Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects

Background: There is growing scientific evidence for the therapeutic benefits of the Amazonian plant-based psychedelic “ayahuasca” for neuropsychiatric disorders such as depression and anxiety. However, there are certain challenges when incorporating botanical ayahuasca into biomedical research and clinical therapy environments. Formulations inspired by ayahuasca, which contain specific and standardized active components, are a potential remedy. Methods: We investigated subjective acute and persisting effects of a novel formulation containing the reversible monoamine oxidase inhibitor harmine (orodispersible tablet containing 100 mg MAO-I) and N,N-dimethyltryptamine (incremental intranasal dosing of up to 100 mg DMT), compared with two other conditions, namely harmine alone and placebo, in a crossover RCT in 31 healthy male subjects. Results: DMT + harmine, but not harmine alone, induced a psychedelic experience assessed with the 5D-ASC rating scale [global score: F(2,60) = 80.21, p < 0.001] and acute experience sampling items over time, characterized by psychological insights [PIQ, F(2,58.5) = 28.514, p < 0.001], emotional breakthroughs [EBI, F(2,60) = 26.509, p < 0.001], and low scores on the challenging experience questionnaire [CEQ, F(2,60) = 12.84, p < 0.001]. Participants attributed personal and spiritual significance to the experience (GSR) with mainly positive persisting effects (PEQ) at 1- and 4-months follow-up. Acute drug effects correlated positively with persisting effects. We found no changes in trait measures of personality, psychological flexibility, or general well-being, and no increases in psychopathology (SCL-90-R) were reported. Discussion and Conclusion: Our results suggest that the experience induced by the standardized DMT + harmine formulation induces a phenomenologically rich psychedelic experience, demonstrates good psychological safety and tolerability, is well tolerated, and induces beneficial psychological processes that could possibly support psychotherapy. Further studies are required to investigate the psychotherapeutic potential in patients

Perception, Cognition and Ayahuasca A Multidimensional Analysis of Alter States of Consciousness

My Ph.D. thesis comprises a series of experiments aimed at investigating the impact of a novel ayahuasca analog, pharmahuasca (PHA), on face perception and creative cognition. These studies were executed with a within-subject, double-blind, placebo-controlled design involving 30 healthy male participants. Chapter 2 centers on the effects of psychedelics on face perception, utilizing electroencephalography (EEG) during a visual oddball task with self, familiar, and unknown faces as stimuli. Notable changes induced by PHA in early visual processing, such as increased P1 and reduced N170 across all face categories, were observed. In late visual processing, a decrease in neural activation in response to the self-face, as indicated by the P300 wave, highlights the significance of psychedelics in altering self-referential information processing. Additionally, the impact of psychedelics on face discrimination was explored through a two-alternative forced choice (2-AFC) task, where faces are incrementally morphed to each other, revealing a decreased sensitivity for discrimination during psychedelic experiences across all face categories. Chapter 3 shifts focus to understanding how psychedelics influence creative cognition. Through task-based methodologies, the findings unveil a reduction in convergent thinking without affecting on divergent thinking. Next, we investigate how utilization of different thinking modes during the artistic creation, specifically in the domain of painting, under the influence of psychedelics. Importantly, there was a significant reduction in transitions between different creative thinking modes during the psychedelic-induced creative process, particularly affecting stages traditionally requiring convergent thinking, offered valuable insights into the phenomenological nuances of the interplay between psychedelics and the dynamics of creative thinking

Validation of the xylazine/ketamine anesthesia test as a predictor of the emetic potential of pharmacological compounds in rats

The xylazine/ketamine anesthesia test is widely used as a predictor of the emetic potential of pharmacological compounds in rats. An emetic reflex is usually triggered by the emetic center, which is populated with many different chemoreceptors. Inhibition of the alpha 2 adrenergic receptor (alpha 2 receptor) is involved in the initiation of the emetic reflex, and this is the key mechanism behind the xylazine/ketamine anesthesia test. In this study, we attempt to validate this test as a predictor of the emetic potential of pharmacological compounds. Furthermore, it was investigated whether an anti-emetic potential of pharmacological compounds could be assessed within this test as well. Rats were anesthetized with a combination of low doses of ketamine and xylazine, and subsequently treated with PDE4 inhibitor rolipram, alpha 2 receptor antagonist yohimbine, alpha 2 receptor agonist clonidine, tricyclic antidepressant imipramine, D2-receptor antagonist haloperidol, or 5-HT3 receptor antagonist (and anti-emetic drug) ondansetron. We were able to successfully reproduce the reduction in anesthesia time after rolipram or yohimbine treatment, as found in previous studies and has been suggested to be indicative of emetic properties of these treatments is humans. Furthermore, clonidine shortened anesthesia duration whereas imipramine and haloperidol lengthened anesthesia duration. Ondansetron was unable to rescue the reduction in duration of anesthesia induced by either rolipram or yohimbine. Altogether, the xylazine/ketamine anesthesia test is a reliable measure for alpha 2 receptor antagonism. However, it may not be appropriate to assess emesis independent of this mechanism

Data_Sheet_1_Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects.PDF

BackgroundThere is growing scientific evidence for the therapeutic benefits of the Amazonian plant-based psychedelic “ayahuasca” for neuropsychiatric disorders such as depression and anxiety. However, there are certain challenges when incorporating botanical ayahuasca into biomedical research and clinical therapy environments. Formulations inspired by ayahuasca, which contain specific and standardized active components, are a potential remedy.MethodsWe investigated subjective acute and persisting effects of a novel formulation containing the reversible monoamine oxidase inhibitor harmine (orodispersible tablet containing 100 mg MAO-I) and N,N-dimethyltryptamine (incremental intranasal dosing of up to 100 mg DMT), compared with two other conditions, namely harmine alone and placebo, in a crossover RCT in 31 healthy male subjects.ResultsDMT + harmine, but not harmine alone, induced a psychedelic experience assessed with the 5D-ASC rating scale [global score: F(2,60) = 80.21, p Discussion and ConclusionOur results suggest that the experience induced by the standardized DMT + harmine formulation induces a phenomenologically rich psychedelic experience, demonstrates good psychological safety and tolerability, is well tolerated, and induces beneficial psychological processes that could possibly support psychotherapy. Further studies are required to investigate the psychotherapeutic potential in patients.</p