expedites the assessment of promising drug therapies for potential approval, to psilocybin therapy for treatment-resistant depression and major depressive disorder. recreational further information: recreational drug use § hallucinogens recreational use of psychedelics is common. a survey published in 2013 found that 13.4% of american adults had used a psychedelic. microdosing main article: psychedelic microdosing 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 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. pharmacology 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-ht1a, 5-ht2a, and 5-ht2c. it is almost unanimously agreed that psychedelics produce their effect by acting as strong partial agonists at the 5-ht2a 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. tryptamines n,n-dmt tryptamine, along with other trace amines, 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, and norepinephrine (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 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. mescaline phenethylamines 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 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 the substituted phenethylamine class. lysergamides lysergic acid diethylamide (lsd) 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. lysergamides contain both tryptamine and phenethylamine structure although it is class as a complex tryptamine. 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 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 molecule of lsd's indole. psychedelic experiences main article: psychedelic experience 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 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 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 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 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, 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, 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 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 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 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. potential adverse effects despite 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 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 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 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-ht1 agonists (e.g. triptans), herbs and others. potential therapeutic effects further information: psychedelic therapy psilocybin session at johns hopkins 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 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 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. surrounding culture psychedelic rock band jefferson airplane in 1967 main article: psychedelia 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 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. legal status 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 the united states, the federal analogue act of 1986 automatically forbids any drugs sharing similar chemical structures or chemical formulas to illicit or prohibited substances if sold for human consumption. u.s. states such as oregon and colorado have also instituted decriminalization and legalization measures of psychedelics and states like new hampshire and others are attempting to do 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 the substances in the united states (as has happened with alcohol and cannabis).