Drug discrimination (DD) is a technique in

behavioral neuroscience Behavioral neuroscience, also known as biological psychology, biopsychology, or psychobiology,Psychobi ...

used to evaluate the discriminative stimulus properties or

interoceptive Interoception is the collection of senses providing information to the organism about the internal state of the body. This can be both conscious and subconscious. It encompasses the brain's process of integrating signals relayed from the body int ...

cues of

psychoactive drug A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system acti ...

s. In drug discrimination, a subject is trained on a training drug, and then it is tested with novel drugs to see if the novel drugs are experienced as similar to the training drug. In essence, the drug discrimination paradigm has the subject "tell" the experimenter "I think you gave me the training drug" or "I don't think you gave me anything". The discriminative stimulus properties of drugs are believed to reflect their subjective effects. When partial or full stimulus generalization of a test drug to a training drug occurs, the test drug can be assumed to have effects that are subjectively similar to those of the training drug. Drug discrimination tests are usually performed in animals, but have also been conducted in humans. Drug discrimination assays have been employed to assess whether drugs have

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...

- or

entactogen Entactogens, also known as empathogens or connectogens, are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, connectedness, emotional openness—that is, empathy—as particularly observe ...

-like effects, among many other varieties of drug effects.

Serotonergic psychedelics

Drug discrimination was first used with

psychedelic drug Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluc ...

s in 1971. This was with rats, whereas the first use of drug discrimination with psychedelics in mice was published in 2003. The area of the brain where the discriminative stimulus properties of

LSD Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a semisynthetic, hallucinogenic compound derived from ergot, known for its powerful psychological effects and serotonergic activity. I ...

and presumably other serotonergic psychedelics in rats is mediated has been identified as the

anterior cingulate cortex In human brains, the anterior cingulate cortex (ACC) is the frontal part of the cingulate cortex that resembles a "collar" surrounding the frontal part of the corpus callosum. It consists of Brodmann areas 24, 32, and 33. It is involved ...

(ACC). Local infusions of LSD into the ACC dose-dependently and up to fully substituted for systemically administered LSD and this substitution could be completely blocked by the highly selective

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT_2A receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.volinanserin (M100907). Although serotonin 5-HT_2A receptor agonism is accepted as the

mechanism Mechanism may refer to: *Mechanism (economics), a set of rules for a game designed to achieve a certain outcome **Mechanism design, the study of such mechanisms *Mechanism (engineering), rigid bodies connected by joints in order to accomplish a ...

mediating the hallucinogenic effects of psychedelics, other receptors, including the serotonin 5-HT_1A receptor, the serotonin 5-HT_2C receptor, and the serotonin 5-HT_5A receptor, also variably contribute to their discriminative stimulus properties and may be involved in their subjective effects. The

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

D₄ receptor is involved in the discriminative stimulus properties of LSD as well. The serotonin 5-HT_1A receptor is involved in the discriminative stimulus properties of

5-MeO-DMT 5-MeO-DMT (5-methoxy-''N'',''N''-dimethyltryptamine), also known as ''O''-methylbufotenin or mebufotenin (), is a naturally occurring psychedelic of the tryptamine family. It is found in a wide variety of plant species, and is also secreted by ...

and

in rodents but not in those of

psilocybin Psilocybin, also known as 4-phosphoryloxy-''N'',''N''-dimethyltryptamine (4-PO-DMT), is a natural product, naturally occurring tryptamine alkaloid and Investigational New Drug, investigational drug found in more than List of psilocybin mushroom ...

or DOM. The 5-MeO-DMT stimulus is mediated primarily by the serotonin 5-HT_1A receptor and partially by the serotonin 5-HT_2A receptor. The serotonin 5-HT_2C receptor is importantly involved in the discriminative stimulus properties of DiPT in rodents but not in those of

dimethyltryptamine Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a Psychedelic drug, serotonergic hallucinogen and Investigational New Drug, investigational drug of the substituted tryptamine, tryptamine family tha ...

(DMT). A serotonin 5-HT_2C receptor antagonist had only modest effects on the discriminative stimulus properties of psilocybin, suggesting against an important involvement of this receptor in psilocybin's subjective effects. Certain psychedelics and related drugs, like

, 25B-NBOMe, and

Ariadne In Greek mythology, Ariadne (; ; ) was a Cretan princess, the daughter of King Minos of Crete. There are variations of Ariadne's myth, but she is known for helping Theseus escape from the Minotaur and being abandoned by him on the island of N ...

, fully substitute for the

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...

in rodents, whereas others, like DOM, DMT, and

25I-NBOMe 25I-NBOMe, also known as 2C-I-NBOMe, Cimbi-5, and shortened to "25I", is a psychedelic drug of the phenethylamine, 2C, and NBOMe (25-NB) families. Since 2010, it has circulated in the recreational drug scene, often misrepresented as LSD. It is ...

, at most partially substitute for MDMA.

Lisuride Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline family which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth. Side effects of l ...

partially to fully substitutes for LSD and other psychedelics in drug discrimination tests in rodents and monkeys. Lisuride is generally thought to be non-hallucinogenic in humans and hence this has been regarded as a false positive for drug discrimination. However, when a modified drug discrimination paradigm is employed in which animals are trained to discriminate two training drugs (lisuride and LSD) and vehicle, lisuride no longer substitutes for LSD. As such, this false positive can be overcome. Species differences, for instance between rats and mice, have been apparent in studies of drug discrimination with psychedelics. For example, DOI was several times more potent in rats than in mice. In addition, the discriminative stimulus properties of DOI in rats appear to be solely mediated by the serotonin 5-HT_2A receptor, whereas its the DOI stimulus in mice is also partially mediated by the serotonin 5-HT_2A receptor. Similarly, the LSD stimulus appears to be solely mediated by the serotonin 5-HT_2A receptor in rats, whereas mice also have a significant 5-HT_1A receptor-mediated component. In monkeys, the discriminative stimulus effects of DOM, dipropyltryptamine (DPT), and

2C-T-7 2C-T-7, also known as 4-propylthio-2,5-dimethoxyphenethylamine, is a psychedelic phenethylamine of the 2C family. In his book '' PiHKAL: A Chemical Love Story'', Alexander Shulgin lists the dosage range as 10–30 mg. 2C-T-7 is generall ...

are all predominantly if not exclusively mediated by serotonin 5-HT_2A receptor activation.

Serotonergic psychedelics

See also

References

Further reading