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A critical safety concern for serotonergic compounds is their potential to induce seizures, as a severe manifestation of serotonin toxicity. The objective of this study was to evaluate the seizure liability of 5-MeO-DMT in a canine model. Beagle dogs (n = 8) were surgically instrumented for continuous telemetric recording of electroencephalography (EEG) and electromyography (EMG), coupled with behavioral video monitoring. Following a baseline period, animals were intranasally administered with control vehicle or escalating doses of 5-MeO-DMT (0.5, 1.0, and 1.5\u00a0mg\/kg\/day), once daily for nine consecutive days. Plasma samples for determination of pharmacokinetic parameters were collected from a satellite group (n = 3). Intranasal administration of 5-MeO-DMT resulted in centrally mediated and dose-dependent behavioral signs, such as head shaking, salivation, repetitive movements, dilated pupils, increased muscle tone, and tremors. A majority of these signs had a rapid onset and offset, which correlated with the peak plasma levels and resolved within 1 hour post-dose, and they were consistent with serotonergic agonism of 5-MeO-DMT. The continuous EEG recording revealed no evidence of seizures or epileptiform discharges at any dose levels throughout the study. In a canine model, considered sensitive to serotonergic drug-induced seizures, daily intranasal administration of escalating doses of 5-MeO-DMT did not induce seizures or epileptiform activity, even at doses causing significant physiological signs of serotonergic stimulation. These results provide robust critical safety information for a low seizure liability of 5-MeO-DMT.<\/jats:p>","DOI":"10.1177\/10915818261419429","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T08:11:37Z","timestamp":1769847097000},"page":"321-329","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["5-Methoxy-N,N-Dimethyltryptamine: Functional Safety Pharmacology and Video-EEG Assessment of a Short-Acting Serotonergic Psychedelic in Beagle Canines"],"prefix":"10.1177","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2491-0984","authenticated-orcid":false,"given":"Amir","family":"Lotfi","sequence":"first","affiliation":[{"name":"Beckley Psytech Limited"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Sparapani","sequence":"additional","affiliation":[{"name":"Charles River Laboratories"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mylene","family":"Pouliot","sequence":"additional","affiliation":[{"name":"Charles River Laboratories"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Charles River Laboratories"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Independent Consultant"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Authier","sequence":"additional","affiliation":[{"name":"Charles River Laboratories"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/02698811211050543"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15587"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1246\/bcsj.11.221"},{"key":"e_1_3_3_5_2","volume-title":"R\u00e4tsch Christian. 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