Pharmacopsychiatry
January 19, 2022
Hitoshi Sakurai, Kengo Yonezawa, Hideaki Tani et al.
35 citations
Nine antidepressant compounds with mechanisms beyond the monoaminergic hypothesis have shown positive results in phase II or III trials. AXS-05 (dextromethorphan and bupropion) and ansofaxine hydrochloride outperformed placebo in phase III trials for major depressive disorder or treatment-resistant depression. MIJ821, nitrous oxide, psilocybin, ayahuasca, botulinum toxin A facial injection, prasterone, and casopitant each showed at least one positive phase II result. Ayahuasca produced a greater response rate than placebo at one week, suggesting rapid antidepressant effects. These novel compounds may expand treatment options if preliminary findings are confirmed.
Psychiatry and clinical neurosciences
December 1, 2024
Yohei Ohtani, Hideaki Tani, Kie Nomoto-Takahashi et al.
13 citations
In a double-blind randomized placebo-controlled trial with 34 Japanese patients suffering from treatment-resistant depression, intravenous ketamine (0.5 mg/kg) given twice a week for two weeks did not show a statistically significant advantage over placebo in reducing depression scores when all participants were analyzed together. However, among those who completed the full treatment protocol, ketamine led to a significantly greater reduction in depressive symptoms than placebo. Higher baseline depression severity and body mass index were linked to greater symptom improvement with ketamine. Adverse events were more common with ketamine but no serious events occurred. These results suggest ketamine may be effective for treatment-resistant depression across diverse ethnic groups.
Drug Science Policy and Law
September 1, 2025
David Nutt, David Erritzøe, Anne Katrin Schlag et al.
9 citations
The field of psychedelic research lacks standardized terminology for clinical development, dosing, safety monitoring, and regulatory classification. A comprehensive framework is proposed that classifies psychedelics by pharmacology (serotonergic, glutamatergic, kappaergic, GABAergic, and atypical), introduces dose-dependent categories (microdose, minidose, mididose, macrodose), and standardizes terms like “short-acting” with specific pharmacokinetic parameters. Safety considerations include cardiovascular and psychological effects, with risk mitigation protocols for higher-risk compounds like ibogaine. A three-phase treatment model—preparation, dosing, and integration—is recommended as a minimum standard. The lack of comparative research on psychotherapy modalities is identified as a critical gap.
Neuropsychopharmacology Reports
March 13, 2024
Kengo Yonezawa, Hideaki Tani, Shinichiro Nakajima et al.
5 citations
A Japanese version of the Mystical Experiences Questionnaire (MEQ30) has been developed to assess mystical experiences induced by psychedelics, which are being studied as potential treatments for mental illness. Two Japanese psychiatrists independently translated the original English questionnaire into Japanese, then reconciled the translations into a unified version. This version was back-translated into English and reviewed by the original authors through an iterative process until they approved the final back-translated version. The authorized Japanese MEQ30 is now available for use in psychedelic-assisted therapy research with Japanese speakers, though further studies are needed to evaluate its reliability and validity.
Journal of affective disorders
August 15, 2025
Yohei Ohtani, Hideaki Tani, Shiori Honda et al.
3 citations
About 30% of people with treatment-resistant depression respond to ketamine, but reliable predictors of response have been lacking. This study examined whether the ratio of glutamate+glutamine (Glx) to GABA in the dorsal anterior cingulate cortex (dACC) could predict ketamine's effectiveness. In a double-blind randomized trial with an open-label extension involving 30 participants, a higher baseline Glx/GABA ratio in the dACC correlated with greater improvement in depression scores (measured by the HDRS-17). After ketamine treatment, a reduction in this ratio also correlated with symptom improvement. The findings suggest that an excitatory-inhibitory imbalance in the dACC may help predict which patients will benefit from ketamine therapy.
Neuropsychopharmacology Reports
March 13, 2024
Keisuke Kusudo, Hideaki Tani, Kengo Yonezawa et al.
2 citations
A Japanese version of the Ego-Dissolution Inventory (EDI) was developed through a translation and back-translation process following international guidelines. Two Japanese psychiatrists independently translated the original English EDI, reconciled differences, and had the resulting version back-translated into English. The original authors reviewed and approved the back-translated version after iterative revisions. The final Japanese EDI is intended to help assess ego-dissolution experiences during psychedelic-assisted therapy in Japanese-speaking populations. Further research is needed to test the reliability and validity of this new instrument.
Psychiatry and clinical neurosciences
July 15, 2025
Hitoshi Sakurai, Daiki Setoyama, Takahiro A Kato et al.
1 citation
In an open-label study of 30 patients with treatment-resistant depression, four intravenous ketamine infusions (0.5 mg/kg) over two weeks rapidly reduced depression severity: the average Montgomery-Åsberg Depression Rating Scale score fell from 30.6 to 20.3 after the fourth infusion, and 26.7% of participants achieved remission. However, only 13.3% remained in remission at 12 months. Early changes in the metabolite 3-hydroxybutyrate predicted the degree of improvement both after the fourth infusion and at 12 months, suggesting it could serve as a biomarker for treatment response. The findings point toward more individualized use of ketamine infusions.
Neuropsychopharmacology Reports
November 8, 2024
Hideaki Tani, Kengo Yonezawa, Keisuke Kusudo et al.
1 citation
A Japanese version of the Challenging Experience Questionnaire (CEQ) was developed to assess difficult aspects of psychedelic experiences in Japanese speakers. Following international guidelines for translation and cultural adaptation, two psychiatrists independently translated the original English CEQ into Japanese, reconciled the versions, and had them back-translated into English. The original authors reviewed the back-translation and approved the final version after revisions. The resulting questionnaire enables evaluation of challenging experiences during psychedelic-assisted therapy for Japanese-speaking populations, though further studies are needed to confirm its reliability and validity.
May 1, 2023
Hiroyuki Uchida
1 citation
Drug development increasingly targets multiple diseases with a single compound, as seen with pimavanserin and psilocybin. Despite major pharmaceutical companies withdrawing from central nervous system drug development, research into drugs with novel mechanisms of action has advanced, marking a new era in clinical psychopharmacology.
Psychiatry research. Neuroimaging
August 1, 2026
Kengo Yonezawa, Shinichiro Nakajima, Shuhei Shibukawa et al.
In patients with treatment-resistant depression, higher baseline levels of magnetic substances in the right nucleus accumbens and the left amygdala, measured by brain imaging, predicted a greater reduction in specific depressive symptoms after repeated ketamine infusions. The study included 17 Japanese patients and used a double-blind, randomized placebo-controlled design followed by an open-label phase. Baseline magnetic susceptibility in the right nucleus accumbens correlated with improvement in retardation symptoms, while baseline R2* in the left amygdala correlated with improvement in vegetative symptoms. These brain markers may help predict which patients will benefit from ketamine treatment.
Journal of affective disorders
August 1, 2026
Taro Kishi, Kenji Sakuma, Masakazu Hatano et al.
A systematic review and meta-analysis of six randomized controlled trials examined how psilocybin's effects on major depressive disorder change over time. Standard-dose psilocybin (25 mg/session or 20-30 mg/70 kg/session) was superior to control conditions (placebo, waiting-list, niacin, or 1 mg psilocybin) in reducing depressive symptoms. Sensitivity analyses excluding waiting-list controls confirmed this benefit with reduced heterogeneity. Standard-dose psilocybin also produced higher response and remission rates at 2-3 weeks and sustained response at 6-12 weeks, and lower all-cause discontinuation. However, it was associated with more headaches and nausea within 1-9 days, which resolved. Low-dose psilocybin showed no superior efficacy. The authors suggest standard-dose psilocybin is a promising treatment but note considerable methodological heterogeneity across trials.
Pharmacopsychiatry
July 7, 2026
Kie Nomoto, Yohei Ohtani, Taisuke Yatomi et al.
In a double-blind, randomized, placebo-controlled trial, 34 Japanese patients with treatment-resistant depression received four intravenous doses of either ketamine (0.5 mg/kg) or saline. No significant differences emerged between the groups on objective or subjective cognitive function measures. Among ketamine-treated patients, those who responded to treatment (at least 50% reduction on the Montgomery-Åsberg Depression Rating Scale) showed greater improvement in subjective cognitive function than non-responders. Participants with weaker inhibitory control at baseline experienced larger reductions in depressive symptoms after ketamine. Repeated ketamine administration did not worsen cognitive function compared to placebo, suggesting cognitive safety, and baseline cognitive control deficits may predict better treatment response.
The International Journal of Neuropsychopharmacology
May 5, 2026
Hiroyuki Uchida, Gabriella Gobbi, Joseph Zohar et al.
Between 2013 and 2026, neuropsychopharmacology advanced from stagnation to momentum, producing several first-in-class treatments: rapid-acting drugs for treatment-resistant depression (intranasal esketamine), psychedelic-assisted therapy for PTSD and depression, neuroactive steroid GABA-A receptor positive allosteric modulators (brexanolone, zuranolone) for postpartum depression, non-dopaminergic muscarinic agonists (xanomeline-trospium) for schizophrenia, orexin receptor antagonists for insomnia, and anti-amyloid monoclonal antibodies (lecanemab, donanemab) for early Alzheimer's disease.
The International Journal of Neuropsychopharmacology
August 1, 2025
Yuko Ohtani, Hiroe Tani, Shiori Honda et al.
A higher baseline ratio of glutamate+glutamine (Glx) to GABA in the dorsal anterior cingulate cortex predicted greater improvement in depressive symptoms after ketamine treatment in adults with treatment-resistant depression. In the ketamine group, a reduction in this Glx/GABA ratio correlated with symptom improvement, but no such association appeared in the placebo group. The findings suggest that the balance between excitatory and inhibitory neurotransmission in this brain region may serve as a biomarker for predicting antidepressant response to ketamine.
Brain and nerve = Shinkei kenkyu no shinpo
December 1, 2023
Hiroyuki Uchida
Psychedelic drugs are being increasingly studied for treating psychiatric disorders like depression. Although their therapeutic effects were confirmed in the 1960s, public abuse led to their classification as narcotics in 1970, halting clinical research. Since 1994, numerous clinical trials have generated excitement. This review examines the history of these drugs and outlines future prospects.