9,10-ジデヒドロ-N,N-ジエチル-6-メチルエルゴリン-8β-カルボアミド

DEA NFLIS-Drug Category -> Psychedelics

DEA Schedule I Controlled Substance -> Hallucinogenic substances

Pharmaceuticals -> Illicit drugs

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

Pharmaceuticals -> Listed in ZINC15

Pointed prisms from benzene

Colorless

176 to 185 °F (NTP, 1992)

82 °C

Crystals (with 1-2 molecules of water) in plates from water. MP: 240 °C (decomposes). Amphoteric; moderately soluble in pyridine; slightly soluble in water and neutral organic sovents; soluble in alkaline and acid solutions /Lysergic acid/

Stable under recommended storage conditions.

LSD ... decomposes in light and at high temperatures.

Danger

H300 (97.6%): Fatal if swallowed [Danger Acute toxicity, oral]

P203, P260, P262, P264, P270, P271, P280, P284, P301+P316, P302+P352, P304+P340, P316, P318, P320, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 42 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H225 (100%): Highly Flammable liquid and vapor [Danger Flammable liquids]

SYMPTOMS: Symptoms of exposure to this chemical are euphoria, hallucinations, distorted perception, excitement, and anorexia. It can cause central nervous system effects, tachycardia, muscular weakness, increased body temperature, wavelike recurrences of perceptual changes, difficulty in locating the source of sound, hypervigilant, withdrawn or may alternate between states, fear of fragmentation or disintegration of the self, prolonged afterimages, overlapping of present and preceding perceptions, synesthesias, colors are heard and sounds may be seen, subjective time is seriously altered and moods may be labile. In addition, it can cause tremor, piloerection, pupillary dilatation, salivation, hyperreflexia, ataxia, and spastic paresis. It can cause vomiting. Other symptoms are hypertension and hypotension, coma, prolonged psychotic state, psychopathic personality disorders, increased homicidal and suicidal risk, and possible chromosome injury. Hyperexcitability and convulsions can also be symptoms of exposure to this chemical. This compound can inhibit the firing of the raphe neurons. It can also be habit forming.

Schedule I shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation, which contains any quantity of the following hallucinogenic substances, or which contains any of its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation (for purposes of this paragraph only, the term "isomer" includes the optical, position and geometric isomers). Lysergic acid diethylamide (DEA Code Number: 7315) is included on this list.

Kuhn C et al; Buzzed. The Straight Facts About The Most Used and Abused Drugs From Alcohol to Ecstasy 4th ed (2014); Handbook features the most recent discoveries about drugs, including new information about biological and behavioral changes in addiction, the prescription-drug abuse epidemic, distinctive drug effects on the adolescent brain, and a perspective on legal trends.

Anon; LSD: Toxicology and Metabolism. (Latest citations from the Life Sciences Collection Database).Govt Reports Announcements & Index (GRA&I), Issue 17, 1992. Citations concerning the metabolism and central nervous system effects of LSD (lysergic acid diethylamide) are included. The action of LSD in humans is discussed and case histories are reported. The citations also explore the action of LSD in animals, including psychological and physiological changes. (Contains a minimum of 60 citations and includes a subject term index and title list.)

Anon; Trends in Drug Abuse Related Hospital Emergency Room Episodes and Medical Examiner Cases for Selected Drugs, DAWN 1976-1985. Topical Data from the Drug Abuse Warning Network (DAWN). Govt Reports Announcements & Index (GRA&I), Issue 16, 1992. The report presents trends in drug abuse data collected through the Drug Abuse Warning Network (DAWN) for the ten-year period from 1976 through 1985. It is based on drug abuse-related cases reported by 564 hospital emergency rooms and 62 medical examiner facilities which participated consistently in DAWN throughout the entire period. Drugs mentioned in conjunction with emergency room episodes and medical examiner cases are the focal point of DAWN data. Frequently, more than one drug is mentioned in conjunction with a single case or episode.

Carroll ME; PCP and Hallucinogens. Adv Alcohol Subst Abuse 9 (1-2): 167-90 (1990). In this review phencyclidine and related arylcyclohexylamines and hallucinogens, using LSD as the prototype, are considered as two distinct classes of abused drugs. Within these classes drugs that are found on the street are discussed, and a current epidemiological summary is provided. The abuse liability and dependence potential of these drugs are evaluated by considering four major determinants of their abuse. First, is the ability of a drug to function as a positive reinforcer and increase the probability of operant behavior leading to its delivery. Animal data describing the reinforcing effects of PCP are reviewed with respect to the influence of variables controlling drug-reinforced behavior; however, there are no animal models of hallucinogen-reinforced behavior. Several methods of quantifying reinforcing efficacy are discussed. A second determinant is the subjective effects of the respective drugs. These effects are described and compared across drugs based on clinical reports in humans and drug discrimination studies in animals. A third determinant is the behavioral and physiological toxicity that results from acute and chronic use of these drugs. Clinical reports and results of sensitive tests that have been developed for laboratory animals are reviewed. A fourth determinant is the dependence potential that exists with these drugs, measured by tolerance development and the extent to which behavioral and physiological disturbances occur when drug use is terminated.

For more Special Reports (Complete) data for LSD (10 total), please visit the HSDB record page.

An amide. Organic amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).

Acute Tox. 2 (97.6%)

Flam. Liq. 2 (100%)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

This compound is a Schedule I DEA Controlled Substance and is to be stored according to State and Federal Regulations.

Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature -20 °C.

Two studies have shown that LSD is stable in urine for more than a month when stored at or below room temperature and protected from direct sunlight or other sources of ultraviolet radiation.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.

Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

The 2012 Monitoring the Future (MTF) report indicated that the annual prevalence of LSD use among students in 8th, 10th, and 12th grades was 0.8%, 1.7% and 2.4%, respectively. According to the American Association of Poison Control Centers, 301 case mentions, 174 single exposures, and 7 major medical outcomes related to LSD were reported to the National Poison Data System in 2010. The 2011 National Survey on Drug Use and Health (NSDUH) indicated that 23.0 million people in the U.S. population, aged 12 and older, used LSD in their lifetime. The Drug Abuse Warning Network(DAWN ED) reports that an estimated 3,817 emergency department visits were associated with LSD in 2010(1).

Adverse effects of psychotropics are often treated with fast-acting benzodiazepines like diazepam or triazolam that have calming and antianxiety effects but do not directly affect the specific actions of psychotropics. Theoretically, specific 5-HT2A receptor antagonists, which most commonly means atypical antipsychotics (quetiapine, olanzapine, risperidone, etc.) or other 5-HT2A antagonist such as trazodone or mirtazapine, would be direct antidotes, although some anecdotal reports claim otherwise. (A308, L1925)

... This study aims to determine if parenteral injections of the hallucinogens LSD, d,l-2,5-dimethoxy-4-methylamphetamine, and 5-methoxy-dimethyltryptamine /to rabbits/ elicit the 5-HT(2A)-mediated behavior of head bobs and whether intrahippocampal injections of LSD would produce head bobs and enhance trace eyeblink conditioning. LSD was infused into the dorsal hippocampus just prior to each of eight conditioning sessions. One day after the last infusion of LSD,(+/-)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) was infused into the hippocampus to determine whether there had been a desensitization of the 5-HT(2A) receptor as measured by a decrease in DOI-elicited head bobs. Acute parenteral or intrahippocampal LSD elicited a 5-HT(2A) but not a 5-HT(2C)-mediated behavior, and chronic administration enhanced conditioned responding relative to vehicle controls. Rabbits that had been chronically infused with 3 or 10 nM per side of LSD during Pavlovian conditioning and then infused with DOI demonstrated a smaller increase in head bobs relative to controls. LSD produced its enhancement of Pavlovian conditioning through an effect on 5-HT(2A) receptors located in the dorsal hippocampus. The slight, short-lived enhancement of learning produced by LSD appears to be due to the development of desensitization of the 5-HT(2A) receptor within the hippocampus as a result of repeated administration of its agonist (LSD).

/Investigators/ report a case of grand mal convulsions following ingestion of LSD in conjunction with a therapeutic regimen of fluoxetine. Mr. A, 16 years old, had an unremarkable medical history, notable for the absence of a seizure disorder, and had been maintained without incident on a regimen of fluoxetine, 20 mg/day, for approximately 1 year. About 1 hr after consuming the second of two doses of "blotter" LSD (and 3 hr after the initial dose), he developed marked stupor. Emergency services were summoned. In transport to the hospital, the patient was observed to develop an apparent focal seizure involving the left arm and face, which progressed to a grand mal convulsion and responded to 10 mg i.v. of diazepam.

A case of severe limb ischemia predominating in the legs in a young female drug addict is reported. Arteriography revealed diffuse spasm of all arteries of the lower limbs associated with localized spasm along the profunda artery in particular. These appearances regressed on control angiography performed 10 days later. The treatment which associated volume expanders and intravenous vasodilatation agents (magnesium sulfate) led to rapid improvement in the clinical condition in 3 days. There were no long-term complications. The causative role of LSD was suggested by the history of greatly increased intake in the period before the onset of symptoms. LSD is a derivative of lysergic acid, the common nucleus of the derivative of the ergot of rye. Analysis of a sample dose taken by the patient showed a very large quantity of LSD and of lysergic acid and a very small amount of other ergot alkaloids known for their peripheral vasoconstrictor effects. ...

In human volunteers, 198 trials were made to determine the threshold dose for recognition of lysergic acid diethylamide (LSD-25) and the effect upon this of chlorpromazine and phenoxybenzamine. The threshold dose of LSD was determined to be 20 ug or 0.260 to 0.295 ug/kg. Chlorpromazine, in a dose of 25 mg., given 30 min beforehand or phenoxybenzamine, in a 10 mg. dose, given at the same time blocked recognition of the dose of LSD, i.e., raised the threshold. The same dose of chlorpromazine when given at the same time as or 30 minutes after LSD did not block recognition. Neither chlorpromazine in this dosage nor phenoxybenzamine in doses up to 30 mg. had any significant physiologic or subjective effect. The results suggest that the mechanisms through which these compounds block the recognition of LSD are different from those producing their peripheral autonomic effects.

For more Interactions (Complete) data for LSD (16 total), please visit the HSDB record page.

Chronic effects of LSD toxicity include flashbacks, psychosis, and exacerbation of latent mental disorders, particularly schizophrenia. Overdosage can result in “bad trips” that are characterized by intense anxiety, combativeness, confusion, and panic attacks. LSD is not considered to be addictive, and withdrawal syndrome are absent. Because of its relatively high therapeutic index, no deaths have been directly attributed to LSD use alone. (A2915, L1925)

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 280(SRC), determined from a log Kow of 2.95(2) and a regression-derived equation(3), indicates that LSD is expected to have moderate mobility in soil(SRC). The estimated pKa of LSD is 7.80(4), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of the neutral species of LSD from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.5X10-16 atm-cu m/mole(SRC), using a fragment constant estimation method(6). LSD is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.0X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Biodegradation data in soil were not available(SRC, 2017).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 280(SRC), determined from a log Kow of 2.95(2) and a regression-derived equation(3), indicates that LSD adsorbs to suspended solids and sediment(SRC). Volatilization of the neutral species from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 1.5X10-16 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). An estimated pKa of 7.80(6) indicates LSD will exist partially in the cation form at pH values of 5 to 9 and, volatilization of the ionized form from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(7), an estimated BCF of 40(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data in water were not available(SRC, 2017).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), LSD, which has an estimated vapor pressure of 2.0X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase LSD is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 53 minutes(SRC), calculated from its rate constant of 4.4X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase LSD may be removed from the air by wet and dry deposition(SRC). LSD contains chromophores that absorb at wavelengths of 311 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Adverse effects are extremely subjective, with significant variability and unpredictability. One patient may experience a positive effect filled with bright hallucinations, sights, and sensations, increased awareness owing to mind expansion, and marked euphoria. The positive spectrum of effects is colloquially called a "good trip." Another patient may experience the total opposite with an experience filled with increased anxiety becoming panic, fear, depression, despair, and disappointment. The negative spectrum is colloquially called a "bad trip." One patient can experience both the positive and negative spectrum at different times of use.

IDENTIFICATION AND USE: LSD is a colorless, odorless and tasteless solid. It is a Schedule I controlled substance. It is used in biochemical research as antagonist to serotonin. LSD has been used experimentally as adjunct in study and treatment of mental disorders. HUMAN STUDIES: LSD has significant cardiovascular effects owing to its sympathomimetic actions. Tachycardia, hypertension, arrhythmias, shock, and respiratory arrest occur with severe overdose. Synesthesias and "trails" are characteristic of LSD. Synesthesias are a translation of one sensory modality into another, such as seeing colored vibrations of music, or smelling purple. Trails are formed positive afterimages that remain immediately behind an object as it moves across the subject's visual field. Adverse reactions to LSD are common. Acutely, LSD can produce a "bad trip." Frightening thoughts overwhelm the user, with a loss of insight that this is a drug experience; the resulting acute panic reaction generally necessitates a visit to the emergency department. Acute mania, schizophrenia, depression, and permanent psychoses have resulted from LSD abuse, particularly in someone of borderline stability. Tolerance occurs, but there is no withdrawal state. Sympathomimetic effects include mydriasis, flushing, tremor, hyperreflexia, hyperthermia, tachycardia, increased blood pressure, piloerection, diaphoresis, and ataxia. Nausea and vomiting may occur, and severe toxicity can result in coma, seizures, and respiratory arrest. Neuroleptic malignant syndrome may occur after LSD use. Muscle biopsy may show myoedema, focal necrosis, and glycogen and lipid depletion. Four chronic reactions were reported: (a) prolonged psychotic reactions, (b) depression and suicidal ideation, (c) flashbacks, and (d) exacerbation of preexisting psychiatric illness. Since then, another diagnostic category has been described: hallucinogen persisting perception disorder (HPPD). One hundred forty women and their consorts, admitting to the use of LSD prior to or during pregnancy were observed through 148 pregnancies. There were 83 live newborns; 8 had major congenital defects. There were 65 abortions; 53 therapeutic and 12 spontaneous. Four of 14 embryos from therapeutic abortions showed gross anomalies. Forty-three percent of first-trimester pregnancies ended in spontaneous abortions. Four of eight serial pregnancies resulted in defective embryos or infants. Eight of 12 women have been unable to conceive again over an 18-month period. Significant changes in human somatic cells and in chromosomes occurred only at high doses of LSD. ANIMAL STUDIES: LSD, when administered chronically to developing animals, can inhibit body growth probably by altering the secretion of growth hormone through modifications of its neuroendocrine control. Central nervous system abnormalities were reported in day 11 mouse embryos after injecting 0.05 to 1.0 ug of LSD on day 7. In rats, fetal loss was produced by administering LSD by mouth or sc (20 ug and 5 ug respectively) between the 1st and 4th day of gestation. No specific congenital defects were reported. Using LSD 0.08 to 410 ug/kg in the hamster on the 8th day, found a small increase in defects of the central nervous system in 12 day embryos.

There is no evidence of organ damage or neuropsychological deficits, even at very high doses. Rarely, non-medical use may result in clinically distressing and persistent perceptual hallucinations, although they have not been observed in clinical research. The biggest concern is that dangerous and erratic behavior will result from intense subjective experiences with LSD.

LSD preferentially inhibits serotonergic cell firing by acting as an agonist at the 5-HT1A receptors in the raphe nuclei, locus coeruleus, and cortex. It also acts as a partial agonist on the postsynaptic 5-HT1A site and has high affinity for the other 5-HT1 subtypes 5-HT1B, 5-HT1D, and 5-HT1E. LSD's hallucinogenic effects are caused by its ability to act as a partial agonist at the 5-HT2A receptor, especially on neocortical pyramidal cells. Activation of 5-HT2A also leads to increased cortical glutamate levels. Effects of LSD on 5-HT2C, 5-HT5A, 5-HT6, and 5-HT7 receptors have also been described, but their significance remains uncertain. In addition, LSD shows agonistic and antagonistic behavior at the central dopamine D1 and D2-receptors. (L1925, A2918)

/AQUATIC SPECIES/ The role of the dopaminergic and serotonergic system was studied during the embryonic development of the pond snail Lymnaea stagnalis, with special attention to the effect of dopamine and serotonin as well as their agonists and antagonists on the rotation of the veliger larvae, and to the effect of precursors and inhibitors of the synthetizing enzymes on the duration of the embryonic life. Serotonin, D-lysergic acid diethylamide and N,N-dimethyltryptamine increased at a concentration of 1 uM the rotation by 50%, 90% and 87% respectively, and among them D-Lysergic acid diethylamide was found to be the most potent agonist. ...

LSD reliably causes pupil dilation, reduced appetite, and wakefulness. Other physical reactions to LSD are highly variable and nonspecific, and some of these reactions may be secondary to the psychological effects of LSD. The following symptoms have been reported: numbness, weakness, nausea, hypothermia or hyperthermia, elevated blood sugar, goose bumps, increase in heart rate, jaw clenching, perspiration, saliva production, mucus production, sleeplessness, hyperreflexia, and tremors. LSD also causes expansion and an altered experience of senses, emotions, memories, time, and awareness. These psychological effects (colloquially called a "trip") vary greatly from person to person. Visual effects may include morphing objects, illusion of movement of static surfaces, after image-like trails of moving objects, the appearance of moving colored geometric patterns, an intensification of colors and brightness, new textures on objects, blurred vision, and shape suggestibility. The auditory effects of LSD may include echo-like distortions of sounds, changes in ability to discern concurrent auditory stimuli, and a general intensification of the experience of music. Higher doses often cause intense and fundamental distortions of sensory perception such as synaesthesia, the experience of additional spatial or temporal dimensions, and temporary dissociation. (L1925)

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of November 16, 2017: http://actor.epa.gov/dashboard/]

LSD has been detected in wastewater effluents(1). In July 2007, LSD was detected in wastewater influent and effluent samples from sewage treatment plants located on the East coast of Spain; concentrations ranged from 1.1-4.7 ng/L in influents and 0.2-1.6 ng/L in effluents(2).

Drugs of abuse and their metabolites have been recently recognized as environmental emerging organic contaminants. Assessment of their concentration in different environmental compartments is essential to evaluate their potential ecotoxicological effects. It also constitutes an indirect tool to estimate drug abuse by the population at the community level. The present work reports for the first time the occurrence of drugs of abuse and metabolites residues along the Ebro River basin (NE Spain) and also evaluates the contribution of sewage treatment plants (STPs) effluents to the presence of these chemicals in natural surface waters. Concentrations measured in influent sewage waters were used to back calculate drug usage at the community level in the main urban areas of the investigated river basin. The most ubiquitous and abundant compounds in the studied aqueous matrices were cocaine, benzoylecgonine, ephedrine and ecstasy. Lysergic compounds, heroin, its metabolite 6-monoacetyl morphine, and Delta(9)-tetradhydrocannabinol were the substances less frequently detected. Overall, total levels of the studied illicit drugs and metabolites observed in surface water (in the low ng/L range) were one and two orders of magnitude lower than those determined in effluent (in the ng/L range) and influent sewage water (microg/L range), respectively. The investigated STPs showed overall removal efficiencies between 45 and 95%. Some compounds, such as cocaine and amphetamine, were very efficiently eliminated (>90%) whereas others, such as ecstasy, methamphetamine, nor-LSD, and THC-COOH where occasionally not eliminated at all. Drug consumption estimates pointed out cocaine as the most abused drug, followed by cannabis, amphetamine, heroin, ecstasy and methamphetamine, which slightly differs from national official estimates (cannabis, followed by cocaine, ecstasy, amphetamine and heroin). Extrapolation of the consumption data obtained for the studied area to Spain points out a total annual consumption of drugs of abuse of the order of 36 tonnes, which would translate into 1100 million Euros in the black market.

Schedule I shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation, which contains any quantity of the following hallucinogenic substances, or which contains any of its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation (for purposes of this paragraph only, the term "isomer" includes the optical, position and geometric isomers). Lysergic acid diethylamide (DEA Code Number: 7315) is included on this list.

The goal of the present study was to better delineate the mechanisms of action of the prototypical hallucinogen LSD. LSD (0.03, 0.1 and 0.3 mg/kg, s.c.) produced locomotor hyperactivity, disruption of /prepulse inhibition (PPI)/ and a number of behaviors indicative of 5-HT activation such as wet-dog shakes, back muscle contractions and forepaw treading. These various behavioral effects of LSD were studied in both Sprague-Dawley and Wistar rats, although with the exception of back muscle contractions which were more prominent in Sprague-Dawley rats, no major strain differences were detected. The PPI disruption induced by LSD (0.1 mg/kg) in Sprague-Dawley rats was completely reversed by pretreatment with the selective 5-HT(2A) antagonist MDL 100907 (0.5 and 1 mg/kg, s.c.). In contrast, pretreatment with antagonists at 5-HT(2C), (SB 242084 (0.5 mg/kg, i.p.)); 5-HT(2B/2C) (SDZ SER 082 (1 mg/kg, s.c.)); 5-HT(1A), ((+)-WAY 100135 (1 and 20 mg/kg, s.c.)) and 5-HT(6) receptors, (RO 04-6790 (30 mg/kg, i.p.)), all failed to influence LSD-induced disruption of PPI. The dopamine DA(2like) receptor antagonist, haloperidol (0.1 and 0.2 mg/kg, s.c.), was without effect against an LSD-induced disruption of PPI. Finally, selective blockade of 5-HT(2A) but not 5-HT(2C) receptors completely abolished the locomotor hyperactivity induced by LSD. These findings provide empirical evidence to support the view that the hallucinogenic effects of LSD are mediated by a direct agonist effect at 5-HT(2A) receptors.

... By genetically expressing /5-HT(2A) receptor (2AR)/ only in cortex, /investigators/show that 2AR-regulated pathways on cortical neurons are sufficient to mediate the signaling pattern and behavioral response to hallucinogens. Hallucinogenic and nonhallucinogenic 2AR agonists both regulate signaling in the same 2AR-expressing cortical neurons. However, the signaling and behavioral responses to the hallucinogens are distinct. While lisuride and LSD both act at 2AR expressed by cortex neurons to regulate phospholipase C, LSD responses also involve pertussis toxin-sensitive heterotrimeric G(i/o) proteins and Src. ...

Lysergic acid diethylamide (LSD) produces altered mood and hallucinations in humans and binds with high affinity to serotonin-2A (5-HT(2A)) receptors. Although LSD interacts with other receptors, the activation of 5-HT(2A) receptors is thought to mediate the hallucinogenic properties of LSD. The goal of this study was to identify the brain sites activated by LSD and to determine the influence of 5-HT(2A) receptors in this activation. Rats were pretreated with the 5-HT(2A) receptor antagonist MDL 100907 (0.3 mg/kg, i.p.) or vehicle 30 min prior to LSD (500 mg/kg, i.p.) administration and killed 3 hr later. Brain tissue was examined for Fos protein expression by immunohistochemistry. LSD administration produced a five- to eight-fold increase in Fos-like immunoreactivity in medial prefrontal cortex, anterior cingulate cortex, and central nucleus of amygdala. However, in dorsal striatum and nucleus accumbens no increase in Fos-like immunoreactivity was observed. Pretreatment with MDL 100907 completely blocked LSD-induced Fos-like immunoreactivity in medial prefrontal cortex and anterior cingulate cortex, but only partially blocked LSD-induced Fos-like immunoreactivity in amygdala. Double-labeled immunohistochemistry revealed that LSD did not induce Fos-like immunoreactivity in cortical cells expressing 5-HT(2A) receptors, suggesting an indirect activation of cortical neurons. These results indicate that the LSD activation of medial prefrontal cortex and anterior cingulate cortex is mediated by 5-HT(2A) receptors, whereas in amygdala 5-HT(2A) receptor activation is a component of the response. These findings support the hypothesis that the medial prefrontal cortex, anterior cingulate cortex, and perhaps the amygdala, are important regions involved in the production of hallucinations.

... The indoleamine hallucinogen D-lysergic acid diethylamide (LSD, which binds to 5-HT1A, 1B, 1D, 1E, 1F, 2A, 2C, 5, 6, 7, dopamine D1 and D2, and alpha1 and alpha2 adrenergic receptors), but not their non-hallucinogenic congeners, inhibited N-methyl-D-aspartate (NMDA)-induced inward current and NMDA receptor-mediated synaptic responses evoked by electrical stimulation of the forceps minor in pyramidal cells of the prefrontal cortical slices. The inhibitory effect of hallucinogens was mimicked by 5-HT in the presence of selective 5-HT1A and 5-HT3 receptor antagonists. The inhibitory action of ... LSD ... on the NMDA transmission was blocked by the 5-HT2A receptor antagonists R-(+)-alpha-(2, 3-dimethoxyphenyl)-1-[4-fluorophenylethyl]-4-piperidinethanol and ketanserin. However, at low concentrations ...LSD... only partially depressed the NMDA response, /and/ blocked the inhibitory effect of 5-HT, suggesting a partial agonist action. Whereas N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide (W-7, a calmodulin antagonist) and N-[2-[[[3-(4'-chlorophenyl)- 2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4'-methoxy-benzenesulfonamide phosphate (KN-93, a Ca2+/CaM-KII inhibitor), but not the negative control 2-[N-4'methoxybenzenesulfonyl]amino-N-(4'-chlorophenyl)-2-propenyl-N -methylbenzylamine phosphate (KN-92), blocked the inhibitory action of LSD ..., the selective protein kinase C inhibitor chelerythrine was without any effect. /The authors/ conclude that phenethylamine and indoleamine hallucinogens may exert their hallucinogenic effect by interacting with 5-HT2A receptors via a Ca2+/CaM-KII-dependent signal transduction pathway as partial agonists and modulating the NMDA receptors-mediated sensory, perceptual, affective and cognitive processes.

For more Mechanism of Action (Complete) data for LSD (9 total), please visit the HSDB record page.

3 hours

Two micrograms per kilogram of LSD-25 was administered intravenously to five normal human subjects. The concentration of drug in plasma was determined serially over the subsequent 8 hours. LSD-25 was found to be present in human plasma in relatively large quantities during the period of peak effect. The half-life of LSD-25 in human plasma was calculated to be 175 min.

LSD has an elimination half life of about 2.5 hours.

Hepatic.

Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). ...

Following a dose of 160 ug to 13 subjects ... in humans, LSD is extensively transformed in the liver by hydroxylation and glucuronide conjugation to inactive metabolites. ...A major metabolite found in urine is 2-oxylysergide.

The metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) was investigated in liver microsomes and cyropreserved hepatocytes from humans. Previous studies have demonstrated that O-H-LSD is present in human urine at concentrations 16-43 times greater than LSD, the parent compound. Additionally, these studies have determined that O-H-LSD is not generated during the specimen extraction and analytical processes or due to parent compound degradation in aqueous urine samples. However, these studies have not been conclusive in demonstrating that O-H-LSD is uniquely produced during in vivo metabolism. Phase I drug metabolism was investigated by incubating human liver microsomes and cryopreserved human hepatocytes with LSD. The reaction was quenched at various time points, and the aliquots were extracted using liquid partitioning and analyzed by liquid chromatography-mass spectrometry. O-H-LSD was positively identified in all human liver microsomal and human hepatocyte fractions incubated with LSD. In addition, O-H-LSD was not detected in any microsomal or hepatocyte fraction not treated with LSD nor in LSD specimens devoid of microsomes or hepatocytes. This study provides definitive evidence that O-H-LSD is produced as a metabolic product following incubation of human liver microsomes and hepatocytes with LSD.

The qualitative and quantitative aspects of the metabolism and elimination of (14)C-LSD in the rat, guinea pig and rhesus monkey have been investigated. ...(14)C-LSD is almost completely metabolized by all three species and little unchanged drug is excreted. The metabolites identified were 13- and 14-hydroxy-LSD and their glucuronic acid conjugates, 2-oxo-LSD, de-ethyl LSD and a naphthostyril derivative. There occur, however, important species differences in the nature and amounts of the various metabolites. In the rat and guinea pig the major metabolites were the glucuronic acid conjugates of 13- and 14-hydroxy-LSD which were found in both urine and bile. The guinea pig excreted significant amounts of 2-oxo-LSD in urine and bile. De-ethyl LSD was a minor urinary metabolite in both species. The metabolism of LSD appeared to be more complicated in the rhesus monkey. The urine contained at least nine metabolites of which four were identified as follows: 13- and 14-hydroxy-LSD (as glucuronic acid conjugates) de-ethyl LSD and a naphthostyril derivative. Unlike the rat and guinea pig the glucuronic acid conjugates of 13- and 14-hydroxy-LSD were only present in small amounts. Of the remaining five unidentified metabolites, three were major. The biliary metabolites of (14)C-iso-LSD in the rat have been studied and been shown to be similar to those produced from (14)C-LSD, namely 13- and 14-hydroxy-iso-LSD and their glucuronic acid conjugates and 2-oxo-iso-LSD.

For more Metabolism/Metabolites (Complete) data for LSD (7 total), please visit the HSDB record page.

Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise.

Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.

Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.

Rapidly absorbed.

/LSD/ is converted metabolized in the liver via hydroxylation and glucuronidation, and excreted predominantly as a pharmacologically inactive compound.

When taken orally, the effects become apparent within about 30 minutes and may continue for 8 to 12 hours or more. The duration and intensity of effects are dose-dependent.

Following a dose of 160 ug to 13 subjects, plasma concentrations varied considerably up to 9 ug/L. Only about 1 % is excreted unchanged in the urine in 24 hours.

The qualitative and quantitative aspects of the metabolism and elimination of (14)C-LSD in the rat, guinea pig and rhesus monkey have been investigated. Rats given an i.p. dose (1 mg/kg) excreted 73% of the (14)C in the feces, 16% in the urine and 3.4% in the expired air as (14)CO2 in 96 hr. Guinea pigs similarly dosed, excreted 40% in the feces, 28% (urine) and 18% (expired (14)CO2) in 96 hr. Rhesus monkeys (0.15 mg/kg i.m.) eliminated 39% of the (14)C in the urine and 23% in the feces in 96 hr. Extensive biliary excretion of (14)C-LSD occurred in both the rat and guinea pig. Bile duct-cannulated rats excreted 68% of an i.v. dose (1.33 mg/kg) in the bile in 5 hr and the guinea pig 52% in 6 hr...

For more Absorption, Distribution and Excretion (Complete) data for LSD (8 total), please visit the HSDB record page.

Lysergic acid diethylamide (DEA Code Number: 7315) is a Schedule I controlled substance.

Schedule I Controlled Substance: (A) The drug or other substance has a high potential for abuse; (B) The drug or other substance has no currently accepted medical use in treatment in the United States; and (C) There is a lack of accepted safety for use of the drug or other substance under medical supervision.

Hallucinogens; Serotonin Agonists; Serotonin Antagonists

In biochemical research as antagonist to serotonin. Has been used experimentally as adjunct in study and treatment of mental disorders

For more Uses (Complete) data for LSD (6 total), please visit the HSDB record page.

Lysergic acid diethylamide, is one of the most widely known psychedelic drugs. It has been used mainly as an entheogen, a tool to supplement various practices for transcendence, including meditation, psychonautics, art projects, and (formerly legal) psychedelic therapy, and as a recreational drug. Formally, LSD is classified as a hallucinogen of the psychedelic type. (L1925)

Methods for producing LSD are complex and require an experienced chemist. Several methods are known, but the majority use lysergic acid as the precursor. Lysergic acid itself is also often produced in clandestine laboratories using ergometrine or ergotamine tartrate as the starting material. ... Depending on the method used, other essential reagents include N,N-carbonyldi-imidazole, diethylamine or hydrazine.

Industrial preparation: Pioch, United States of America patent 2736728; Garbrecht, United States of America patent 2774763 (both to Lilly); Patelli, Bernardi, United States of America patent 3141887 (1964 to Farmitalia).

LSD is normally produced as tartrate salt ... The common street dose forms are 'blotters' or 'paper squares' - sheets of absorbent paper printed with distinctive designs and perforated so they may be torn into single small (typically 7 mm) squares each containing a single dose. Each sheet typically contains 100 or more doses. LSD is less commonly seen as small tablets ('microdots') that are 2-3 mm in diameter, as thin gelatine squares ('window panes') or in capsules. Solutions of LSD in water or alcohol are occasionally encountered.

Common names for LSD include: Acid, Blotter Acid, Dots, Mellow Yellow, and Window Pane.

LSD is sold on the street in tablets, capsules, and occasionally in liquid form. ... LSD is often added to absorbent paper, such as blotter paper, and divided into small decorated squares, with each square representing one dose.

Synthetic derivative of lysergic acid. Only the D-form is active.

LSD is abused for its hallucinogenic effects. LSD is abused by teenagers and young adults in connection with 'raves', night club and concert settings.