LSD
LSD is a semisynthetic psychedelic of the lysergamide class, first synthesized by Albert Hofmann in 1938 from ergot alkaloids, with its psychoactive properties discovered in 19431. It is perhaps the most widely researched and culturally influential psychedelic substance, having played a central role in the 1960s counterculture movement1. LSD is among the most potent psychoactive compounds known, producing effects at microgram doses2. It is considered non-addictive2 with extremely low toxicity relative to dose1.
Contents
Dosage & Duration
Dosage
Tolerance builds almost immediately after ingestion, reducing by about half after 3 days and returning to baseline after roughly 7 days without further use.
Duration
Subjective Effects
Effects vary widely by individual, dose, and context.
Physical
Cognitive
In comparison to other psychedelics such as Psilocin, LSA and Ayahuasca, LSD is significantly more stimulating and fast paced in terms of the specific style of thought stream which it produces and contains a large number of potential effects.
Visual
Geometry
The visual geometry of LSD can be described as more similar in appearance to that of 2C-B and the 2C-x family than psilocin, LSA, or DMT. They can be comprehensively described as unstructured in organization, algorithmic and digital in geometric style, intricate in complexity, large in size, fast and smooth in motion, multicoloured in scheme, bright and flat in colour, and sharp in their edges with extremely angular corners. At higher dosages they consistently result in states of Level 7A visual geometry.
Hallucinatory States
LSD is capable of producing a full range of low and high level hallucinatory states in a fashion that is significantly less consistent and reproducible than that of many other commonly used psychedelics.
Auditory
Reagent Testing
Loading reagent data
Pharmacology
Pharmacodynamics
LSD primarily acts as a partial agonist at the serotonin 5-HT2A receptor13, which is understood to be the principal mechanism responsible for its psychedelic effects, though the precise nature of this relationship remains incompletely characterized. It displays high affinity at the 5-HT2A site relative to other psychedelics and is broadly non-selective across serotonin receptor subtypes, with agonist activity spanning the 5-HT1, 5-HT2, 5-HT5, 5-HT6, and 5-HT7 receptor families. LSD also acts as an agonist at all five dopamine receptor subtypes (D1 through D5)1 and has been found to bind to adrenoreceptor subtypes4.
Pharmacokinetics
LSD is rapidly absorbed1 and undergoes hepatic metabolism via CYP450 isoenzymes5. Its elimination half-life is approximately 3 hours5, and the primary metabolite produced is 2-oxo-3-hydroxy-LSD51.
Dangerous
Highest riskThese combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.
Unsafe
AvoidThere is considerable risk of physical harm when taking these combinations, they should be avoided where possible.
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
Serotonergic psychedelics, All psychedelics (via 5-HT2A receptor downregulation)
Harm Potential
Addiction & Dependence
Psychological
Extremely LowLSD is widely considered non-addictive and the desire to use it can actually decrease with continued use, making it largely self-regulating.3 Attempts to train laboratory animals to self-administer LSD have been largely unsuccessful.3 While a small number of individuals have reported developing a problematic relationship with LSD or taking it daily for extended periods, psychological dependence is rare.
Physical
Extremely LowLSD does not produce physical dependence.1 No withdrawal syndrome has been reported following discontinuation of use, even after repeated administration.3 A DSM-IV review noted that almost no hallucinogens produced dependence unlike other psychoactive drug classes.3
Toxicity
A theoretical risk of cardiac fibrosis and valvulopathy from 5-HT2B receptor agonism has been proposed for long-term or chronic use, but preliminary animal studies found no heart structure changes or valvulopathy from chronic microdosing,6 and research is mixed on whether LSD is a potent 5-HT2B agonist at all.
Rare cases of dangerous hyperthermia have been reported in the medical literature, typically at higher doses; one documented non-fatal case involved body temperature exceeding 106°F (41°C).
Expert review indicates no evidence that LSD causes damage to any human organ at reasonable doses in careful contexts, with no negative cognitive, psychiatric, or toxic physical consequences documented from acute exposure.7
Psychosis Risk
LSD can precipitate psychotic symptoms in individuals predisposed to psychosis or with pre-existing psychiatric conditions, though this appears to be quite rare.1 A Medline search in 2003 found only three case reports of LSD-induced psychosis in the previous 20 years. LSD does not appear to produce psychiatric illness de novo in otherwise emotionally healthy individuals.1 People whose relatives have schizophrenia or early-onset mental illness face heightened risk.
Seizure Risk
Seizures are very rare but can occur in individuals who are predisposed to them, particularly under physically taxing conditions such as dehydration, inadequate nutrition, overheating, or fatigue.
History & Culture
Discovery and Synthesis
LSD was first synthesized on November 16, 1938, by Swiss chemist Albert Hofmann while working at Sandoz Laboratories in Basel, Switzerland.2 The compound emerged from a research program investigating potentially useful derivatives of ergot, a fungus that grows…
Trip Reports
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Legality
International
UN Convention on Psychotropic Substances 1971 (Schedule I)
By Country
References
Source Pages
Citations
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- Nichols DE. (2018). Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD). ACS Chemical Neuroscience, 9(10), 2331-2343. https://doi.org/10.1021/acschemneuro.8b0004312345678
- Nichols DE. (2016). Psychedelics. Pharmacological Reviews, 68(2), 264-355. https://doi.org/10.1124/pr.115.011478123456789
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