Trip killer

Trip killer
Drug class
Chemical structure of ketanserin, a serotonin 5-HT2A receptor antagonist and one of the best-studied trip killers for serotonergic psychedelics.
Class identifiers
SynonymsHallucinogen antidote; Hallucinogen antagonist; Psychedelic antidote; Psychedelic antagonist
UseMedical, harm reduction
Mechanism of actionVarious
Biological targetVarious
Chemical classVarious
Legal status
In Wikidata

A trip killer, also known as a hallucinogen antidote or hallucinogen antagonist, is a drug that aborts or reduces the effects of a hallucinogenic drug experience (or 'trip').[1][2][3][4][5] As there are different types of hallucinogens that work in different ways, there are different types of trip killers.[6][7][8] They can completely block or reduce the effects of hallucinogens,[6] or they can simply provide anxiety relief and sedation.[3]

Examples of trip killers, in the case of serotonergic psychedelics, include serotonin receptor antagonists, such as antipsychotics like risperidone and quetiapine and certain antidepressants like trazodone and mirtazapine, and benzodiazepines, for instance diazepam and alprazolam.[4][6]

Trip killers can be used clinically to manage effects of hallucinogens, like hallucinogenic effects, anxiety, and psychomotor agitation, for instance in the emergency department and in the setting of psychedelic therapy.[9][3][10][5] They are also sometimes used by recreational psychedelic users as a form of harm reduction to manage "bad trips" or challenging experiences, for instance emotionally difficult experiences with prominent anxiety.[2][4] While used for harm-reduction purposes, this use of trip killers has raised concerns about safety and possible adverse effects.[2][4]

Serotonergic psychedelic antidotes

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Serotonin 5-HT2A receptor antagonists

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See also: Trazodone § Antagonism of serotonergic psychedelics

Serotonergic psychedelics, such as psilocybin (found in psilocybin mushrooms), lysergic acid diethylamide (LSD), mescaline (found in peyote cactii), and dimethyltryptamine (DMT) (found in ayahuasca), mediate their hallucinogenic effects by acting as agonists of the serotonin 5-HT2A receptor.[11][12][6] As a result, serotonin 5-HT2A receptor antagonists would theoretically be expected to block the hallucinogenic effects of serotonergic psychedelics.[6] Accordingly, the serotonin 5-HT2A receptor antagonists ketanserin, an antihypertensive agent, and risperidone, an antipsychotic, have been shown to block the effects of serotonergic psychedelics in clinical studies.[6][13][14][15] This includes the effects of psilocybin,[16][17][18] LSD,[19][20] mescaline,[21] and ayahuasca.[22] Ketanserin is under formal clinical investigation as a "neutralizer" or "off-switch" for psychedelics.[23][24][25][20][19] The more selective serotonin 5-HT2A receptor antagonist pimavanserin is also being studied as a blocker of the effects of psychedelics.[26]

Other potent serotonin 5-HT2A receptor antagonists that may block or reduce the effects of serotonergic psychedelics besides the above-listed drugs include other antipsychotics like quetiapine, olanzapine, aripiprazole, and pipamperone, antidepressants like trazodone, mirtazapine, mianserin, nefazodone, and etoperidone, and the antimigraine agent pizotifen, among others.[6][4][27] The typical antipsychotic chlorpromazine, which has significant but less-potent serotonin 5-HT2A receptor antagonism than many other antipsychotics, has shown inconsistent effects in reversing psychedelic effects in clinical studies,[6][27] while the typical antipsychotic haloperidol, which is a dopamine D2 receptor antagonist but not a significant serotonin 5-HT2A receptor antagonist, is ineffective and has actually been found to increase anxiety and dysphoria in the setting of psychedelic experiences.[6][28][9][16] In spite of variably acting as serotonin 5-HT2A receptor antagonists, tricyclic antidepressants (TCAs), including desipramine, imipramine, and clomipramine, have paradoxically been reported to potentiate the effects of serotonergic psychedelics rather than diminish them, albeit based on very limited data.[6][27]

Cyproheptadine, a non-selective serotonin receptor antagonist including of the serotonin 5-HT2A receptor, is used as an antidote in the treatment of serotonin syndrome (serotonin toxicity) caused by serotonergic drugs, including the toxicity of serotonergic psychedelics like the NBOMe drugs.[29][30][31] Certain other serotonin receptor antagonists, like chlorpromazine, have also been used for such purposes.[31][32]

Non-hallucinogenic partial agonists of the serotonin 5-HT2A receptor with sufficiently low intrinsic activity, such as 2-bromo-LSD (bromolysergide; BOL-148) and lisuride, are effective in blocking the hallucinogenic-related effects of psychedelics in animals and/or humans as well.[33][34]

Serotonergic psychedelics are being developed as novel treatments for psychiatric disorders and other conditions such as depression.[35][36][37] A practical limitation in terms of clinical use of many major psychedelics, for instance psilocybin, LSD, and mescaline, is their long durations of action (4–12 hours), which may require a whole day of clinical monitoring.[37][38][39] In relation to this, shorter-acting psychedelics, like DMT, 5-MeO-DMT (mebufotenin), and bretisilocin (5-fluoro-MET; GM-2505), are also being investigated for potential therapeutic use.[37][38][39][40] However, an alternative approach that is being investigated is use of serotonin 5-HT2A receptor antagonists like ketanserin as trip killers to shorten the experiences of psychedelics.[37][41][20] In a clinical trial, ketanserin given 1 hour after LSD shortened its duration from 8.5 hours to 3.5 hours (by ~60%).[6][20] It did not modify the pharmacokinetics of LSD, and its side effects, such as nasal congestion, were minimal.[6][20]

GABAA receptor positive allosteric modulators

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Benzodiazepines, such as diazepam and alprazolam, are sometimes used to manage the effects of serotonergic psychedelics, including clinically.[3][42][9] They act as positive allosteric modulators of the GABAA receptor, and do not specifically antagonize hallucinogenic effects (i.e., are not antidotes), but instead have anxiolytic, sedative, and memory-impairing effects that can lessen the negative effects of psychedelic experiences.[43] Alcohol, which is also a GABAA receptor positive allosteric modulator with similar effects, has been used for such purposes as well.[4][5]

Other agents

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Besides serotonin 5-HT2A receptor antagonists, chronic use of other serotonergic drugs may also diminish the effects of serotonergic psychedelics.[6][27] Examples include serotonin 5-HT1A receptor agonists like buspirone, serotonin reuptake inhibitors such as selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, paroxetine, and sertraline and serotonin–norepinephrine reuptake inhibitors (SNRIs) like venlafaxine, duloxetine, and milnacipran, and monoamine oxidase inhibitors (MAOIs) such as phenelzine, tranylcypromine, and moclobemide.[6][27] Buspirone, a partial agonist of the serotonin 5-HT1A receptor, has specifically been found to markedly attenuate the visual and certain other effects of psilocybin, although it did not completely block the hallucinogenic effects of psilocybin.[6][44][45] The reduced effects of psychedelics in the case of concomitant drugs that elevate serotonin levels may be due to desensitization of serotonin 5-HT2A receptors.[6][27] In contrast to earlier studies however, other more recent studies have found that SSRIs like escitalopram may not diminish the hallucinogenic effects of psychedelics like psilocybin and DMT.[27][46] Instead, in one study, escitalopram resulted in greater mystical experience, emotional breakthrough, and ego dissolution scores with DMT than in people not on escitalopram.[46]

Although MAOIs can diminish the effects of serotonergic psychedelics, it must be noted that some serotonergic psychedelics, such as DMT, are highly susceptible substrates for monoamine oxidase (MAO), and hence can simultaneously be greatly potentiated by MAOIs (as in ayahuasca).[6][47] The 2C drugs, such as 2C-B, 2C-I, and 2C-E, are also notable substrates of both MAO-A and MAO-B, and may likewise be greatly potentiated by MAOIs.[48][49]

High-dose nicotinic acid (niacin, a B3 vitamer) was reported to reduce and block the effects of LSD in one early clinical study.[6][50][51] However, a subsequent clinical study attempting to replicate the findings found that it was not effective for this purpose.[50] Azacyclonol, a claimed ataractive (i.e., non-antipsychotic hallucination-suppressing medication) that is no longer marketed, likewise seems to be ineffective.[6] Other non-serotonergic drugs that may block or reduce the effects of serotonergic psychedelics based on animal studies include AMPA receptor antagonists, metabotropic glutamate mGlu2 and mGlu3 receptor agonists, μ-opioid receptor agonists, and adenosine A1 receptor agonists.[28][52][53]

Some drugs that have been reported to potentiate rather than inhibit the effects of serotonergic psychedelics include lithium, reserpine, pindolol, and methysergide.[6] Pindolol, a beta blocker and serotonin 5-HT1A receptor antagonist, has been reported to potentiate the hallucinogenic effects of DMT by 2- to 3-fold in humans.[45][54] A high rate of seizures has been reported with the combination of lithium and psychedelics.[27][9][55]

Use by recreational psychedelic users

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Trip killers on Reddit[4]
Drug Dose
Alprazolam 0.5–4 mg
Diazepam 3–20 mg
Quetiapine 25–600 mg
Trazodone 50–150 mg

Recreational psychedelic users sometimes employ trip killers to abort psychedelic trips.[2][4][5] The most commonly encountered putative trip killers in a 2024 online study of Reddit social media postings were the benzodiazepines alprazolam and diazepam, the antipsychotic quetiapine, the antidepressant trazodone, and alcohol.[4][5][56] Others used less frequently included the benzodiazepines lorazepam, clonazepam, and etizolam, the antipsychotic olanzapine, and the antidepressant mirtazapine, among others.[4][5] While employed by recreational users for harm-reduction purposes, the use of trip killers to abort the effects of psychedelics is not fully characterized and could pose medical risks.[1][4][5][56] In addition, doses of trip killers used by recreational psychedelic users may be non-optimal or excessive and increase risks.[4][5]

Antidotes of other hallucinogens

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Cannabinoid CB1 receptor antagonists like rimonabant, drinabant, surinabant, and selonabant have been found to block or reduce the psychoactive effects of cannabinoids in clinical studies and could be useful as antidotes against cannabinoid toxicity.[7][57][58] Likewise, the hallucinogenic and other effects of κ-opioid receptor agonists like salvinorin A (found in Salvia divinorum), butorphanol, and pentazocine have been shown to be blocked by the non-selective opioid receptor antagonist naltrexone in clinical studies.[8][59][60][61] Although clinical management of antimuscarinic deliriant intoxication and poisoning, for instance due to scopolamine, is usually supportive, acetylcholinesterase inhibitors, such as physostigmine, have sometimes been used in this context as well.[62][63] Benzodiazepines and antipsychotics have also been used in such situations.[62][63]

Although trip killers exist for certain types of hallucinogens, antidotes do not exist for all types of hallucinogens, for instance NMDA receptor antagonist dissociatives like ketamine and phencyclidine (PCP).[64][3][65] NMDA receptor agonists, which theoretically could reverse the effects of NMDA receptor antagonists, can produce excitotoxic neurotoxicity and convulsions, which restricts their potential medical use.[66][67][68] In any case, benzodiazepines can be useful in managing dissociative intoxication, but can also augment sedation and associated risks.[5][10][64] As with NMDA receptor antagonists, there is no antidote for Amanita muscaria intoxication, in which the hallucinogenic GABAA receptor agonist muscimol is the active constituent.[69][70]

Entactogens like MDMA and MDA are generally only mildly hallucinogenic at best, but use of "trip killers" to reverse the effects of these drugs has also been described.[4] Entactogens act primarily as serotonin releasing agents that indirectly activate serotonin receptors and require entry into serotonergic neurons via the serotonin transporter (SERT) to induce their entactogenic effects.[13][71] Serotonin reuptake inhibitors (SRIs), for instance selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and citalopram and serotonin–norepinephrine reuptake inhibitors (SNRIs) like duloxetine, can markedly block or abolish the serotonin release induced by entactogens by preventing their transport into these neurons, and thus can strongly reduce most of their subjective effects in humans.[13][71][72] The serotonin 5-HT2A receptor antagonist ketanserin has also been found to partially reduce some of the subjective effects of MDMA, particularly its perceptual effects, whereas the serotonin 5-HT1A receptor antagonist pindolol was largely ineffective.[13][73][72][74] Non-selective serotonin receptor antagonists like cyproheptadine have been used in the clinical management of serotonin toxicity induced by MDMA, for instance in overdose or precipitated by drug interactions like with monoamine oxidase inhibitors (MAOIs).[75][76][77]

See also

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References

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  37. ^ a b c d Nutt, D. J.; Peill, J. M.; Weiss, B.; Godfrey, K.; Carhart-Harris, R. L.; Erritzoe, D. (2023). "Psilocybin and Other Classic Psychedelics in Depression". Emerging Neurobiology of Antidepressant Treatments. Vol. 66. Cham: Springer International Publishing. pp. 149–174. doi:10.1007/7854_2023_451. ISBN 978-3-031-66355-0. PMID 37955822. Retrieved 12 May 2025. 5.1 Duration of Trip for Psychedelics: Why Does This Matter? [...] There are profound differences in the duration of action of serotonin psychedelics. LSD and mescaline are long lasting with effects for up to a day and so; often requiring overnight stays in clinical studies. Oral Psilocybin lasts approximately 4–6 h. Other psychedelics, like DMT (i.v. or smoked/intranasal) or 5-MEO-DMT (i.v./im/intranasal) can produce very short altered experiences (just 5–10 min). A key question is: are each equally effective for depression? If short acting psychedelics such as DMT and 5-MEO-DMT prove just as effective for treating depression, this would offer a cost-benefit when compared to longer lasting psychedelics such as psilocybin or LSD. [...] An alternative approach, being considered by some companies, is utilising a 5-HT2A receptor antagonist such as ketanserin (Becker et al. 2023) which can terminate an LSD trip after a given time, so shortening the treatment period in the clinic. Going forward, if psychedelics are integrated into health services; cost-benefit analyses will be crucial in delivering them as a viable treatment option. Overall, a shortened experience with similar antidepressant effects will be favourable. {{cite book}}: |journal= ignored (help)
  38. ^ a b Ramaekers JG, Reckweg JT, Mason NL (January 2025). "Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression". Am J Psychiatry. 182 (1): 33–46. doi:10.1176/appi.ajp.20230890. PMID 39741439.
  39. ^ a b Ramaekers JG (May 2025). "Less is more? Antidepressant effects of short-acting psychedelics". Neuropsychopharmacology. 50 (6): 875–876. doi:10.1038/s41386-025-02103-5. PMC 12032289. PMID 40258989.
  40. ^ Peplow, Mark (22 June 2024). "Should Next-Generation Psychedelics Skip the Trip?". Scientific American. Archived from the original on 26 June 2024. Retrieved 20 February 2025. But the psychoactive effects of [psychedelics] pose some major challenges. [...] And patients typically need close supervision for many hours while under the influence of the drugs, making it burdensome, expensive and impractical for many patients. To avoid these problems, some companies are tweaking psychedelic drugs to induce shorter or milder 'trips' that will not require such intensive patient oversight from clinicians. [...] Gilgamesh is also working on GM-2505, a 5-HT2A agonist that is structurally related to psilocybin and DMT. GM-2505 completed a phase 1 trial late last year and should enter phase 2 for major depressive disorder this year. Its psychedelic effect lasts 60 to 90 minutes — long enough for patients to "explore the altered state of consciousness that might be needed for long-term durable efficacy," Krugel says, yet within a timeframe that is manageable for healthcare systems. [...]
  41. ^ Aday, Jacob S.; Barnett, Brian S.; Grossman, Dan; Murnane, Kevin S.; Nichols, Charles D.; Hendricks, Peter S. (1 September 2023). "Psychedelic Commercialization: A Wide-Spanning Overview of the Emerging Psychedelic Industry". Psychedelic Medicine. 1 (3): 150–165. doi:10.1089/psymed.2023.0013. ISSN 2831-4425. PMC 11661494. PMID 40046566. Recent work supported by MindMed demonstrated that ketanserin is able to shorten the duration of LSD's mind-altering effects while preserving LSD-induced elevations of brain-derived neurotrophic factor, a marker of neuroplasticity, suggesting the possibility that LSDinduced therapeutic effects might be retained despite the psychedelic experience being prematurely aborted.84 [...] Many of the formulation and chemical strategies target shortening the duration of action of psychedelics to promote patient compliance, reduce clinical utilization costs, and enhance their fit to the payment system of our current model of care. [...] Further, at present, very little is known about best practices for psychedelic-assisted psychotherapy, including the quantity and types of therapeutic support needed to maximize safety and efficacy, and companies are forced to navigate the tension between providing adequate support to participants while minimizing costs. One of the greatest costs will undoubtedly be therapist/monitor time, leading some companies to invest in researching and/or developing short-acting psychedelic compounds that theoretically reduce the amount of therapist time needed, or leading them to minimize the support offered in their trials (e.g., MindMed's LSD for generalized anxiety disorder study87).
  42. ^ Halpern, John H.; Suzuki, Joji; Huertas, Pedro E.; Passie, Torsten (2010). "Hallucinogens". Addiction Medicine. New York, NY: Springer New York. pp. 1083–1098. doi:10.1007/978-1-4419-0338-9_54. ISBN 978-1-4419-0337-2.
  43. ^ Olsen RW (July 2018). "GABAA receptor: Positive and negative allosteric modulators". Neuropharmacology. 136 (Pt A): 10–22. doi:10.1016/j.neuropharm.2018.01.036. PMC 6027637. PMID 29407219.
  44. ^ Brandt SD, Kavanagh PV, Twamley B, Westphal F, Elliott SP, Wallach J, Stratford A, Klein LM, McCorvy JD, Nichols DE, Halberstadt AL (February 2018). "Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775)". Drug Test Anal. 10 (2): 310–322. doi:10.1002/dta.2222. PMC 6230476. PMID 28585392. Additionally, pretreatment with the 5‐HT1A agonist buspirone (20 mg p.o.) markedly attenuates the visual effects of psilocybin in human volunteers.59 Although buspirone failed to completely block the hallucinogenic effects of psilocybin, the limited inhibition is not necessarily surprising because buspirone is a low efficacy 5‐HT1A partial agonist.60 The level of 5‐HT1A activation produced by buspirone may not be sufficient to completely counteract the stimulation of 5‐HT2A receptors by psilocin (the active metabolite of psilocybin). Another consideration is that psilocin acts as a 5‐HT1A agonist.30 If 5‐HT1A activation by psilocin buffers its hallucinogenic effects similar to DMT58 then competition between psilocin and a weaker partial agonist such as buspirone would limit attenuation of the hallucinogenic response.
  45. ^ a b Pokorny T, Preller KH, Kraehenmann R, Vollenweider FX (April 2016). "Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience". Eur Neuropsychopharmacol. 26 (4): 756–766. doi:10.1016/j.euroneuro.2016.01.005. PMID 26875114.
  46. ^ a b James E, Joel Z, Attwooll V, Benway T, Good M, Tziras G, Routledge C, Macek T (2024). "ACNP 63rd Annual Meeting: Poster Abstracts P1-P304: P160. SPL026 (DMT Fumarate) in Combination With Selective Serotonin Reuptake Inhibitors (SSRIs) for Patients With Major Depressive Disorder" (PDF). Neuropsychopharmacology. 49 (S1): 65–235 (155–156). doi:10.1038/s41386-024-02011-0. ISSN 0893-133X. PMC 11627186. PMID 39643633. Retrieved 31 January 2025.
  47. ^ Egger, Klemens; Aicher, Helena D.; Cumming, Paul; Scheidegger, Milan (10 September 2024). "Neurobiological research on N,N-dimethyltryptamine (DMT) and its potentiation by monoamine oxidase (MAO) inhibition: from ayahuasca to synthetic combinations of DMT and MAO inhibitors". Cellular and Molecular Life Sciences. 81 (1). Springer Science and Business Media LLC: 395. doi:10.1007/s00018-024-05353-6. ISSN 1420-682X. PMC 11387584. PMID 39254764.
  48. ^ Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM (June 2013). "2C or not 2C: phenethylamine designer drug review". J Med Toxicol. 9 (2): 172–178. doi:10.1007/s13181-013-0295-x. PMC 3657019. PMID 23494844.
  49. ^ Theobald DS, Maurer HH (January 2007). "Identification of monoamine oxidase and cytochrome P450 isoenzymes involved in the deamination of phenethylamine-derived designer drugs (2C-series)". Biochem Pharmacol. 73 (2): 287–297. doi:10.1016/j.bcp.2006.09.022. PMID 17067556.
  50. ^ a b Murphree, Henry (1983). "The Pharmacology of Hallucinogens". Research Advances in Alcohol and Drug Problems. Boston, MA: Springer US. pp. 175–205. doi:10.1007/978-1-4613-3626-6_5. ISBN 978-1-4613-3628-0. In older work, various steroids (Bergen et al., 1960) including progesterone (Krus et al., 1961) were reported to be effective antagonists. This has not been replicated. In other early work, some compounds initially reported to be effective were not found to be so by other workers. These include azacyclonal (Fabing, 1955) and niacin (Agnew and Hoffer, 1955).
  51. ^ Agnew N, Hoffer A (January 1955). "Nicotinic acid modified lysergic acid diethylamide psychosis". J Ment Sci. 101 (422): 12–27. doi:10.1192/bjp.101.422.12. PMID 14368207.
  52. ^ Marek GJ, Schoepp DD (2021). "Cortical influences of serotonin and glutamate on layer V pyramidal neurons". 5-HT Interaction with Other Neurotransmitters: Experimental Evidence and Therapeutic Relevance - Part B. Progress in Brain Research. Vol. 261. pp. 341–378. doi:10.1016/bs.pbr.2020.11.002. ISBN 978-0-444-64258-5. PMID 33785135. {{cite book}}: |journal= ignored (help)
  53. ^ Marek GJ (August 2003). "Behavioral evidence for mu-opioid and 5-HT2A receptor interactions". Eur J Pharmacol. 474 (1): 77–83. doi:10.1016/s0014-2999(03)01971-x. PMID 12909198.
  54. ^ Strassman RJ (1996). "Human psychopharmacology of N,N-dimethyltryptamine". Behav Brain Res. 73 (1–2): 121–124. doi:10.1016/0166-4328(96)00081-2. PMID 8788488.
  55. ^ Nayak SM, Gukasyan N, Barrett FS, Erowid E, Erowid F, Griffiths RR (September 2021). "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports" (PDF). Pharmacopsychiatry. 54 (5): 240–245. doi:10.1055/a-1524-2794. PMID 34348413.
  56. ^ a b Davidson, Colin (14 February 2024). "Using "trip killers" to cut short bad drug trips is potentially dangerous". The Conversation (UK Edition). SyndiGate Media Inc.: NA. Retrieved 3 October 2024.
  57. ^ Bosquez-Berger, Taryn; Szanda, Gergő; Straiker, Alex (30 August 2023). "Requiem for Rimonabant: Therapeutic Potential for Cannabinoid CB1 Receptor Antagonists after the Fall". Drugs and Drug Candidates. 2 (3): 689–707. doi:10.3390/ddc2030035. ISSN 2813-2998.
  58. ^ Gorbenko AA, Heuberger JA, Juachon M, Klaassen E, Tagen M, Lawler JF, Schneeberger D, Cundy KC, Klumpers LE, Groeneveld GJ (February 2025). "CB1 Receptor Antagonist Selonabant (ANEB-001) Blocks Acute THC Effects in Healthy Volunteers: A Phase II Randomized Controlled Trial". Clin Pharmacol Ther. 117 (5): 1427–1436. doi:10.1002/cpt.3581. PMC 11993283. PMID 39898464.
  59. ^ Maqueda AE, Valle M, Addy PH, Antonijoan RM, Puntes M, Coimbra J, Ballester MR, Garrido M, González M, Claramunt J, Barker S, Lomnicka I, Waguespack M, Johnson MW, Griffiths RR, Riba J (July 2016). "Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans". Int J Neuropsychopharmacol. 19 (7): pyw016. doi:10.1093/ijnp/pyw016. PMC 4966277. PMID 26874330.
  60. ^ Walsh SL, Chausmer AE, Strain EC, Bigelow GE (January 2008). "Evaluation of the mu and kappa opioid actions of butorphanol in humans through differential naltrexone blockade". Psychopharmacology (Berl). 196 (1): 143–155. doi:10.1007/s00213-007-0948-z. PMC 2766188. PMID 17909753.
  61. ^ Preston KL, Bigelow GE (February 1993). "Differential naltrexone antagonism of hydromorphone and pentazocine effects in human volunteers". J Pharmacol Exp Ther. 264 (2): 813–823. doi:10.1016/S0022-3565(25)10212-7. PMID 7679737.
  62. ^ a b Shim KH, Kang MJ, Sharma N, An SS (September 2022). "Beauty of the beast: anticholinergic tropane alkaloids in therapeutics". Nat Prod Bioprospect. 12 (1): 33. doi:10.1007/s13659-022-00357-w. PMC 9478010. PMID 36109439. The treatment of TA poisoning including gastric emptying, use of activated charcoal (0.5 to 1 g/kg in children or 25 to 100 g in adults) to absorb the drug and benzodiazepines for managing agitation [157, 158]. Physostigmine (an AChE inhibitor) is recommended in the case when both PNS and CNS are afected by anticholinergic poisoning [159, 160]. In such cases, intravenous dose of physostigmine (0.02 mg/kg for children and 0.5 to 2 mg/ kg for adults) is recommended [159]. Physostigmine is helpful in restoring the level of consciousness to its baseline [157] which is diferent from sedative action of benzodiazepines.
  63. ^ a b Bulut NS, Arpacıoğlu ZB (September 2022). "Acute onset psychosis with complex neurobehavioural symptomatology following the intramuscular injection of hyoscine butylbromide: a case report with an overview of the literature". Eur J Hosp Pharm. 29 (5): 294–297. doi:10.1136/ejhpharm-2020-002583. PMC 9660700. PMID 33376193. The most crucial intervention in the treatment of anticholinergic intoxication is without doubt the discontinuation of the suspected agent. Hospitalisation may be necessary for the close monitoring of severe cases. While physostigmine is commonly used as a specific antidote for anticholinergic toxicity, benzodiazepines and antipsychotics can prove to be useful in managing agitation, hallucinations, and aggressive and self-mutilative behaviours as in our case.2
  64. ^ a b Schep LJ, Slaughter RJ, Watts M, Mackenzie E, Gee P (June 2023). "The clinical toxicology of ketamine". Clin Toxicol (Phila). 61 (6): 415–428. doi:10.1080/15563650.2023.2212125. PMID 37267048.
  65. ^ Jenkins, Amanda J.; Gates, Madeleine J. (2020). "Hallucinogens and Psychedelics". Principles of Forensic Toxicology. Cham: Springer International Publishing. pp. 467–489. doi:10.1007/978-3-030-42917-1_26. ISBN 978-3-030-42916-4.
  66. ^ Gonda X (2012). "Basic pharmacology of NMDA receptors". Curr Pharm Des. 18 (12): 1558–1567. doi:10.2174/138161212799958521. PMID 22280436.
  67. ^ Rana V, Ghosh S, Bhatt A, Bisht D, Joshi G, Purohit P (2024). "N-Methyl-D-Aspartate (NMDA) Receptor Antagonists and their Pharmacological Implication: A Medicinal Chemistry-oriented Perspective Outline". Curr Med Chem. 31 (29): 4725–4744. doi:10.2174/0109298673288031240405061759. PMID 38638036.
  68. ^ Rothman, Steven M.; Olney, John W. (1987). "Excitotoxity and the NMDA receptor". Trends in Neurosciences. 10 (7). Elsevier BV: 299–302. doi:10.1016/0166-2236(87)90177-9. ISSN 0166-2236.
  69. ^ Mitchel DH (1980). "Amanita mushroom poisoning". Annu Rev Med. 31: 51–57. doi:10.1146/annurev.me.31.020180.000411. PMID 6772091.
  70. ^ Rampolli FI, Kamler P, Carnevale Carlino C, Bedussi F (2021). "The Deceptive Mushroom: Accidental Amanita muscaria Poisoning". Eur J Case Rep Intern Med. 8 (3): 002212. doi:10.12890/2021_002212. PMC 7977045. PMID 33768066.
  71. ^ a b Price CM, Feduccia AA, DeBonis K (2022). "Effects of Selective Serotonin Reuptake Inhibitor Use on 3,4-Methylenedioxymethamphetamine-Assisted Therapy for Posttraumatic Stress Disorder: A Review of the Evidence, Neurobiological Plausibility, and Clinical Significance". J Clin Psychopharmacol. 42 (5): 464–469. doi:10.1097/JCP.0000000000001595. PMID 36018231. Anecdotal reports for decades have suggested that current SSRI use can significantly dampen or abolish the subjective effects of MDMA and serotonergic hallucinogens,16–22 although this was not always observed.23 Controlled studies beginning in the 2000s began to shed further light on this phenomenon by examining the impact of SSRI and MDMA coadministration in healthy controls. The SSRIs citalopram, paroxetine, and fluoxetine were all shown to reduce most of the psychological effects of MDMA when given as pretreatment, either orally for 3 to 5 days24–26 or intravenously for 90 minutes27,28 before MDMA oral dosing. The psychological effects of MDMA that were attenuated by SSRIs included positive mood/euphoria, alterations in thought process and content, extraversion/self-confidence, and dissociative phenomena. Not all psychological effects of MDMA were attenuated by SSRIs, however; effects on emotional excitability, sensitivity, and anxiety remained even with SSRI pretreatment.25,29 Selective serotonin reuptake inhibitors also reduced the effects of MDMA on various physiological parameters, including increases in blood pressure, heart rate, temperature, and pupil diameter.24–29 [...] 9 Studies in animal models support the idea that such attenuation of MDMA's effects via acute SSRI pretreatment occurs primarily through blockage of the serotonin reuptake transporter (SERT). Serotonin reuptake transporter–knockout animals have a marked reduction in MDMA-mediated serotonin release and subsequent depletion and neurotoxicity.30,31 Pretreatment of rats with SSRIs similarly attenuated MDMA-mediated increases in extracellular serotonin and led to preservation of serotonin metabolite concentrations and SERT binding that is normally depleted by MDMA after 1 week.32–35
  72. ^ a b Liechti ME, Vollenweider FX (December 2001). "Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies". Hum Psychopharmacol. 16 (8): 589–598. doi:10.1002/hup.348. PMID 12404538.
  73. ^ Liechti ME, Saur MR, Gamma A, Hell D, Vollenweider FX (October 2000). "Psychological and physiological effects of MDMA ("Ecstasy") after pretreatment with the 5-HT(2) antagonist ketanserin in healthy humans". Neuropsychopharmacology. 23 (4): 396–404. doi:10.1016/S0893-133X(00)00126-3. PMID 10989266.
  74. ^ van Wel JH, Kuypers KP, Theunissen EL, Bosker WM, Bakker K, Ramaekers JG (2012). "Effects of acute MDMA intoxication on mood and impulsivity: role of the 5-HT2 and 5-HT1 receptors". PLOS ONE. 7 (7): e40187. Bibcode:2012PLoSO...740187V. doi:10.1371/journal.pone.0040187. PMC 3393729. PMID 22808116.
  75. ^ Rusyniak DE, Sprague JE (November 2005). "Toxin-induced hyperthermic syndromes". Med Clin North Am. 89 (6): 1277–1296. doi:10.1016/j.mcna.2005.06.002. PMID 16227063.
  76. ^ Doyle AJ, Meyer J, Breen K, Hunt BJ (July 2020). "N-Methyl-3,4-methylendioxymethamphetamine (MDMA)-related coagulopathy and rhabdomyolysis: A case series and literature review". Res Pract Thromb Haemost. 4 (5): 829–834. doi:10.1002/rth2.12360. PMC 7354411. PMID 32685891.
  77. ^ Krolikowski, Allana M.; Koyfman, Alex (2014). "Methamphetamine and MDMA: 'Safe' drugs of abuse". African Journal of Emergency Medicine. 4 (1): 34–38. doi:10.1016/j.afjem.2013.01.005.
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