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Trip killer
Drugs that block hallucinogen effects

A trip killer is a drug that reduces or aborts the effects of hallucinogenic drugs during a psychedelic experience. Different types exist depending on the hallucinogen involved, from those that block effects entirely to those providing anxiety relief and sedation. Examples include serotonin receptor antagonists like the antipsychotics risperidone and quetiapine, as well as benzodiazepines such as diazepam. Clinically, trip killers help manage hallucinogenic effects, anxiety, and psychomotor agitation, useful in settings like the emergency department or psychedelic therapy. Recreational users also employ them for harm reduction during bad trips, though concerns remain about safety and adverse effects.

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Serotonergic psychedelic antidotes

Serotonin 5-HT2A receptor antagonists

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.212223 As a result, serotonin 5-HT2A receptor antagonists would theoretically be expected to block the hallucinogenic effects of serotonergic psychedelics.24 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.25262728 This includes the effects of psilocybin,293031 LSD,3233 mescaline,34 and ayahuasca.35 Ketanserin is under formal clinical investigation as a "neutralizer" or "off-switch" for psychedelics.3637383940 The more selective serotonin 5-HT2A receptor antagonist pimavanserin is also being studied as a blocker of the effects of psychedelics.41

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.424344 The typical antipsychotic chlorpromazine, which has significant but less-potent serotonin 5-HT2A receptor antagonism than many other antipsychotics, has shown incomplete and inconsistent effects in reversing psychedelic effects in clinical studies,454647 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.48495051 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.5253

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.545556 Certain other serotonin receptor antagonists, like chlorpromazine, have also been used for such purposes.5758

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.5960 However, it has been argued that lisuride may actually be a psychedelic or hallucinogen itself at sufficiently high doses in humans.61

Serotonergic psychedelics are being developed as novel treatments for psychiatric disorders and other conditions such as depression.626364 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.656667 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.68697071 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.727374 In a clinical trial, ketanserin given 1 hour after LSD shortened its duration from 8.5 hours to 3.5 hours (by ~60%).7576 It did not modify the pharmacokinetics of LSD, and its side effects, such as nasal congestion, were minimal.7778

GABAA receptor positive allosteric modulators

Benzodiazepines, such as diazepam and alprazolam, are sometimes used to manage the effects of serotonergic psychedelics, including clinically.798081 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.82 Alcohol, which is also a GABAA receptor positive allosteric modulator with similar effects, has been used for such purposes as well.8384

Other agents

Besides serotonin 5-HT2A receptor antagonists, chronic use of other serotonergic drugs may also diminish the effects of serotonergic psychedelics.8586 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.8788 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.899091 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.9293 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.9495 Instead, in one study, escitalopram resulted in greater mystical experience, emotional breakthrough, and ego dissolution scores with DMT than in people not on escitalopram.96

Although MAOIs can diminish the effects of serotonergic psychedelics, 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).9798 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.99100

High-dose nicotinic acid (niacin, a B3 vitamer) was reported to reduce and block the effects of LSD in one early clinical study.101102103 However, a subsequent clinical study attempting to replicate the findings found that it was not effective for this purpose.104 Azacyclonol, a claimed ataractive (i.e., non-antipsychotic hallucination-suppressing medication) that is no longer marketed, likewise seems to be ineffective.105 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.106107108

Some drugs that have been reported to potentiate rather than inhibit the effects of serotonergic psychedelics include lithium, reserpine, pindolol, and methysergide.109 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.110111 A high rate of seizures has been reported with the combination of lithium and psychedelics.112113114

Use by recreational psychedelic users

Trip killers on Reddit115
DrugDose
Alprazolam0.5–4 mg
Diazepam3–20 mg
Quetiapine25–600 mg
Trazodone50–150 mg

Recreational psychedelic users sometimes employ trip killers to abort psychedelic trips.116117118 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.119120121 Others used less frequently included the benzodiazepines lorazepam, clonazepam, and etizolam, the antipsychotic olanzapine, and the antidepressant mirtazapine, among others.122123 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.124125126127 In addition, doses of trip killers used by recreational psychedelic users may be non-optimal or excessive and increase risks.128129

Antidotes of other hallucinogens

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.130131132 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.133134135136 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.137138 Benzodiazepines and antipsychotics have also been used in such situations.139140

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).141142143 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.144145146 In any case, benzodiazepines can be useful in managing dissociative intoxication, but can also augment sedation and associated risks.147148149 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.150151

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.152 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.153154 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.155156157 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.158159160161 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).162163164

See also

References

  1. Muir OS, Shinozuka K, Beutler BD, Arenas A, Cherian K, Evans VD, Fasano C, Tabaac BJ (2024). "Psychedelic Therapy: A Primer for Primary Care Clinicians-The Strengths, Weaknesses, Opportunities, and Threats of Psychedelic Therapeutics". Am J Ther. 31 (2): e178 – e182. doi:10.1097/MJT.0000000000001720. PMID 38518273. When psychedelics are used in recreational contexts without adequate supervision, they can lead to tragic outcomes.20 There are rare reports of serious adverse effects, including psychosis and even suicide, arising from recreational use.21 Methods for subduing socalled "bad trips" in recreational settings include potentially dangerous habits, such as taking benzodiazepines, which are known to be "trip killers."22 https://www.researchgate.net/publication/379188134 ↩

  2. Bellanavidanalage Gothami Ayanthie Vis Jayasinha (8 February 2024). Towards Safer Trips: Exploring Harm Reduction Strategies for Recreational Psychedelic Use in Aotearoa New Zealand (Thesis). University of Otago. Retrieved 3 October 2024. Another form of mixing substances involves the use of trip killers; a pharmacological coping strategy aimed to reduce the negative effects of a psychedelic experience by consuming a different substance (Suran, 2024). While this is a new concept and an under researched area, there are reports of trip killers being effective in reducing the negative effects of a psychedelic experience (Suran, 2024). One study gathered research from reddit, an online social media platform, investigating the usage of trip killers during challenging psychedelic experiences (Suran, 2024). The most popular and effective trip killers used were prescription medication, with 47% reporting the use of benzodiazepines as they reduce anxiety, followed by the use of antipsychotic and antidepressant medication (Suran, 2024). However, there are risks in mixing substances with psychedelic drugs, and subjectivity in the effectiveness. As some individuals may experience positive effects, while for others it may lead to negative effects (Suran, 2024). Therefore, it is recommended that before using trip killers, individuals should try other non- pharmacological coping strategies to reduce the negative effects of the psychedelic drug (Gable, 2004; Van Amsterdam et al., 2011). These factors discussed above, demonstrate the effectiveness of protective behaviours and harm reduction practices, in promoting safe psychedelic use and reducing harm. https://ourarchive.otago.ac.nz/esploro/outputs/graduate/Towards-Safer-Trips-Exploring-Harm-Reduction/9926550679501891 ↩

  3. Leikin, Jerrold B.; Krantz, Anne J.; Zell-Kanter, Michele; Barkin, Robert L.; Hryhorczuk, Daniel O. (1989). "Clinical Features and Management of Intoxication Due to Hallucinogenic Drugs". Medical Toxicology and Adverse Drug Experience. 4 (5). Springer Science and Business Media LLC: 324–350. doi:10.1007/bf03259916. ISSN 0113-5244. PMID 2682130. /wiki/Doi_(identifier) ↩

  4. Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961. https://web.archive.org/web/20250511111827oe_/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 ↩

  5. Suran M (February 2024). "Study Finds Hundreds of Reddit Posts on "Trip-Killers" for Psychedelic Drugs". JAMA. 331 (8): 632–634. doi:10.1001/jama.2023.28257. PMID 38294772. /wiki/Doi_(identifier) ↩

  6. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  7. Skolnick P, Crystal R (February 2020). "Cannabinoid1 (CB-1) receptor antagonists: a molecular approach to treating acute cannabinoid overdose". J Neural Transm (Vienna). 127 (2): 279–286. doi:10.1007/s00702-019-02132-7. PMC 7035232. PMID 31893308. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035232 ↩

  8. Clark SD, Abi-Dargham A (October 2019). "The Role of Dynorphin and the Kappa Opioid Receptor in the Symptomatology of Schizophrenia: A Review of the Evidence". Biol Psychiatry. 86 (7): 502–511. doi:10.1016/j.biopsych.2019.05.012. PMID 31376930. Finally, in a double-blind study of 24 healthy volunteers, Maqueda et al. (27) found that salvinorin A produced both visual and auditory changes that could be blocked by the kappa, mu, and delta receptor antagonist naltrexone (Table 2). https://doi.org/10.1016%2Fj.biopsych.2019.05.012 ↩

  9. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  10. Leikin, Jerrold B.; Krantz, Anne J.; Zell-Kanter, Michele; Barkin, Robert L.; Hryhorczuk, Daniel O. (1989). "Clinical Features and Management of Intoxication Due to Hallucinogenic Drugs". Medical Toxicology and Adverse Drug Experience. 4 (5). Springer Science and Business Media LLC: 324–350. doi:10.1007/bf03259916. ISSN 0113-5244. PMID 2682130. /wiki/Doi_(identifier) ↩

  11. Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961. https://web.archive.org/web/20250511111827oe_/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 ↩

  12. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  13. Holze F, Liechti ME, Müller F (July 2024). "Pharmacological Properties of Psychedelics with a Special Focus on Potential Harms". Current Topics in Behavioral Neurosciences. Curr Top Behav Neurosci. doi:10.1007/7854_2024_510. PMID 39080236. /wiki/Doi_(identifier) ↩

  14. Leikin, Jerrold B.; Krantz, Anne J.; Zell-Kanter, Michele; Barkin, Robert L.; Hryhorczuk, Daniel O. (1989). "Clinical Features and Management of Intoxication Due to Hallucinogenic Drugs". Medical Toxicology and Adverse Drug Experience. 4 (5). Springer Science and Business Media LLC: 324–350. doi:10.1007/bf03259916. ISSN 0113-5244. PMID 2682130. /wiki/Doi_(identifier) ↩

  15. Bey T, Patel A (February 2007). "Phencyclidine intoxication and adverse effects: a clinical and pharmacological review of an illicit drug". Cal J Emerg Med. 8 (1): 9–14. PMC 2859735. PMID 20440387. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859735 ↩

  16. Suran M (February 2024). "Study Finds Hundreds of Reddit Posts on "Trip-Killers" for Psychedelic Drugs". JAMA. 331 (8): 632–634. doi:10.1001/jama.2023.28257. PMID 38294772. /wiki/Doi_(identifier) ↩

  17. Bellanavidanalage Gothami Ayanthie Vis Jayasinha (8 February 2024). Towards Safer Trips: Exploring Harm Reduction Strategies for Recreational Psychedelic Use in Aotearoa New Zealand (Thesis). University of Otago. Retrieved 3 October 2024. Another form of mixing substances involves the use of trip killers; a pharmacological coping strategy aimed to reduce the negative effects of a psychedelic experience by consuming a different substance (Suran, 2024). While this is a new concept and an under researched area, there are reports of trip killers being effective in reducing the negative effects of a psychedelic experience (Suran, 2024). One study gathered research from reddit, an online social media platform, investigating the usage of trip killers during challenging psychedelic experiences (Suran, 2024). The most popular and effective trip killers used were prescription medication, with 47% reporting the use of benzodiazepines as they reduce anxiety, followed by the use of antipsychotic and antidepressant medication (Suran, 2024). However, there are risks in mixing substances with psychedelic drugs, and subjectivity in the effectiveness. As some individuals may experience positive effects, while for others it may lead to negative effects (Suran, 2024). Therefore, it is recommended that before using trip killers, individuals should try other non- pharmacological coping strategies to reduce the negative effects of the psychedelic drug (Gable, 2004; Van Amsterdam et al., 2011). These factors discussed above, demonstrate the effectiveness of protective behaviours and harm reduction practices, in promoting safe psychedelic use and reducing harm. https://ourarchive.otago.ac.nz/esploro/outputs/graduate/Towards-Safer-Trips-Exploring-Harm-Reduction/9926550679501891 ↩

  18. Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961. https://web.archive.org/web/20250511111827oe_/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 ↩

  19. Bellanavidanalage Gothami Ayanthie Vis Jayasinha (8 February 2024). Towards Safer Trips: Exploring Harm Reduction Strategies for Recreational Psychedelic Use in Aotearoa New Zealand (Thesis). University of Otago. Retrieved 3 October 2024. Another form of mixing substances involves the use of trip killers; a pharmacological coping strategy aimed to reduce the negative effects of a psychedelic experience by consuming a different substance (Suran, 2024). While this is a new concept and an under researched area, there are reports of trip killers being effective in reducing the negative effects of a psychedelic experience (Suran, 2024). One study gathered research from reddit, an online social media platform, investigating the usage of trip killers during challenging psychedelic experiences (Suran, 2024). The most popular and effective trip killers used were prescription medication, with 47% reporting the use of benzodiazepines as they reduce anxiety, followed by the use of antipsychotic and antidepressant medication (Suran, 2024). However, there are risks in mixing substances with psychedelic drugs, and subjectivity in the effectiveness. As some individuals may experience positive effects, while for others it may lead to negative effects (Suran, 2024). Therefore, it is recommended that before using trip killers, individuals should try other non- pharmacological coping strategies to reduce the negative effects of the psychedelic drug (Gable, 2004; Van Amsterdam et al., 2011). These factors discussed above, demonstrate the effectiveness of protective behaviours and harm reduction practices, in promoting safe psychedelic use and reducing harm. https://ourarchive.otago.ac.nz/esploro/outputs/graduate/Towards-Safer-Trips-Exploring-Harm-Reduction/9926550679501891 ↩

  20. Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961. https://web.archive.org/web/20250511111827oe_/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 ↩

  21. Nichols DE (April 2016). "Psychedelics". Pharmacol Rev. 68 (2): 264–355. doi:10.1124/pr.115.011478. PMC 4813425. PMID 26841800. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813425 ↩

  22. Nichols DE (2018). Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524. 978-3-662-55878-2 ↩

  23. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  24. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  25. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  26. Halberstadt AL, Nichols DE (2020). "Serotonin and serotonin receptors in hallucinogen action". Handbook of the Behavioral Neurobiology of Serotonin. Handbook of Behavioral Neuroscience. Vol. 31. pp. 843–863. doi:10.1016/B978-0-444-64125-0.00043-8. ISBN 9780444641250. ISSN 1569-7339. S2CID 241134396. Pretreatment with the selective 5-HT reuptake inhibitors citalopram, fluoxetine, and paroxetine significantly attenuated most of the subjective effects of MDMA, consistent with the proposed involvement of carriermediated 5-HT release in the effects of MDMA (Farre et al., 2007; Liechti, Baumann, et al., 2000; Tancer & Johanson, 2007). Citalopram also inhibits the effect of MDMA on PPI (Liechti, Geyer, Hell, & Vollenweider, 2001). According to another report (Hysek, Simmler et al., 2012), the mixed SERT/NET inhibitor duloxetine robustly blocked most of the subjective response to MDMA, raising the possibility that NE release contributes to its effects. In a follow-up study, the selective NET inhibitor reboxetine significantly reduced the emotional excitation and feelings of stimulation produced by MDMA but did not alter its entactogenic or mood-elevating effects (Hysek et al., 2011). Therefore, although NE release contributes to the stimulant effects produced by MDMA, 5-HT release appears to be principally responsible for the unique entactogenic effects of the drug. [...] Several studies have examined the contribution of 5-HT and DA receptors to the effects of MDMA. Pretreatment with ketanserin produced some attenuation of the subjective effects of MDMA (Liechti, Saur, et al., 2000). However, the most significant reduction of MDMA effects by ketanserin occurred in the VR dimension of the APZ, indicating that 5-HT2A receptors are responsible for the effects of MDMA on perception. Ketanserin also blocked MDMA-induced impairment of performance on a verbal memory task (van Wel et al., 2011), but had no effect on the ability of MDMA to induce depersonalization and derealization (Puxty et al., 2017). 9780444641250 ↩

  27. Canal CE (2018). "Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action". Handb Exp Pharmacol. Handbook of Experimental Pharmacology. 252: 227–260. doi:10.1007/164_2018_107. ISBN 978-3-030-10560-0. PMC 6136989. PMID 29532180. Reports from clinical trials conclude that the psychedelic effects of psilocybin and LSD are mediated by 5-HT2A receptors, because they are blocked by ketanserin (40 mg, P.O.), typically viewed as a selective 5-HT2A antagonist (Kometer et al. 2012; Kraehenmann et al. 2017; Preller et al. 2017; Quednow et al. 2012). Haloperidol, typically viewed as a selective dopamine D2 antagonist, is much less effective than ketanserin at blocking psilocybin's effects, but risperidone, an antipsychotic with combined D2/5-HT2 activity, is as effective as ketanserin (Vollenweider et al. 1998). 978-3-030-10560-0 ↩

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  59. Lewis V, Bonniwell EM, Lanham JK, Ghaffari A, Sheshbaradaran H, Cao AB, Calkins MM, Bautista-Carro MA, Arsenault E, Telfer A, Taghavi-Abkuh FF, Malcolm NJ, El Sayegh F, Abizaid A, Schmid Y, Morton K, Halberstadt AL, Aguilar-Valles A, McCorvy JD (March 2023). "A non-hallucinogenic LSD analog with therapeutic potential for mood disorders". Cell Rep. 42 (3): 112203. doi:10.1016/j.celrep.2023.112203. PMC 10112881. PMID 36884348. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10112881 ↩

  60. Glatfelter GC, Pottie E, Partilla JS, Stove CP, Baumann MH (March 2024). "Comparative Pharmacological Effects of Lisuride and Lysergic Acid Diethylamide Revisited". ACS Pharmacol Transl Sci. 7 (3): 641–653. doi:10.1021/acsptsci.3c00192. PMC 10928901. PMID 38481684. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10928901 ↩

  61. Kehler J, Lindskov MS (May 2025). "Are the LSD-analogs lisuride and ergotamine examples of non-hallucinogenic serotonin 5-HT2A receptor agonists?". Journal of Psychopharmacology: 2698811251330741. doi:10.1177/02698811251330741. PMID 40322975. /wiki/Doi_(identifier) ↩

  62. McClure-Begley TD, Roth BL (June 2022). "The promises and perils of psychedelic pharmacology for psychiatry". Nat Rev Drug Discov. 21 (6): 463–473. doi:10.1038/s41573-022-00421-7. PMID 35301459. https://cdr.lib.unc.edu/downloads/jw827p78p ↩

  63. Rhee TG, Davoudian PA, Sanacora G, Wilkinson ST (December 2023). "Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders". Drug Discov Today. 28 (12): 103818. doi:10.1016/j.drudis.2023.103818. PMID 37925136. /wiki/Doi_(identifier) ↩

  64. 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) 978-3-031-66355-0 ↩

  65. 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) 978-3-031-66355-0 ↩

  66. 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. /wiki/Doi_(identifier) ↩

  67. 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. /wiki/Doi_(identifier) ↩

  68. 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) 978-3-031-66355-0 ↩

  69. 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. /wiki/Doi_(identifier) ↩

  70. 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. /wiki/Doi_(identifier) ↩

  71. 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. [...] https://archive.today/20240626183623/https://www.scientificamerican.com/article/should-next-generation-psychedelics-skip-the-trip/ ↩

  72. 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) 978-3-031-66355-0 ↩

  73. 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). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661494 ↩

  74. Becker AM, Klaiber A, Holze F, Istampoulouoglou I, Duthaler U, Varghese N, Eckert A, Liechti ME (February 2023). "Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants". Int J Neuropsychopharmacol. 26 (2): 97–106. doi:10.1093/ijnp/pyac075. PMC 9926053. PMID 36342343. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926053 ↩

  75. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  76. Becker AM, Klaiber A, Holze F, Istampoulouoglou I, Duthaler U, Varghese N, Eckert A, Liechti ME (February 2023). "Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants". Int J Neuropsychopharmacol. 26 (2): 97–106. doi:10.1093/ijnp/pyac075. PMC 9926053. PMID 36342343. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926053 ↩

  77. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  78. Becker AM, Klaiber A, Holze F, Istampoulouoglou I, Duthaler U, Varghese N, Eckert A, Liechti ME (February 2023). "Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants". Int J Neuropsychopharmacol. 26 (2): 97–106. doi:10.1093/ijnp/pyac075. PMC 9926053. PMID 36342343. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926053 ↩

  79. Leikin, Jerrold B.; Krantz, Anne J.; Zell-Kanter, Michele; Barkin, Robert L.; Hryhorczuk, Daniel O. (1989). "Clinical Features and Management of Intoxication Due to Hallucinogenic Drugs". Medical Toxicology and Adverse Drug Experience. 4 (5). Springer Science and Business Media LLC: 324–350. doi:10.1007/bf03259916. ISSN 0113-5244. PMID 2682130. /wiki/Doi_(identifier) ↩

  80. 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. 978-1-4419-0337-2 ↩

  81. Holze F, Liechti ME, Müller F (July 2024). "Pharmacological Properties of Psychedelics with a Special Focus on Potential Harms". Current Topics in Behavioral Neurosciences. Curr Top Behav Neurosci. doi:10.1007/7854_2024_510. PMID 39080236. /wiki/Doi_(identifier) ↩

  82. 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027637 ↩

  83. Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961. https://web.archive.org/web/20250511111827oe_/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 ↩

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  85. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  86. Fradet M, Kelly CM, Donnelly AJ, Suppes T (December 2024). "Psilocybin and hallucinogenic mushrooms". CNS Spectr. 29 (6): 611–632. doi:10.1017/S1092852924002487. PMID 39789676. https://doi.org/10.1017%2FS1092852924002487 ↩

  87. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  88. Fradet M, Kelly CM, Donnelly AJ, Suppes T (December 2024). "Psilocybin and hallucinogenic mushrooms". CNS Spectr. 29 (6): 611–632. doi:10.1017/S1092852924002487. PMID 39789676. https://doi.org/10.1017%2FS1092852924002487 ↩

  89. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  90. 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230476 ↩

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  92. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  93. Fradet M, Kelly CM, Donnelly AJ, Suppes T (December 2024). "Psilocybin and hallucinogenic mushrooms". CNS Spectr. 29 (6): 611–632. doi:10.1017/S1092852924002487. PMID 39789676. https://doi.org/10.1017%2FS1092852924002487 ↩

  94. Fradet M, Kelly CM, Donnelly AJ, Suppes T (December 2024). "Psilocybin and hallucinogenic mushrooms". CNS Spectr. 29 (6): 611–632. doi:10.1017/S1092852924002487. PMID 39789676. https://doi.org/10.1017%2FS1092852924002487 ↩

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  96. 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. https://www.nature.com/articles/s41386-024-02011-0.pdf ↩

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  115. Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961. https://web.archive.org/web/20250511111827oe_/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 ↩

  116. Bellanavidanalage Gothami Ayanthie Vis Jayasinha (8 February 2024). Towards Safer Trips: Exploring Harm Reduction Strategies for Recreational Psychedelic Use in Aotearoa New Zealand (Thesis). University of Otago. Retrieved 3 October 2024. Another form of mixing substances involves the use of trip killers; a pharmacological coping strategy aimed to reduce the negative effects of a psychedelic experience by consuming a different substance (Suran, 2024). While this is a new concept and an under researched area, there are reports of trip killers being effective in reducing the negative effects of a psychedelic experience (Suran, 2024). One study gathered research from reddit, an online social media platform, investigating the usage of trip killers during challenging psychedelic experiences (Suran, 2024). The most popular and effective trip killers used were prescription medication, with 47% reporting the use of benzodiazepines as they reduce anxiety, followed by the use of antipsychotic and antidepressant medication (Suran, 2024). However, there are risks in mixing substances with psychedelic drugs, and subjectivity in the effectiveness. As some individuals may experience positive effects, while for others it may lead to negative effects (Suran, 2024). Therefore, it is recommended that before using trip killers, individuals should try other non- pharmacological coping strategies to reduce the negative effects of the psychedelic drug (Gable, 2004; Van Amsterdam et al., 2011). These factors discussed above, demonstrate the effectiveness of protective behaviours and harm reduction practices, in promoting safe psychedelic use and reducing harm. https://ourarchive.otago.ac.nz/esploro/outputs/graduate/Towards-Safer-Trips-Exploring-Harm-Reduction/9926550679501891 ↩

  117. Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961. https://web.archive.org/web/20250511111827oe_/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 ↩

  118. Suran M (February 2024). "Study Finds Hundreds of Reddit Posts on "Trip-Killers" for Psychedelic Drugs". JAMA. 331 (8): 632–634. doi:10.1001/jama.2023.28257. PMID 38294772. /wiki/Doi_(identifier) ↩

  119. Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961. https://web.archive.org/web/20250511111827oe_/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 ↩

  120. Suran M (February 2024). "Study Finds Hundreds of Reddit Posts on "Trip-Killers" for Psychedelic Drugs". JAMA. 331 (8): 632–634. doi:10.1001/jama.2023.28257. PMID 38294772. /wiki/Doi_(identifier) ↩

  121. 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. https://go.gale.com/ps/i.do?p=HRCA&sw=w&v=2.1&it=r&id=GALE%7CA782593467&sid=googleScholar&linkaccess=abs&userGroupName=anon~65c6fefa&aty=open-web-entry ↩

  122. Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961. https://web.archive.org/web/20250511111827oe_/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 ↩

  123. Suran M (February 2024). "Study Finds Hundreds of Reddit Posts on "Trip-Killers" for Psychedelic Drugs". JAMA. 331 (8): 632–634. doi:10.1001/jama.2023.28257. PMID 38294772. /wiki/Doi_(identifier) ↩

  124. Muir OS, Shinozuka K, Beutler BD, Arenas A, Cherian K, Evans VD, Fasano C, Tabaac BJ (2024). "Psychedelic Therapy: A Primer for Primary Care Clinicians-The Strengths, Weaknesses, Opportunities, and Threats of Psychedelic Therapeutics". Am J Ther. 31 (2): e178 – e182. doi:10.1097/MJT.0000000000001720. PMID 38518273. When psychedelics are used in recreational contexts without adequate supervision, they can lead to tragic outcomes.20 There are rare reports of serious adverse effects, including psychosis and even suicide, arising from recreational use.21 Methods for subduing socalled "bad trips" in recreational settings include potentially dangerous habits, such as taking benzodiazepines, which are known to be "trip killers."22 https://www.researchgate.net/publication/379188134 ↩

  125. Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961. https://web.archive.org/web/20250511111827oe_/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 ↩

  126. Suran M (February 2024). "Study Finds Hundreds of Reddit Posts on "Trip-Killers" for Psychedelic Drugs". JAMA. 331 (8): 632–634. doi:10.1001/jama.2023.28257. PMID 38294772. /wiki/Doi_(identifier) ↩

  127. 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. https://go.gale.com/ps/i.do?p=HRCA&sw=w&v=2.1&it=r&id=GALE%7CA782593467&sid=googleScholar&linkaccess=abs&userGroupName=anon~65c6fefa&aty=open-web-entry ↩

  128. Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961. https://web.archive.org/web/20250511111827oe_/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 ↩

  129. Suran M (February 2024). "Study Finds Hundreds of Reddit Posts on "Trip-Killers" for Psychedelic Drugs". JAMA. 331 (8): 632–634. doi:10.1001/jama.2023.28257. PMID 38294772. /wiki/Doi_(identifier) ↩

  130. Skolnick P, Crystal R (February 2020). "Cannabinoid1 (CB-1) receptor antagonists: a molecular approach to treating acute cannabinoid overdose". J Neural Transm (Vienna). 127 (2): 279–286. doi:10.1007/s00702-019-02132-7. PMC 7035232. PMID 31893308. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035232 ↩

  131. 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. https://doi.org/10.3390%2Fddc2030035 ↩

  132. 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993283 ↩

  133. Clark SD, Abi-Dargham A (October 2019). "The Role of Dynorphin and the Kappa Opioid Receptor in the Symptomatology of Schizophrenia: A Review of the Evidence". Biol Psychiatry. 86 (7): 502–511. doi:10.1016/j.biopsych.2019.05.012. PMID 31376930. Finally, in a double-blind study of 24 healthy volunteers, Maqueda et al. (27) found that salvinorin A produced both visual and auditory changes that could be blocked by the kappa, mu, and delta receptor antagonist naltrexone (Table 2). https://doi.org/10.1016%2Fj.biopsych.2019.05.012 ↩

  134. 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966277 ↩

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  137. 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 different from sedative action of benzodiazepines. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478010 ↩

  138. 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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9660700 ↩

  139. 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 different from sedative action of benzodiazepines. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478010 ↩

  140. 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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9660700 ↩

  141. 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. /wiki/Doi_(identifier) ↩

  142. Leikin, Jerrold B.; Krantz, Anne J.; Zell-Kanter, Michele; Barkin, Robert L.; Hryhorczuk, Daniel O. (1989). "Clinical Features and Management of Intoxication Due to Hallucinogenic Drugs". Medical Toxicology and Adverse Drug Experience. 4 (5). Springer Science and Business Media LLC: 324–350. doi:10.1007/bf03259916. ISSN 0113-5244. PMID 2682130. /wiki/Doi_(identifier) ↩

  143. 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. 978-3-030-42916-4 ↩

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  145. 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. /wiki/Doi_(identifier) ↩

  146. 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. /wiki/Doi_(identifier) ↩

  147. Suran M (February 2024). "Study Finds Hundreds of Reddit Posts on "Trip-Killers" for Psychedelic Drugs". JAMA. 331 (8): 632–634. doi:10.1001/jama.2023.28257. PMID 38294772. /wiki/Doi_(identifier) ↩

  148. Bey T, Patel A (February 2007). "Phencyclidine intoxication and adverse effects: a clinical and pharmacological review of an illicit drug". Cal J Emerg Med. 8 (1): 9–14. PMC 2859735. PMID 20440387. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859735 ↩

  149. 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. /wiki/Doi_(identifier) ↩

  150. Mitchel DH (1980). "Amanita mushroom poisoning". Annu Rev Med. 31: 51–57. doi:10.1146/annurev.me.31.020180.000411. PMID 6772091. /wiki/Doi_(identifier) ↩

  151. 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977045 ↩

  152. Yates G, Melon E (January 2024). "Trip-killers: a concerning practice associated with psychedelic drug use" (PDF). Emerg Med J. 41 (2): 112–113. doi:10.1136/emermed-2023-213377. PMID 38123961. https://web.archive.org/web/20250511111827oe_/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 ↩

  153. Halberstadt AL, Nichols DE (2020). "Serotonin and serotonin receptors in hallucinogen action". Handbook of the Behavioral Neurobiology of Serotonin. Handbook of Behavioral Neuroscience. Vol. 31. pp. 843–863. doi:10.1016/B978-0-444-64125-0.00043-8. ISBN 9780444641250. ISSN 1569-7339. S2CID 241134396. Pretreatment with the selective 5-HT reuptake inhibitors citalopram, fluoxetine, and paroxetine significantly attenuated most of the subjective effects of MDMA, consistent with the proposed involvement of carriermediated 5-HT release in the effects of MDMA (Farre et al., 2007; Liechti, Baumann, et al., 2000; Tancer & Johanson, 2007). Citalopram also inhibits the effect of MDMA on PPI (Liechti, Geyer, Hell, & Vollenweider, 2001). According to another report (Hysek, Simmler et al., 2012), the mixed SERT/NET inhibitor duloxetine robustly blocked most of the subjective response to MDMA, raising the possibility that NE release contributes to its effects. In a follow-up study, the selective NET inhibitor reboxetine significantly reduced the emotional excitation and feelings of stimulation produced by MDMA but did not alter its entactogenic or mood-elevating effects (Hysek et al., 2011). Therefore, although NE release contributes to the stimulant effects produced by MDMA, 5-HT release appears to be principally responsible for the unique entactogenic effects of the drug. [...] Several studies have examined the contribution of 5-HT and DA receptors to the effects of MDMA. Pretreatment with ketanserin produced some attenuation of the subjective effects of MDMA (Liechti, Saur, et al., 2000). However, the most significant reduction of MDMA effects by ketanserin occurred in the VR dimension of the APZ, indicating that 5-HT2A receptors are responsible for the effects of MDMA on perception. Ketanserin also blocked MDMA-induced impairment of performance on a verbal memory task (van Wel et al., 2011), but had no effect on the ability of MDMA to induce depersonalization and derealization (Puxty et al., 2017). 9780444641250 ↩

  154. 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 https://escholarship.org/uc/item/0rw3v152 ↩

  155. Halberstadt AL, Nichols DE (2020). "Serotonin and serotonin receptors in hallucinogen action". Handbook of the Behavioral Neurobiology of Serotonin. Handbook of Behavioral Neuroscience. Vol. 31. pp. 843–863. doi:10.1016/B978-0-444-64125-0.00043-8. ISBN 9780444641250. ISSN 1569-7339. S2CID 241134396. Pretreatment with the selective 5-HT reuptake inhibitors citalopram, fluoxetine, and paroxetine significantly attenuated most of the subjective effects of MDMA, consistent with the proposed involvement of carriermediated 5-HT release in the effects of MDMA (Farre et al., 2007; Liechti, Baumann, et al., 2000; Tancer & Johanson, 2007). Citalopram also inhibits the effect of MDMA on PPI (Liechti, Geyer, Hell, & Vollenweider, 2001). According to another report (Hysek, Simmler et al., 2012), the mixed SERT/NET inhibitor duloxetine robustly blocked most of the subjective response to MDMA, raising the possibility that NE release contributes to its effects. In a follow-up study, the selective NET inhibitor reboxetine significantly reduced the emotional excitation and feelings of stimulation produced by MDMA but did not alter its entactogenic or mood-elevating effects (Hysek et al., 2011). Therefore, although NE release contributes to the stimulant effects produced by MDMA, 5-HT release appears to be principally responsible for the unique entactogenic effects of the drug. [...] Several studies have examined the contribution of 5-HT and DA receptors to the effects of MDMA. Pretreatment with ketanserin produced some attenuation of the subjective effects of MDMA (Liechti, Saur, et al., 2000). However, the most significant reduction of MDMA effects by ketanserin occurred in the VR dimension of the APZ, indicating that 5-HT2A receptors are responsible for the effects of MDMA on perception. Ketanserin also blocked MDMA-induced impairment of performance on a verbal memory task (van Wel et al., 2011), but had no effect on the ability of MDMA to induce depersonalization and derealization (Puxty et al., 2017). 9780444641250 ↩

  156. 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 https://escholarship.org/uc/item/0rw3v152 ↩

  157. 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. /wiki/Doi_(identifier) ↩

  158. Halberstadt AL, Nichols DE (2020). "Serotonin and serotonin receptors in hallucinogen action". Handbook of the Behavioral Neurobiology of Serotonin. Handbook of Behavioral Neuroscience. Vol. 31. pp. 843–863. doi:10.1016/B978-0-444-64125-0.00043-8. ISBN 9780444641250. ISSN 1569-7339. S2CID 241134396. Pretreatment with the selective 5-HT reuptake inhibitors citalopram, fluoxetine, and paroxetine significantly attenuated most of the subjective effects of MDMA, consistent with the proposed involvement of carriermediated 5-HT release in the effects of MDMA (Farre et al., 2007; Liechti, Baumann, et al., 2000; Tancer & Johanson, 2007). Citalopram also inhibits the effect of MDMA on PPI (Liechti, Geyer, Hell, & Vollenweider, 2001). According to another report (Hysek, Simmler et al., 2012), the mixed SERT/NET inhibitor duloxetine robustly blocked most of the subjective response to MDMA, raising the possibility that NE release contributes to its effects. In a follow-up study, the selective NET inhibitor reboxetine significantly reduced the emotional excitation and feelings of stimulation produced by MDMA but did not alter its entactogenic or mood-elevating effects (Hysek et al., 2011). Therefore, although NE release contributes to the stimulant effects produced by MDMA, 5-HT release appears to be principally responsible for the unique entactogenic effects of the drug. [...] Several studies have examined the contribution of 5-HT and DA receptors to the effects of MDMA. Pretreatment with ketanserin produced some attenuation of the subjective effects of MDMA (Liechti, Saur, et al., 2000). However, the most significant reduction of MDMA effects by ketanserin occurred in the VR dimension of the APZ, indicating that 5-HT2A receptors are responsible for the effects of MDMA on perception. Ketanserin also blocked MDMA-induced impairment of performance on a verbal memory task (van Wel et al., 2011), but had no effect on the ability of MDMA to induce depersonalization and derealization (Puxty et al., 2017). 9780444641250 ↩

  159. 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. /wiki/Doi_(identifier) ↩

  160. 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. /wiki/Doi_(identifier) ↩

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