Many psychedelic drugs are illegal 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 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.
Etymology and nomenclature
The term psychedelic was coined by the psychiatrist Humphrey Osmond during written correspondence with author Aldous Huxley and presented to the New York Academy of Sciences by Osmond in 1957. It is irregularly derived from the Greek words ψυχή psychḗ 'soul, mind' and δηλείν dēleín 'to manifest', with the intended meaning "mind manifesting," the implication being that psychedelics can reveal unused potentials of the human mind. The term was loathed by American ethnobotanistRichard Schultes but championed by American psychologist Timothy Leary.
Aldous Huxley had suggested his own coinage phanerothyme (Greek phaneroein- "visible" and Greek thymos "soul", thus "visible soul") to Osmond in 1956. Recently, the term entheogenic 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 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 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 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 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."
LSD (Lysergic acid diethylamide) is a derivative of lysergic acid, which is obtained from the hydrolysis of ergotamine. Ergotamine is an alkaloid found in the fungus claviceps purpurea, which primarily infects rye. LSD is both the prototypical psychedelic and the prototypical lysergamide. As a lysergamide, LSD contains both a tryptamine and phenethylamine group within its structure. As a result of containing a phenethylamine group LSD agonises dopamine receptors as well as serotonin receptors, making it more energetic in effect in contrast to the more sedating effects of psilocin, which isn't a dopamine agonist.
Mescaline (3,4,5-trimethoxyphenethylamine) is a phenthylamine alkaloid found in various species of cacti, the most well known being Peyote (Lophophora williamsii). Mescaline has effects comparable to those of LSD and psilocybin, albeit with a greater emphasis on colors and patterns.
DMT (N,N-dimethyltryptamine) is an indole alkaloid found in various species of plants. Traditionally it is consumed by tribes in South America in the form of ayahuasca. A brew is used that consists of DMT-containing plants as well as plants containing MAOIs, specifically harmaline, which allows DMT to be consumed orally without being rendered inactive by monoamine oxidase enzymes in the digestive system. In the Western world DMT is more commonly consumed via the vaporisation of freebase DMT. Whereas Ayahuasca typically lasts for several hours, inhalation has an onset measured in seconds and has effects measured in minutes, being significantly more intense. Particularly in vaporised form, DMT has the ability to cause users to enter a hallucinatory realm fully detached from reality, being typically characterised by hyperbolic geometry, and described as defying visual or verbal description. Users have also reported encountering and communicating with entitites within this hallucinatory state. DMT is the archetypal substituted tryptamine, being the structural scaffold of psilocybin and - to a lesser extent - the lysergamides.
Psychedelic therapy (or psychedelic-assisted therapy) 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 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, 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 the assessment of promising drug therapies for potential approval,[note 1] to psilocybin therapy for treatment-resistant depression and major depressive disorder.
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.
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, and color variations. Users often report intense colors that they have not previously experienced, and repetitive geometric shapes are common. Higher doses often cause intense and fundamental alterations of sensory perception, such as synesthesia or the experience of additional spatial or temporal dimensions.
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. Tryptamines are well documented to cause classic psychedelic states, such as increased empathy, visual distorsions (drifting, morphing, breathing, melting of various surfaces and objects), auditory hallucinations, ego dissolution or ego death with high enough dose, mystical and spiritual experiences, closed eye hallucinations and complete detachment from reality with a high enough dose.
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.
The usage of most psychedelics entails some risk of eliciting flashbacks of the drug experience even after the effects have worn off, albeit rarely.HPPD or other after-effects may also occur. 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.
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.
Different countries have come to be associated with particular psychedelic entheogens such as ayahuasca's spiritual importance in regions of Peru near the Amazon Basin and the entheogenic use of psilocybe mushrooms by the native Mazatec people of Oaxaca, Mexico.
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.
^The Food and Drug Administration describes the designation of breakthrough therapy as "a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s)."
^R. R. Griffiths; W. A. Richards; U. McCann; R. Jesse (7 July 2006). "Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance". Psychopharmacology. 187 (3): 268–283. doi:10.1007/s00213-006-0457-5. PMID16826400. S2CID7845214.
^ abcdBender, David; Hellerstein, David J. (2022). "Assessing the risk–benefit profile of classical psychedelics: a clinical review of second-wave psychedelic research". Psychopharmacology. 239 (6): 1907–1932. doi:10.1007/s00213-021-06049-6. PMID35022823.
^ abcReiff, Collin M.; Richman, Elon E.; Nemeroff, Charles B.; Carpenter, Linda L.; Widge, Alik S.; Rodriguez, Carloyn I.; Kalin, Ned H.; McDonald, William M.; the Work Group on Biomarkers and Novel Treatments, a Division of the American Psychiatric Association Council of Research (2020). "Psychedelics and Psychedelic-Assisted Psychotherapy". The American Journal of Psychiatry. 177 (5): 391–410. doi:10.1176/appi.ajp.2019.19010035. PMID32098487. S2CID211524704.
^Wölfel, Reinhard; Graefe, Karl-Heinz (February 1992). "Evidence for various tryptamines and related compounds acting as substrates of the platelet 5-hydroxytryptamine transporter". Naunyn-Schmiedeberg's Archives of Pharmacology. 345 (2): 129–136. doi:10.1007/BF00165727. ISSN0028-1298. PMID1570019. S2CID2984583.
^Shimazu, Seiichiro; Miklya, Ildikó (May 2004). "Pharmacological studies with endogenous enhancer substances: β-phenylethylamine, tryptamine, and their synthetic derivatives". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 28 (3): 421–427. doi:10.1016/j.pnpbp.2003.11.016. PMID15093948. S2CID37564231.
^Little, Karley Y.; Krolewski, David M.; Zhang, Lian; Cassin, Bader J. (January 2003). "Loss of Striatal Vesicular Monoamine Transporter Protein (VMAT2) in Human Cocaine Users". American Journal of Psychiatry. 160 (1): 47–55. doi:10.1176/appi.ajp.160.1.47. ISSN0002-953X. PMID12505801.
^Preller, Katrin H.; Vollenweider, Franz X. (2016). "Phenomenology, Structure, and Dynamic of Psychedelic States". In Adam L. Halberstadt; Franz X. Vollenweider; David E. Nichols (eds.). Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. Vol. 36. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 221–256. doi:10.1007/7854_2016_459. ISBN978-3-662-55878-2. PMID28025814.
^Rucker, James J. H. (2015). "Psychedelic drugs should be legally reclassified so that researchers can investigate their therapeutic potential". British Medical Journal. 350: h2902. doi:10.1136/bmj.h2902. PMID26014506. S2CID46510541.
Halberstadt, Adam L.; Franz X. Vollenweider; David E. Nichols, eds. (2018). Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. Vol. 36. Berlin, Heidelberg: Springer. ISBN978-3-662-55878-2.