12-Hydroxy-LSD is a
drug
A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...
of the
ergoline
Ergoline is a core structure in many alkaloids and their synthetic derivatives. Ergoline alkaloids were first characterized in ergot. Some of these are implicated in the condition of ergotism, which can take a convulsive form or a gangrenous for ...
and
lysergamide
Lysergamides, also known as ergoamides or as lysergic acid amides, are amides of lysergic acid (LA). They are ergolines, with some lysergamides being found naturally in ergot as well as other fungi. Lysergamides are notable in containing embedd ...
families and a
derivative
In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...
of
lysergic acid diethylamide
Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a Semisynthesis, semisynthetic, Hallucinogen, hallucinogenic compound derived from ergot, known for its powerful psychological effects and ...
(LSD).
In terms of
chemical structure
A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...
, 12-hydroxy-LSD is to LSD as
bufotenin
Bufotenin, also known as dimethylserotonin or as 5-hydroxy-''N'',''N''-dimethyltryptamine (5-HO-DMT), is a serotonergic psychedelic of the tryptamine family. It is a derivative of the psychedelic dimethyltryptamine (DMT) and of the neurotransmi ...
(5-HO-DMT) is to
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), with 12-hydroxy-LSD notably containing bufotenin within its
rigidified structure.
12-Hydroxy-LSD produces
psychedelic
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 halluci ...
-like effects in animals,
whereas reports on its activities in humans are very limited and have been conflicting.
Pharmacology
12-Hydroxy-LSD is known to be
pharmacologically active in
animal studies
Animal studies is a recently recognised field in which animals are studied in a variety of cross-disciplinary ways. Scholars who engage in animal studies may be formally trained in a number of diverse fields, including art history, anthropology ...
.
The drug's effects in rabbits include
antiserotonergic
A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action of serotonin and serotonergic drugs at serotonin (5-HT) receptors.
Types
5-HT2A antagonists
Antagonists of the 5-HT2A receptor are sometimes used ...
activity (25% of that of LSD) and
hyperthermia
Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...
(dose ratio relative to of 1:44 for 12-hydroxy-LSD and 1:725 for LSD).
In addition, like LSD, it is highly
potent in terms of
lethality
Lethality (also called deadliness or perniciousness) is how capable something is of causing death. Most often it is used when referring to diseases, chemical weapons, biological weapons, or their toxic chemical components. The use of this term ...
, with a
median lethal dose
In toxicology, the median lethal dose, LD50 (abbreviation for " lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a given substance. The value of LD50 for a substance is the dose re ...
(LD
50) of 0.3mg/kg in rabbits (relative to 0.1mg/kg for LSD).
12-Hydroxy-LSD also produces LSD-like
electroencephalogram
Electroencephalography (EEG)
is a method to record an electrogram of the spontaneous electrical activity of the brain. The bio signals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neoc ...
(EEG) changes in rabbits.
According to Robert C. Pfaff and
David E. Nichols and colleagues, 12-hydroxy-LSD substitutes for LSD in rodent
drug discrimination
Drug discrimination (DD) is a technique in behavioral neuroscience used to evaluate the discriminative stimulus properties or interoceptive cues of psychoactive drugs. In drug discrimination, a subject is trained on a training drug, and then i ...
tests.
Hence, it appears to show psychedelic-like effects in animals.
However, 12-hydroxy-LSD was described as having unremarkable properties in this assay and only having about 20 to 50% of the
potency
Potency may refer to:
* Potency (pharmacology), a measure of the activity of a drug in a biological system
* Virility
* Cell potency, a measure of the differentiation potential of stem cells
* In homeopathic dilutions, potency is a measure of ho ...
of LSD.
Its reduced potency compared to LSD could be due to its increased
polarity and associated
pharmacokinetic
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific subs ...
differences.
It was reported in the 1960s that 12-hydroxy-LSD does not produce
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 ...
ic effects in humans.
On the other hand however, Michael Valentine Smith claimed in his 1981 book ''Psychedelic Chemistry'' that 12-hydroxy-LSD has "about the same activity as LSD".
Presumably 12-hydroxy-LSD acts as an
agonist
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
of
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, ...
and
dopamine receptor
Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diff ...
s, as with LSD and other related lysergamides, but its
pharmacology
Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur betwee ...
has not been studied with modern techniques.
Chemistry
Synthesis
The
chemical synthesis
Chemical synthesis (chemical combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In modern laboratory uses ...
of 12-hydroxy-LSD is described as being very difficult.
Analogues
An
analogue of 12-hydroxy-LSD is
12-methoxy-LSD, which would be structurally akin to
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 ...
.
As with 12-hydroxy-LSD, it has been reported that 12-methoxy-LSD is inactive as a
psychedelic
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 halluci ...
in humans.
History
12-Hydroxy-LSD was first described in the
scientific literature
Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical ...
by 1962.
Subsequently, it was further described in the 1970s and 1980s.
David E. Nichols and colleagues reported that 12-hydroxy-LSD produces
psychedelic
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 halluci ...
-like effects in animals in 1994.
It was initially thought that 12-hydroxy-LSD might be a
metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
of LSD,
but this proved not to be the case.
See also
*
12-Methoxy-LSD
*
13-Hydroxy-LSD
13-Hydroxy-LSD is a lysergamide and a metabolite of the psychedelic drug lysergic acid diethylamide (LSD). It is a major metabolite of LSD in rats and guinea pigs but a minor metabolite of LSD in monkeys and humans. Following its formation, 13-h ...
*
14-Hydroxy-LSD
*
2-Bromo-LSD
*
Bufotenin
Bufotenin, also known as dimethylserotonin or as 5-hydroxy-''N'',''N''-dimethyltryptamine (5-HO-DMT), is a serotonergic psychedelic of the tryptamine family. It is a derivative of the psychedelic dimethyltryptamine (DMT) and of the neurotransmi ...
(5-HO-DMT)
References
External links
12-Hydroxy-LSD - Isomer Design
{{Ergolines
Diethylamino compounds
Hydroxyarenes
Psychedelic lysergamides
Serotonin receptor modulators