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2. Index

Author

Yamamoto, Takahiro

Published
2023

4. Conclusion

Author

Yamamoto, Takahiro

Published
2023

38. Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine benzoate) in healthy participants.

Author

Rucker, James Jonathan, Roberts, Claire, Seynaeve, Mathieu, Young, Allan H., Suttle, Ben, Yamamoto, Takahiro, Ermakova, Anna O., Dunbar, Fiona, and Wiegand, Frank

Subjects
PHARMACOKINETICS, PHARMACODYNAMICS, NAUSEA, EXCRETION, VOMITING
Abstract

Aims: To investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BPL-003, a novel intranasal benzoate salt formulation of 5-methoxy- N,N -dimethyltryptamine (5-MeO-DMT), in healthy participants. Methods: In all, 44 psychedelic-naïve participants enrolled in the double-blind, placebo-controlled single ascending dose study (1–12 mg BPL-003). Concentrations of 5-MeO-DMT and its pharmacologically active metabolite, bufotenine, were determined in plasma and urine. PD endpoints included subjective drug intensity (SDI) rating, the Mystical Experience Questionnaire (MEQ-30) and the Ego Dissolution Inventory (EDI). Results: BPL-003 was well tolerated at doses up to 12 mg. There were no serious adverse events (AEs), and most AEs were mild; the most common being nasal discomfort, nausea, headache and vomiting. 5-MeO-DMT was rapidly absorbed and eliminated; the median time to peak plasma concentration was approximately 8–10 min and the mean terminal elimination half-life was <27 min. 5-MeO-DMT systemic exposure increased approximately dose-proportionally, while plasma bufotenine concentrations and urinary excretion of 5-MeO-DMT and bufotenine were negligible. The intensity of the SDI ratings was associated with plasma 5-MeO-DMT concentrations. MEQ-30 and EDI scores generally increased with the BPL-003 dose; 60% of participants had a 'complete mystical experience' at 10 and 12 mg doses. Profound and highly emotional consciousness-altering effects were observed with BPL-003, with a rapid onset and short-lasting duration. Conclusion: The novel intranasal formulation of BPL-003 was well tolerated with dose-proportional increases in PK and PD effects. The short duration of action and induction of mystical experiences suggest clinical potential, warranting further trials. Clinical trial registration: NCT05347849. [ABSTRACT FROM AUTHOR]

Published
2024
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40. Improvement in gait velocity variability after cerebrospinal fluid elimination and its relationship to clinical symptoms in patients with idiopathic normal pressure hydrocephalus.

Author

Yamamoto, Takahiro, Fujito, Ryoko, Chadani, Yoshihiro, Kashibayashi, Tetsuo, Kamimura, Naoto, Tsuda, Atsushi, Akamatsu, Masanori, Matsushita, Takuya, Yamagami, Takuji, Ueba, Tetsuya, Saito, Motoaki, Inoue, Keiji, Izumi, Masashi, and Kazui, Hiroaki

Subjects
*HYDROCEPHALUS, *CEREBROSPINAL fluid leak, *RESEARCH funding, *MULTIPLE regression analysis, *GAIT disorders, *RETROSPECTIVE studies, *DESCRIPTIVE statistics, *NEUROLOGICAL disorders, *COGNITION disorders, *NEUROPSYCHOLOGICAL tests, *WALKING speed
Abstract

Aim: This study aimed to investigate the improvement in gait velocity variability after cerebrospinal fluid (CSF) elimination, and the association between gait velocity variability and gait and cognitive impairment in patients with idiopathic normal pressure hydrocephalus. Methods: The gait velocity of 44 patients with idiopathic normal pressure hydrocephalus was measured using the Timed Up and Go Test (TUG) for a total of 10 times over 3 days each before and after CSF elimination. The coefficient of variation (CV) in the time required for the sequence of actions in TUG (TUG‐CV) was calculated using 10 TUG data, and used for measuring intraindividual gait velocity variability. Gait quality was evaluated with the Gait Status Scale Revised (GSSR), and cognitive function was evaluated with the Mini‐Mental State Examination and the Frontal Assessment Battery. Results: The TUG, TUG‐CV, GSSR and Frontal Assessment Battery results improved significantly after CSF elimination. The analyses using pre‐CSF elimination results showed that the TUG‐CV significantly and positively correlated with the TUG and GSSR results, and negatively with Mini‐Mental State Examination results, but not with age and the Frontal Assessment Battery results. The stepwise multiple regression analysis indicates that the TUG, GSSR and Mini‐Mental State Examination results were significant predictors of the TUG‐CV. The analysis using data of change after CSF elimination showed that ΔTUG and ΔGSSR were significant predictors of ΔTUG‐CV. Conclusions: Gait velocity variability improved after CSF elimination, and gait velocity variability was associated with gait disturbances and cognitive impairment in patients with idiopathic normal pressure hydrocephalus. Geriatr Gerontol Int 2024; 24: 693–699. [ABSTRACT FROM AUTHOR]

Published
2024
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43. Error suppression by a virtual two-qubit gate.

Author

Yamamoto, Takahiro and Ohira, Ryutaro

Subjects
*ISING model, *QUANTUM computers, *DIGITAL computer simulation, *QUBITS
Abstract

Sparse connectivity of a superconducting quantum computer results in large experimental overheads of SWAP gates. In this study, we consider employing a virtual two-qubit gate (VTQG) as an error suppression technique. The VTQG enables a non-local operation between a pair of distant qubits using only single qubit gates and projective measurements. Here, we apply the VTQG to the digital quantum simulation of the transverse-field Ising model on an IBM quantum computer to suppress the errors due to the noisy two-qubit operations. We present an effective use of VTQG, where the reduction in multiple SWAP gates results in increasing the fidelity of output states. The obtained results indicate that the VTQG can be useful for suppressing the errors due to additional SWAP gates. In our experiments, we have observed one order of magnitude improvement in accuracy for the quantum simulation of the transverse-field Ising model with 8 qubits. Finally, we have demonstrated an efficient implementation of the VTQG by utilizing dynamic circuits. This scheme reduces experimental overheads for implementing m VTQGs from O (10 m) to O (6 m). [ABSTRACT FROM AUTHOR]

Published
2023
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50. Balance of favour : the emergence of territorial boundaries around Japan, 1861-1875

Author

Yamamoto, Takahiro

Subjects
327.52, DS Asia
Abstract

The existing scholarship has typically explained the emergence of modern Japan as a territorial sovereign in the late-nineteenth century to be a result of its response to Western imperialism, which paved the way for it to build its own empire. Scholars have found Japan’s motivation for drawing territorial boundaries either in the pursuit of the maintenance of independence or its entry into the international society. However their narratives do not fully explain why the process led to the establishment of Japan’s sovereignty over border zones with ambiguous territorial status, such as the Kuril Islands and the Ryukyu Kingdom. Approaching the question by investigating local developments, this thesis presents a twofold explanation for the emergence of territorial boundaries around Japan: that the rise of sovereignty had origins in the long-term decline of the border zones’ political institutions; and that Japan’s expansion into these zones was enabled by a diplomatic equilibrium (which the thesis calls the balance of favour) among the Western powers. The rise of trans-Pacific commercial activities, the decline of tributary trade in East Asia, and Russia’s strategic shift to the Far East prompted fundamental changes in the political landscape for the border zones. The Western imperialists in the 1860s and the 1870s saw it as best that Japan control these areas, because one imperial power’s territorial gain would have unleashed a scramble that none of them saw as worth fighting. The above argument provides an alternative to the conventional Japan-centred narratives of interactions between Western imperialism and the East Asians. It also adds to the historical study of the border zones by providing a comparative analysis and connecting them with a broader context. It thus bridges the historiographical gap between the diplomatic history of bakumatsu and Meiji Japan and the local histories around the archipelago.

Published
2015

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