Editing LSD (section)

==Interactions==
{{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

Some psychedelics, including LSD, are [[drug metabolism|metabolized]] by the [[cytochrome P450]] [[enzyme]] [[CYP2D6]]. Concurrent use of [[selective serotonin reuptake inhibitor]]s (SSRIs), some of which are [[potency (pharmacology)|potent]] [[enzyme inhibitor|inhibitor]]s of CYP2D6, with LSD may heighten the risk of [[serotonin syndrome]].<ref name="drug-interaction"/>{{rp|145}} Chronic usage of SSRIs, [[tricyclic antidepressant]]s (TCAs), and [[monoamine oxidase inhibitor]]s (MAOIs) is believed to diminish the subjective effects of psychedelics, likely due to [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]] [[receptor downregulation|downregulation or desensitization]] induced by elevated [[serotonin]] levels.<ref name="PassieHalpernStrichtenoth2008" /><ref name="drug-interaction"/>{{rp|145}} Contrary to the preceding notions however, a clinical study found that administration of LSD to people taking [[paroxetine]], an SSRI and strong CYP2D6 inhibitor, increased LSD exposure by about 1.5-fold, was well-tolerated, and did not modify the pleasant subjective effects or physiological effects of LSD, whereas negative effects of LSD, including "bad drug effect", [[anxiety]], and [[nausea]], were reduced.<ref name="BeckerHumbert-DrozMueller2025">{{cite journal | vauthors = Becker AM, Humbert-Droz M, Mueller L, Jelušić A, Tolev A, Straumann I, Avedisian I, Erne L, Thomann J, Luethi D, Grünblatt E, Meyer Zu Schwabedissen H, Liechti ME | title = Acute Effects and Pharmacokinetics of LSD after Paroxetine or Placebo Pre-Administration in a Randomized, Double-Blind, Cross-Over Phase I Trial | journal = Clin Pharmacol Ther | volume = | issue = | pages = | date = February 2025 | pmid = 40022427 | doi = 10.1002/cpt.3618 | url = | doi-access = free }}</ref> Similarly, a clinical study with LSD found that LSD levels were 75% higher in people with non-functional CYP2D6 ([[poor metabolizer]]s) compared to those with functional CYP2D6.<ref name="HalmanKongSarris2024">{{Cite journal |vauthors=Halman A, Kong G, Sarris J, Perkins D |date=January 2024 |title=Drug-drug interactions involving classic psychedelics: A systematic review |journal=J Psychopharmacol |volume=38 |issue=1 |pages=3–18 |doi=10.1177/02698811231211219 |pmc=10851641 |pmid=37982394}}</ref><ref name="VizeliStraumannHolze2021">{{cite journal | vauthors = Vizeli P, Straumann I, Holze F, Schmid Y, Dolder PC, Liechti ME | title = Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis | journal = Sci Rep | volume = 11 | issue = 1 | pages = 10851 | date = May 2021 | pmid = 34035391 | pmc = 8149637 | doi = 10.1038/s41598-021-90343-y | bibcode = 2021NatSR..1110851V | url = }}</ref> In contrast to certain other psychedelics, MAOIs do not inhibit the [[drug metabolism|metabolism]] of or potentiate the effects of LSD and instead reduce its effects.<ref name="PassieHalpernStrichtenoth2008" /> Interactions between psychedelics and [[antipsychotic]]s or [[anticonvulsant]]s are not well-documented; however, co-use with [[mood stabilizer]]s like [[lithium (medication)|lithium]] may induce [[seizure]]s and [[dissociative disorder|dissociative effects]], particularly in individuals with [[bipolar disorder]].<ref name="drug-interaction"/>{{rp|146}}<ref>{{cite journal |journal=Drug and Alcohol Dependence |volume=239 |at=109586 |vauthors=Simonsson O, Goldberg SB, Chambers R, Osika W, Long DM, Hendricks PS |date=1 October 2022 |pmid=35981469 |pmc=9627432 |title=Prevalence and associations of classic psychedelic-related seizures in a population-based sample |doi=10.1016/j.drugalcdep.2022.109586}}</ref><ref>{{cite journal |year=1967 |journal=Western Journal of Medicine |vauthors=Fisher D, Ungerleider J |pmid=4962683 |pmc=1502729 |volume=106 |issue=3 |pages=201–211 |title=Grand mal seizures following ingestion of LSD}}</ref> Lithium notably intensifies LSD reactions, potentially leading to acute comatose states when combined.<ref name="PassieHalpernStrichtenoth2008" />