LSD (Lysergic acid diethylamide)


Lysergic acid diethylamide (LSD)

Pregnancy category C

Dependence liability Low

Addiction liability None

Routes of administration By mouth, under the tongue

Drug class Hallucinogen (psychedelic)

Bioavailability 71%

Metabolism Liver (CYP450)

Metabolites 2-Oxo-3-hydroxy-LSD

Onset of action 30–40 minutes

Elimination half-life 3.6 hours

Duration of action 8–20 hours

Excretion Kidneys

Lysergic acid diethylamide, commonly known as LSD is a potent psychedelic drug.

Effects include: ntensified thoughts, emotions, and sensory perception.

At high dosages LSD manifests primarily mental, visual, and auditory hallucinations, dilated pupils, increased blood pressure, and increased body temperature.

Effects typically begin within half an hour and can last for up to 20 hours.

It can cause mystical experiences and ego dissolution.

It is used mainly as a recreational drug or for spiritual reasons.

LSD is one of the classical psychedelic agents.

LSD is synthesized as a solid compound, typically in the form of a powder or a crystalline material. 

LSD dissolved in a liquid solvent, such as ethanol or distilled water, creates a solution that serves as a carrier for the LSD.

LSD is either swallowed or held under the tongue.

LSD is considered to be non-addictive with low potential for abuse. 

Adverse psychological reactions are possible; anxiety, paranoia, and delusions.

It is active in small amounts relative to other psychoactive compounds; in micrograms.

LSD can induce either intermittent or chronic visual hallucinations, even after no further use: hallucinogen persisting perception disorder (HPPD).

No known cases of death from LSD directly, but overdose can cause injury and death as a result of accidents stemming from psychological impairment.

LSD effects thought to be from it being an agonist at the 5-HT2A (serotonin) receptor, and increased glutamatergic neurotransmission.

LSD also binds to dopamine D1 and D2 receptors.

LSD is more stimulating than compounds such as psilocybin.

LSD is clear or white in color, has no smell, and is crystalline.

LSD can induce transcendent experiences that transcend the experience of everyday consciousness, with lasting psychological benefit.

It is estimated about 10% of people in the United States have used LSD at some point in their lives.

LSD is commonly used as a recreational drug.

LSD can cause intense spiritual experiences and is thus considered an entheogen. 

A meta analysis concluded that a single dose was shown to be effective at reducing alcohol consumption in people suffering from alcoholism.

With depression, anxiety, and drug dependence, studies show positive preliminary results.

LSD can cause pupil dilation, reduced appetite, profuse sweating and wakefulness, elevated body temperature, blood sugar, and heart rate, alongside goose bumps, jaw clenching, mouth dryness, and hyperreflexia. 

Its negative experiences include: numbness, weakness, nausea, and tremors.

Its most common immediate psychological effects of LSD are visual hallucinations and illusions (‘trips”).

Psychological effects of LSD usually start within 20–30 minutes of the oral intake, and less if snorted or taken intravenously.

Psychological effects of LSD peak three to four hours after ingestion, and can last up to 20 hours in high doses. 

Users may also experience an improved mood or perceived mental state for days or even weeks after ingestion in some experiences (afterglow).

Good trips could be described as stimulating, pleasurable, involving intense joy/euphoria, a greater appreciation for life, reduced anxiety, a sense of spiritual enlightenment, and a sense of belonging or interconnectedness with the universe.

Bad trips are negative experiences that evoke dark emotions, such as irrational fear, anxiety, panic, paranoia, dread, distrustfulness, hopelessness, and even suicidal ideation.

To minimize the risk of a bad trip mood, surroundings, sleep, hydration, social setting, and other factors are controlled to minimize the risk

LSD causes an animated sensory experience of senses, emotions, memories, time, and awareness for 6 to 20 hours, depending on dosage and the individuals tolerance.

Generally beginning within 30 to 90 minutes after ingestion.

Experience range from subtle changes in perception to overwhelming cognitive shifts, along with auditory and visual alterations.

Sensory effects include more vibrant colors, objects and surfaces appearing to ripple,  or otherwise move, spinning fractals, colored patterns behind closed eyelids, an altered sense of time, geometric patterns emerging on walls and other textured objects, and morphing objects.

Food’s texture or taste may be different, and users of LSD may also have an aversion to foods that they would normally enjoy. 

Some individuals report that the inanimate appears to animate in an inexplicable ways.

Many of the basic visual effects resemble the phosphenes seen after applying pressure to the eye.

Some  effects and patterns can be changed when concentrated on, or can change based on thoughts, emotions or music.

The auditory effects of LSD include: echo-like distortions of sounds, impaired ability to discern auditory and visual stimuli, and a general intensification of the experience of music. 

High doses often cause distortions of sensory perception such as synesthesia, the experience of additional spatial or temporal dimensions, and temporary dissociation.

Addiction experts ranking 20 popular recreational drugs: LSD was ranked 14th in dependence, 15th in physical harm, and 13th in social harm.

LSD, a classical psychedelic, is considered physiologically safe when taken at standard dosages (50-200μg).

LSD’s most significant adverse response lies principally in their psychological effects.

LSD may trigger panic attacks or feelings of extreme anxiety, known as a “bad trip”. 

People with severe mental illnesses like schizophrenia have a higher likelihood of experiencing adverse effects from taking LSD.

Hallucinogens, including LSD, can catalyze the onset of psychiatric disorders such as psychosis and depression, but these problems appear to be precipitated in predisposed individuals and they do not appear to produce illness in otherwise emotionally healthy individuals.

Several behavioral-related fatalities and suicides have occurred due to LSD.

Evidence indicates that both mentally ill and healthy people are more suggestible while under its influence.

Flashbacks are a psychological phenomenon in which an individual experiences an episode of some of LSD’s subjective effects after the drug has worn off, persisting for days or months after hallucinogen use.

Individuals with hallucinogen persisting perception disorder experience intermittent or chronic flashbacks that cause distress or impairment in life and work.

The prevalence of HPPD appears to be very rare, with estimates ranging from 1 in 20 users for the transitory and less serious type 1 HPPD, to 1 in 50,000 users for the more concerning type 2 HPPD.

LSD has a short half-life of 175 minutes, undergoing enzymatic metabolism into more water-soluble compounds.

 There is no evidence of long-term storage of LSD in the body exists.

It is suggests that LSD-induced flashbacks are potentiated by chronic use of SSRIs even months after stopping LSD use.

Several psychedelics, including LSD, are metabolized by CYP2D6, and a number of SSRIs are potent inhibitors of CYP2D6, therefore coadministration of SSRIs with LSD may increase the risk of serotonin syndrome (SS).

The co-use of psychedelics with mood stabilizers such as lithium may provoke seizure and dissociative effects in individuals with bipolar disorder.

Lithium may  increase LSD reactions, and medical reports suggests it may lead to acute comatose states when combined.

It is estimated the lethal oral dose of LSD in humans to be 100 mg.

LSD exhibits significant tachyphylaxis with tolerance manifesting 24 hours after a one-time administration.

Tolerance to LSD also builds up with consistent use.

Although tolerance to LSD builds up rapidly, a withdrawal syndrome does not appear.

Almost no hallucinogens produced dependence, unlike psychoactive drugs of other classes such as stimulants and depressants.

Studies showed no evidence of teratogenic or mutagenic effects.

There have been no documented fatal human overdoses.

Massive doses are largely managed by symptomatic treatments, and benzodiazepines.

The agonism of the D2 receptor by LSD may contribute to its psychoactive effects in humans.

The effects of a dose of LSD lasts for up to 12 hours and is closely correlated with the concentrations of LSD present in circulation over time, with no acute tolerance observed.

Only 1% of the drug is eliminated in urine unchanged, whereas 13% is eliminated as the major metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) within 24 hours.

The oral bioavailability of LSD is estimated as approximately 71%.

Neuroimaging studies using resting state fMRI suggest LSD changes the cortical functional architecture.

Subcortical structures, particularly the thalamus, play a synergistic role with the cerebral cortex in mediating the psychedelic experience. 

Lysergic acid is made by alkaline hydrolysis of lysergamides like ergotamine, a substance usually derived from the ergot fungus on agar plate.

A single dose of LSD may be between 40 and 500 micrograms

Threshold effects can be felt with as little as 25 micrograms of LSD.

LSD may be quantified in urine as part of a drug abuse testing program.

LSD may be measured in plasma or serum to confirm a diagnosis of poisoning in hospitalized victims, to assist in a forensic investigation of a traffic or other criminal violation or a case of sudden death. 

Maximum plasma concentrations were found to be 1.4 and 1.5 hours after oral administration of 100 µg and 200 µg respectively with a plasma half-life of 2.6 hours.

 LSD is Schedule I in the United States, according to the Controlled Substances Act of 1970.[179] This means LSD is illegal to manufacture, buy, possess, process, or distribute without a license from the Drug Enforcement Administration (DEA). 

The DEA holds that it has a high potential for abuse and no legitimate medical use, and is unsafe to use even under medical supervision.

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