Mueller Michael J, Aicher Helena D, Dornbierer Dario A, Marten Laurenz, Suay Dila, Meling Daniel, Elsner Claudius, Wicki Ilhui A, Müller Jovin, Poetzsch Sandra N, Caflisch Luzia, Hempe Alexandra, Steinhart Camilla P, Puchkov Maxim, Kost Jonas, Landolt Hans-Peter, Seifritz Erich, Quednow Boris B, Scheidegger Milan
Department of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Department of Health Science & Technology, ETH Zurich, Zurich, Switzerland.
Int J Neuropsychopharmacol. 2024 Dec 28;28(1). doi: 10.1093/ijnp/pyaf001.
Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects in various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) and β-carboline alkaloids such as harmine. However, its use is often accompanied by distressing effects like nausea, vomiting, and intense hallucinations, possibly due to complex pharmacokinetic/pharmacodynamic (PK-PD) interactions and lack of dose standardization.
This study addresses these limitations by testing a novel pharmaceutical formulation containing pure forms of DMT and harmine in a double-blind, randomized, placebo-controlled trial with 31 healthy male volunteers. We evaluated PK-PD by monitoring drug and metabolite plasma levels, subjective effects, adverse events, and cardiovascular parameters. Each participant received 3 randomized treatments: (1) 100 mg buccal harmine with 100 mg intranasal DMT, (2) 100 mg buccal harmine with intranasal placebo, and (3) full placebo, using a repeated-intermittent dosing scheme, such that 10 mg of DMT (or placebo) was administered every 15 minutes.
N,N-dimethyltryptamine produced consistent PK profiles with Cmax values of 22.1 ng/mL and acute drug effects resembling the psychological effects of ayahuasca with a duration of 2-3 hours. Likewise, buccal harmine produced sustained-release PK profiles with Cmax values of 32.5 ng/mL but lacked distinguishable subjective effects compared to placebo. All drug conditions were safe and well tolerated, indicating the formulation's suitability for clinical applications.
This study underscores the potential of a patient-oriented pharmaceutical formulation of DMT and harmine to reduce risks and improve therapeutic outcomes in treating mental health disorders.
Neurodynamics of prosocial emotional processing following serotonergic stimulation with N,N-dimethyltryptamine (DMT) and harmine in healthy subjects (NCT04716335) https://clinicaltrials.gov/ct2/show/NCT04716335.
近期对迷幻药临床应用的关注凸显了诸如死藤水等植物源药物在各种精神疾病中显示出速效且可持续的治疗效果。这种传统的亚马逊植物煎剂含有N,N -二甲基色胺（DMT）和β -咔啉生物碱如 harmine。然而，其使用常常伴随着令人不适的效果，如恶心、呕吐和强烈幻觉，这可能是由于复杂的药代动力学/药效学（PK - PD）相互作用以及缺乏剂量标准化。
本研究通过在一项双盲、随机、安慰剂对照试验中对31名健康男性志愿者测试一种含有纯形式DMT和 harmine的新型药物制剂来解决这些局限性。我们通过监测药物和代谢物血浆水平、主观效果、不良事件和心血管参数来评估PK - PD。每位参与者接受3种随机治疗：（1）100毫克口腔 harmine与100毫克鼻内DMT，（2）100毫克口腔 harmine与鼻内安慰剂，（3）完全安慰剂，采用重复间歇给药方案，即每15分钟给予10毫克DMT（或安慰剂）。
N,N -二甲基色胺产生了一致的药代动力学曲线，Cmax值为22.1纳克/毫升，急性药物效果类似于死藤水的心理效果，持续时间为2 - 3小时。同样，口腔 harmine产生了缓释药代动力学曲线，Cmax值为32.5纳克/毫升，但与安慰剂相比缺乏明显的主观效果。所有药物条件均安全且耐受性良好，表明该制剂适用于临床应用。
本研究强调了以患者为导向的DMT和 harmine药物制剂在降低治疗心理健康障碍的风险和改善治疗结果方面的潜力。
健康受试者中N,N -二甲基色胺（DMT）和 harmine血清素能刺激后亲社会情绪加工的神经动力学（NCT04716335）https://clinicaltrials.gov/ct2/show/NCT04716335 。
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