Psychedelic: Difference between revisions

'''Psychedelics''' (also known as '''[[serotonergic]] [[hallucinogens]]''') are a class of [[psychoactive substances]] that produce an altered state of consciousness marked by unusual changes in perception, mood, and cognitive processes.<ref name="Nichols2016">{{cite journal | vauthors=((Nichols, D. E.)) | veditors=((Barker, E. L.)) | journal=Pharmacological Reviews | title=Psychedelics | volume=68 | issue=2 | pages=264–355 | date= April 2016 | url=http://pharmrev.aspetjournals.org/lookup/doi/10.1124/pr.115.011478 | issn=0031-6997 | doi=10.1124/pr.115.011478}}</ref>  

While the precise mechanism of action is not known, psychedelic substances are thought to produce their effects by binding to [[serotonin]] ('''5'''-'''h'''ydroxy'''t'''ryptamine or '''5-HT''') [[receptors]] in the central nervous system, particularly the 5-HT_2a subtype. Serotonin plays a number of critical roles throughout the human body and is a key [[neurotransmitter]] involved in the functioning and regulation of sensory perception, behavior, mood, cognition and memory.<ref name="nichols5HT">{{cite journal | vauthors=((Nichols, D. E.)), ((Nichols, C. D.)) | journal=Chemical Reviews | title=Serotonin Receptors | volume=108 | issue=5 | pages=1614–1641 | date=1 May 2008 | url=https://pubs.acs.org/doi/10.1021/cr078224o | issn=0009-2665 | doi=10.1021/cr078224o}}</ref>  

Human usage of psychedelics predates written history, and there is growing evidence that they were employed by early cultures in a variety of sociocultural and ritual contexts.<ref name="Nichols2016"/> In modern times, psychedelic substances are used for a number of purposes that span from the traditional shamanic forms (such as the use of [[ayahuasca]] in the Amazon jungle, or [[peyote]] among Native Americans) to more modern forms of New Age spiritual, [[transpersonal]], or religious practices.  

Psychedelics can be divided into three major sub-classes: [[tryptamines]], [[lysergamides]], and [[phenethylamines]]. Psychedelic tryptamines (e.g. [[psilocybin mushrooms|psilocybin]], [[4-AcO-DMT]]) are either based on or derived from [[dimethyltryptamine]] (DMT), lysergamides (e.g. [[LSA]], [[AL-LAD]]) from [[LSD]], and phenethylamines (e.g. [[2C-B]], [[DOM]]) from [[mescaline]].

Unlike other highly prohibited substances, most psychedelics have not been shown to be physiologically toxic and none have been shown to be addictive.<ref name="Nichols2016"/> However, adverse psychological reactions such as severe [[anxiety]], [[paranoia]], [[delusions]], and [[psychosis]] are always possible, particularly for those predisposed to mental disorders.<ref>{{cite journal|last=Strassmann|first=Rick|title=Adverse reactions to psychedelic drugs. A review of the literature|journal=Journal of Nervous and Mental Disease|volume=172|issue=10|pages=577–595|doi=10.1097/00005053-198410000-00001|pmid=6384428|year=1984|issn=0022-3018|oclc=1754691}}</ref>  

 

As a result, it is highly advised to use [[Harm reduction#Hallucinogens|harm reduction practices]] if using these substances.  

The term "psychedelic" was coined by psychiatrist Humphry Osmond in 1956 as an alternative descriptor for [[hallucinogens]] in the context of psychedelic psychotherapy.<ref>{{cite book | vauthors=((Murray, N.)) | date= 2003 | title=Aldous Huxley: a biography | publisher=Thomas Dunne Books/St. Martin’s Press | edition=1st U.S. ed | isbn=9780312302375}}</ref>  

 

Seeking a name for the experience induced by [[LSD]], Osmond contacted [[Aldous Huxley]], a personal acquaintance and advocate for the therapeutic use of the substance. Huxley coined the term "phanerothyme," from the Greek terms for "manifest" (φανερός) and "spirit" (θύμος).  

Just take a pinch of psychedelic<ref>{{cite journal | journal=BMJ | title=Humphry Osmond | volume=328 | issue=7441 | pages=713 | date=20 March 2004 | url=https://www.bmj.com/lookup/doi/10.1136/bmj.328.7441.713 | issn=0959-8138 | doi=10.1136/bmj.328.7441.713}}</ref>}}

"Psychedelic" derives from the Greek words ''ψυχή'' (psyche, "soul, mind") and ''δηλείν'' (delein, "to manifest") which taken together mean "mind-manifesting" or "soul-manifesting." The implication was that psychedelics can allow one to access the soul and develop unused potentials of the human mind.<ref>{{cite book | vauthors=((Weil, A.)), ((Rosen, W.)) | date= 1993 | title=From Chocolate to Morphine: Everything You Need to Know about Mind-altering Drugs | publisher=Houghton Mifflin | isbn=9780395660799}}</ref><ref>{{Citation | title=Erowid Humphry Osmond Vault | url=https://erowid.org/culture/characters/osmond_humphry/osmond_humphry.shtml}}</ref>  

 

Due to the expanded use of the term "psychedelic" in pop culture and a perceived incorrect verbal formulation, Carl A.P. Ruck, Jeremy Bigwood, Danny Staples, [[Jonathan Ott]], and [[R. Gordon Wasson]] later proposed the term "[[entheogen]]" to describe the religious or spiritual experience produced by such substances.<ref>{{cite book | vauthors=((Wasson, R. G.)), ((Hofmann, A.)), ((Ruck, C. A. P.)) | date= 2008 | title=The road to Eleusis: unveiling the secret of the mysteries | publisher=North Atlantic Books | edition=30th anniversary ed | isbn=9781556437526}}</ref>

[[File:Psilocybin neural connections.jpg|350px|thumbnail|right|The diagram above demonstrates the neural connections associated with sobriety in comparison to being under the influence of psilocybin as demonstrated through the use of MRI scans. <p>The width of the links is proportional to their weight and the size of the nodes is proportional to their strength. Note that the proportion of heavy links between communities is much higher (and very different) in the psilocybin group, suggesting greater integration<ref>{{cite journal | vauthors=((Petri, G.)), ((Expert, P.)), ((Turkheimer, F.)), ((Carhart-Harris, R.)), ((Nutt, D.)), ((Hellyer, P. J.)), ((Vaccarino, F.)) | journal=Journal of The Royal Society Interface | title=Homological scaffolds of brain functional networks | volume=11 | issue=101 | pages=20140873 | date=6 December 2014 | url=https://royalsocietypublishing.org/doi/10.1098/rsif.2014.0873 | issn=1742-5689 | doi=10.1098/rsif.2014.0873}}</ref>]]

[[File:Lsd brain scan.jpg|thumbnail|350px|right|This image shows how, with eyes-closed, much more of the brain contributes to the visual experience under LSD (right image) than under placebo (left image). The magnitude of this effect correlates with participants’ reports of complex, dreamlike visions.<ref>{{cite journal | vauthors=((Carhart-Harris, R. L.)), ((Muthukumaraswamy, S.)), ((Roseman, L.)), ((Kaelen, M.)), ((Droog, W.)), ((Murphy, K.)), ((Tagliazucchi, E.)), ((Schenberg, E. E.)), ((Nest, T.)), ((Orban, C.)), ((Leech, R.)), ((Williams, L. T.)), ((Williams, T. M.)), ((Bolstridge, M.)), ((Sessa, B.)), ((McGonigle, J.)), ((Sereno, M. I.)), ((Nichols, D.)), ((Hellyer, P. J.)), ((Hobden, P.)), ((Evans, J.)), ((Singh, K. D.)), ((Wise, R. G.)), ((Curran, H. V.)), ((Feilding, A.)), ((Nutt, D. J.)) | journal=Proceedings of the National Academy of Sciences | title=Neural correlates of the LSD experience revealed by multimodal neuroimaging | volume=113 | issue=17 | pages=4853–4858 | date=26 April 2016 | url=https://pnas.org/doi/full/10.1073/pnas.1518377113 | issn=0027-8424 | doi=10.1073/pnas.1518377113}}</ref>]]

[[File:NeuroPsychDiagram.png|thumbnail|350px|right|Figure 1 - Activation of the prefrontal network and glutamate release by psychedelics. The figure shows a model in which hallucinogens, such as psilocin, lysergic acid diethylamide (LSD) and dimethyltryptamine (DMT), increase extracellular glutamate levels in the prefrontal cortex through stimulation of postsynaptic serotonin 2A (5-HT_2A) receptors that are located on large glutamatergic pyramidal cells in deep cortical layers (V and VI) projecting to layer V pyramidal neurons. <p>This glutamate release leads to an activation of [[AMPA]] and [[NMDA]] receptors on cortical pyramidal neurons. in addition, hallucinogens directly activate 5-HT2A receptors located on cortical pyramidal neurons. This activation is thought to ultimately lead to increased expression of brain-derived neurotrophic factor (BDNF).<ref>{{cite journal | vauthors=((Vollenweider, F. X.)), ((Kometer, M.)) | journal=Nature Reviews Neuroscience | title=The neurobiology of psychedelic drugs: implications for the treatment of mood disorders | volume=11 | issue=9 | pages=642–651 | date= September 2010 | url=https://www.nature.com/articles/nrn2884 | issn=1471-003X | doi=10.1038/nrn2884}}</ref>]]

Many serotonergic psychedelics share very close chemical and structural similarities to serotonin itself. There is a consensus that serotonergic psychedelics produce their effects by acting as uniquely effective [[Agonist#Agonists|partial agonists]] at 5-HT_2A receptor sites.<ref name="Nichols2016"/>

*[[Addiction suppression]]<ref>{{Citation | vauthors=((Lawrence, J.)) | title=Psychedelics: entering a new age of addiction therapy | url=https://pharmaceutical-journal.com/article/feature/psychedelics-entering-a-new-age-of-addiction-therapy}}</ref>

The "classical psychedelics" are all classed as [[Serotonergic psychedelic|serotonergic]] in nature.<ref name="Nichols2016"/> This means that they structurally mimic the endogenous [[neurotransmitter]] known as [[serotonin]], the neurotransmitter that regulates higher-level brain functions such as mood, sensory perception, cognition, and memory.<ref name="nichols5HT" />  

[[File:harmchart.png|thumb|right|315px|Radar plot showing relative physical harm, social harm, and dependence of LSD and psilocybin, which can tentatively be taken to apply psychedelics as a whole.<ref>{{cite journal | vauthors=((Nutt, D.)), ((King, L. A.)), ((Saulsbury, W.)), ((Blakemore, C.)) | journal=The Lancet | title=Development of a rational scale to assess the harm of drugs of potential misuse | volume=369 | issue=9566 | pages=1047–1053 | date= March 2007 | url=https://linkinghub.elsevier.com/retrieve/pii/S0140673607604644 | issn=01406736 | doi=10.1016/S0140-6736(07)60464-4}}</ref>]]

While more research is needed, most psychedelics (and especially classical psychedelics) appear to be physiologically well-tolerated and have [[Toxicity::very low toxicity]] relative to dose.<ref name="Nichols2016"/> Most psychedelics have very few physical side effects associated with acute exposure.  

Various studies have shown that, in reasonable doses in a sufficiently [[Set and setting|prepared context]], they are unlikely to present negative physical, cognitive, psychiatric or other toxic consequences. There is no evidence that classical psychedelics cause damage to any human body organ.<ref name="Nichols2004">{{cite journal | vauthors=((Nichols, D. E.)) | journal=Pharmacology & Therapeutics | title=Hallucinogens | volume=101 | issue=2 | pages=131–181 | date= February 2004 | url=https://linkinghub.elsevier.com/retrieve/pii/S0163725803001657 | issn=01637258 | doi=10.1016/j.pharmthera.2003.11.002}}</ref>

 

 

 

 

Psychedelics may trigger or exacerbate symptoms (e.g. [[delusions]], [[mania]], [[psychosis]]) in those who have or are predisposed to mental illness such as bipolar disorder or schizophrenia.<ref name="Nichols2004"/> Those with a personal or family history of mental illness (including anxiety and depression) should not use LSD without the advice of a qualified medical professional.  

Psychedelics are considered to have [[Addiction potential::low abuse potential]].<ref name="Nichols2004"/> There are no literature reports of successful attempts to train animals to self-administer psychedelics — an animal model predictive of abuse liability — indicating that it does not have the necessary pharmacology to either initiate or maintain dependence.<ref name="Nichols2004"/> Likewise, there is no human clinical evidence that psychedelics cause addiction. Finally, there is virtually no withdrawal syndrome when chronic use of these substances is stopped.<ref>{{cite book | vauthors=((Diaz, J.)) | date= 1997 | title=How drugs influence behavior: a neuro behavioral approach | publisher=Prentice Hall | isbn=9780023287640}}</ref>

Notable exceptions to this include [[DMT]] and related base tryptamines like [[DPT]] and [[MET]], which are thought to produce little to no tolerance or cross-tolerance.  

 

Another exception includes psychedelic [[phenethylamines]] like [[2C-B]]. While the exact mechanism is not understood, generally tolerance is thought to rise immediately, but does not reach a peak unless with prolonged and repeated use. This means that the immediate tolerance does not rise as high as with [[lysergamides]] or [[tryptamines]] and can wear off faster and can be reduced to half within 1-2 days in the absence of further consumption. Mostly there will be less psychedelic and more stimulating effects.