Misplaced Pages

#332667

106-799: Lysergic acid diethylamide , commonly known as LSD (from German Lysergsäure-diethylamid ), is a potent psychedelic drug that intensifies thoughts, emotions, and sensory perception. Often referred to as acid or lucy , LSD can cause mystical, spiritual, or religious experiences. At higher doses, it primarily induces visual and auditory hallucinations. While LSD does not cause physical addiction, it can lead to adverse psychological reactions, such as anxiety, paranoia, and delusions. Additionally, it may trigger "flashbacks," also known as hallucinogen persisting perception disorder , where individuals experience persistent visual distortions after use. The effects of LSD begin within 30 minutes of ingestion and can last up to 20 hours, with most trips averaging 8–12 hours. It

212-807: A calm, safe environment is beneficial. Antipsychotic agents such as neuroleptics and haloperidol are not recommended as they may have adverse psychotomimetic effects . Gastrointestinal decontamination with activated charcoal is of little use due to the rapid absorption of LSD, unless done within 30–60 minutes of ingesting exceedingly huge amounts. Administration of anticoagulants , vasodilators , and sympatholytics may be useful for treating ergotism . Many novel psychoactive substances of 25-NB (NBOMe) series, such as 25I-NBOMe and 25B-NBOMe , are regularly sold as LSD in blotter papers. NBOMe compounds are often associated with life-threatening toxicity and death. Fatalities involved in NBOMe intoxication suggest that

318-419: A psychotherapeutic setting reveal that psychedelic drugs may assist with treating depression , alcohol addiction , and nicotine addiction . Although further research is needed, existing results suggest that psychedelics could be effective treatments for certain forms of psychopathology. A 2022 survey found that 28% of Americans had used a psychedelic at some point in their life. The term psychedelic

424-400: A withdrawal syndrome does not appear, suggesting that a potential syndrome does not necessarily relate to the possibility of acquiring rapid tolerance to a substance. A report examining substance use disorder for DSM-IV noted that almost no hallucinogens produced dependence, unlike psychoactive drugs of other classes such as stimulants and depressants . The mutagenic potential of LSD

530-509: A bad trip after LSD intoxication may be presented with severe anxiety, tachycardia, often accompanied by phases of psychotic agitation and varying degrees of delusions. Cases of death on a bad trip have been reported due to prone maximal restraint (commonly known as a hogtie) and positional asphyxia when the individuals were restrained by law enforcement personnel . Massive doses are largely managed by symptomatic treatments , and agitation can be addressed with benzodiazepines . Reassurance in

636-513: A bad trip will occur, one's mood, surroundings, sleep, hydration , social setting, and other factors can be controlled (colloquially referred to as " set and setting ") to minimize the risk of a bad trip. The concept of "set and setting" also generally appears to be more applicable to psychedelics than to other types of hallucinogens such as deliriants, hypnotics and dissociative anesthetics. Classic psychedelics are considered to be those found in nature like psilocybin, DMT, mescaline, and LSD which

742-541: A causal relationship between psilocybin and the onset of psychosis has not been established as of 2011, researchers have called for investigation of the relationship. Many of the persistent negative perceptions of psychological risks are unsupported by the currently available scientific evidence, with the majority of reported adverse effects not being observed in a regulated and/or medical context. A population study on associations between psychedelic use and mental illness published in 2013 found no evidence that psychedelic use

848-798: A classical psychedelic, is deemed physiologically safe at standard dosages (50–200 μg) and its primary risks lie in psychological effects rather than physiological harm. A 2010 study by David Nutt ranked LSD as significantly less harmful than alcohol , placing it near the bottom of a list assessing the harm of 20 drugs. LSD can induce panic attacks or extreme anxiety, colloquially termed a " bad trip ". Despite lower rates of depression and substance abuse found in psychedelic drug users compared to controls, LSD presents heightened risks for individuals with severe mental illnesses like schizophrenia. These hallucinogens can catalyze psychiatric disorders in predisposed individuals, although they do not tend to induce illness in emotionally healthy people. While research from

954-471: A condition that follows the use of various substances, including alcohol . Common effects of afterglow are described by many drug users: Most drugs do not typically cause afterglow, but some (like MDMA ) can. Afterglow may also occur after the usage of dissociative drugs, such as the NMDA antagonists , DXM , ketamine and PCP . These forms of afterglows, in contrast to psychedelic afterglows, often leave

1060-491: A decrease in activity and connectivity was observed in cortical areas that are dense with 5-HT 1A receptor. Experimental data suggest that subcortical structures, particularly the thalamus, play a synergistic role with the cerebral cortex in mediating the psychedelic experience. LSD, through its binding to cortical 5-HT 2A receptor, may enhance excitatory neurotransmission along frontostriatal projections and, consequently, reduce thalamic filtering of sensory stimuli towards

1166-400: A greater appreciation for life, reduced anxiety, a sense of spiritual enlightenment, and a sense of belonging or interconnectedness with the universe. Negative experiences, colloquially known as "bad trips," evoke an array of dark emotions, such as irrational fear, anxiety, panic, paranoia, dread, distrustfulness, hopelessness, and even suicidal ideation. While it is impossible to predict when

SECTION 10

#1732765538333

1272-431: A high affinity for LSD. The psychedelic effects of LSD are attributed to cross-activation of 5-HT 2A receptor heteromers . Many but not all 5-HT 2A agonists are psychedelics and 5-HT 2A antagonists block the psychedelic activity of LSD. LSD exhibits functional selectivity at the 5-HT 2A and 5-HT 2C receptors in that it activates the signal transduction enzyme phospholipase A2 instead of activating

1378-445: A high enough dose. Luis Luna describes psychedelic experiences as having a distinctly gnosis -like quality, and says that they offer "learning experiences that elevate consciousness and can make a profound contribution to personal development ." Czech psychiatrist Stanislav Grof studied the effects of psychedelics like LSD early in his career and said of the experience, that it commonly includes "complex revelatory insights into

1484-790: A lid over the diethylamide end of the binding cavity which explains the slow rate of LSD unbinding from serotonin receptors. The related lysergamide lysergic acid amide (LSA) that lacks the diethylamide moiety is far less hallucinogenic in comparison. LSD, like other psychedelics, has been found to increase the expression of genes related to synaptic plasticity. This is in part due to binding to brain-derived neurotrophic factor (BDNF) receptor TrkB. The acute effects of LSD normally last between 6 and 10 hours depending on dosage, tolerance, and age. Aghajanian and Bing (1964) found LSD had an elimination half-life of only 175 minutes (about 3 hours). However, using more accurate techniques, Papac and Foltz (1990) reported that 1 μg/kg oral LSD given to

1590-474: A lower prevalence of use at 7.6%. Notably, less than 1% of U.S. adults reported using any psychedelic drugs within the past month. Psychedelic microdosing is the practice of using sub-threshold doses ( microdoses ) of psychedelics in an attempt to improve creativity, boost physical energy level, emotional balance, increase performance on problems-solving tasks and to treat anxiety, depression and addiction. The practice of microdosing has become more widespread in

1696-428: A median of 1.5 hours (range 0.5–4 hours) post-administration. Concentrations of LSD decreased following first-order kinetics with a half-life of 3.6±0.9 hours and a terminal half-life of 8.9±5.9 hours. The effects of the dose of LSD given lasted for up to 12 hours and were closely correlated with the concentrations of LSD present in circulation over time, with no acute tolerance observed. Only 1% of

1802-455: A negative result for NBOMe compounds. Most serotonergic psychedelics are not significantly dopaminergic , and LSD is therefore atypical in this regard. The agonism of the D 2 receptor by LSD may contribute to its psychoactive effects in humans. LSD binds to most serotonin receptor subtypes except for the 5-HT 3 and 5-HT 4 receptors . However, most of these receptors are affected at too low affinity to be sufficiently activated by

1908-562: A preference for evoking serotonin and dopamine release over norepinephrine (epinephrine) release. Psychedelic tryptamines found in nature include psilocin, DMT , 5-MeO-DMT, and tryptamines that have been synthesized in the laboratory include 4-HO-MET , 4-HO-MiPT , and 5-MeO-DALT . Phenethylamine is also a trace amine but to a lesser extent acts as a neurotransmitter in the human central nervous system (CNS). Phenethylamine instead regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1), which plays

2014-593: A psychedelic. A June 2024 report by the RAND Corporation suggests psilocybin mushrooms may be the most prevalent psychedelic drug among adults in the United States. The RAND national survey indicated that 3.1% of U.S. adults reported using psilocybin in the past year. Roughly 12% of respondents acknowledged lifetime use of psilocybin, while a similar percentage reported having used LSD at some point in their lives. MDMA , also known as ecstasy, showed

2120-666: A qualified professional with appropriate set and setting. However, he called for an "abundance of caution" because in the absence of these conditions a range of negative reactions is possible, including "fear, a prolonged sense of dread, or full panic." He notes that driving or even walking in public can be dangerous during a psychedelic experience because of impaired hand-eye coordination and fine motor control . In some cases, individuals taking psychedelics have performed dangerous or fatal acts because they believed they possessed superhuman powers. Psilocybin-induced states of mind share features with states experienced in psychosis , and while

2226-406: A sense of spiritual enlightenment, and a feeling of interconnectedness with the universe. Negative experiences, commonly known as " bad trips ", can induce feelings of fear, agitation, anxiety, panic and paranoia. While the occurrence of a bad trip is unpredictable, factors such as mood, surroundings, sleep, hydration, and social setting, collectively referred to as " set and setting ", can influence

SECTION 20

#1732765538333

2332-505: A significant number of individuals ingested the substance which they believed was LSD, and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently". Researchers state that the alleged physiological toxicity of LSD is likely due to psychoactive substances other than LSD. NBOMe compounds are reported to have a bitter taste, are not active orally, and are usually taken sublingually. When NBOMes are administered sublingually, numbness of

2438-452: A significant role in regulating neurotransmission in dopamine, norepinephrine, and serotonin neurons in the CNS and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. When VMAT2 is inhibited monoamine neurotransmitters such as dopamine cannot be released into the synapse via typical release mechanisms. Mescaline is a naturally occurring psychedelic protoalkaloid of

2544-467: A single male volunteer had an apparent plasma half-life of 5.1 hours, with a peak plasma concentration of 5 ng/mL at 3 hours post-dose. The pharmacokinetics of LSD were not properly determined until 2015, which is not surprising for a drug with the kind of low-μg potency that LSD possesses. In a sample of 16 healthy subjects, a single mid-range 200 μg oral dose of LSD was found to produce mean maximal concentrations of 4.5 ng/mL at

2650-419: A speech on his 100th birthday, the inventor of LSD, Albert Hofmann said of the drug: "It gave me an inner joy, an open mindedness , a gratefulness, open eyes and an internal sensitivity for the miracles of creation... I think that in human evolution it has never been as necessary to have this substance LSD. It is just a tool to turn us into what we are supposed to be." With certain psychedelics and experiences,

2756-419: A standard concentration of 270 μg, while street samples of the 1970s contained 30 to 300 μg. By the 1980s, the amount had reduced to between 100 and 125 μg, dropping more in the 1990s to the 20–80 μg range, and even more in the 2000s (decade). "LSD," writes the chemist Alexander Shulgin , "is an unusually fragile molecule ... As a salt, in water, cold, and free from air and light exposure, it

2862-484: A substantially altered state of consciousness . They have had the largest influence on science and culture, and include mescaline , LSD , psilocybin , and DMT . Most psychedelic drugs fall into one of the three families of chemical compounds: tryptamines , phenethylamines , or lysergamides (LSD is considered both a tryptamine and lysergamide). They act via serotonin 2A receptor agonism . When compounds bind to serotonin 5-HT 2A receptors, they modulate

2968-524: A user may also experience an " afterglow " of improved mood or perceived mental state for days or even weeks after ingestion in some cases. In 1898, the English writer and intellectual Havelock Ellis reported a heightened perceptual sensitivity to "the more delicate phenomena of light and shade and color" for a prolonged period of time after his exposure to mescaline. Good trips are reportedly deeply pleasurable, and typically involve intense joy or euphoria,

3074-405: A very strong correlation between 5-HT 2A receptor affinity and human hallucinogenic potency . In addition, the intensity of hallucinogenic effects in humans is directly correlated with the level of serotonin 5-HT 2A receptor occupancy as measured with positron emission tomography (PET) imaging . Serotonin 5-HT 2A receptor blockade with drugs like the semi-selective ketanserin and

3180-423: Is a biased agonist that induces a conformation in serotonin receptors that preferentially recruits β-arrestin over activating G proteins . LSD also has an exceptionally long residence time when bound to serotonin receptors lasting hours, consistent with the long lasting effects of LSD despite its relatively rapid clearance . A crystal structure of 5-HT 2B bound to LSD reveals an extracellular loop that forms

3286-554: Is a derivative and functional analogue of LSD and a homologue of ALD-52 . It modifies the LSD molecule by adding a propionyl group to the nitrogen atom of LSD's indole . Although several attempts have been made, starting in the 19th and 20th centuries, to define common phenomenological structures of the effects produced by classic psychedelics, a universally accepted taxonomy does not yet exist. At lower doses, features of psychedelic experiences include sensory alterations, such as

LSD - Misplaced Pages Continue

3392-714: Is almost unanimously agreed that psychedelics produce their effect by acting as strong partial agonists at the 5-HT 2A receptors. How this produces the psychedelic experience is unclear, but it is likely that it acts by increasing excitation in the cortex, possibly by specifically facilitating input from the thalamus , the major relay for sensory information input to the cortex . Additionally, researchers discovered that many psychedelics are potent psychoplastogens , compounds capable of promoting rapid and sustained neural plasticity . Psychedelics are thought to mediate their hallucinogenic effects by activation of serotonin 5-HT 2A receptors. Serotonergic psychedelics, such as

3498-405: Is an inaccurate descriptor of the actual effects of these drugs. In the lay press, the term psychedelic is still the most popular and has held sway for nearly four decades. Most recently, there has been a movement in nonscientific circles to recognize the ability of these substances to provoke mystical experiences and evoke feelings of spiritual significance. Thus, the term entheogen , derived from

3604-416: Is derived from naturally occurring ergotamine, and non-classic psychedelics are considered to be newer analogs and derivatives of pharmacophore lysergamides, tryptamine, and phenethylamine structures like 2C-B . Many of these psychedelics cause remarkably similar effects, despite their different chemical structure. However, many users report that the three major families have subjectively different qualities in

3710-473: Is estimated at 100 mg, based on LD 50 and lethal blood concentrations observed in rodent studies. LSD shows significant tachyphylaxis , with tolerance developing 24 hours after administration. The progression of tolerance at intervals shorter than 24 hours remains largely unknown. Tolerance typically resets to baseline after 3–4 days of abstinence. Significant cross-tolerance occurs between LSD, mescaline and psilocybin . A slight cross-tolerance to DMT

3816-596: Is evidence that psychedelics induce molecular and cellular adaptations related to neuroplasticity and that these could potentially underlie therapeutic benefits. Psychedelics have also been shown to have potent anti-inflammatory activity and therapeutic effects in animal models of inflammatory diseases including asthma, and cardiovascular disease and diabetes. Psychedelic culture includes manifestations such as psychedelic music , psychedelic art , psychedelic literature , psychedelic film , and psychedelic festivals . Examples of psychedelic music would be rock bands like

3922-1181: Is exceptionally potent, with as little as 20 μg capable of producing a noticeable effect. LSD can induce physical effects such as pupil dilation , decreased appetite , increased sweating, and wakefulness. The physical reactions to LSD vary greatly and some may be a result of its psychological effects. Commonly observed symptoms include increased body temperature, blood sugar , and heart rate, as well as goose bumps , jaw clenching, dry mouth, and hyperreflexia . In cases of adverse reactions, users may experience numbness, weakness, nausea, and tremors. The primary immediate psychological effects of LSD are visual hallucinations and illusions , often referred to as "trips". These effects typically begin within 20–30 minutes of oral ingestion, peak three to four hours after ingestion, and can last up to 20 hours, particularly with higher doses. An " afterglow " effect, characterized by an improved mood or perceived mental state, may persist for days or weeks following ingestion. Positive experiences, or "good trips", are described as intensely pleasurable and can include feelings of joy, euphoria, an increased appreciation for life, decreased anxiety,

4028-433: Is found in the central nervous system of mammals . It is hypothesized to play a role as a neuromodulator on classical monoamine neurotransmitters , such as dopamine , serotonin, norepinephrine and epinephrine . Tryptamine acts as a non-selective serotonin receptor agonist to activate serotonin receptors, and a serotonin–norepinephrine–dopamine releasing agent (SNDRA) to release more monoamine neurotransmitter, with

4134-402: Is induced by serotonergic psychedelics and is a behavioral proxy of psychedelic-like effects in animals. The HTR is invariably induced by serotonergic psychedelics, is blocked by selective serotonin 5-HT 2A receptor antagonists, and is abolished in serotonin 5-HT 2A receptor knockout mice . In addition, there is a strong correlation between hallucinogenic potency in humans and potency in

4240-544: Is made by alkaline hydrolysis of lysergamides like ergotamine , a substance usually derived from the ergot fungus on agar plate ; or, theoretically possible, but impractical and uncommon, from ergine (lysergic acid amide, LSA) extracted from morning glory seeds. Lysergic acid can also be produced synthetically, although these processes are not used in clandestine manufacture due to their low yields and high complexity. The precursor for LSD, lysergic acid , has been produced by GMO baker's yeast . A single dose of LSD

4346-497: Is observed in humans highly tolerant to LSD. Tolerance to LSD also builds up with consistent use, and is believed to result from serotonin 5-HT 2A receptor downregulation . Researchers believe that tolerance returns to baseline after two weeks of not using psychedelics. LSD is widely considered to be non-addictive, despite its potential for abuse . Attempts to train laboratory animals to self-administer LSD have been largely unsuccessful. Although tolerance to LSD builds up rapidly,

LSD - Misplaced Pages Continue

4452-638: Is often described as a key feature of the psychedelic experience. Many psychedelic drugs are illegal to possess without lawful authorisation, exemption or license worldwide under the UN conventions , with occasional exceptions for religious use or research contexts. Despite these controls, recreational use of psychedelics is common. Legal barriers have made the scientific study of psychedelics more difficult. Research has been conducted, however, and studies show that psychedelics are physiologically safe and rarely lead to addiction. Studies conducted using psilocybin in

4558-712: Is overwhelming. The serotonin 5-HT 2A receptor activates several downstream signaling pathways . These include the G q , β-arrestin2 , and other pathways. Activation of both the G q and β-arrestin2 pathways have been implicated in mediating the hallucinogenic effects of serotonergic psychedelics. However, subsequently, activation of the G q pathway and not β-arrestin2 has been implicated. Interestingly, G q signaling appeared to mediate hallucinogenic-like effects, whereas β-arrestin2 mediated receptor downregulation and tachyphylaxis . The lack of psychedelic effects with non-hallucinogenic serotonin 5-HT 2A receptor agonists may be due to partial agonism of

4664-411: Is sometimes used for a much broader range of drugs, including empathogen–entactogens , dissociatives , and atypical hallucinogens/psychoactives such as Amanita muscaria , Cannabis sativa , Nymphaea nouchali and Salvia divinorum . Thus, the term serotonergic psychedelic is sometimes used for the narrower class. It is important to check the definition of a given source. This article uses

4770-505: Is stable indefinitely." LSD has two labile protons at the tertiary stereogenic C5 and C8 positions, rendering these centers prone to epimerisation . The C8 proton is more labile due to the electron-withdrawing carboxamide attachment, but removal of the chiral proton at the C5 position (which was once also an alpha proton of the parent molecule tryptophan ) is assisted by the inductively withdrawing nitrogen and pi electron delocalisation with

4876-442: Is synthesized from lysergic acid and commonly administered via tabs of blotter paper. LSD is mainly used recreationally or for spiritual purposes. As a serotonin receptor agonist , LSD's precise effects are not fully understood, but it is known to alter the brain’s default mode network , leading to its powerful psychedelic effects. The drug was first synthesized by Swiss chemist Albert Hofmann in 1938 and became widely studied in

4982-485: Is the proposed use of psychedelic drugs to treat mental disorders . As of 2021, psychedelic drugs are controlled substances in most countries and psychedelic therapy is not legally available outside clinical trials, with some exceptions. The procedure for psychedelic therapy differs from that of therapies using conventional psychiatric medications . While conventional medications are usually taken without supervision at least once daily, in contemporary psychedelic therapy

5088-429: Is typically between 40 and 500 micrograms—an amount roughly equal to one-tenth the mass of a grain of sand. Threshold effects can be felt with as little as 25 micrograms of LSD. The practice of using sub-threshold doses is called microdosing . Dosages of LSD are measured in micrograms (μg), or millionths of a gram. In the mid-1960s, the most important black market LSD manufacturer ( Owsley Stanley ) distributed LSD at

5194-797: Is unclear. Overall, the evidence seems to point to limited or no effect at commonly used doses. Studies showed no evidence of teratogenic or mutagenic effects. There have been no documented fatal human overdoses from LSD, although there has been no "comprehensive review since the 1950s" and "almost no legal clinical research since the 1970s". Eight individuals who had accidentally consumed an exceedingly high amount of LSD, mistaking it for cocaine, and had gastric levels of 1000–7000 μg LSD tartrate per 100 mL and blood plasma levels up to 26 μg/ml, had suffered from comatose states , vomiting, respiratory problems, hyperthermia , and light gastrointestinal bleeding ; however, all of them survived without residual effects upon hospital intervention. Individuals experiencing

5300-461: Is varied. Some cases are attributed to somatic symptom disorder , where individuals fixate on normal somatic experiences previously unnoticed prior to drug consumption. Other instances are linked to associative reactions to contextual cues, similar to responses observed in individuals with past trauma or emotional experiences. The risk factors for flashbacks remain unclear, but pre-existing psychopathologies may be significant contributors. Estimating

5406-659: The Grateful Dead , Jefferson Airplane and The Beatles . Many psychedelic bands and elements of the psychedelic subculture originated in San Francisco during the mid to late 1960s. Many psychedelics are classified under Schedule I of the United Nations Convention on Psychotropic Substances of 1971 as drugs with the greatest potential to cause harm and no acceptable medical uses. In addition, many countries have analogue laws; for example, in

SECTION 50

#1732765538333

5512-685: The Rio Grande Valley in North America by native tribes as an entheogen . In the Andean region of South America, the San Pedro cactus ( Trichocereus macrogonus var. pachanoi , syn. Echinopsis pachanoi ) has a long history of use, possibly as a traditional medicine . Archaeological studies have found evidence of use going back two thousand years, to Moche culture, Nazca culture , and Chavín culture . Although authorities of

5618-654: The Roman Catholic church attempted to suppress its use after the Spanish conquest, this failed, as shown by the Christian element in the common name "San Pedro cactus" – Saint Peter cactus. The name has its origin in the belief that just as St Peter holds the keys to heaven, the effects of the cactus allow users "to reach heaven while still on earth." In 2022, the Peruvian Ministry of Culture declared

5724-669: The indole ring. Psychedelic drug Psychedelic film 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 hallucinogens or serotonergic hallucinogens , the term psychedelic is sometimes used more broadly to include various types of hallucinogens, such as those which are atypical or adjacent to psychedelia like salvia and MDMA , respectively. Classic psychedelics generally cause specific psychological, visual, and auditory changes, and oftentimes

5830-474: The locus coeruleus , nucleus accumbens , and amygdala , and activation of the PFC by serotonergic psychedelics may thereby modulate these areas. In addition to the PFC, there is moderate to high expression of serotonin 5-HT 2A receptors in the primary visual cortex (V1) as well as expression of the serotonin 5-HT 2A receptor in other visual areas, and activation of these receptors may contribute to or mediate

5936-610: The medial prefrontal cortex (mPFC). Activation of serotonin 5-HT 2A receptors in this area results in marked excitatory and inhibitory effects as well as increased release of glutamate and GABA . Direct injection of serotonin 5-HT 2A receptor agonists into the mPFC produces the HTR. Drugs that suppress glutamatergic activity in the mPFC, including AMPA receptor antagonists, metabotropic glutamate mGlu 2 / 3 receptor agonists, μ-opioid receptor agonists, and adenosine A 1 receptor agonists, block or suppress many of

6042-409: The sacred scriptures of the great religions of the world and the texts of ancient civilizations . LSD currently has no approved uses in medicine . A meta analysis concluded that a single dose was shown to be effective at reducing alcohol consumption in people suffering from alcoholism . LSD has also been studied in depression, anxiety, and drug dependence, with positive preliminary results. LSD

6148-556: The serotonin 5-HT 2A receptor but also of the serotonin 5-HT 2B receptor and other serotonin receptors . A potential risk of frequent repeated use of serotonergic psychedelics is cardiac fibrosis and valvulopathy caused by 5-HT 2B receptor activation. However, single high doses or widely spaced doses (e.g., months) are widely thought to be safe and concerns about cardiac toxicity apply more to chronic psychedelic microdosing or very frequent use (e.g., weekly). Selective 5-HT 2A receptor agonists that do not activate

6254-555: The substituted phenethylamine class. Amides of lysergic acid are collectively known as lysergamides , and include a number of compounds with potent agonist and/or antagonist activity at various serotonin and dopamine receptors . The structure of lysergamides contains the structure of both tryptamines and phenethylamines. LSD (Lysergic Acid Diethylamide) is one of many lysergamides. A wide range of lysergamides have emerged in recent years, inspired by existing scientific literature. Others, have appeared from chemical research. 1P-LSD

6360-400: The tryptamines psilocin , DMT , and 5-MeO-DMT , the phenethylamines mescaline , DOM , and 2C-B , and ergolines and lysergamides like LSD , all act as agonists of the serotonin 5-HT 2A receptors. In addition, some psychedelics, such as phenethylamines like DOM and 2C-B, show high selectivity for the serotonin 5-HT 2 receptors over other serotonin receptors . There is

6466-413: The "feel" of the experience, which are difficult to describe. Some compounds, such as 2C-B, have extremely tight "dose curves", meaning the difference in dose between a non-event and an overwhelming disconnection from reality can be very slight. There can also be very substantial differences between the drugs; for instance, 5-MeO-DMT rarely produces the visual effects typical of other psychedelics. Despite

SECTION 60

#1732765538333

6572-672: The 1950s and 1960s. It was used experimentally in psychiatry for treating alcoholism and schizophrenia . However, its association with the counterculture movement of the 1960s led to its classification as a Schedule I drug in the U.S. in 1968. It was also listed as a Schedule 1 controlled substance by the United Nations in 1971 and remains without approved medical uses. Despite its legal restrictions, LSD remains influential in scientific and cultural contexts. Its therapeutic potential has been explored, particularly in treating mental health disorders. As of 2017, about 10% of people in

6678-706: The 1960s indicated increased suggestibility under the influence of LSD among both mentally ill and healthy individuals, recent documents suggest that the CIA and Department of Defense have discontinued research into LSD as a means of mind control. Flashbacks are psychological episodes where individuals re-experience some of LSD's subjective effects after the drug has worn off, persisting for days or months post- hallucinogen use. These experiences are associated with hallucinogen persisting perception disorder (HPPD), where flashbacks occur intermittently or chronically, causing distress or functional impairment. The etiology of flashbacks

6784-599: The 21st century with more people claiming long-term benefits from the practice. A 2022 study recognized signatures of psilocybin microdosing in natural language and concluded that low amount of psychedelics have potential for application, and ecological observation of microdosing schedules. While the method of action of psychedelics is not fully understood, they are known to show affinities for various 5-HT (serotonin) receptors in different ways and levels, and may be classified by their activity at different 5-HT sub-types, particularly 5-HT 1A , 5-HT 2A , and 5-HT 2C . It

6890-545: The 5-HT 2B receptor or other serotonin receptors, such as 25CN-NBOH , DMBMPP , and LPH-5 , have been developed and are being studied. Selective 5-HT 2A receptor agonists are expected to avoid the cardiac risks of 5-HT 2B receptor activation. Psychedelic substances which may have therapeutic uses include psilocybin, LSD, and mescaline. During the 1950s and 1960s, lack of informed consent in some scientific trials on psychedelics led to significant, long-lasting harm to some participants. Since then, research regarding

6996-533: The Greek word entheos , which means "god within", was introduced by Ruck et al. and has seen increasing use. This term suggests that these substances reveal or allow a connection to the "divine within". Although it seems unlikely that this name will ever be accepted in formal scientific circles, its use has dramatically increased in the popular media and on internet sites. Indeed, in much of the counterculture that uses these substances, entheogen has replaced psychedelic as

7102-440: The HTR assay. Moreover, the HTR paradigm is one of the only animal tests that can distinguish between hallucinogenic serotonin 5-HT 2A receptor agonists and non-hallucinogenic serotonin 5-HT 2A receptor agonists, such as lisuride . In accordance with the preceding animal and human findings, it has been said that the evidence that the serotonin 5-HT 2A receptor mediates the hallucinogenic effects of serotonergic psychedelics

7208-690: The U.S. had used LSD at some point, with 0.7% having used it in the past year. Usage rates have risen, with a 56.4% increase in adult use in the U.S. from 2015 to 2018. LSD is commonly used as a recreational drug. LSD can catalyze intense spiritual experiences and is thus considered an entheogen . Some users have reported out of body experiences. In 1966, Timothy Leary established the League for Spiritual Discovery with LSD as its sacrament . Stanislav Grof has written that religious and mystical experiences observed during LSD sessions appear to be phenomenologically indistinguishable from similar descriptions in

7314-746: The United States, the Federal Analogue Act of 1986 automatically forbids any drugs sharing similar chemical structures or chemical formulas to prohibited substances if sold for human consumption. In July 2022, though, under the United States Food and Drug Administration, the drug psilocybin was on track to be approved of as a treatment for depression, and MDMA as a treatment for post-traumatic stress disorder. U.S. states such as Oregon and Colorado have also instituted decriminalization and legalization measures for accessing psychedelics and states like New Hampshire are attempting to do

7420-527: The activity of key circuits in the brain involved with sensory perception and cognition. However, the exact nature of how psychedelics induce changes in perception and cognition via the 5-HT 2A receptor is still unknown. The psychedelic experience is often compared to non-ordinary forms of consciousness such as those experienced in meditation, mystical experiences , and near-death experiences , which also appear to be partially underpinned by altered default mode network activity. The phenomenon of ego death

7526-413: The assessment of promising drug therapies for potential approval, to psilocybin therapy for treatment-resistant depression and major depressive disorder. Recreational use of psychedelics has been common since the psychedelic era of the mid-1960s and continues to play a role in various festivals and events, including Burning Man . A survey published in 2013 found that 13.4% of American adults had used

7632-549: The body of high-quality evidence on psychedelic therapy remains relatively small and more, larger studies are needed to reliably show the effectiveness and safety of psychedelic therapy's various forms and applications. On the basis of favorable early results, ongoing research is examining proposed psychedelic therapies for conditions including major depressive disorder , and anxiety and depression linked to terminal illness . The United States Food and Drug Administration has granted "breakthrough therapy" status, which expedites

7738-413: The brain concentration of approximately 10–20  nM . In humans, recreational doses of LSD can affect 5-HT 1A (K i = 1.1 nM), 5-HT 2A (K i = 2.9 nM), 5-HT 2B (K i = 4.9 nM), 5-HT 2C (K i = 23 nM), 5-HT 5A (K i = 9 nM [in cloned rat tissues]), and 5-HT 6 receptors (K i = 2.3 nM). Although not present in humans, 5-HT 5B receptors found in rodents also have

7844-566: The case of iboga. Different countries and/or regions have come to be associated with traditional or spiritual use of particular psychedelics, such as the ancient and entheogenic use of psilocybe mushrooms by the native Mazatec people of Oaxaca , Mexico or the use of the ayahuasca brew in the Amazon basin , particularly in Peru for spiritual and physical healing as well as for religious festivals. Peyote has also been used for several thousand years in

7950-637: The context of finding out what is wrong with the individual, such as using psychedelic states to "identify" a disease and/or its cause, locate lost objects, and identify a victim or even perpetrator of sorcery . In some cultures and regions, even psychedelics themselves, such as ayahuasca and the psychedelic lichen of eastern Ecuador ( Dictyonema huaorani ) that supposedly contains both 5-MeO-DMT and psilocybin, have also been used by witches and sorcerers to conduct their malicious magic , similarly to nightshade deliriants like brugmansia and latua . Psychedelic therapy (or psychedelic-assisted therapy)

8056-497: The contrary perception of much of the public, psychedelic drugs are not addictive and are physiologically safe. As of 2016, there have been no known deaths due to overdose of LSD, psilocybin, or mescaline. Risks do exist during an unsupervised psychedelic experience, however; Ira Byock wrote in 2018 in the Journal of Palliative Medicine that psilocybin is safe when administered to a properly screened patient and supervised by

8162-426: The cortex. This phenomenon appears to selectively involve ventral, intralaminar, and pulvinar nuclei. LSD is a chiral compound with two stereocenters at the carbon atoms C-5 and C-8, so that theoretically four different optical isomers of LSD could exist. LSD, also called (+)- d -LSD, has the absolute configuration (5 R ,8 R ). 5 S stereoisomers of lysergamides do not exist in nature and are not formed during

8268-530: The drug is administered in a single session (or sometimes up to three sessions) in a therapeutic context. The therapeutic team prepares the patient for the experience beforehand and helps them integrate insights from the drug experience afterwards. After ingesting the drug, the patient normally wears eyeshades and listens to music to facilitate focus on the psychedelic experience, with the therapeutic team interrupting only to provide reassurance if adverse effects such as anxiety or disorientation arise. As of 2022,

8374-487: The drug was eliminated in urine unchanged, whereas 13% was eliminated as the major metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) within 24 hours. O-H-LSD is formed by cytochrome P450 enzymes , although the specific enzymes involved are unknown, and it does not appear to be known whether O-H-LSD is pharmacologically active or not. The oral bioavailability of LSD was crudely estimated as approximately 71% using previous data on intravenous administration of LSD. The sample

8480-739: The effectiveness of psychedelic therapy has been conducted under strict ethical guidelines, with fully informed consent and a pre-screening to avoid people with psychosis taking part. Although the history behind these substances has hindered research into their potential medicinal value, scientists are now able to conduct studies and renew research that was halted in the 1970s. Some research has shown that these substances have helped people with such mental disorders as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), alcoholism, depression, and cluster headaches . It has long been known that psychedelics promote neurite growth and neuroplasticity and are potent psychoplastogens . There

8586-656: The enzyme phospholipase C as the endogenous ligand serotonin does. Exactly how LSD produces its effects is unknown, but it is thought that it works by increasing glutamate release in the cerebral cortex and therefore excitation in this area, specifically in layer V . LSD, like many other drugs of recreational use, has been shown to activate DARPP-32 -related pathways. The drug enhances dopamine D 2 receptor protomer recognition and signaling of D 2 –5-HT 2A receptor complexes, which may contribute to its psychotropic effects. LSD has been shown to have low affinity for H1 receptors , displaying antihistamine effects. LSD

8692-444: The intended meaning "mind manifesting" or alternatively "soul manifesting", and the implication that psychedelics can reveal unused potentials of the human mind. The term was loathed by American ethnobotanist Richard Schultes but championed by American psychologist Timothy Leary . Aldous Huxley had suggested his own coinage phanerothyme (Greek phaneroein - "to make manifest or visible" and Greek thymos "soul", thus "to reveal

8798-638: The more common, narrower definition of psychedelic . A number of frequently mentioned or traditional psychedelics such as Ayahuasca (which contains DMT ), San Pedro , Peyote , and Peruvian torch (which all contain mescaline ), Psilocybe mushrooms (which contain psilocin / psilocybin ) and Tabernanthe iboga (which contains the unique psychedelic ibogaine ) all have a long and extensive history of spiritual , shamanic and traditional usage by indigenous peoples in various world regions, particularly in Latin America, but also Gabon , Africa in

8904-501: The name of choice and we may expect to see this trend continue. Robin Carhart-Harris and Guy Goodwin write that the term psychedelic is preferable to hallucinogen for describing classical psychedelics because of the term hallucinogen ' s "arguably misleading emphasis on these compounds' hallucinogenic properties." While the term psychedelic is most commonly used to refer only to serotonergic hallucinogens, it

9010-436: The nature of existence… typically accompanied by a sense of certainty that this knowledge is ultimately more relevant and 'real' than the perceptions and beliefs we share in everyday life." Traditionally, the standard model for the subjective phenomenological effects of psychedelics has typically been based on LSD, with anything that is considered "psychedelic" evidently being compared to it and its specific effects . During

9116-547: The neurochemical and behavioral effects of serotonergic psychedelics, including the HTR. Metabotropic glutamate mGlu 2 receptors are primarily expressed as presynaptic autoreceptors and may have inhibitory effects on glutamate release. Serotonergic psychedelics have been found to produce frontal cortex hyperactivity in humans in PET and single-photon emission computed tomography (SPECT) imaging studies. The PFC projects to many other cortical and subcortical brain areas, such as

9222-588: The non-selective risperidone can abolish the hallucinogenic effects of psychedelics in humans. However, studies with more selective serotonin 5-HT 2A receptor antagonists, like pimavanserin , are still needed. In animals, potency for stimulus generalization to the psychedelic DOM in drug discrimination tests is strongly correlated with serotonin 5-HT 2A receptor affinity. Non-selective serotonin 5-HT 2A receptor antagonists, like ketanserin and pirenperone , and selective serotonin 5-HT 2A receptor antagonists, like volinanserin (MDL-100907), abolish

9328-696: The perception of food's texture and taste are also noted, sometimes leading to aversion towards certain foods. There are reports of inanimate objects appearing animated, with static objects seeming to move in additional spatial dimensions. The auditory effects of LSD may include echo -like distortions of sounds. Basic visual effects often resemble phosphenes and can be influenced by concentration, thoughts, emotions, or music. Auditory effects may include echo -like distortions and an intensified experience of music. Higher doses can lead to more intense sensory perception alterations, including synesthesia, perception of additional dimensions, and temporary dissociation . LSD,

9434-801: The prevalence of HPPD is challenging. It is considered rare, with occurrences ranging from 1 in 20 users experiencing the transient and less severe type 1 HPPD, to 1 in 50,000 for the more concerning type 2 HPPD. Contrary to internet rumors, LSD is not stored long-term in the spinal cord or other body parts. Pharmacological evidence indicates LSD has a half-life of 175 minutes and is metabolized into water-soluble compounds like 2-oxo-3-hydroxy-LSD, eliminated through urine without evidence of long-term storage. Clinical evidence also suggests that chronic use of SSRIs can potentiate LSD-induced flashbacks, even months after stopping LSD use. Several psychedelics, including LSD, are metabolized by CYP2D6 . Concurrent use of SSRIs , potent inhibitors of CYP2D6, with LSD may heighten

9540-657: The risk and are considered important in minimizing the likelihood of a negative experience. LSD induces an animated sensory experience affecting senses, emotions, memories, time, and awareness, lasting from 6 to 20 hours, with the duration dependent on dosage and individual tolerance. Effects typically commence within 30 to 90 minutes post-ingestion, ranging from subtle perceptual changes to profound cognitive shifts . Alterations in auditory and visual perception are common. Users may experience enhanced visual phenomena, such as vibrant colors, objects appearing to morph, ripple or move, and geometric patterns on various surfaces. Changes in

9646-657: The risk of serotonin syndrome . Chronic usage of SSRIs, TCAs , and MAOIs is believed to diminish the subjective effects of psychedelics, likely due to SSRI-induced 5-HT 2A receptor downregulation and MAOI-induced 5-HT 2A receptor desensitization. Interactions between psychedelics and antipsychotics or anticonvulsants are not well-documented; however, co-use with mood stabilizers like lithium may induce seizures and dissociative effects , particularly in individuals with bipolar disorder . Lithium notably intensifies LSD reactions, potentially leading to acute comatose states when combined. The lethal oral dose of LSD in humans

9752-410: The same. J.D. Tuccille argues that increasing rates of use of psychedelics in defiance of the law are likely to result in more widespread legalization and decriminalization of access to the substances in the United States (as has happened with alcohol and cannabis ). Psychedelic Timeline by Tom Frame, Psychedelic Times Afterglow (drug culture) This phenomenon contrasts with hangovers ,

9858-1002: The serotonin 5-HT 2A receptor with efficacy insufficient to produce psychedelic effects or may be due to biased agonism of the serotonin 5-HT 2A receptor. There appears to be a threshold level of G q activation (in terms of intrinsic activity , with E max Tooltip maximal efficacy >70%) required for production of hallucinogenic effects. Full agonists and partial agonists above this threshold are psychedelic 5-HT 2A receptor agonists, whereas partial agonists below this threshold, such as lisuride, 2-bromo-LSD , 6-fluoro-DET , 6-MeO-DMT , and Ariadne , are non-hallucinogenic 5-HT 2A receptor agonists. In addition, biased agonists that activate β-arrestin2 signaling but not G q signaling, such as ITI-1549 , IHCH-7086 , and 25N-N1-Nap , are non-hallucinogenic serotonin 5-HT 2A receptor agonists. The hallucinogenic effects of serotonergic psychedelics may be mediated in part or full by serotonin 5-HT 2A receptor activation in

9964-427: The soul") to Osmond in 1956. Recently, the term entheogen (meaning "that which produces the divine within") has come into use to denote the use of psychedelic drugs, as well as various other types of psychoactive substances, in a religious, spiritual, and mystical context. In 2004, David E. Nichols wrote the following about the nomenclature used for psychedelic drugs: Many different names have been proposed over

10070-574: The stimulus generalization of psychedelics in drug discrimination tests. Conversely, serotonin 5-HT 2B and 5-HT 2C receptor antagonists are ineffective. The potencies of serotonin 5-HT 2 receptor antagonists in blocking psychedelic substitution are strongly correlated with their serotonin 5-HT 2A receptor affinities. Highly selective serotonin 5-HT 2A receptor agonists have recently been developed and show stimulus generalization to psychedelics, whereas selective serotonin 5-HT 2C receptor agonists do not do so. The head-twitch response (HTR)

10176-491: The synthesis can be separated by chromatography and can be isomerized to LSD. Pure salts of LSD are triboluminescent , emitting small flashes of white light when shaken in the dark. LSD is strongly fluorescent and will glow bluish-white under UV light . LSD is an ergoline derivative. It is commonly synthesized by reacting diethylamine with an activated form of lysergic acid . Activating reagents include phosphoryl chloride and peptide coupling reagents . Lysergic acid

10282-531: The synthesis from d -lysergic acid. Retrosynthetically , the C-5 stereocenter could be analysed as having the same configuration of the alpha carbon of the naturally occurring amino acid L- tryptophan , the precursor to all biosynthetic ergoline compounds. However, LSD and iso-LSD, the two C-8 isomers, rapidly interconvert in the presence of bases , as the alpha proton is acidic and can be deprotonated and reprotonated. Non-psychoactive iso-LSD which has formed during

10388-424: The tongue and mouth followed by a metallic chemical taste was observed, and researchers describe this physical side effect as one of the main discriminants between NBOMe compounds and LSD. Despite its high potency, recreational doses of LSD have only produced low incidents of acute toxicity, but NBOMe compounds have extremely different safety profiles. Testing with Ehrlich's reagent gives a positive result for LSD and

10494-500: The traditional use of San Pedro cactus in northern Peru as cultural heritage . Although people of Western culture have tended to use psychedelics for either psychotherapeutic or recreational reasons, most indigenous cultures, particularly in South America, have seemingly tended to use psychedelics for more supernatural reasons such as divination . This can often be related to "healing" or health as well but typically in

10600-453: The user with a decreased mental capacity. Many report that their brain feels like "mush". The trip may leave the user with a bizarre sense of self. Afterglow occurs after the comedown . Afterglow slowly fades, but can last as short as 24-hours, while some positive post-acute phase of psychedelic drug effects (characterized by elevated mood and openness) have been reported to extend between 6 and 8 weeks. This hallucinogen -related article

10706-491: The visual effects of serotonergic psychedelics. Serotonergic psychedelics also directly or indirectly modulate a variety of other brain areas. Although the hallucinogenic effects of serotonergic psychedelics are thought to be mediated by serotonin 5-HT 2A receptor activation, interactions with other receptors, such as the serotonin 5-HT 1A and 5-HT 2C receptors, may modulate and additionally contribute to their effects. Tryptamine , along with other trace amines ,

10812-862: The warping of surfaces, shape suggestibility, pareidolia and color variations. Users often report intense colors that they have not previously experienced, and repetitive geometric shapes or form constants are common as well. Higher doses often cause intense and fundamental alterations of sensory (notably visual ) perception, such as synesthesia or the experience of additional spatial or temporal dimensions. Tryptamines are well documented to cause classic psychedelic states, such as increased empathy , visual distortions (drifting, morphing, breathing, melting of various surfaces and objects), auditory hallucinations, ego dissolution or ego death with high enough dose, mystical, transpersonal and spiritual experiences, autonomous " entity " encounters, time distortion, closed eye hallucinations and complete detachment from reality with

10918-422: The years for this drug class. The famous German toxicologist Louis Lewin used the name phantastica earlier in this century, and as we shall see later, such a descriptor is not so farfetched. The most popular names—hallucinogen, psychotomimetic, and psychedelic ("mind manifesting")—have often been used interchangeably. Hallucinogen is now, however, the most common designation in the scientific literature, although it

11024-642: Was associated with increased prevalence of any mental illness. Using psychedelics poses certain risks of re-experiencing of the drug's effects, including flashbacks and hallucinogen persisting perception disorder (HPPD). These non-psychotic effects are poorly studied, but the permanent symptoms (also called "endless trip") are considered to be rare. Serotonin syndrome can be caused by combining psychedelics with other serotonergic drugs, including certain antidepressants, opioids, CNS stimulants (e.g. MDMA), 5-HT 1 agonists (e.g. triptans ), herbs and others. Serotonergic psychedelics are agonists not only of

11130-523: Was coined by the psychiatrist Humphrey Osmond during written correspondence with author Aldous Huxley (written in a rhyme: “To fathom Hell or soar angelic/Just take a pinch of psychedelic.” ) and presented to the New York Academy of Sciences by Osmond in 1957. It is irregularly derived from the Greek words ψυχή ( psychḗ , meaning 'mind, soul') and δηλείν ( dēleín , meaning 'to manifest'), with

11236-483: Was equally divided between male and female subjects and there were no significant sex differences observed in the pharmacokinetics of LSD. Neuroimaging studies using resting state fMRI recently suggested that LSD changes the cortical functional architecture. These modifications spatially overlap with the distribution of serotoninergic receptors. In particular, increased connectivity and activity were observed in regions with high expression of 5-HT 2A receptor, while

#332667