97-417: TIHKAL: The Continuation is a 1997 book written by Alexander Shulgin and Ann Shulgin about a family of psychoactive drugs known as tryptamines . A sequel to PIHKAL: A Chemical Love Story , TIHKAL is an acronym that stands for "Tryptamines I Have Known and Loved". TIHKAL , much like its predecessor PIHKAL , is divided into two parts. The first part, for which all rights are reserved, begins with
194-419: 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
291-403: A May 31 update on Facebook she said that, although appearing frail, he seemed to be experiencing his last moments in peace and without pain. Shulgin died at his home on June 2, 2014, at the age of 88. In a 2014 review of the synthesis of designer drugs , the effects of Shulgin's work were described as "by far the most far-reaching" effects associated with the cultural climate of interest at
388-513: 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
485-541: 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
582-495: A fictionalized autobiography, picking up where the similar section of PIHKAL left off; it then continues with a collection of essays on topics ranging from psychotherapy and the Jungian mind to the prevalence of DMT in nature, ayahuasca and the War on Drugs . The second part of TIHKAL , which may be conditionally distributed for non-commercial reproduction (see external links below),
679-408: A great deal of career autonomy. Shulgin used this freedom to synthesize and test the effects of potentially psychoactive drugs . In 1976, Shulgin was introduced to MDMA by a student in the medicinal chemistry group he advised at San Francisco State University. MDMA had been synthesized in 1912 by Merck and patented in 1913 as an intermediate of another synthesis in order to block competitors, but
776-400: 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
873-445: 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
970-654: A home-based lab on his property, known as "the Farm", and became a private consultant. He also taught classes in the local universities and at the San Francisco General Hospital . Through his friend Bob Sager, head of the U.S. DEA 's Western Laboratories, Shulgin formed a relationship with the DEA and began holding pharmacology seminars for the agents, supplying the DEA with samples of various compounds, and occasionally serving as an expert witness in court. In 1988, he authored
1067-474: 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
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#17330862368141164-562: 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
1261-578: 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
1358-666: 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
1455-448: A scholarship student, and was enrolled there at the age of 16. He dropped out to join the U.S. Navy , during his second year at Harvard. In 1944 a military nurse gave Shulgin a glass of orange juice prior to a surgery for a thumb infection, while serving on USS Pope during World War II ; he drank the juice and, assuming that crystals at the bottom of the glass were a sedative , "fell unconscious". Upon waking he learned that
1552-488: A series of psychedelic experiences that helped to shape his further goals and research, the first of which was brought on by mescaline . "I first explored mescaline in the late '50s ... Three-hundred-fifty to 400 milligrams. I learned there was a great deal inside me." Shulgin later reported personal revelations that "had been brought about by a fraction of a gram of a white solid, but that in no way whatsoever could it be argued that these memories had been contained within
1649-461: A series of N-allylated tryptamines including 5-MeO-DALT and 5-MeO-MALT . Shulgin was married to Nina Gordon until her death from a stroke in 1977. He then married author Ann Gotlieb in 1981. He spent most of his later life at the Farm in Lafayette, California . On April 8, 2008, at the age of 82, he underwent surgery to replace a defective aortic valve . On November 16, 2010, he suffered
1746-449: 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
1843-419: 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,
1940-504: A stroke, from which he largely recovered. Also at the close of 2010, a skin-grafting surgery saved his left foot from being amputated. Around this time, Shulgin began showing early signs of dementia, mostly severe loss of short-term memory. With progression of the dementia since 2010, his wife, Ann Shulgin, had been trying to sell part of their property to raise more money to cover care costs. On April 17, 2014, Ann Shulgin reported on Facebook that her husband had developed liver cancer, and in
2037-579: 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
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#17330862368142134-484: 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
2231-427: A then-definitive law enforcement reference book on controlled substances, and received several awards from the DEA. In order to work with scheduled psychoactive chemicals, Shulgin obtained a DEA Schedule I license for an analytical laboratory, which allowed him to synthesize and possess any otherwise illicit drug. Shulgin set up a chemical synthesis laboratory in a small building behind his house, which gave him
2328-519: 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,
2425-405: 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
2522-454: A viola player, and would I be interested in sitting in for a couple of evenings? ... The Club proved to be a group of gentlemen from a broad array of political and professional backgrounds, leaning somewhat toward the political right and the well-to-do. ... At my first evening at the Club... Andrew was appointed my Pater Familias ..." Psychedelic drugs Psychedelic film Psychedelics are
2619-730: A way to protect the public's access to information about psychedelic compounds, a goal Alexander Shulgin has noted many times. Following a raid of his laboratory in 1994 by the United States DEA , Richard Meyer, spokesman for DEA's San Francisco Field Division, stated that "It is our opinion that those books [referring to the previous work, PIHKAL ] are pretty much cookbooks on how to make illegal drugs. Agents tell me that in clandestine labs that they have raided, they have found copies of those books." Alexander Shulgin Alexander Theodore "Sasha" Shulgin (June 17, 1925 – June 2, 2014)
2716-551: 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
2813-459: Is a detailed synthesis manual for 55 psychedelic compounds (many discovered by Alexander Shulgin himself), including their chemical structures, dosage recommendations, and qualitative comments. Shulgin has made the second part freely available on Erowid.org while the first part is available only in the printed text. As with PIHKAL , the Shulgins were motivated to release the synthesis information as
2910-714: 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
3007-405: 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
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3104-416: 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
3201-596: 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
3298-433: 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
3395-402: 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
3492-635: 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
3589-712: 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
3686-411: 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
3783-485: 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
3880-529: The Journal of Organic Chemistry . One of these patents, approved in 1970, involved phenethylamines. Eventually, Dow Chemical requested that he no longer use their name on his publications. In late 1966, Shulgin left Dow in order to pursue his own interests. He first spent two years studying neurology at the University of California, San Francisco School of Medicine , leaving to work on a consulting project. He set up
3977-541: The 2C* family ), and tryptamines (family containing DMT and psilocin ). There are a seemingly infinite number of slight chemical variations, which can produce variations in effect — some pleasant and some unpleasant, depending on the person, substance, and situation — all of which are meticulously recorded in Shulgin's lab notebooks. Shulgin published many of these objective and subjective reports in his books and papers. About 2C-B he said in 2003: "It is, in my opinion, one of
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4074-634: 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
4171-661: 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
4268-629: 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
4365-461: The University of California, Berkeley , Through the late 1950s, Shulgin completed post-doctoral work in the fields of psychiatry and pharmacology at University of California, San Francisco . After working at Bio-Rad Laboratories as a research director for a brief period, he began work at Dow Chemical Company , One of his early achievements at Dow was the invention of the first known biodegradable pesticide ( mexacarbate ). At this time he had
4462-497: The locus coeruleus , nucleus accumbens , and amygdala , among others, and activation of the PFC by serotonergic psychedelics may thereby indirectly 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
4559-607: 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
4656-555: 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
4753-400: 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
4850-413: 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
4947-424: The "godfather of psychedelics" ). Writing in 2005—in the decade before Shulgin's death—a retrospective by Drake Bennett of The New York Times Magazine noted that as a consequence of Shulgin's testing his various synthetic compounds "for activity by taking the chemicals himself... most of the scientific community consider[ed] Shulgin at best a curiosity and at worst a menace", but Bennett goes on to say that "near
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#17330862368145044-464: The 15 years preceding the publication of PIHKAL , two announced and scheduled reviews failed to find any irregularities. Richard Meyer, spokesman for DEA's San Francisco Field Division, has stated that, "It is our opinion that those books are pretty much cookbooks on how to make illegal drugs. Agents tell me that in clandestine labs that they have raided, they have found copies of those books." Prior to his 2010 health issues, Shulgin had been working on
5141-599: 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
5238-545: 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
5335-529: 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
5432-440: 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
5529-729: 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
5626-527: 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
5723-413: 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
5820-549: 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
5917-412: The broad use of psychedelics. In 1991 and 1997, he and his wife Ann Shulgin compiled the books PiHKAL and TiHKAL ( Phenethylamines I Have Known And Loved , likewise for Tryptamines ), from notebooks that extensively described their work and personal experiences with these two classes of psychoactive drugs . Shulgin documented the chemical synthesis of many of these compounds. Some of
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#17330862368146014-558: 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
6111-637: 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)
6208-444: 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
6305-434: The crystals were undissolved sugar, and that doctors had administered anesthesia after he was already unconscious—an experience Drake Bennett of The New York Times Magazine referred to as "revelatory", and a "tantalizing hint of the mind's odd strength", as "his collapse was caused entirely by the placebo effect". After serving in the armed forces, Shulgin returned to California, and earned his PhD in biochemistry from
6402-530: 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,
6499-739: 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
6596-431: The end... [Shulgin's] faith in the potential of psychedelics ha[d] at least a chance at vindication", going on to note the various clinical trials underway on compounds of interest to Shulgin. The early 2000s also was a period where Shulgin was witness to a series of incidents in which young men overdosed on a novel psychoactive agent whose preparation was disclosed by Shulgin in one of his books. Before his death (and before
6693-444: 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
6790-410: The latter through presentations and academic publications, including to psychologists; and for the rediscovery, occasional discovery, and regular synthesis and personal use and distribution, possibly of hundreds of psychoactive compounds (for their psychedelic and MDMA-like empathogenic bioactivities ). As such, Shulgin is seen both as a pioneering and a controversial participant in the emergence of
6887-631: 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
6984-475: The most graceful, erotic, sensual, introspective compounds I have ever invented. For most people, it is a short-lived and comfortable psychedelic, with neither toxic side-effects nor next-day hang-over." In 1994, two years after the publication of PIHKAL , the DEA raided his lab. The agency requested that Shulgin turn over his license for violating the license's terms, and he was fined $ 25,000 for possession of anonymous samples sent to him for quality testing. In
7081-494: 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
7178-436: 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
7275-546: 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
7372-588: 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
7469-724: The onset of his late life dementia), Shulgin expressed sadness over the deaths, but argued that all drugs, including aspirin, carry risks with incorrect use. Shulgin was born in Berkeley, California , to Theodore Stevens Shulgin (1893–1978) and Henrietta D. (Aten) Shulgin (1894–1960). His father was born in Chelyabinsk , Russia; his mother was born in Illinois . Theodore and Henrietta were public school teachers in Alameda County . Shulgin studied organic chemistry at Harvard University as
7566-412: 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 the serotonin 5-HT 2A receptor but also of
7663-506: 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
7760-997: 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 critically mediated by serotonin 5-HT 2A receptor activation in
7857-427: 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
7954-574: 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)
8051-456: The syntheses catalogued by Shulgin in his books include chemicals in the 2C family (such as 2C-B ), compounds of the DOx family (such as DOM ), and tryptamines (such as 4-HO-MET and 4-HO-MiPT ). In describing Shulgin's work in psychedelic research and his preparation and experimentation with psychedelic drugs , he has been dubbed the "godfather of ecstasy" (and to a much more limited extent,
8148-471: The time in hallucinogenic compounds generally and mescaline in particular, with which various artists and writers had experimented. Shulgin said that mescaline made him aware of a world submerged in human spirit, whose "availability" was "catalyzed" by such chemicals; the consequences of his insights were called "devastating" by the reviewers. In the same review, an example of his insights was given by his description of MDMA as "his low-calorie Martini". Shulgin
8245-493: 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
8342-545: The visual effects of serotonergic psychedelics. Serotonergic psychedelics also directly or indirectly modulate a variety of other brain areas, and this may be involved in their effects as well. 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 ,
8439-862: 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
8536-445: The white solid ... I understood that our entire universe is contained in the mind and the spirit. We may choose not to find access to it, we may even deny its existence, but it is indeed there inside us, and there are chemicals that can catalyze its availability." Shulgin's professional activities continued to lean in the direction of psychopharmacology , furthered by his personal experiences with psychedelics. But during this period he
8633-422: 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
8730-403: Was a handsome, proper gentleman with a small grey moustache and the residues of an English accent. During coffee, after the music was over, he struck up a conversation. He asked me if I had ever heard of The Owl Club in San Francisco? I had not, so he began painting a picture of a rather fascinating group, with many interests in all sorts of art, drama and music. He mentioned that there was need for
8827-569: Was a member of Mensa International and frequently attended Mensa events in California. Alexander was a Bohemian Club member . The Bohemian club is located in California where Alexander lived. Alexander refers to "The Owl Club" in chapter 11 of PiHKAL : One evening in the late 1950s, I was invited to a musical soiree at an old comfortable home in the Berkeley Hills. I brought my viola with me... The only person I can remember from that evening
8924-511: Was an American biochemist , broad researcher of synthetic psychoactive compounds , and author of works regarding these, who independently explored the organic chemistry and pharmacology of such agents—in his mid-life and later, many through preparation in his home laboratory, and testing on himself. He is acknowledged to have introduced to broader use, in the late 1970s, the prior synthesized compound, MDMA ("ecstasy") in research psychopharmacology and in combination with conventional therapy,
9021-457: Was associated with increased prevalence of any mental illness. In any case, induction of psychosis has been associated with psychedelics in small percentages of individuals, and the rates appear to be higher in people with schizophrenia . 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
9118-511: 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
9215-575: Was her fourth marriage, and she had four children. After judicious self-experiments, Shulgin enlisted a small group of friends with whom he regularly tested his creations, starting in 1960. They developed a systematic way of ranking the effects of the various drugs, known as the Shulgin Rating Scale , with a vocabulary to describe the visual, auditory and physical sensations. He personally tested hundreds of drugs, mainly analogues of various phenethylamines (family containing MDMA , mescaline , and
9312-468: Was never explored in its own right. Shulgin went on to develop a new synthesis method, and in 1976, introduced the chemical to Leo Zeff , a psychologist from Oakland, California . Zeff used the substance in his practice in small doses as an aid to talk therapy . Zeff introduced the substance to hundreds of psychologists and lay therapists around the nation, including Ann (born Laura Ann Gotlieb) , whom Alexander Shulgin met in 1979, and married in 1981. It
9409-525: Was unable to do much independent research. His opportunity for further research came in 1961 after his development of Zectran , the first biodegradable pesticide, a highly profitable product. In his book PiHKAL , Shulgin limits his pesticide days at Dow Chemical to one sentence in 978 pages. Dow Chemical Company, in return for Zectran's valuable patent, gave Shulgin great freedom. During this time, he created and patented drugs when Dow asked, and published findings on other drugs in journals such as Nature and
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