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TripSit · Diphenhydramine

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本条目为第三方公开资料的归档，仅用于学术研究与科普，不构成任何操作指导或医学建议；物质处理涉及法律与健康风险，请在专业、合法的条件下自行核验。

正文中文为机器翻译，仅供参考；专业内容以折叠的原文为准。

详情

别名

diphenhydramine dph benadryl

分类

抑制剂谵妄剂常规

相互作用

alcohol

备注

这两种物质会强烈且不可预测地相互增强，并可能迅速导致昏迷。它们都会增加彼此的副作用，如共济失调、镇静和中枢神经系统抑制。昏厥和记忆丧失显着增加。如果使用者在醉酒状态下失去知觉，且不采取恢复姿势，则存在严重的呕吐物误吸风险。酒精也可能会增加苯海拉明的谵妄作用。还应该注意的是，如果饮酒的人通常对酒精有脸红反应，苯海拉明可能会减少这种反应并掩盖酒精的一些影响。

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The two substances potentiate each other strongly and unpredictably, and may rapidly lead to unconsciousness. They both increase each other's side effects such as ataxia, sedation, and CNS depression. Blackouts and memory loss are significantly increased. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position. Alcohol may also increase the deliriant effects of diphenhydramine. It should also be noted if the individual consuming alcohol typically has a flushing response to alcohol, diphenhydramine may reduce the reaction and mask some of the effects of the alcohol.

来源

author: ScienceDirect
标题: Diphenhydramine - an overview (2024)
链接: https://www.sciencedirect.com/topics/chemistry/diphenhydramine

author: ScienceDirect
标题: Ethanol - an overview (2024)
链接: https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/ethanol

author: Miller, N. S., Goodwin, D. W., Jones, F. C., Gabrielli, W. F., Pardo, M. P., Anand, M. M., & Hall, T. B.
标题: Antihistamine blockade of alcohol-induced flushing in orientals. Journal of Studies on Alcohol, 49(1), 16-20 (1988)
链接: https://doi.org/10.15288/jsa.1988.49.16

author: Sicari, V., & Zabbo, C. P.
标题: Diphenhydramine. In StatPearls. StatPearls Publishing (2024)
链接: http://www.ncbi.nlm.nih.gov/books/NBK526010/

author: Weathermon, R., & Crabb, D. W.
标题: Alcohol and Medication Interactions. Alcohol Research & Health, 23(1), 40-54 (1999)
链接: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761694/

风险等级

危险（应避免）（Dangerous）

amphetamines

备注

安非他明作为兴奋剂可能会掩盖 DPH 的一些负面副作用，导致清醒妄想，这在谵妄状态下更令人担忧。兴奋剂的组合会增加心脏的压力，并可能引起一些身体不适，并有机会引起危及生命的心血管问题。在较高剂量下，该组合还可能增加彼此的神经毒性。除了增加彼此的负面副作用之外，这种组合可能会增加焦虑水平和较高剂量的思维循环风险。据报道，每种物质的医疗剂量和常用剂量都不是问题。此外，除了其他相互作用（例如通过抑制 CYP2D6 和组胺 H1 和 H2 受体增强作用等）之外，DPH 还可以增强安非他明精神运动激活。

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Amphetamines as a stimulant may mask some of the negative side effects of DPH, leading to delusions of sobriety which has additional concern in states of delirium. The combination of stimulants will increase strain on the heart and may cause some physical discomfort, and has the chance to cause life-threatening cardiovascular issues. The combination may also increase each other's neurotoxicity at higher dosages. The combination may increase anxiety levels and risks of thought loops on higher dosages, in addition to increasing each others negative side effects. Medical and common dosages of each substances are reported to not be a concern. Additionally, it is suggested that DPH potentiates amphetamine psychomotor activation, in addition to other interactions such as potentiation through inhibition of CYP2D6 and histamine H1 and H2 receptors, among other alterations.

来源

author: Berman, S. M.; Kuczenski, R.; McCracken, J. T.; London, E. D.
标题: Potential adverse effects of amphetamine treatment on brain and behavior: a review. Molecular Psychiatry, 14(2), 123–142 (2009)
链接: https://doi.org/10.1038/mp.2008.90

author: Clark, J. H.; Meltzer, E. O.; Naclerio, R. M.
标题: Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027 (2025)
链接: https://doi.org/10.1016/j.waojou.2025.101027

author: Martin, D.; Le, J. K.
标题: Amphetamine. In StatPearls. StatPearls Publishing (2025)
链接: http://www.ncbi.nlm.nih.gov/books/NBK556103/

author: McAtee, K. J.; Brillhart, D.; Barbuto, A. F.; Hiller, H. M.
标题: Wide complex tachycardia secondary to massive diphenhydramine overdose: a case report. Journal of Emergency and Critical Care Medicine, 6 (2022)
链接: https://doi.org/10.21037/jeccm-21-33

author: Mohs, R. C.; Tinklenberg, J. R.; Roth, W. T.; Kopell, B. S.
标题: Methamphetamine and diphenhydramine effects on the rate of cognitive processing. Psychopharmacology (1978)
链接: https://doi.org/10.1007/BF00428024

author: Okuda, T.; Ito, Y.; Nakagawa, N.; Hishinuma, T.; Tsukamoto, H.; Iwabuchi, K.; Watanabe, T.; Kitaichi, K.; Goto, J.; Yanai, K.
标题: Drug interaction between methamphetamine and antihistamines: behavioral changes and tissue concentrations of methamphetamine in rats. European Journal of Pharmacology, 505(1), 135–144 (2004)
链接: https://doi.org/10.1016/j.ejphar.2004.10.022

author: Sicari, V.; Patel, P.; Zabbo, C. P.
标题: Diphenhydramine. In StatPearls. StatPearls Publishing (2025)
链接: http://www.ncbi.nlm.nih.gov/books/NBK526010/

author: Steinkellner, T.; Freissmuth, M.; Sitte, H. H.; Montgomery, T.
标题: The ugly side of amphetamines: short- and long-term toxicity of MDMA, methamphetamine and d-amphetamine. Biological Chemistry, 392(0) (2011)
链接: https://doi.org/10.1515/BC.2011.016

author: Vasan, S.; Murray, B. P.; Olango, G. J.
标题: Amphetamine Toxicity. In StatPearls. StatPearls Publishing (2025)
链接: http://www.ncbi.nlm.nih.gov/books/NBK470276/

风险等级

谨慎（Caution）

benzodiazepines

备注

这两种物质都会增强另一种物质引起的共济失调和镇静作用，高剂量时可能会导致意外的意识丧失。在失去知觉时，如果不处于恢复姿势，则有呕吐物误吸的风险。内存中断是有可能的。低医疗剂量不太可能引起关注。

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来源

author: Bounds, Connor G., and Preeti Patel. (2025)
标题: Benzodiazepines. StatPearls, StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK470159/

author: Montoro, J., et al. (2013)
标题: H1 Antihistamines and Benzodiazepines. Pharmacological Interactions and Their Impact on Cerebral Function. Journal of Investigational Allergology & Clinical Immunology, 23 Suppl 1, 17–26.
链接: https://pubmed.ncbi.nlm.nih.gov/24672891/

author: Sicari, Vincent, et al. (2025)
标题: Diphenhydramine. StatPearls, StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK526010/

风险等级

不安全（Unsafe）

caffeine

备注

咖啡因作为兴奋剂可能会掩盖 DPH 的一些负面副作用，导致清醒妄想，这在谵妄状态下会引起额外的担忧。兴奋剂的组合会增加心脏的负担，可能会引起一些身体不适，并有机会引起心血管问题，例如复杂性心动过速。除了增加彼此的负面副作用之外，这种组合在较高剂量下可能会增加焦虑水平和思维循环的风险。据报道，医疗剂量不是一个问题。

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Caffeine as a stimulant may mask some negative side effects of DPH, leading to delusions of sobriety, which has additional concerns in states of delirium. The combination of stimulants will increase strain on the heart and may cause some physical discomfort, and has the chance to cause cardiovascular issues such as complex tachycardia. The combination may increase anxiety levels and risks of thought loops at higher dosages, in addition to increasing each other's negative side effects. Medical dosages are reported to not be a concern.

来源

author: Clark, J. H.; Meltzer, E. O.; Naclerio, R. M. (2025)
标题: Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027.
链接: https://doi.org/10.1016/j.waojou.2025.101027

author: Evans, J.; Richards, J. R.; Battisti, A. S. (2025)
标题: Caffeine. In StatPearls. StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK519490/

author: McAtee, K. J.; Brillhart, D.; Barbuto, A. F.; Hiller, H. M. (2022)
标题: Wide complex tachycardia secondary to massive diphenhydramine overdose: a case report. Journal of Emergency and Critical Care Medicine, 6(0).
链接: https://doi.org/10.21037/jeccm-21-33

author: Murray, A.; Traylor, J. (2025)
标题: Caffeine Toxicity. In StatPearls. StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK532910/

author: Institute of Medicine (US) Committee on Military Nutrition Research (2001)
标题: Pharmacology of Caffeine. In Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. National Academies Press (US).
链接: https://www.ncbi.nlm.nih.gov/books/NBK223808/

author: Sicari, V.; Patel, P.; Zabbo, C. P. (2025)
标题: Diphenhydramine. In StatPearls. StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK526010/

author: Tharion, W. J.; Kobrick, J. L.; Lieberman, H. R.; Fine, B. J. (1993)
标题: Effects of caffeine and diphenhydramine on auditory evoked cortical potentials. Perceptual and Motor Skills, 76(3 Pt 1), 707–715.
链接: https://doi.org/10.2466/pms.1993.76.3.707

风险等级

谨慎（Caution）

cocaine

备注

兴奋剂会增加呼吸频率，从而允许使用比正常剂量更高的镇静剂。如果可卡因先失效，娱乐性剂量的 DPH 可能会抑制个体并导致呼吸停止。这两种物质在娱乐剂量下都会使心脏紧张，并可能导致进一步危险的心脏并发症。当较高剂量的 DPH 与可卡因结合在一起时，这两种物质可能会产生更强的增强作用，并具有更大的高铁血红蛋白血症风险。

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Stimulants increase respiration rate allowing for a higher dose of sedatives than normal. If cocaine wears off first, recreational dosages of DPH may overcome the individual and cause respiratory arrest. Both substances at recreational dosages strain the heart and may lead to further dangerous heart complications. When taken together, both substances can potentially be more reinforcing and have greater risk of methemoglobinemia when higher dosages of DPH are combined with cocaine.

来源

author: Alanazi, M. Q.
标题: Drugs may be Induced Methemoglobinemia. Journal of Hematology & Thromboembolic Diseases, 06(01). (2017)
链接: https://doi.org/10.4172/2329-8790.1000270

author: Banks, M. L., Andersen, M. L., Murnane, K. S., Meyer, R. C., & Howell, L. L.
标题: Behavioral and neurochemical effects of cocaine and diphenhydramine combinations in rhesus monkeys. Psychopharmacology, 205(3), 467–474. (2009)
链接: https://doi.org/10.1007/s00213-009-1555-y

author: chrisn
标题: Diphenhydramine [Online post]. Drug-Forum. (2021)
链接: https://drugs-forum.com/wiki/Diphenhydramine

author: Eshmandi, M., Mohamed, A., Khalil, B., & Belhaj, A.
标题: Methaemoglobinaemia Associated With Mixed Cocaine and Amphetamine Overdose: A Case Report. Cureus, 16(1), e51748. (2024)
链接: https://doi.org/10.7759/cureus.51748

author: Karch, S. B.
标题: Diphenhydramine toxicity: comparisons of postmortem findings in diphenhydramine-, cocaine-, and heroin-related deaths. The American Journal of Forensic Medicine and Pathology, 19(2), 143–147. (1998)
链接: https://doi.org/10.1097/00000433-199806000-00008

author: Pennefather, J. N.
标题: The effects pf cocaine and diphenhydramine upon the reactivity of rat vas deferens to supramaximal doses of noradrenaline and of other agonists: The mode of action of cocaine. European Journal of Pharmacology, 35(2), 333–339. (1976)
链接: https://doi.org/10.1016/0014-2999(76)90236-3

author: Pergolizzi, J. V., Magnusson, P., LeQuang, J. A. K., Breve, F., & Varrassi, G.
标题: Cocaine and Cardiotoxicity: A Literature Review. Cureus, 13(4), e14594. (2021)
链接: https://doi.org/10.7759/cureus.14594

author: Sicari, V., Patel, P., & Zabbo, C. P.
标题: Diphenhydramine. In StatPearls. StatPearls Publishing. (2025)
链接: http://www.ncbi.nlm.nih.gov/books/NBK526010/

author: Tanda, G., Kopajtic, T. A., & Katz, J. L.
标题: Cocaine-Like Neurochemical Effects of Antihistaminic Medications. Journal of Neurochemistry, 106(1), 147–157. (2008)
链接: https://doi.org/10.1111/j.1471-4159.2008.05361.x

author: Wang, Z., & Woolverton, W. L.
标题: Self-administration of cocaine-antihistamine combinations: Super-additive reinforcing effects. European Journal of Pharmacology, 557(2–3), 159–160. (2007)
链接: https://doi.org/10.1016/j.ejphar.2006.11.056

author: Wang, Z., & Woolverton, W. L.
标题: Super-additive interaction of the reinforcing effects of cocaine and H1-antihistamines in rhesus monkeys. Pharmacology Biochemistry and Behavior, 91(4), 590–595. (2009)
链接: https://doi.org/10.1016/j.pbb.2008.09.013

author: Weichert, I.
标题: Acute Management of Cocaine-Associated Methaemoglobinaemia. Case Reports in Medicine, 2011, 1–3. (2011)
链接: https://doi.org/10.1155/2011/136396

风险等级

谨慎（Caution）

dextromethorphan

备注

据报道，这种组合可以减少每种药物的副作用并增强许多娱乐效果。存在血清素综合征、谵妄增加、中枢神经系统抑制、认知抑制、身体损伤、高热、躁狂、偏执和精神病的风险，特别是在较高剂量时。 There is an additional concern of tachycardia, hypertension, and in extreme cases, heart failure.据报道，苯海拉明可抑制 CYP2D6 酶，从而增加 DXM 的水平。据报道，医疗剂量不是一个问题。强烈建议谨慎使用此组合。

查看原文

The combination is reported to reduce the side effects of each drug and potentiate many of the recreational effects. There is a significant risk of serotonin syndrome, increased delirium, CNS depression, cognitive inhibition, risk of physical injury, hyperthermia, mania, paranoia, and psychosis, especially at higher dosages. There is an additional concern of tachycardia, hypertension, and in extreme cases, heart failure. Diphenhydramine is reported to inhibit the CYP2D6 enzyme which can increase levels of DXM. Medical dosages are not reported to be a concern. Caution is strongly recommended with this combination.

来源

author: Abdul Manap, Wright, Gregory, Rostami‐Hodjegan, Meller, Kelm, Lennard, Tucker, & Morice. (1999)
标题: The antitussive effect of dextromethorphan in relation to CYP2D6 activity. British Journal of Clinical Pharmacology, 48(3), 382–387.
链接: https://doi.org/10.1046/j.1365-2125.1999.00029.x

author: Akutsu, T., Kobayashi, K., Sakurada, K., Ikegaya, H., Furihata, T., & Chiba, K. (2007)
标题: Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 35(1), 72–78.
链接: https://doi.org/10.1124/dmd.106.012088

author: Clark, J. H., Meltzer, E. O., & Naclerio, R. M. (2025)
标题: Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027.
链接: https://doi.org/10.1016/j.waojou.2025.101027

author: Crazy Steve. (2004)
标题: Mind Expansion: An Experience with DXM & Diphenhydramine (exp33999). Erowid.org.
链接: https://www.erowid.org/experiences/exp.php?ID=33999

author: De Leon, J., & Nikoloff, D. M. (2008)
标题: Paradoxical Excitation on Diphenhydramine May Be Associated with Being a CYP2D6 Ultrarapid Metabolizer: Three Case Reports. CNS Spectrums, 13(2), 133–135.
链接: https://doi.org/10.1017/S109285290001628X

author: Hamelin, B. (2000a)
标题: Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity. Clinical Pharmacology & Therapeutics, 67(5), 466–477.
链接: https://doi.org/10.1067/mcp.2000.106464

author: HANS. (2022)
标题: First Overdose: An Experience with DXM & Diphenhydramine (exp116238). Erowid.org.
链接: https://www.erowid.org/experiences/exp.php?ID=116238

author: Jun, J. H., Thorndike, E. B., & Schindler, C. W. (2004a)
标题: Abuse liability and stimulant properties of dextromethorphan and diphenhydramine combinations in rats. Psychopharmacology, 172(3), 277–282.
链接: https://doi.org/10.1007/s00213-003-1650-4

author: Josie Kins
标题: The DXM and DPH combination, broken down and described
链接: https://disregardeverythingisay.com/post/39670297758/the-dxm-and-dph-combination-broken-down-and

author: Lessard, E., Yessine, M. A., Hamelin, B. A., Gauvin, C., Labbé, L., O’Hara, G., LeBlanc, J., & Turgeon, J. (2001)
标题: Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans. Journal of Clinical Psychopharmacology, 21(2), 175–184.
链接: https://doi.org/10.1097/00004714-200104000-00009

author: Psychonaut Wiki
标题: DXM & DPH
链接: https://psychonautwiki.org/wiki/DXM_%26_DPH

author: Romanelli, F., & Smith, K. M. (2009)
标题: Dextromethorphan abuse: Clinical effects and management. Journal of the American Pharmacists Association, 49(2), e20–e27.
链接: https://doi.org/10.1331/JAPhA.2009.08091

author: Schwartz, A. R., Pizon, A. F., & Brooks, D. E. (2008)
标题: Dextromethorphan-induced serotonin syndrome. Clinical Toxicology, 46(8), 771–773.
链接: https://doi.org/10.1080/15563650701668625

author: The Salvia Shaman. (2025)
标题: Delirium Visions and Teleportation: An Experience with DXM & Diphenhydramine (exp113902). Erowid.org.
链接: https://www.erowid.org/experiences/exp.php?ID=113902

author: u/syrup_ben_goed (n.d.)
标题: The "right way" to do DXM + DPH combo, from an experienced user
链接: https://www.reddit.com/r/Drugs/comments/ajlupr/the_right_way_to_do_dxm_dph_comb

风险等级

不安全（Unsafe）

dmt

备注

25-50 毫克的 DPH 可能有助于缓解 DMT 的副作用，例如恶心和焦虑。在较高剂量时，应注意不要将谵妄剂 (DPH) 与 DMT 联合使用。除了增加严重伤害和精神创伤的风险外，DMT 还可能增加 DPH 的精神错乱和负面影响。

查看原文

At 25-50mg, DPH may assist with side effects of the DMT such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and DMT is cautioned against. DMT is likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma.

来源

author: Carbonaro, T. M., & Gatch, M. B. (2016)
标题: Neuropharmacology of N,N-Dimethyltryptamine. Brain Research Bulletin, 126(Pt 1), 74–88.
链接: https://doi.org/10.1016/j.brainresbull.2016.04.016

author: Chapy, H., Smirnova, M., André, P., Schlatter, J., Chiadmi, F., Couraud, P.-O., Scherrmann, J.-M., Declèves, X., & Cisternino, S. (2014)
标题: Carrier-Mediated Cocaine Transport at the Blood-Brain Barrier as a Putative Mechanism in Addiction Liability. International Journal of Neuropsychopharmacology, 18(1), pyu001.
链接: https://doi.org/10.1093/ijnp/pyu001

author: Schaefer, T. S., Patel, P., & Zito, P. M. (2025)
标题: Antiemetic Histamine H1 Receptor Blockers. In StatPearls. StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK533003/

author: Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)
标题: Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.
链接: https://doi.org/10.3389/fpsyt.2021.657397

author: Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)
标题: Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.
链接: https://doi.org/10.1016/j.jaip.2022.07.018

风险等级

谨慎（Caution）

dox

备注

25-50 毫克的 DPH 可能有助于缓解 DOx 药物的副作用，例如恶心和焦虑。在较高剂量时，应注意不要将谵妄剂 (DPH) 和 DOx 药物联合使用。 DOx 药物除了增加严重伤害和精神创伤的风险外，还可能增加 DPH 的神志不清和负面影响。消遣剂量的 DOx 药物和 DPH 会产生额外的心脏问题，例如血管收缩、心动过速、高血压，这些问题组合起来可能会加剧。

查看原文

At 25-50mg, DPH may assist with side effects of DOx drugs such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and DOx drugs is cautioned against. DOx drugs are likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma. DOx drugs and DPH at recreational dosages have additional cardiac concerns such as vasoconstriction, tachycardia, hypertension, which in combination may be exacerbated.

来源

author: ScienceDirect Topics (n.d.)
标题: 2,5-Dimethoxy-4-iodoamphetamine - an overview
链接: https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/2-5-dimethoxy-4-iodoamphetamine

author: Barnett, R. Y., Baker, D. D., Kelly, N. E., McGuire, C. E., Fassette, T. C., & Gorniak, J. M. (2014)
标题: A Fatal Intoxication of 2,5-Dimethoxy-4-Chloroamphetamine: A Case Report. Journal of Analytical Toxicology, 38(8), 589–591.
链接: https://doi.org/10.1093/jat/bku087

author: Burish, M. J., Thoren, K. L., Madou, M., Toossi, S., & Shah, M. (2015)
标题: Hallucinogens Causing Seizures? A Case Report of the Synthetic Amphetamine 2,5-Dimethoxy-4-Chloroamphetamine. The Neurohospitalist, 5(1), 32–34.
链接: https://doi.org/10.1177/1941874414528939

author: Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)
标题: Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.
链接: https://doi.org/10.3389/fpsyt.2021.657397

author: Trout, K., & Daley, P. F. (2024)
标题: The origin of 2,5‐dimethoxy‐4‐methylamphetamine (DOM, STP). Drug Testing and Analysis, 16(12), 1496–1508.
链接: https://doi.org/10.1002/dta.3667

author: Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)
标题: Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.
链接: https://doi.org/10.1016/j.jaip.2022.07.018

风险等级

谨慎（Caution）

ghb/gbl

备注

这两种物质都是中枢神经系统抑制剂，彼此之间会产生不可预测的强烈增强作用，增加记忆丧失、严重共济失调和意识丧失的可能性。 The interaction will cause greater inhibition and risk of injury. If the user falls unconscious it is strongly recommended to put them into the recovery position and monitor breathing.

查看原文

Both substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and unconsciousness. The interaction will cause greater inhibition and risk of injury. If the user falls unconscious it is strongly recommended to put them into the recovery position and monitor breathing.

来源

author: William J Tharion, Donna J. McMenemy, Terry M. Rauch
标题: Antihistamine Effects on the Central Nervous System, Cognitive Performance and Subjective States.
链接: https://doi.org/10.1159/000119069

author: Sicari V, Zabbo CP. Diphenhydramine.
标题: Diphenhydramine
链接: https://www.ncbi.nlm.nih.gov/books/NBK526010/

author: Couper FJ, Marinetti LJ.
标题: γ-Hydroxybutyrate (GHB) - Effects on Human Performance and Behavior
链接: https://pubmed.ncbi.nlm.nih.gov/26256488/

author: Busardò FP, Jones AW.
标题: GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome
链接: https://doi.org/10.2174%2F1570159X13666141210215423

风险等级

危险（应避免）（Dangerous）

ketamine

备注

这两种物质都会增强另一种物质引起的共济失调和镇静作用，高剂量时可能会导致意外的意识丧失。在失去知觉时，如果不处于恢复姿势，则有呕吐物误吸的风险。较高剂量的氯胺酮很可能会增加 DPH 的谵妄作用，并且会大大增加受伤、躁狂和精神病的风险。 Medical dosages of both substances are unlikely to cause concern.

查看原文

Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Ketamine has a high likelihood of increasing DPH's deliriant effects at higher dosages and can greatly increase the risk of injury, mania, and psychosis. Medical dosages of both substances are unlikely to cause concern.

来源

author: Bylund, W., Delahanty, L., & Cooper, M.
标题: The Case of Ketamine Allergy. Clinical Practice and Cases in Emergency Medicine, 1(4), 323–325. (2017)
链接: https://doi.org/10.5811/cpcem.2017.7.34405

author: Clark, J. H., Meltzer, E. O., & Naclerio, R. M.
标题: Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027. (2025)
链接: https://doi.org/10.1016/j.waojou.2025.101027

author: Rosenbaum, S. B., Gupta, V., Patel, P., & Palacios, J. L.
标题: Ketamine. In StatPearls. StatPearls Publishing. (2025)
链接: http://www.ncbi.nlm.nih.gov/books/NBK470357/

author: Sicari, V., Patel, P., & Zabbo, C. P.
标题: Diphenhydramine. In StatPearls. StatPearls Publishing. (2025)
链接: http://www.ncbi.nlm.nih.gov/books/NBK526010/

风险等级

危险（应避免）（Dangerous）

lithium

备注

较高剂量的这种组合可能会导致血清素综合征。建议谨慎限制苯海拉明的医疗剂量（25-50 毫克）。锂盐和苯海拉明都有 QT 延长的风险，联合服用时可能会增加 QT 延长；由于使用者的健康和药物剂量等多种因素，风险会增加。此外，组合可能会增加每种药物的副作用，例如头晕和意识丧失。

查看原文

There is a concern of serotonin syndrome at higher dosages of this combination. Caution is recommended in restricting diphenhydramine to medical dosages (25-50mg). Lithium and diphenhydramine both have concerns of QT prolongation which may be increased when taken in combination; risks increase due to a variety of factors such as the health of the user and drug dosages. Additionally, the combination may increase each drug's side effects, such as dizziness and loss of consciousness.

来源

author: Clark, J. H., Meltzer, E. O., & Naclerio, R. M.
标题: Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027. (2025)
链接: https://doi.org/10.1016/j.waojou.2025.101027

author: Crouch, M. A., Limon, L., & Cassano, A. T.
标题: Clinical Relevance and Management of Drug‐Related QT Interval Prolongation. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 23(7), 881–908. (2003)
链接: https://doi.org/10.1592/phco.23.7.881.32730

author: Farzam, K., & Tivakaran, V. S.
标题: QT Prolonging Drugs. In StatPearls. StatPearls Publishing. (2025)
链接: http://www.ncbi.nlm.nih.gov/books/NBK534864/

author: Finley, P. R.
标题: Drug Interactions with Lithium: An Update. Clinical Pharmacokinetics, 55(8), 925–941. (2016)
链接: https://doi.org/10.1007/s40262-016-0370-y

author: Hawley, C. J., Loughlin, P. J., Quick, S. J., Gale, T. M., Sivakumaran, T., Hayes, J., & McPhee, S.
标题: Efficacy, safety and tolerability of combined administration of lithium and selective serotonin reuptake inhibitors: a review of the current evidence. International Clinical Psychopharmacology, 15(4), 197–206. (2000)
链接: https://doi.org/10.1097/00004850-200015040-00002

author: Husain, Z., Hussain, K., Nair, R., & Steinman, R.
标题: Diphenhydramine induced QT prolongation and torsade de pointes: An uncommon effect of a common drug. Cardiology Journal, 17(5), 509–511. (2010)
链接: https://journals.viamedica.pl/cardiology_journal/article/view/21341

author: Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J.
标题: Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus. (2018)
链接: https://doi.org/10.7759/cureus.2421

author: Massot, O., Rousselle, J.-C., Fillion, M.-P., Januel, D., Plantefol, M., & Fillion, G.
标题: 5-HT1B Receptors: A Novel Target for Lithium: Possible Involvement in Mood Disorders. Neuropsychopharmacology, 21(4), 530–541. (1999)
链接: https://doi.org/10.1016/S0893-133X(99)00042-1

author: Mehta, N., & Vannozzi, R.
标题: Lithium‐induced electrocardiographic changes: A complete review. Clinical Cardiology, 40(12), 1363–1367. (2017)
链接: https://doi.org/10.1002/clc.22822

author: Müller-Oerlinghausen, B.
标题: Drug Interactions with Lithium: A Guide for Clinicians. CNS Drugs, 11(1), 41–48. (1999)
链接: https://doi.org/10.2165/00023210-199911010-00004

author: Rosenberg, A. E., Wang, R., & Rosenberg, M. H.
标题: Serotonin Syndrome Associated With High-dose Diphenhydramine Use Complicating Abdominoplasty and Mastopexy. Plastic and Reconstructive Surgery - Global Open, 13(3), e6634. (2025)
链接: https://doi.org/10.1097/GOX.0000000000006634

author: Truedson, P., Ott, M., Lindmark, K., Ström, M., Maripuu, M., Lundqvist, R., & Werneke, U.
标题: Effects of Toxic Lithium Levels on ECG—Findings from the LiSIE Retrospective Cohort Study. Journal of Clinical Medicine, 11(19), 5941. (2022)
链接: https://doi.org/10.3390/jcm11195941

风险等级

谨慎（Caution）

lsd

备注

25-50 毫克的 DPH 可能有助于缓解 LSD 的副作用，例如恶心和焦虑。在较高剂量时，应注意不要将谵妄剂 (DPH) 与 LSD 联合使用。除了增加严重伤害和精神创伤的风险外，LSD 还可能增加 DPH 的精神错乱和负面影响。休闲剂量的 LSD 和 DPH 会产生额外的心脏问题，例如血管收缩、心动过速、高血压，这些问题组合起来可能会加剧。

查看原文

At 25-50mg, DPH may assist with side effects of the LSD such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and LSD is cautioned against. LSD is likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma. LSD and DPH at recreational dosages have additional cardiac concerns such as vasoconstriction, tachycardia, hypertension, which in combination may be exacerbated.

来源

author: Marraffa, J. M. (2014)
标题: Drugs of Abuse. In Encyclopedia of Toxicology (pp. 248–251). Elsevier.
链接: https://doi.org/10.1016/B978-0-12-386454-3.00684-9

author: Passie, T., Halpern, J. H., Stichtenoth, D. O., Emrich, H. M., & Hintzen, A. (2008)
标题: The Pharmacology of Lysergic Acid Diethylamide: A Review. CNS Neuroscience & Therapeutics, 14(4), 295–314.
链接: https://doi.org/10.1111/j.1755-5949.2008.00059.x

author: Schaefer, T. S., Patel, P., & Zito, P. M. (2025)
标题: Antiemetic Histamine H1 Receptor Blockers. In StatPearls. StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK533003/

author: Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)
标题: Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.
链接: https://doi.org/10.3389/fpsyt.2021.657397

author: The drugs of misuse. (2009)
标题: In Auricular Acupuncture & Addiction (pp. 93–135). Elsevier.
链接: https://doi.org/10.1016/B978-0-443-06885-0.50018-5

author: Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)
标题: Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.
链接: https://doi.org/10.1016/j.jaip.2022.07.018

风险等级

谨慎（Caution）

maois

备注

这种组合存在发生血清素综合征的显着风险。单胺氧化酶 A 抑制剂可能会延长和增强 DPH 的抗胆碱能作用。这种组合会增加彼此的副作用，例如嗜睡、头晕、口干和头痛。据报道，医疗剂量不值得关注。

查看原文

There is a significant risk of serotonin syndrome with this combination. Monoamine oxidase A inhibitors may extend and increase the anticholinergic effects of DPH. The combination increases each other’s side effects, such as drowsiness, dizziness, dry mouth, and headaches. Medical dosages are not reported to be of concern.

来源

author: Adawi Awdish, R. L., Whitmill, M., Coba, V., & Killu, K. (2008)
标题: Serotonin Reuptake Inhibition by Diphenhydramine and concomitant Linezolid use can result in Serotonin Syndrome Chest, 134(4), 4C.
链接: https://doi.org/10.1378/chest.134.4_MeetingAbstracts.c4002

author: Clark, J. H., Meltzer, E. O., & Naclerio, R. M. (2025)
标题: Diphenhydramine: It is time to say a final goodbye. The World Allergy Organization Journal, 18(2), 101027.
链接: https://doi.org/10.1016/j.waojou.2025.101027

author: Edinoff, A. N., Swinford, C. R., Odisho, A. S., Burroughs, C. R., Stark, C. W., Raslan, W. A., Cornett, E. M., Kaye, A. M., & Kaye, A. D. (n.d.)
标题: Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors. Health Psychology Research, 10(4), 39576.
链接: https://doi.org/10.52965/001c.39576

author: Gillman, P. K. (2005)
标题: Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434–441.
链接: https://doi.org/10.1093/bja/aei210

author: Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J. (2018)
标题: Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus.
链接: https://doi.org/10.7759/cureus.2421

author: López-Álvarez, J., Sevilla-Llewellyn-Jones, J., & Agüera-Ortiz, L. (2019)
标题: Anticholinergic Drugs in Geriatric Psychopharmacology. Frontiers in Neuroscience, 13, 1309.
链接: https://doi.org/10.3389/fnins.2019.01309

author: Sub Laban, T., & Saadabadi, A. (2025)
标题: Monoamine Oxidase Inhibitors (MAOI). In StatPearls. StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK539848/

风险等级

不安全（Unsafe）

mephedrone

备注

休闲剂量的血清素综合征风险很高。两者都会减弱彼此的效果，因此，如果一种药物先于另一种药物失效，则可能会因缺乏对抗作用而服用过量。据报道，医疗剂量并不是普通人群所关心的问题。这两种物质都会影响心脏，如果剂量较高，可能会导致进一步危险的心脏并发症。合用可能会增加彼此的副作用，如头晕、嗜睡等。在较高剂量下，组合可能会增加彼此的副作用，例如谵妄、躁狂和精神病。

查看原文

There is a high risk of serotonin syndrome at recreational dosages. Both can dull each other's effects, so if one wears off before the other it's possible to overdose due to the lack of counteraction. Medical dosages are reported not to be a concern for the general population. Both substances affect the heart and may lead to further dangerous heart complications at higher dosages. The combination may increase each other's side effects, such as dizziness and drowsiness. At higher dosages, the combination may increase each other's side effects, such as delirium, mania, and psychosis.

来源

author: Clark, J. H., Meltzer, E. O., & Naclerio, R. M.
标题: Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027 (2025)
链接: https://doi.org/10.1016/j.waojou.2025.101027

author: Ener, R. A., Meglathery, S. B., Decker, W. A. V., & Gallagher, R. M.
标题: Serotonin Syndrome and Other Serotonergic Disorders: Table 1. Pain Medicine, 4(1), 63-74 (2003)
链接: https://doi.org/10.1046/j.1526-4637.2003.03005.x

author: Hadlock, G. C., Webb, K. M., McFadden, L. M., Chu, P. W., Ellis, J. D., Allen, S. C., Andrenyak, D. M., Vieira-Brock, P. L., German, C. L., Conrad, K. M., Hoonakker, A. J., Gibb, J. W., Wilkins, D. G., Hanson, G. R., & Fleckenstein, A. E.
标题: 4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse. The Journal of Pharmacology and Experimental Therapeutics, 339(2), 530-536 (2011)
链接: https://doi.org/10.1124/jpet.111.184119

author: Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T.
标题: Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949-1958 (2011)
链接: https://doi.org/10.1111/j.1476-5381.2011.01499.x

author: Meng, H., Cao, J., Kang, J., Ying, X., Ji, J., Reynolds, W., & Rampe, D.
标题: Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicology Letters, 208(1), 62-68 (2012)
链接: https://doi.org/10.1016/j.toxlet.2011.10.010

author: Varghese, E., Abate, M. A., Hu, L., Kaplan, J., Kraner, J., Long, D. L., Sorg, M., Mock, A., Greenwald, M., & Andrew, T.
标题: Characterization of Diphenhydramine-Related Accidental Overdose Deaths. Academic Forensic Pathology, 5(1), 105-115 (2015)
链接: https://doi.org/10.23907/2015.011

风险等级

危险（应避免）（Dangerous）

mescaline

备注

25-50 毫克的 DPH 可能有助于缓解麦司卡林的副作用，例如恶心和焦虑。在较高剂量时，应注意不要将谵妄剂 (DPH) 与麦斯卡林联合使用。麦斯卡林除了增加严重伤害和精神创伤的风险外，还可能增加 DPH 的神志不清和负面影响。

查看原文

At 25-50mg, DPH may assist with side effects of the mescaline such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and mescaline is cautioned against. Mescaline is likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma.

来源

author: Dinis-Oliveira, R. J., Pereira, C. L., & Dias da Silva, D. (2019)
标题: Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions. Current Molecular Pharmacology, 12(3), 184–194.
链接: https://doi.org/10.2174/1874467211666181010154139

author: ScienceDirect Topics. (n.d.)
标题: Mescaline - an overview.
链接: https://www.sciencedirect.com/topics/neuroscience/mescaline

author: Schaefer, T. S., Patel, P., & Zito, P. M. (2025)
标题: Antiemetic Histamine H1 Receptor Blockers. In StatPearls. StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK533003/

author: Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)
标题: Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.
链接: https://doi.org/10.3389/fpsyt.2021.657397

author: Vamvakopoulou, I. A., Narine, K. A. D., Campbell, I., Dyck, J. R. B., & Nutt, D. J. (2023)
标题: Mescaline: The forgotten psychedelic. Neuropharmacology, 222, 109294.
链接: https://doi.org/10.1016/j.neuropharm.2022.109294

author: Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)
标题: Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.
链接: https://doi.org/10.1016/j.jaip.2022.07.018

风险等级

谨慎（Caution）

mushrooms

备注

25-50 毫克的 DPH 可能有助于缓解裸盖菇素的副作用，例如恶心和焦虑。在较高剂量时，应注意不要将谵妄剂 (DPH) 与裸盖菇素联合使用。裸盖菇素除了增加严重伤害和精神创伤的风险外，还可能增加 DPH 的昏迷和负面影响。

查看原文

At 25-50mg, DPH may assist with side effects of the psilocybin such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and psilocybin is cautioned against. Psilocybin is likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma.

来源

author: Goel, D. B., & Zilate, S. (2022)
标题: Potential Therapeutic Effects of Psilocybin: A Systematic Review. Cureus, 14(10), e30214.
链接: https://doi.org/10.7759/cureus.30214

author: Passie, T., Seifert, J., Schneider, U., & Emrich, H. M. (2002)
标题: The pharmacology of psilocybin. Addiction Biology, 7(4), 357–364.
链接: https://doi.org/10.1080/1355621021000005937

author: Schaefer, T. S., Patel, P., & Zito, P. M. (2025)
标题: Antiemetic Histamine H1 Receptor Blockers. In StatPearls. StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK533003/

author: Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)
标题: Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12.
链接: https://doi.org/10.3389/fpsyt.2021.657397

author: Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)
标题: Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.
链接: https://doi.org/10.1016/j.jaip.2022.07.018

author: Yerubandi, A., Thomas, J. E., Bhuiya, N. M. M. A., Harrington, C., Villa Zapata, L., & Caballero, J. (2024)
标题: Acute Adverse Effects of Therapeutic Doses of Psilocybin. JAMA Network Open, 7(4), e245960.
链接: https://doi.org/10.1001/jamanetworkopen.2024.5960

风险等级

谨慎（Caution）

mxe

备注

这种组合导致血清素综合征的风险很高。这两种物质都会增强另一种物质引起的共济失调和镇静作用，高剂量时可能会导致意外的意识丧失。在失去知觉时，如果不处于恢复姿势，则有呕吐物误吸的风险。较高剂量的 MXE 很可能会增加 DPH 的谵妄作用，并可能大大增加受伤、躁狂和精神病的风险。医疗剂量不太可能引起关注。

查看原文

There is a high risk of serotonin syndrome from this combination. Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. MXE has a high likelihood of increasing DPH's deliriant effects at higher dosages and can greatly increase the risk of injury, mania, and psychosis. Medical dosages are unlikely to be of concern.

来源

author: Clark, J. H., Meltzer, E. O., & Naclerio, R. M. (2025)
标题: Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027.
链接: https://doi.org/10.1016/j.waojou.2025.101027

author: Ener, R. A., Meglathery, S. B., Decker, W. A. V., & Gallagher, R. M. (2003)
标题: Serotonin Syndrome and Other Serotonergic Disorders: Table 1. Pain Medicine, 4(1), 63–74.
链接: https://doi.org/10.1046/j.1526-4637.2003.03005.x

author: Marti, M., Talani, G., Miliano, C., Bilel, S., Biggio, F., Bratzu, J., Diana, M., De Luca, M. A., & Fattore, L. (2021)
标题: New insights into methoxetamine mechanisms of action: Focus on serotonergic 5-HT2 receptors in pharmacological and behavioral effects in the rat. Experimental Neurology, 345, 113836.
链接: https://doi.org/10.1016/j.expneurol.2021.113836

author: Roth, B. L., Gibbons, S., Arunotayanun, W., Huang, X.-P., Setola, V., Treble, R., & Iversen, L. (2013)
标题: The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor. PLoS ONE, 8(3), e59334.
链接: https://doi.org/10.1371/journal.pone.0059334

author: Varghese, E., Abate, M. A., Hu, L., Kaplan, J., Kraner, J., Long, D. L., Sorg, M., Mock, A., Greenwald, M., & Andrew, T. (2015)
标题: Characterization of Diphenhydramine-Related Accidental Overdose Deaths. Academic Forensic Pathology, 5(1), 105–115.
链接: https://doi.org/10.23907/2015.011

风险等级

危险（应避免）（Dangerous）

nbomes

备注

25-50 毫克的 DPH 可能有助于缓解 NBOMe 药物的副作用，例如恶心和焦虑。在较高剂量时，应避免将谵妄剂 (DPH) 和 NBOMe 药物联合使用。除了增加严重伤害和精神创伤的风险外，NBOM 还可能增加 DPH 的精神错乱和负面影响。休闲剂量的 NBOMes 和 DPH 会产生额外的心脏问题，例如血管收缩、心动过速、高血压，这些问题组合起来可能会加剧。

查看原文

At 25-50mg, DPH may assist with side effects of the NBOMe drugs such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and NBOMe drugs is cautioned against. NBOMes are likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma. NBOMes and DPH at recreational dosages have additional cardiac concerns such as vasoconstriction, tachycardia, hypertension, which in combination may be exacerbated.

来源

author: Kyriakou, C., Marinelli, E., Frati, P., Santurro, A., Afxentiou, M., Zaami, S., & Busardo, F. P. (2015)
标题: NBOMe: new potent hallucinogens--pharmacology, analytical methods, toxicities, fatalities: a review. European Review for Medical and Pharmacological Sciences, 19(17), 3270–3281.
链接: https://pubmed.ncbi.nlm.nih.gov/26400534/

author: Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)
标题: Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.
链接: https://doi.org/10.3389/fpsyt.2021.657397

author: Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)
标题: Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.
链接: https://doi.org/10.1016/j.jaip.2022.07.018

author: Zawilska, J. B., Kacela, M., & Adamowicz, P. (2020)
标题: NBOMes–Highly Potent and Toxic Alternatives of LSD. Frontiers in Neuroscience, 14, 78.
链接: https://doi.org/10.3389/fnins.2020.00078

风险等级

谨慎（Caution）

opioids

备注

这两种物质都是中枢神经系统抑制剂，彼此之间会产生不可预测的强烈增强作用，增加记忆丧失、严重共济失调和意识丧失的可能性。这种相互作用会造成更大的抑制和受伤的风险。 DPH 减少阿片类药物释放的组胺，从而减少阿片类药物的瘙痒副作用。 DPH 可以减少阿片类药物引起的恶心。 DPH 抑制 CYP2D6 活性，从而导致某些阿片类药物的作用减弱，而另一些阿片类药物的作用增强。

查看原文

Both substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and unconsciousness. The interaction will cause greater inhibition and risk of injury. DPH reduces histamine release by opioids, which reduces the itching side effect from opioids. DPH may reduce the nausea caused by opioids. DPH inhibits CYP2D6 activity which can lead to a reduction of effects in some opioids and potentiation of effects in others.

来源

author: Akutsu, T., Kobayashi, K., Sakurada, K., Ikegaya, H., Furihata, T., & Chiba, K. (2007)
标题: Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 35(1), 72–78.
链接: https://doi.org/10.1124/dmd.106.012088

author: Dinwiddie, A. T., Tanz, L. J., & Bitting, J. (2022)
标题: Notes from the Field: Antihistamine Positivity and Involvement in Drug Overdose Deaths — 44 Jurisdictions, United States, 2019–2020. Morbidity and Mortality Weekly Report, 71(41), 1308–1310.
链接: https://doi.org/10.15585/mmwr.mm7141a4

author: Grönlund, J., Saari, T. I., Hagelberg, N. M., Neuvonen, P. J., Olkkola, K. T., & Laine, K. (2010)
标题: Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone. British Journal of Clinical Pharmacology, 70(1), 78–87.
链接: https://doi.org/10.1111/j.1365-2125.2010.03653.x

author: Hamelin, B. (2000)
标题: Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity. Clinical Pharmacology & Therapeutics, 67(5), 466–477.
链接: https://doi.org/10.1067/mcp.2000.106464

author: Heiskanen, T., & Kalso, E. (2012)
标题: Non-analgesic effects of opioids: interactions between opioids and other drugs. Current Pharmaceutical Design, 18(37), 6079–6089.
链接: https://doi.org/10.2174/138161212803582423

author: Nahid, N. A., McDonough, C. W., Wei, Y.-J. J., Cicali, E. J., Gong, Y., Fillingim, R. B., & Johnson, J. A. (2024)
标题: Use of CYP2D6 Inhibitors with CYP2D6 Opioids: Association with Emergency Department Visits for Pain. Clinical Pharmacology and Therapeutics, 116(4), 1005–1012.
链接: https://doi.org/10.1002/cpt.3314

author: Okutani, H., Lo Vecchio, S., & Arendt‐Nielsen, L. (2024)
标题: Mechanisms and treatment of opioid‐induced pruritus: Peripheral and central pathways. European Journal of Pain, 28(2), 214–230.
链接: https://doi.org/10.1002/ejp.2180

author: Sicari, V., Patel, P., & Zabbo, C. P. (2025)
标题: Diphenhydramine. In StatPearls. StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK526010/

author: Swegle, J. M., & Logemann, C. (2006)
标题: Management of common opioid-induced adverse effects. American Family Physician, 74(8), 1347–1354.
链接: https://pubmed.ncbi.nlm.nih.gov/17087429/

author: Wei, Y.-J. J., Winterstein, A. G., Schmidt, S., Fillingim, R. B., Daniels, M. J., DeKosky, S. T., & Schmidt, S. (2025)
标题: Association of initiating CYP2D6-metabolized opioids with risks of adverse outcomes in older adults receiving antidepressants: A retrospective cohort study. PLOS Medicine, 22(6), e1004620.
链接: https://doi.org/10.1371/journal.pmed.1004620

author: Whitt, A., & Jortani, S. (2023)
标题: B-337 Case Report: Fatal Opioid Overdose Induced by Over-the-Counter Cold Medication Diphenhydramine. Clinical Chemistry, 69(Supplement_1), hvad097.656.
链接: https://doi.org/10.1093/clinchem/hvad097.656

风险等级

不安全（Unsafe）

pregabalin

备注

这种组合存在癫痫发作的显着风险。这种组合很可能会增加彼此的负面副作用，例如恶心、头晕和失去意识。在较高剂量下，普瑞巴林可能会增加苯海拉明的谵妄作用、抑制作用和受伤风险。据报道，医疗剂量不是一个问题。

查看原文

There is a significant risk of seizures from this combination. The combination is likely to increase each other’s negative side effects, such as nausea, dizziness, and loss of consciousness. At higher dosages, pregabalin is likely to increase diphenhydramine’s deliriant effects, inhibition, and risk of injury. Medical dosages are not reported to be a concern.

来源

author: Altair. (n.d.-a)
标题: Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”
链接: https://www.erowid.org/experiences/exp.php?ID=69917

author: Barker-Haliski, M., & White, H. S. (2015)
标题: Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.
链接: https://doi.org/10.1101/cshperspect.a022863

author: Ben-Menachem, E. (2004)
标题: Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.
链接: https://doi.org/10.1111/j.0013-9580.2004.455003.x

author: Medline Plus Medical Encyclopedia (2023)
标题: Diphenhydramine overdose
链接: https://medlineplus.gov/ency/article/002636.htm

author: Douke, R. (n.d.)
标题: Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”
链接: https://www.erowid.org/experiences/exp.php?ID=83232

author: Fakhr, M. S., Motamed Chaboki, P., Ashayeri, H., Sahranavard, P., Mohammadipanah, S., & Zamanabadi, M. N. (2023)
标题: Comparison of the effects of pregabalin and famotidine with pregabalin and diphenhydramine on postoperative abdominal pain. International Journal of Surgery Open, 58, 100674.
链接: https://doi.org/10.1016/j.ijso.2023.100674

author: French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)
标题: Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.
链接: https://doi.org/10.1212/WNL.0000000000000119

author: Gayatri, N. A., & Livingston, J. H. (2006)
标题: Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.
链接: https://doi.org/10.1017/S0012162206000843

author: Hitchings, A. W. (2016)
标题: Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.
链接: https://doi.org/10.1097/FAD.0000000000000016

author: Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)
标题: Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.
链接: https://doi.org/10.1111/bcp.14348

author: Jang, D. H., Manini, A. F., Trueger, N. S., Duque, D., Nestor, N. B., Nelson, L. S., & Hoffman, R. S. (2010)
标题: Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose. Clinical Toxicology, 48(9), 945–948.
链接: https://doi.org/10.3109/15563650.2010.527850

author: Kim, H., Kim, S. H., & Kim, J. B. (2021)
标题: Antihistamines as a common cause of new-onset seizures: a single-center observational study. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 42(6), 2505–2508.
链接: https://doi.org/10.1007/s10072-021-05043-2

author: Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)
标题: Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.
链接: https://doi.org/10.1111/j.1471-4159.2010.06625.x

author: Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)
标题: Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.
链接: https://doi.org/10.3389/fpsyt.2021.657397

author: Sean. (n.d.-b)
标题: Pregabalin - Erowid Exp - “Stay Away.”
链接: https://www.erowid.org/experiences/exp.php?ID=67302

author: Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)
标题: Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.
链接: https://doi.org/10.1080/24734306.2018.1458465

author: Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)
标题: Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.
链接: https://doi.org/10.1016/j.jaip.2022.07.018

风险等级

不安全（Unsafe）

ssris

备注

休闲剂量的血清素综合征风险很高。据报道，医疗剂量并不是普通人群所关心的问题。合用可能会增加彼此的副作用，如头晕、嗜睡等。

查看原文

There is a high risk of serotonin syndrome at recreational dosages. Medical dosages are reported not to be a concern for the general population. The combination may increase each other's side effects, such as dizziness and drowsiness.

来源

author: Clark, J. H., Meltzer, E. O., & Naclerio, R. M.
标题: Diphenhydramine: It is time to say a final goodbye. The World Allergy Organization Journal, 18(2), 101027 (2025)
链接: https://doi.org/10.1016/j.waojou.2025.101027

author: Ener, R. A., Meglathery, S. B., Decker, W. A. V., & Gallagher, R. M.
标题: Serotonin Syndrome and Other Serotonergic Disorders: Table 1. Pain Medicine, 4(1), 63-74 (2003)
链接: https://doi.org/10.1046/j.1526-4637.2003.03005.x

author: Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J.
标题: Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus, 10(4), e2421 (2018)
链接: https://doi.org/10.7759/cureus.2421

author: Lane, R., Baldwin, D., & Preskorn, S.
标题: The SSRIs: advantages, disadvantages and differences. Journal of Psychopharmacology, 9(2 Suppl), 163-178 (1995)
链接: https://doi.org/10.1177/0269881195009002011

author: Sproule, B. A., Naranjo, C. A., Brenmer, K. E., & Hassan, P. C.
标题: Selective serotonin reuptake inhibitors and CNS drug interactions. A critical review of the evidence. Clinical Pharmacokinetics, 33(6), 454-471 (1997)
链接: https://doi.org/10.2165/00003088-199733060-00004

author: van Harten, J.
标题: Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clinical Pharmacokinetics, 24(3), 203-220 (1993)
链接: https://doi.org/10.2165/00003088-199324030-00003

author: Varghese, E., Abate, M. A., Hu, L., Kaplan, J., Kraner, J., Long, D. L., Sorg, M., Mock, A., Greenwald, M., & Andrew, T.
标题: Characterization of Diphenhydramine-Related Accidental Overdose Deaths. Academic Forensic Pathology, 5(1), 105-115 (2015)
链接: https://doi.org/10.23907/2015.011

风险等级

危险（应避免）（Dangerous）

tramadol

备注

这两种药物都会增加血清素综合征的风险。在医疗剂量下，这不太可能引起关注，但应避免娱乐剂量。苯海拉明可能会增加曲马多癫痫发作的风险。

查看原文

Both drugs increase the risk of serotonin syndrome. While at medical dosages, this is unlikely to be of concern, recreational doses should be avoided. Diphenhydramine may increase tramadol’s seizure risk.

来源

author: Benson, B. E., Farooqi, M. F., Klein-Schwartz, W., Litovitz, T., Webb, A. N., Borys, D. J., Lung, D., Rutherfoord Rose, S., Aleguas, A., Sollee, D. R., & Seifert, S. A. (2010)
标题: Diphenhydramine dose–response: a novel approach to determine triage thresholds. Clinical Toxicology, 48(8), 820–831.
链接: https://doi.org/10.3109/15563650.2010.514269

author: Dhesi, M., Maldonado, K. A., Patel, P., & Maani, C. V. (2025)
标题: Tramadol. In StatPearls. StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK537060/

author: Hughes, A. R., Lin, A., Hendrickson, R. G., & on behalf of Toxicology Investigator’s Consortium (ToxIC). (2021)
标题: Clinical and patient characteristics associated with severe outcome in diphenhydramine toxicity. Clinical Toxicology, 59(10), 918–925.
链接: https://doi.org/10.1080/15563650.2021.1891244

author: Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J. (2018)
标题: Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus.
链接: https://doi.org/10.7759/cureus.2421

author: Kim, H., Kim, S. H., & Kim, J. B. (2021)
标题: Antihistamines as a common cause of new-onset seizures: a single-center observational study. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 42(6), 2505–2508.
链接: https://doi.org/10.1007/s10072-021-05043-2

author: Kim, H., Wang, I.-N., Park, J.-S., Kim, K.-T., Kong, J., Kim, J. B., & Kim, D.-J. (2023)
标题: Inherent seizure susceptibility in patients with antihistamine-induced acute symptomatic seizure: a resting-state EEG analysis. Scientific Reports, 13(1), 9146.
链接: https://doi.org/10.1038/s41598-023-36415-7

author: Sanaei-Zadeh, H. (2012)
标题: Diphenhydramine overdose and serotonin syndrome. Psychiatry and Clinical Neurosciences, 66(3), 244–245.
链接: https://doi.org/10.1111/j.1440-1819.2012.02320.x

author: Sicari, V., Patel, P., & Zabbo, C. P. (2025)
标题: Diphenhydramine. In StatPearls. StatPearls Publishing.
链接: http://www.ncbi.nlm.nih.gov/books/NBK526010/

风险等级

危险（应避免）（Dangerous）

剂量说明

NOTE: The doses provided are for recreational usage. For use as a sleep aid the dose ranges from 25-100mg, or as specified on the product packaging.

后遗时间

1-12 小时

剂量

口服

常规: 200-500mg
轻度: 100-250mg
强效: 450-700mg

持续时间

6-8 小时

效应

Delirium dream-like experiences paranoia visual and audio distortions dry mouth muscle cramps nausea dysphoria tremors Often described as a pretty negative experience

起效时间

60-120 分钟

相关链接

经验报告: https://www.erowid.org/experiences/subs/exp_Diphenhydramine.shtml

名称

diphenhydramine

通用名

Diphenhydramine

属性

后遗效应: 1–12 小时.
别名: diphenhydramine dph benadryl
avoid: Many oral diphenhydramine preparations contain analgesics such as acetaminophen or aspirin, which can be toxic to the liver in high doses.
分类: 抑制剂谵妄剂常规
剂量: Oral Light: 100-250mg Common: 200-500mg Strong: 450-700mg NOTE: The doses provided are for recreational usage. For use as a sleep aid the dose ranges from 25-75mg, or as specified on the product packaging. For medical allergy use doses tend to range from 25-50mg, or as specified on the product packaging.
持续: 6–8 小时
效应: Delirium, dream-like experiences, paranoia, visual and audio distortions, dry mouth, muscle cramps, nausea, dysphoria, tremors. Often described as a pretty negative experience.
起效: 60–120 分钟
摘要: An antihistamine which, when taken in smaller doses relieves allergies and insomnia. In larger doses works as a deliriant and can actually keep the user awake. Generally the 'high' of this drug is reported as dysphoric, potentially causing hallucinations indistinguishable from reality.

效应

Abnormal heartbeat: https://psychonautwiki.org/wiki/Abnormal_heartbeat
Acuity suppression: https://psychonautwiki.org/wiki/Acuity_suppression
After images: https://psychonautwiki.org/wiki/After_images
Amnesia: https://psychonautwiki.org/wiki/Amnesia
Anxiety: https://psychonautwiki.org/wiki/Anxiety
Auditory hallucinations: https://psychonautwiki.org/wiki/Auditory_hallucinations
Auditory suppression: https://psychonautwiki.org/wiki/Auditory_suppression
Autonomous entities: https://psychonautwiki.org/wiki/Autonomous_entities
Brightness alteration: https://psychonautwiki.org/wiki/Brightness_alteration
Cognitive dysphoria: https://psychonautwiki.org/wiki/Cognitive_dysphoria
Dehydration: https://psychonautwiki.org/wiki/Dehydration
Depression: https://psychonautwiki.org/wiki/Depression
Difficulty urinating: https://psychonautwiki.org/wiki/Difficulty_urinating
Dizziness: https://psychonautwiki.org/wiki/Dizziness
Double vision: https://psychonautwiki.org/wiki/Double_vision
Dream potentiation: https://psychonautwiki.org/wiki/Dream_potentiation
Drifting: https://psychonautwiki.org/wiki/Drifting
Emotion suppression: https://psychonautwiki.org/wiki/Emotion_suppression
External hallucinations: https://psychonautwiki.org/wiki/External_hallucinations
Feelings of impending doom: https://psychonautwiki.org/wiki/Feelings_of_impending_doom
Frequent urination: https://psychonautwiki.org/wiki/Frequent_urination
Increased heart rate: https://psychonautwiki.org/wiki/Increased_heart_rate
Information processing suppression: https://psychonautwiki.org/wiki/Information_processing_suppression
Internal hallucinations: https://psychonautwiki.org/wiki/Internal_hallucinations
Language suppression: https://psychonautwiki.org/wiki/Language_suppression
Memory suppression: https://psychonautwiki.org/wiki/Memory_suppression
Motor control loss: https://psychonautwiki.org/wiki/Motor_control_loss
Muscle cramps: https://psychonautwiki.org/wiki/Muscle_cramps
Muscle spasms: https://psychonautwiki.org/wiki/Muscle_spasms
Nausea: https://psychonautwiki.org/wiki/Nausea
Paranoia: https://psychonautwiki.org/wiki/Paranoia
Pattern recognition suppression: https://psychonautwiki.org/wiki/Pattern_recognition_suppression
Peripheral information misinterpretation: https://psychonautwiki.org/wiki/Peripheral_information_misinterpretation
Perspective alterations: https://psychonautwiki.org/wiki/Perspective_alterations
Photophobia: https://psychonautwiki.org/wiki/Photophobia
Physical fatigue: https://psychonautwiki.org/wiki/Physical_fatigue
Psychosis: https://psychonautwiki.org/wiki/Psychosis
Restless leg syndrome: https://psychonautwiki.org/wiki/Restless_leg_syndrome
Scenarios and plots: https://psychonautwiki.org/wiki/Scenarios_and_plots
Sedation: https://psychonautwiki.org/wiki/Sedation
Settings, sceneries, and landscapes: https://psychonautwiki.org/wiki/Settings,_sceneries,_and_landscapes
Shadow people: https://psychonautwiki.org/wiki/Shadow_people
Tactile hallucinations: https://psychonautwiki.org/wiki/Tactile_hallucinations
Thought deceleration: https://psychonautwiki.org/wiki/Thought_deceleration
Thought disorganization: https://psychonautwiki.org/wiki/Thought_disorganization
Time distortion: https://psychonautwiki.org/wiki/Time_distortion
Unspeakable horrors: https://psychonautwiki.org/wiki/Unspeakable_horrors
Vibrating vision: https://psychonautwiki.org/wiki/Vibrating_vision
Visual haze: https://psychonautwiki.org/wiki/Visual_haze

来源

general: Dose-dependent toxicity of diphenhydramine overdose - http://www.ncbi.nlm.nih.gov/pubmed/11204550

来源与许可

TripSit · 药物资料

TripSit 数据规则：仅限非商业使用，需署名并在每个展示页附来源链接；组合数据仅为快速参考，需结合个体研究判断。

Reference snapshot, not a forum post. Source: TripSit. Noncommercial reuse with TripSit attribution and a source link on every display page; combination data is a quick reference requiring further individual research. https://wiki.tripsit.me/wiki/Factsheets ; https://wiki.tripsit.me/wiki/Drug_combinations . The package.json ISC software tag does not replace these data-specific terms. Raw source: https://raw.githubusercontent.com/TripSit/drugs/83670cb6bc8863615fcb9be081c87f061b42dea4/drugs.json Fetched at: 2026-10-23T07:01:06.728397+00:00 Record key: drug:diphenhydramine

来源主页：https://wiki.tripsit.me/wiki/Factsheets
组合说明：https://wiki.tripsit.me/wiki/Drug_combinations