Bioscience Biotechnology and Biochemistry
August 23, 2009
Yoshihiro Matsushima, Osamu Shirota, Ruri Kikura-Hanajiri et al.
77 citations
A hallucinogenic mushroom, Psilocybe argentipes, reduced marble-burying behavior in mice, a model for obsessive-compulsive disorder, without affecting their general movement. The same dose of authentic psilocybin also inhibited burying, but P. argentipes was more effective. These results suggest the mushroom could be useful in clinical therapy for obsessive-compulsive disorder.
Current Neuropharmacology
March 1, 2011
Chiharu Sogawa, Norio Sogawa, Kazumi Ohyama et al.
50 citations
Methylone, a synthetic hallucinogenic amphetamine analog similar to MDMA, inhibits the activity of dopamine, norepinephrine, and serotonin transporters in a concentration-dependent manner, with the strongest effect on the norepinephrine transporter, followed by dopamine and then serotonin transporters. Compared to methamphetamine, methylone is less effective at blocking dopamine and norepinephrine transporters but more effective at blocking the serotonin transporter. Methylone alone is not toxic to cells except at high concentrations, but when combined with methamphetamine, it produces a synergistic toxic effect in cells that express monoamine transporters, likely because methylone acts as a transportable substrate that inhibits transporter function.
YAKUGAKU ZASSHI
October 1, 2008
Nahoko Uchiyama, Ruri Kikura-Hanajiri, Nobuo Kawahara et al.
46 citations
In Japan, 32 psychotropic substances were controlled under the Pharmaceutical Affairs Law starting April 2007 to curb drug abuse, but new designer drugs continue to emerge. Just before a law amendment, 7 designer drugs were detected in 15 products using NMR, GC-MS, and LC-MS analyses. These included three methylone derivatives (MDPV, bk-MBDB, bk-MDEA), a MDMA derivative (N-OH MDMA), a methamphetamine derivative (N-Me-4-FMP), a tryptamine derivative (5-MeO-EIPT), and indan-2-amine. 5-MeO-EIPT was newly identified in this study.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
August 15, 2007
Ruri Kikura-Hanajiri, Maiko Kawamura, Kazuhiro Saisho et al.
35 citations
In an animal model, the incorporation of methylone and other designer drugs into hair was measured and compared with related compounds. Methylone's hair-to-plasma concentration ratio was 14 times higher than methcathinone's, supporting earlier findings that a methylenedioxy group on the benzene ring increases incorporation. However, methylone's ratio was five-sevenths that of MDMA, suggesting a beta-carbonyl group lowers incorporation. MBDB, with a methylenedioxyphenyl-2-butanamine structure, had a higher ratio than MDMA, while methcathinone's ratio was extremely low. The authors conclude that methylone and MBDB, like methamphetamine and MDMA, have relatively high incorporation into hair, making hair samples useful for confirming retrospective use of these drugs.
YAKUGAKU ZASSHI
June 1, 2009
Maiko Kawamura, Yukihiro Goda, Ruri Kikura-Hanajiri
19 citations
A rapid screening method using Direct Analysis in Real Time time-of-flight mass spectrometry (DART-TOFMS) was developed to identify psychotropic compounds in plant products of abuse in Japan without sample preparation. Among 36 products, protonated molecular ions corresponding to six hallucinogenic constituents—mescaline, salvinorin A, N,N-dimethyltryptamine, harmine, harmaline, and lysergamide—were detected in 21 products, with contents ranging from 0.05 to 45 micrograms per milligram. Results matched those from liquid chromatography-mass spectrometry. Controlled narcotics such as tetrahydrocannabinol, opioid alkaloids, and psilocin were also directly detected in marijuana, opium gum, and magic mushrooms. DART-TOFMS offers a simple, rapid screening tool for targeted psychotropic natural products, though matrix effects from other plant ingredients remain difficult to estimate.
Forensic Toxicology
July 1, 2023
Rie Tanaka, Maiko Kawamura, Sakumi Mizutani et al.
18 citations
Three new analogs of LSD have been identified in paper sheet products sold as designer drugs in Japan. Using mass spectrometry and nuclear magnetic resonance spectroscopy, the compounds were determined to be 1cP-AL-LAD, 1cP-MIPLA, 1V-LSD, and LSZ. Compared to LSD, 1cP-AL-LAD is modified at two positions (N1 and N6), and 1cP-MIPLA at N1 and N18. The metabolic pathways and biological activities of 1cP-AL-LAD and 1cP-MIPLA are not yet reported. This is the first report of LSD analogs with multiple structural modifications detected in sheet products in Japan, raising concerns about future distribution and highlighting the need for continued monitoring.
Journal of Pharmaceutical and Biomedical Analysis
July 21, 2020
Izumi Morita, Hiroyuki Oyama, Yuki Kiguchi et al.
17 citations
Two independent monoclonal antibodies were generated against psilocybin and its dephosphorylated metabolite psilocin, the psychoactive compounds in hallucinogenic mushrooms. Novel immunogenic conjugates were prepared by modifying the side chains of these molecules and linking them to carrier proteins. Mice were immunized, and hybridoma clones secreting the specific antibodies were established. Competitive enzyme-linked immunosorbent assays (ELISAs) using these antibodies enabled detection of psilocybin and psilocin at ranges of approximately 0.20–20 μg/assay and 0.040–2.0 μg/assay, respectively, with low cross-reactivity between the two compounds. In dried Psilocybe cubensis powder, psilocybin and psilocin contents were 0.39% and 0.32% by weight. These ELISAs offer a promising tool for identifying illegal hallucinogenic mushrooms.
Forensic Toxicology
July 1, 2017
Genri Kawahara, Hideyuki Maeda, Ruri Kikura-Hanajiri et al.
17 citations
25B-NBOMe, a potent designer drug that activates the serotonin-2A receptor, can cause lethal rhabdomyolysis—a severe breakdown of skeletal muscle—in zebrafish larvae. Treatment with 25B-NBOMe reduced survival, impaired movement, and disrupted muscle structure, as shown by changes in birefringence and immunostaining for dystroglycan and myosin heavy chain. This rhabdomyolysis was blocked by the 5-HT_2A receptor antagonists ritanserin and aripiprazole, but not by antagonists for other serotonin receptors, indicating a 5-HT_2A-dependent mechanism. The 25B-NBOMe-treated zebrafish provides a useful animal model for studying rhabdomyolysis and screening potential therapies.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
October 1, 2008
Jun Zhe Min, Yoshiha Shimizu, Toshimasa Toyo'Oka et al.
17 citations
A new method using ultra-fast liquid chromatography with fluorescence detection (UFLC-FL) was developed to simultaneously identify and measure 11 phenethylamine-type drugs. The drugs were chemically labeled and separated on a specialized column, with detection limits ranging from 10 femtomoles to 2.5 picomoles. The method showed good accuracy and precision. When applied to real products from the Japanese market, it identified and quantified BDB (0.24 mg/mg), MMDA-2 (0.98 mg/mL), and 2C-I (0.016 mg/mg) in powder, liquid, and mushroom-like samples. The procedure is simple, selective, and sensitive, making it useful for analyzing these designated drugs in various samples, including biological specimens.
YAKUGAKU ZASSHI
February 1, 2010
Nahoko Uchiyama, Norimasa Miyazawa, Maiko Kawamura et al.
16 citations
By July 2009, Japan had designated 40 psychoactive substances (including 12 tryptamines, 17 phenethylamines, 3 piperazines, 6 alkyl nitrites, 1 diterpene, and 1 plant) as controlled substances under the Pharmaceutical Affairs Law to prevent abuse. Despite these controls, new designer drugs continue to appear in the illegal market. Analysis of two products purchased in Japan between October 2008 and February 2009 identified four compounds: three phenethylamine derivatives—N-Me-2-FMP, ALEPH-4, and DON—and one tryptamine derivative, 5-MeO-EPT. N-Me-2-FMP and 5-MeO-EPT were newly identified, while ALEPH-4 and DON were found as novel illegal drugs in Japan.
YAKUGAKU ZASSHI
October 31, 2020
Rie Tanaka, Maiko Kawamura, Takashi Hakamatsuka et al.
15 citations
Three new LSD-like designer drugs were identified in paper sheet products seized in Japan between September 2019 and March 2020. Using methanol extraction followed by LC-MS, high-resolution MS, GC-MS, and NMR analyses, the compounds were identified as 1cP-LSD, MIPLA, and 1B-LSD. Like other N1-acylated LSD derivatives, 1cP-LSD and 1B-LSD easily break down into LSD during GC-MS analysis, requiring caution when testing.
YAKUGAKU ZASSHI
April 30, 2020
Rie Tanaka, Maiko Kawamura, Takashi Hakamatsuka et al.
15 citations
From 2014 to 2017 in Japan, four lysergic acid diethylamide (LSD) derivatives were detected in paper sheet products sold as designer drugs. The compounds were identified as ALD-52, ETH-LAD, AL-LAD, and 1P-LSD using GC-MS, LC-MS, LC-Q-TOF-MS, and NMR analyses. Extraction methods and analytical conditions for GC-MS, LC-MS, and LC-FL were studied. As of September 2019, 2372 substances and two plants are controlled as "Designated Substances" under Japanese law. Only 1P-LSD was already regulated since April 2016; pharmacological evaluation of the other derivatives is ongoing to inform future legislation.
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
August 1, 2009
Ruri Kikura-Hanajiri, Takuro Maruyama, Akinori Miyashita et al.
15 citations
Products sold as Voacanga africana, a tree whose bark and seeds contain psychoactive alkaloids, fall into two chemical types: ibogaine-type (0.05–0.6% ibogaine plus voacamine, voacamidine, and voacangine) and tabersonine-type (0.6–1.6% tabersonine). DNA analysis of the chloroplast trnL-F region showed most products came from V. africana or closely related plants, with four distinct genotypes. The study developed a simultaneous LC/MS method to quantify these alkaloids and used DNA barcoding to verify botanical origins, providing tools to monitor the distribution of this non-controlled psychotropic plant.
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
January 1, 2008
Takuro Maruyama, Hiroyuki Kamakura, Ruri Kikura-Hanajiri et al.
14 citations
Before Salvia divinorum was regulated under Japan's Pharmaceutical Affairs Law, commercial Salvia cultivars sold in Japan were tested for the hallucinogen salvinorin A. Ultra performance liquid chromatography/mass spectrometry showed that none of the cultivars contained salvinorin A, whereas S. divinorum leaves and its processed product "concentrated salvia" contained 0.19% to 0.58% of the compound. A DNA-based authentication method using amplification refractory mutation system clearly distinguished S. divinorum from the cultivars. The authors conclude that this authentication method is simple and accurate, making it useful for practical regulation.
Drug Testing and Analysis
May 1, 2024
Rie Tanaka, Maiko Kawamura, Sakumi Mizutani et al.
11 citations
A paper-sheet product sold as containing the LSD analog 1D-LSD actually contained a different, previously unreported compound: 1-thiophenoyl LSD (1T-LSD). Using mass spectrometry and nuclear magnetic resonance spectroscopy, the compound was identified as having a thiophene-2-carbonyl group instead of the claimed 1,2-dimethylcyclobutane-carbonyl group. Each unit of the sheet contained 87–100 μg of 1T-LSD free base. The compound slowly converted to LSD in methanol-d4 during analysis. Its UV spectrum differed from other LSD analogs, and its fluorescence was much lower. The authors recommend continued monitoring of sheet products for new LSD analogs.
Forensic Toxicology
April 3, 2025
Rie Tanaka, Maiko Kawamura, Michiho Ito et al.
3 citations
Two new LSD analogs, 1S-LSD and 1T-AL-LAD, were identified in sheet products sold in Japan. Their structures were determined using gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, and nuclear magnetic resonance. A trace amount of iso-1S-LSD, a C8-epimerization product, was also suggested in one product. This is the first report of these compounds in sheet products in Japan. The metabolic pathways and biological activities of 1S-LSD and 1T-AL-LAD remain unexplored, and further investigation into their possible in vivo deacylation and conversion into LSD or AL-LAD is needed.
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
January 1, 2022
Rie Tanaka, Maiko Kawamura, Sakumi Mizutani et al.
3 citations
Three new derivatives of the dissociative drug methoxetamine (MXE) were identified in illegal products in Japan: methoxpropamine (MXPr), methoxisopropamine (MXiPr), and deoxymethoxetamine (DMXE). MXE itself, an analog of the anesthetic ketamine, is already controlled as a narcotic in Japan, and its overdoses have caused health problems. All arylcyclohexylamines, including these new substances, act as antagonists of the NMDA receptor. The findings highlight the ongoing emergence of novel psychoactive substances designed to evade legal controls.
Analytical methods : advancing methods and applications
September 16, 2021
Izumi Morita, Yuki Kiguchi, Hiroyuki Oyama et al.
3 citations
A new test detects psilocin, the main psychoactive compound in hallucinogenic mushrooms, with much higher sensitivity than before. The method first converts psilocin into a heavier chemical form (TBS/Psi), then uses an antibody that binds strongly to this modified compound. The antibody showed 69-fold higher affinity than an earlier version, and the test's detection midpoint was over 100-fold lower than the previous assay, reaching the desired low-picomole sensitivity. When applied to dried Psilocybe cubensis mushroom powder, the test gave positive signals indicating expected psilocin levels, while four edible mushroom species produced no detectable response.
Journal of Pharmacological Sciences
December 1, 2022
Tomohiko Irie, Yuta Yanase, Yosuke Demizu et al.
2 citations
Methoxetamine and its derivatives deoxymethoxetamine and methoxisopropamine, sold online as designer drugs, block N-methyl-D-aspartate receptors (NMDARs) in the brain. Computer docking simulations suggested these compounds interact with NMDARs. Using patch-clamp recordings from mouse neurons expressing NMDARs, the half-maximal inhibitory concentrations (IC50s) were determined: methoxetamine 0.524 μM, deoxymethoxetamine 0.679 μM, methoxisopropamine 0.661 μM, and the methoxetamine metabolites N-desethyl methoxetamine 1.649 μM and O-desmethyl methoxetamine 0.227 μM. All acted as potent NMDAR blockers, indicating that deoxymethoxetamine and methoxisopropamine may cause harm by blocking these receptors, and the metabolites may contribute to adverse effects when methoxetamine is metabolized.
Drug Testing and Analysis
June 1, 2024
Takuji Shoda, Genichiro Tsuji, Maiko Kawamura et al.
1 citation
Lysergic acid diethylamide (LSD) is a hallucinogen that activates the serotonin 2A receptor and is a controlled substance in Japan. Recently, MiPLA, an N-methyl-N-isopropyl derivative of LSD, has appeared in paper-sheet products in several countries. This work describes the three-step synthesis of MiPLA starting from ergometrine maleate, which also produced the (8S)-isomer, iso-MiPLA, as a by-product. Liquid chromatography-mass spectrometry showed that LSD, MiPLA, and iso-MiPLA have different retention times. Nuclear magnetic resonance spectroscopy determined their chemical structures and revealed rotamers involving the N-methyl-N-isopropyl groups of tertiary amides in MiPLA and iso-MiPLA.
Drug Testing and Analysis
February 18, 2026
Rie Tanaka, Maiko Kawamura, Michiho Ito et al.
Two new lysergic acid diethylamide (LSD) analogs, 1Bz-LSD and 1-TMSBz-LSD, were identified in tablet and paper sheet products sold in Japan. Using gas chromatography-mass spectrometry, liquid chromatography-photodiode array-mass spectrometry, liquid chromatography with hybrid quadrupole time-of-flight mass spectrometry, and nuclear magnetic resonance, the structures of the compounds were determined. 1Bz-LSD was found in a tablet product, and 1-TMSBz-LSD was found in a paper sheet product. This is the first report of these specific analogs being detected in such products in Japan.
Legal medicine (Tokyo, Japan)
September 1, 2015
Keiko Kudo, Yosuke Usumoto, Ruri Kikura-Hanajiri et al.
A woman in her thirties was found dead with aroma liquid, bath salt products, and hypnotic drug tablets nearby. Autopsy revealed pulmonary congestion and edema. Analysis detected four designer drugs: 4-methoxy PV8, PV9, 4-methoxy PV9, and diphenidine, plus three benzodiazepines (triazolam, flunitrazepam, nitrazepam) and alcohol. Femoral blood concentrations of the cathinones and diphenidine were 2.69, 0.743, 0.261, and 1.38 μg/ml, respectively, markedly higher than earlier cases; alcohol was 1.52 mg/ml. The cause of death was poisoning from these cathinone drugs and diphenidine, compounded by benzodiazepines and alcohol.
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
June 1, 2008
Ruri Kikura-Hanajiri, Maiko Kawamura, Nahoko Uchiyama et al.
Japan's Ministry of Health, Labor and Welfare amended the Pharmaceutical Affairs Law in 2006 to control 31 non-controlled psychotropic substances and one plant as "Designated Substances" as of April 2007, with five more compounds added in January 2008. These substances had been sold as video cleaners, incense, and reagents via the Internet or in video shops. The authors developed simultaneous analytical methods using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) and present retention times, UV spectra, and mass spectrometry data for these substances.