Psychoactive drugs, such as caffeine, amphetamine, mescaline, lysergic acid diethylamide (LSD), cannabis, chloral hydrate, theophylline, IBMX and others, can have strong effects on certain animals. It is believed that plants developed caffeine as a chemical defense against insects. [3]
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 from between 2:00 a.m. and 5:00 a.m., which was decidedly inconvenient for Peters, to earlier hours. [4] 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. [2]
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. [5] 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. [2]
Witt's research was discontinued, but it became reinvigorated in 1984 after a paper by J.A. Nathanson in the journal Science , [6] which is discussed below. In 1995, a NASA research group repeated Witt's experiments on the effect of caffeine, benzedrine, marijuana and chloral hydrate on European garden spiders. 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. [1] [7]
In 1984, Nathanson reported an effect of methylxanthines on larvae of the tobacco hornworm. 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 and tremor. 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 on mosquito larvae, mealworm larvae, butterfly larvae and milkweed bug nymphs, that is, inhibition of feeding and death at higher doses. Flour beetles were unaffected by IBMX up to 3% concentrations, but long-term experiments revealed suppression of reproductive activity. [6]
Further, Nathanson fed tobacco hornworm larvae with leaves sprayed with such psychoactive drugs as caffeine, formamidine pesticide didemethylchlordimeform (DDCDM), IBMX or theophylline. He observed a similar effect, namely inhibition of feeding followed by death. Nathanson concluded that caffeine and related methylxanthines could be natural pesticides developed by plants as protection against worms: Caffeine is found in many plant species, with high levels in seedlings that are still developing foliage, but are lacking mechanical protection; [8] caffeine paralyzes and kills certain insects feeding upon the plant. [6] 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 Biopesticide and as an inhibitor of seed germination of other nearby coffee seedlings, thus giving it a better chance of survival. [9]
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. [10] This study was further developed by changing the solvent for caffeine. Although aqueous caffeine solutions had indeed no effect on the beetles, oleate emulsions 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. [11]
These results and conclusions were confirmed by a similar study on slugs and snails. Cabbage leaves were sprayed with caffeine solutions and fed to Veronicella cubensis slugs and Zonitoides arboreus snails. Cabbage consumption reduced over time, followed by the death of the molluscs. [12] Inhibition of feeding by caffeine was also observed for caterpillars. [13]
"Tusko" was the name of a male Indian elephant at the Oklahoma City Zoo. On August 3, 1962, [14] researchers from the University of Oklahoma injected (human use involves oral ingestion) 297 mg of LSD to him, which is nearly three thousand times the human recreational dose (for an animal weighing roughly one hundred times as much as a human). [note 1] 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. [15] [16] [17] [18] [19] [20] In 1984 psychologist Ronald K. Siegel repeated the experiment with two elephants, using LSD only. Both survived. [20]
Bottlenose dolphins were administered LSD in the 1960s as part of NASA-funded experiments by John C. Lilly to study human–animal communication. The drug caused the animals to become more vocal, but did not enable meaningful communication. [21] [22] [23]
Macaque monkeys administered with the antipsychotics haloperidol and olanzapine 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. [24]
In a scientific study, researchers looked at how different drugs are self-administered by squirrel monkeys. The drugs they studied included cocaine and a few others that have some similarities to cocaine in how they affect the brain.
They trained the monkeys to give themselves these drugs through injections and observed their behavior. They wanted to see if the drugs had similar effects on the monkeys.
The results showed that cocaine and some of the other drugs had similar effects in maintaining the monkeys' self-administration behavior. However, one of the drugs, mazindol, didn't have the same effect on all the monkeys.
This suggests that the drugs that had similar effects may work in similar ways in the brain, affecting the monkeys' behavior in a comparable manner. The study also indicated that the reinforcing (addictive) and stimulating effects of these drugs might be related to how they interact with specific areas in the brain.
Overall, the research provides insights into how these drugs affect behavior and their potential for addiction. [25]
The researchers used a resident-intruder model to simulate social stress, with a focus on how social rank influenced the effects. The results showed that the confrontation influenced the monkeys' response to cocaine. When subordinate monkeys acted as intruders, their self-administration of low-dose cocaine increased, and their dose-response curve shifted to the left. In contrast, dominant monkeys experienced a decrease in cocaine self-administration and a rightward shift in the dose-response curve.
Brain glucose metabolism measurements revealed differences between dominant and subordinate monkeys, shedding light on the underlying mechanisms of these opposing behavioral effects. Dominant monkeys showed higher activity in brain regions related to visual processing, attention, and vigilance, while subordinate monkeys exhibited higher activity in areas linked to emotional processing and anxiety.
Both groups showed increased brain activity in regions associated with the reward system and stress response. Dominant monkeys also displayed higher aggression during the confrontations, suggesting that the opportunity to aggress might serve as a reinforcer.
The study indicated that the social context strongly influences behavior and drug effects, offering insights into individual differences in drug self-administration. It emphasized the need to consider the influence of social factors when developing treatments for cocaine use disorders, tailoring interventions to individuals based on their responses to social and environmental stressors. Understanding the neural and behavioral mechanisms at play in these scenarios can lead to more effective, personalized treatments for individuals with cocaine use disorders. [26]
Zebrafish 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 increased, the zebrafish became sluggish. Another study by the same institute found that when a "drunk" (blood alcohol concentration of over 0.1) zebrafish is introduced to a group of sober ones, the sober fish will follow the drunk individual as their leader. [27]
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. [28]
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. [29] A study looking into the antidepressant properties of ketamine 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. [30] 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, and had increased cortisol levels. These could show possible side effects of LSD if used as a therapeutic drug. [31]
A study conducted by the Aquaculture Institute looked into the effects of cannabis oil on the metabolism and immune system of the Nile tilapia (Oreochromis niloticus). They found that cannabis has no measurable effect on the white blood cell count or plasma protein 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. [32]
Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an intoxicating effect. Recreational drugs are commonly divided into three categories: depressants, stimulants, and hallucinogens.
Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, behavior, judgment and evaluation, and memory. It is distinguished from neuropsychopharmacology, which emphasizes the correlation between drug-induced changes in the functioning of cells in the nervous system and changes in consciousness and behavior.
Club drugs, also called rave drugs or party drugs, are a loosely defined category of recreational drugs which are associated with discothèques in the 1970s and nightclubs, dance clubs, electronic dance music (EDM) parties, and raves in the 1980s to today. Unlike many other categories, such as opiates and benzodiazepines, which are established according to pharmaceutical or chemical properties, club drugs are a "category of convenience", in which drugs are included due to the locations they are consumed and/or where the user goes while under the influence of the drugs. Club drugs are generally used by adolescents and young adults.
Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of such action, dissociatives are unique in that they do so in such a way that they produce hallucinogenic effects, which may include dissociation, a general decrease in sensory experience, hallucinations, dream-like states or anesthesia. Despite most dissociatives' main mechanism of action being tied to NMDA receptor antagonism, some of these substances, which are nonselective in action and affect the dopamine and/or opioid systems, may be capable of inducing more direct and repeatable euphoria or symptoms which are more akin to the effects of typical "hard drugs" or common drugs of abuse. This is likely why dissociatives are considered to be addictive with a fair to moderate potential for abuse, unlike psychedelics. Despite some dissociatives, such as phencyclidine (PCP) possessing stimulating properties, most dissociatives seem to have a general depressant effect and can produce sedation, respiratory depression, nausea, disorientation, analgesia, anesthesia, ataxia, cognitive and memory impairment as well as amnesia.
The Beckley Foundation is a UK-based think tank and UN-accredited NGO, dedicated to activating global drug policy reform and initiating scientific research into psychoactive substances. The foundation is a charitable trust which collaborates with leading scientific and political institutions worldwide to design and develop research and global policy initiatives. It also investigates consciousness and its modulation from a multidisciplinary perspective, working in collaboration with scientists. The foundation is based at Beckley Park near Oxford, United Kingdom. It was founded in 1998, and is directed by Amanda Feilding, Countess of Wemyss.
An anxiogenic or panicogenic substance is one that causes anxiety. This effect is in contrast to anxiolytic agents, which inhibits anxiety. Together these categories of psychoactive compounds may be referred to as anxiotropic compounds.
Dimethocaine, also known as DMC or larocaine, is a compound with a stimulatory effect. This effect resembles that of cocaine, although dimethocaine appears to be less potent. Just like cocaine, dimethocaine is addictive due to its stimulation of the reward pathway in the brain. However, dimethocaine is a legal cocaine replacement in some countries and is even listed by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) under the category “synthetic cocaine derivatives”. The structure of dimethocaine, being a 4-aminobenzoic acid ester, resembles that of procaine. It is found as a white powder at room temperature.
25I-NBOMe is a novel synthetic psychoactive substance with strong hallucinogenic properties, synthesized in 2003 for research purposes. Since 2010, it has circulated in the recreational drug scene, often misrepresented as LSD. The recreational usage of 25I is associated with severe intoxication and deaths in humans.
Hallucinogens are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized as either being psychedelics, dissociatives, or deliriants.
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a psychoactive stimulant drug. It can have both positive and negative effects on different aspects of memory.
Self-administration is, in its medical sense, the process of a subject administering a pharmacological substance to themself. A clinical example of this is the subcutaneous "self-injection" of insulin by a diabetic patient.
25C-NBOMe is a psychedelic drug and derivative of the psychedelic phenethylamine 2C-C. 25C-NBOMe appeared on online vendor sites in 2010 but was not reported in the literature until 2011. It acts as a potent agonist of the 5-HT2A receptor, and has been studied in its 11C radiolabelled form as a potential ligand for mapping the distribution of 5-HT2A receptors in the brain, using positron emission tomography (PET). Multiple deaths have occurred from usage of 25C-NBOMe due to the ease of accidental overdose. The long-term toxic effects of the drug have not been researched.
A psychoactive drug, psychopharmaceutical, psychoactive agent, or psychotropic drug is a chemical substance that changes the function of the nervous system and results in alterations of perception, mood, cognition, and behavior. These substances may be used medically, recreationally, for spiritual reasons, or for research. Some categories of psychoactive drugs may be prescribed by physicians and other healthcare practitioners because of their therapeutic value.
25D-NBOMe is a derivative of the phenethylamine derived hallucinogen 2C-D. It acts in a similar manner to related compounds such as 25I-NBOMe, which is a potent agonist at the 5-HT2A receptor. 25D-NBOMe has been sold as a street drug since 2010 and produces similar effects in humans to related compounds such as 25I-NBOMe and 25C-NBOMe. It was banned as a Temporary Class Drug in the UK on 10 June 2013 after concerns about its recreational use.
25N-NBOMe is a derivative of the hallucinogen 2C-N. The pharmacological properties of 25N-NBOMe have not been described in the scientific literature, but it is believed to act in a similar manner to related compounds such as 25I-NBOMe and 25C-NBOMe, which are potent agonists at the 5HT2A receptor. 25N-NBOMe has been sold as a street drug and has only been described in the literature in terms of identification by forensic analysis.
25E-NBOMe is a derivative of the phenethylamine 2C-E. It acts in a similar manner to related compounds such as 25I-NBOMe, which are potent agonists at the 5-HT2A receptor. 25E-NBOMe has been sold as a drug and produces similar effects in humans to related compounds such as 25I-NBOMe and 25C-NBOMe.
Harris Isbell was an American pharmacologist and the director of research for the NIMH Addiction Research Center at the Public Health Service Hospital in Lexington, Kentucky from 1945 to 1963. He did extensive research on the physical and psychological effects of various drugs on humans. Early work investigated aspects of physical dependence with opiates and barbiturates, while later work investigated psychedelic drugs, including LSD. The research was extensively reported in academic journals such as the Journal of Pharmacology and Experimental Therapeutics, Psychopharmacologia, and the AMA Archives of Neurology and Psychiatry.
25G-NBOMe (NBOMe-2C-G) is a derivative of the phenethylamine hallucinogen 2C-G, which acts as a highly potent agonist for the human 5-HT2A receptor.
25H-NBOMe (NBOMe-2C-H) is a derivative of the phenethylamine hallucinogen 2C-H, which acts as a highly potent full agonist for the human 5-HT2A receptor.
25iP-NBOMe is a derivative of the phenethylamine hallucinogen 2C-iP, which acts as a highly potent agonist for the human 5-HT2A receptor.