veronicella cubensis'', common name the Cuban slug, is a species of air-breathing land slug, a terrestrial pulmonate gastropod mollusk in the family Veronicellidae, the leatherleaf slugs. Distribution This species occurs in countries and area ...
'' slugs and ''
Zonitoides arboreus ''Zonitoides arboreus'', commonly known as the quick gloss snail, is a species of small air-breathing land snail, a terrestrial pulmonate gastropod mollusk in the family Gastrodontidae. Distribution The native distribution of ''Z. arboreus'' ...
'' snails. Cabbage consumption reduced over time, followed by the death of the
molluscs Mollusca is the second-largest phylum of invertebrate animals after the Arthropoda, the members of which are known as molluscs or mollusks (). Around 85,000 extant taxon, extant species of molluscs are recognized. The number of fossil sp ...
. Inhibition of feeding by caffeine was also observed for
caterpillar Caterpillars ( ) are the larval stage of members of the order Lepidoptera (the insect order comprising butterflies and moths). As with most common names, the application of the word is arbitrary, since the larvae of sawflies (suborder Sym ...
s.


Mammals


Elephants

"Tusko" was the name of a male
Indian elephant The Indian elephant (''Elephas maximus indicus'') is one of four extant recognised subspecies of the Asian elephant and native to mainland Asia. Since 1986, the Asian elephant has been listed as Endangered on the IUCN Red List as the wild po ...
at the
Oklahoma City Oklahoma City (), officially the City of Oklahoma City, and often shortened to OKC, is the capital and largest city of the U.S. state of Oklahoma. The county seat of Oklahoma County, it ranks 20th among United States cities in population, a ...
Zoo A zoo (short for zoological garden; also called an animal park or menagerie) is a facility in which animals are kept within enclosures for public exhibition and often bred for Conservation biology, conservation purposes. The term ''zoological g ...
. On August 3, 1962, researchers from the
University of Oklahoma The University of Oklahoma (OU) is a Public university, public research university in Norman, Oklahoma. Founded in 1890, it had existed in Oklahoma Territory near Indian Territory for 17 years before the two Territories became the state of Oklahom ...
injected (human use involves oral ingestion) 297 mg of LSD to him, which is nearly three thousand times the human recreational dose. Within five minutes he collapsed to the ground and one hour and forty minutes later he died. It is believed that the LSD was the cause of his death, although some speculate that the drugs the researchers used in an attempt to revive him may have contributed to his death. In 1984 psychologist
Ronald K. Siegel Ronald Keith Siegel (January 2, 1943 – March 24, 2019) was an American psychopharmacologist who was an associate research professor in the Department of Psychiatry and Biobehavioral Sciences at the University of California, Los Angeles. Siegel ...
repeated the experiment with two elephants, using LSD only. Both survived.


Dolphins

Bottlenose dolphin Bottlenose dolphins are aquatic mammals in the genus ''Tursiops.'' They are common, cosmopolitan members of the family Delphinidae, the family of oceanic dolphins. Molecular studies show the genus definitively contains two species: the common ...
s were administered LSD in the 1960s as part of NASA-funded experiments by
John C. Lilly John Cunningham Lilly (January 6, 1915 – September 30, 2001)John C. Lilly
at
to study
human–animal communication Human–animal communication is the communication observed between humans and other animals, ranging from non-verbal cues and vocalizations to the use of language. Some human–animal communication may be observed in casual circumstances, such a ...
. The drug caused the animals to become more vocal, but did not enable meaningful communication.


Macaque monkeys

Macaque monkeys administered with the
antipsychotics Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...
and
olanzapine Olanzapine (sold under the trade name Zyprexa among others) is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is ta ...
over a 17–27 month period showed reduced brain volume. These results have not been observed in humans who also take the drug, due to the lack of available data.


Fish


Zebrafish

Zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family ( Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...
have long acted as a model for humans to test the effects of various psychoactive substances. One study conducted by the Research Society on Alcoholism concluded that when given a moderate dose of ethanol, zebrafish became more active and swam faster. When the dose of
alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...
increased, the zebrafish became sluggish. Another study by the same institute found that when a "drunk" (
blood alcohol concentration Blood alcohol content (BAC), also called blood alcohol concentration or blood alcohol level, is a measurement of alcohol intoxication used for legal or medical purposes; it is expressed as mass of alcohol per volume or mass of blood. For example ...
of over 0.1) zebrafish is introduced to a group of sober ones, the sober fish will follow the drunk individual as their leader. In a study testing the effects of THC on memory in zebrafish, researchers found that THC impairs spatial memory but has no effect on associative memory. Zebrafish were able to remember color patterns associated with them getting fed after being put under the influence of THC, but were unable to remember the spatial pattern associated with them getting fed after being put under the influence of THC. Zebrafish have also been used to test the medicinal benefits of certain psychoactive drugs, particularly how they can be used to treat mental health problems. A study looking into the
antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
properties of
ketamine Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...
using zebrafish as subjects found that when exposed to small amounts of ketamine (2 mg/L), zebrafish displayed more aggressive behavior. However, when the zebrafish were exposed to higher doses of ketamine (20 mg/L & 40 mg/L), their aggressive behavior subsided. Moreover, the highest dose of ketamine increased locomotion and circling behavior. In another study testing the behavioral effects of LSD on zebrafish found that zebrafish that were exposed to the substance demonstrated increased inter-fish distance when
shoaling In biology, any group of fish that stay together for social reasons are shoaling, and if the group is swimming in the same direction in a coordinated manner, they are schooling. In common usage, the terms are sometimes used rather loosely. Ab ...
, and had increased
cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
levels. These could show possible side effects of LSD if used as a therapeutic drug.


Nile Tilapia

A study conducted by the Aquaculture Institute looked into the effects of
cannabis oil Hash oil or cannabis oil, is an oleoresin obtained by the extraction of cannabis or hashish. It is a cannabis concentrate containing many of its resins and terpenes – in particular, tetrahydrocannabinol (THC), cannabidiol (CBD), and other ca ...
on the metabolism and immune system of the
Nile tilapia The Nile tilapia (''Oreochromis niloticus'') is a species of tilapia, a cichlid fish native to the northern half of Africa and the Levante area, including Israel, and Lebanon. Numerous introduced populations exist outside its natural range. It i ...
(''Oreochromis niloticus''). They found that
cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: ''Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternatively ...
has no measurable effect on the
white blood cell count A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and pl ...
or
plasma protein Blood-proteins, also termed plasma proteins, are proteins present in blood plasma. They serve many different functions, including transport of lipids, hormones, vitamins and minerals in activity and functioning of the immune system. Other blood pr ...
concentration, and therefore has no effect on the immune system of the Nile tilapia. However, the tilapia that were fed food pellets laced with THC demonstrated a higher food conversion rate. This higher food conversion rate lead researchers to believe that THC increases the metabolic rate of Nile tilapia.


Further reading

* Siegel, Ronald K. (1989, 2005) ''Intoxication: The Universal Drive for Mind-Altering Substances''


See also

* Rat park * Venom resistant animals


References

{{reflist, 2


External links


Nets made by spiders fed on drug-dosed flies
Effects of psychoactive drugs Animal cognition Animal testing