Prevalence of Kratom Use Disorder Among Kratom Consumers.

OBJECTIVES: Kratom leaf products are increasingly consumed in the United States, with many consumers reporting they experience beneficial effects from kratom use. However, there is a growing concern for kratom's potential to result in dependence when used regularly. As such, we sought to assess, using Diagnostic and Statistical Manual of Mental Disorders , (DSM-5) , diagnostic criteria for substance use disorder, the prevalence of "kratom use disorder" (KUD) among kratom consumers. METHODS: Our cross-sectional study used an online, anonymous survey between February and May 2023. Through nonprobability sampling, we recruited people older than 18 years who currently consume kratom. Participants were asked about their kratom consumption patterns, adverse effects perceived to stem from kratom consumption, comorbid diagnoses, and components for a DSM-5 , substance use disorder, adapted for kratom. RESULTS: Among the total sample ( N = 2061), KUD criteria were met by 25.5% of participants ( n = 525); the most commonly reported symptoms were tolerance ( n = 427, 81.3%) and withdrawal ( n = 357, 68.0%). After adjusting for age, gender, daily frequency of kratom consumption, and history of either a substance use disorder or a mental health condition, those with a concurrent diagnosis of another substance use disorder had 2.83 times higher odds of meeting KUD criteria (95% CI, 2.19-3.67) compared with those without one. CONCLUSIONS: In this large cross-sectional study, most participants who met the criteria for a KUD diagnosis were categorized as having a mild or moderate KUD. Individual characteristics associated with KUD were related to being male, young, consuming kratom frequently, and having psychiatric and substance use disorder comorbidities.

The New Hampshire Hospital Screening and Referral Algorithm (NHHSRA) for Substance Use in People With Serious Mental Illness.

Objective: Substance use is a common co-occurrence among psychiatrically hospitalized adults, yet it is especially difficult to identify in those with serious mental illness. Existing screening instruments are not feasible for individuals with serious mental illness, as they rely heavily on subjective self-report. This study aimed to develop and validate an objective substance use screening instrument for use in seriously mentally ill patient populations.Methods: Objective elements were extracted from existing substance use screening instruments and used to develop a new, data-driven referral tool, the New Hampshire Hospital screening and referral algorithm (NHHSRA). Descriptive statistics were employed to compare NHHSRA summed score and individual patient data elements in a convenience sample of patients who were referred to the Addiction Services by expert addiction psychiatrist evaluation to those who were not referred. Pearson correlation coefficients and logistic regression models assessed the association between patient referral and the overall NHHSRA score and individual items. The NHHSRA was then piloted in a smaller convenience sample of patients against the standard clinical-based identification for substance use treatment needs.Results: The instrument consists of 5 objective items. These were tested in a sample of 302 sequentially admitted adults with serious mental illness. Three of the items were significantly associated with likelihood of benefitting from referral for substance use interventions (maximum likelihood estimate and standard deviation [SD] for positive non-tetrahydrocannabinol [non-THC] toxicology screen or > 0% blood alcohol level = 3.61 [0.6]; diagnosis of a substance use disorder = 4.89 [0.73]; and medication-assisted treatment or relapse prevention = 2.78 [0.67]), and these were prioritized in building a decision tree algorithm. The area under the receiver operating characteristic (ROC) curve for the NHHSRA was 0.96, indicating that the NHHSRA has high overall sensitivity and the algorithm was capable of distinguishing between patients needing substance use intervention versus those who do not with 96% accuracy. In the pilot implementation study of another 20 patient admissions, the NHHSRA accurately identified 100% (n = 6) of patients deemed to benefit from substance use interventions by expert addiction psychiatric evaluation. The standard clinical-based referral process identified only 33% (n = 2) and erroneously identified another 4 for referral to substance use intervention that would not have been warranted.Conclusions: The NHHSRA holds promise in its ability to improve objective and timely identification of substance use in a seriously mentally ill inpatient population, helping to facilitate treatment.

Evaluating health information provided to kratom consumers by good manufacturing practice-qualified vendors.

BACKGROUND: "Kratom" commonly refers to the botanical Mitragyna speciosa, native to Southeast Asia, which is increasingly used globally for its unique pharmacological effects. Motives for using the whole plant material or kratom-derived products include self-management of pain, mental health disorders, symptoms related to substance use disorders, and/or to increase energy. In the United States, kratom products have varying alkaloid content, potencies, and marketing profiles. There is little regulatory oversight over kratom, as it is currently not approved as a dietary supplement by the Food and Drug Administration. This results in substantial variability in labeling of kratom products and the product information provided to consumers. METHODS: In January 2023, we evaluated the American Kratom Association's Good Manufacturing Practices (GMP) qualified vendors' websites (n = 42) using the well-established and validated DISCERN instrument to examine the quality of health information provided to consumers. DISCERN contains 15 five-point Likert-scale questions on specific criteria, with the highest possible score being 75, indicating that all the DISCERN criteria have been fulfilled by the website (i.e., the highest quality information is provided to consumers). RESULTS: The mean DISCERN score for all evaluated online kratom vendors was 32.72 (SD = 6.69; score range 18.00-43.76). Overall, vendors scored higher on DISCERN questions assessing the website's reliability, as vendors typically provided clear information for consumers about product availability, purchasing, shipping, etc. On average, vendors scored poorly on the DISCERN section pertaining to the quality of the health information provided. Information on kratom's potential risks and benefits was particularly insufficient. CONCLUSIONS: Consumers require high quality information in order to make informed decisions concerning use, which entails disclosure of known risks and potential benefits. The online kratom vendors evaluated in this study should consider enhancing the quality of health information provided, especially information regarding kratom's risks and benefits. Further, consumers should be made aware of current knowledge gaps related to kratom's effects. Clinicians must also be aware of the lack of evidence-based information available to their patients who use kratom or are interested in using kratom products, in order to facilitate educational discussions with them.

The Impact of THC and CBD in Schizophrenia: A Systematic Review.

Background: People with schizophrenia are more likely to develop cannabis use disorder (CUD) and experience worse outcomes with use. Yet as cannabis is legalized for medical and recreational use, there is interest in its therapeutic potential. Objectives: To conduct a systematic review summarizing the design and results of controlled trials using defined doses of THC and CBD in schizophrenia. Method: A keyword search of eight online literature databases identified 11 eligible reports. Results: One placebo controlled trial (13 stable patients without CUD) found that intravenous THC increased psychosis and worsened learning/recall. Two reports of a functional magnetic resonance (fMRI) study of smoked or oral THC in 12 abstinent patients with schizophrenia and CUD found no change in symptoms and cognition, and an amelioration of impaired resting state brain function in areas implicated in reward function and the default mode network. One 4 week trial in acutely psychotic inpatients without CUD (mean age 30 y) found 800 mg CBD to be similarly efficacious to amisupride in improving psychosis and cognition. Two 6 week studies of CBD augmentation of antipsychotics in stable outpatients reported mixed results: CBD 600 mg was not more effective than placebo; CBD 1,000 mg reduced symptoms in a sample that did not exclude cannabis use and CUD. A brain fMRI and proton magnetic resonance spectroscopy study of single dose CBD in a sample that did not exclude CUD and cannabis use found that CBD improved symptoms and brain function during a learning/recall task and was associated with increased hippocampal glutamate. Discussion: There is substantial heterogeneity across studies in dose, method of drug delivery, length of treatment, patient age, whether patients with cannabis use/CUD were included or excluded, and whether patients were using antipsychotic medication. Conclusion: There is insufficient evidence for an effect of THC or CBD on symptoms, cognition, and neuroimaging measures of brain function in schizophrenia. At this time, research does not support recommending medical cannabis (THC or CBD) for treating patients with schizophrenia. Further research should examine THC and CBD in schizophrenia with and without comorbid CUD and consider the role of CBD in mitigating symptom exacerbation from THC.

Evidence for Use of Cannabinoids in Mood Disorders, Anxiety Disorders, and PTSD: A Systematic Review.

OBJECTIVE: Two primary compounds of the cannabis plant (Cannabis sativa), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), differentially and dose-dependently affect mood and anxiety. In this systematic review, the authors summarize the design and results of controlled trials assessing the effects of THC and CBD on affective disorders, anxiety disorders, and posttraumatic stress disorder (PTSD). METHODS: A keyword search of eight online literature databases identified eight randomized controlled trials of defined CBD or THC doses for the target populations. RESULTS: A 1-month trial of daily THC (up to 3 mg per day) for DSM-II anxiety disorder reduced anxiety symptoms, but symptoms were very low throughout the study. Another trial of sequential, single-day, low-dose THC in social anxiety disorder found no symptom changes. Two studies reported that single-dose CBD pretreatment reduced anxiety in laboratory paradigms among individuals with social anxiety disorder. A study of daily CBD for 4 weeks among adolescents with social anxiety disorder indicated modest symptom improvements. One crossover trial involving 10 patients with PTSD showed that THC added to standard pharmacotherapy reduced self-reported nightmares. Two small studies of THC for hospitalized patients with unipolar or bipolar depression found no improvement of depression; instead, anxiety and psychotic symptoms emerged in >50% of patients. CONCLUSIONS: With only eight very small studies, insufficient evidence was found for efficacy of CBD and THC to manage affective disorders, anxiety disorders, or PTSD. Therefore, medical cannabis should not be recommended for treating patients with these disorders. Further research should investigate the safety and efficacy of managing psychiatric disorders with cannabinoids.

Palladium-catalyzed allylic substitution with (η6-arene-CH2Z)Cr(CO)(3)-based nucleophiles.

Although the palladium-catalyzed Tsuji-Trost allylic substitution reaction has been intensively studied, there is a lack of general methods to employ simple benzylic nucleophiles. Such a method would facilitate access to "α-2-propenyl benzyl" motifs, which are common structural motifs in bioactive compounds and natural products. We report herein the palladium-catalyzed allylation reaction of toluene-derived pronucleophiles activated by tricarbonylchromium. A variety of cyclic and acyclic allylic electrophiles can be employed with in situ generated (η(6)-C(6)H(5)CHLiR)Cr(CO)(3) nucleophiles. Catalyst identification was performed by high throughput experimentation (HTE) and led to the Xantphos/palladium hit, which proved to be a general catalyst for this class of reactions. In addition to η(6)-toluene complexes, benzyl amine and ether derivatives (η(6)-C(6)H(5)CH(2)Z)Cr(CO)(3) (Z = NR(2), OR) are also viable pronucleophiles, allowing C-C bond-formation α to heteroatoms with excellent yields. Finally, a tandem allylic substitution/demetalation procedure is described that affords the corresponding metal-free allylic substitution products. This method will be a valuable complement to the existing arsenal of nucleophiles with applications in allylic substitution reactions.

Synthesis and structural characterization of a series of dimeric metal(II) imido complexes {M(mu-NAr(#))}2 [M = Ge, Sn, Pb; Ar(#) = C6H3-2,6-(C6H2-2,4,6-Me3)2] and the related monomeric primary amido derivatives M{N(H)Ar(#)}2 (M = Ge, Sn, Pb): spectroscopic manifestations of secondary metal-ligand interactions.

The solvent-free reaction of M{N(SiMe(3))(2)}(2) (M = Ge, Sn, or Pb) with the sterically encumbered primary amine 2,6-dimesitylaniline Ar(#)NH(2) [Ar(#) = C(6)H(3)-2,6(C(6)H(2)-2,4,6-Me(3))(2)] at ca. 165-175 degrees C afforded the highly colored imido dimers {M(mu-NAr(#))}(2), where M = Ge (1), Sn (2), or Pb (3), with disilylamine elimination. The compounds were characterized by single-crystal X-ray crystallography and heteronuclear NMR spectroscopy. The structures of 1-3 were very similar and had nonplanar four-membered M(2)N(2) ring cores that are folded along the M---M axis. The nitrogen atoms are planar-coordinated, and the M-N distances are consistent with single bonding. The reaction of M{N(SiMe(3))(2)}(2) with Ar(#)NH(2) in a 2:1 ratio in solution at lower temperature afforded the relatively stable monomeric primary amido species M{N(H)Ar(#)}(2), where M = Ge (4), Sn (5), or Pb (6). Complexes 4-6 displayed V-shaped MN(2) structures, and 5 and 6 revealed close approaches between the metal atom and ipso-carbon atoms of two flanking Mes groups of the terphenyl substituents [Sn(II)---C (2.957 A) and Pb(II)---C (2.965 A)]. The secondary metal-ligand interactions exerted large effects on their electronic and NMR spectra.

Mechanistic detail revealed via comprehensive kinetic modeling of [rac-C(2)H4(1-indenyl)2ZrMe2]-catalyzed 1-hexene polymerization.

Thorough kinetic characterization of single-site olefin polymerization catalysis requires comprehensive, quantitative kinetic modeling of a rich multiresponse data set that includes monomer consumption, molecular weight distributions (MWDs), end group analysis, etc. at various conditions. Herein we report the results obtained via a comprehensive, quantitative kinetic modeling of all chemical species in the batch polymerization of 1-hexene by rac-C(2)H(4)(1-Ind)(2)ZrMe(2) activated with B(C(6)F(5))(3). While extensive studies have been published on this catalyst system, the previously acknowledged kinetic mechanism is unable to predict the MWD. We now show it is possible to predict the entire multiresponse data set (including the MWDs) using a kinetic model featuring a catalytic event that renders 43% of the catalyst inactive for the duration of the polymerization. This finding has significant implications regarding the behavior of the catalyst and the polymer produced and is potentially relevant to other single-site polymerization catalysts, where it would have been undetected as a result of incomplete kinetic modeling. In addition, comprehensive kinetic modeling of multiresponse data yields robust values of rate constants (uncertainties of less than 16% for this catalyst) for future use in developing predictive structure-activity relationships.

C(aryl)-O activation of aryl carboxylates in nickel-catalyzed biaryl syntheses.

Crucial breakthroughs in the activation of the C(aryl)-O bond of phenol derivatives were achieved almost simultaneously by two research groups (see scheme; Cy = cyclohexyl). Garg et al. coupled a range of aryl pivalates with arylboronic acids to give unsymmetrical biaryls. Shi et al. achieved this through C(aryl)-O activation of aryl carboxylates; the best results for the coupling of aryl boroxines were again obtained with aryl pivalates.

Synthesis and Characterization of Ge(II), Sn(II), and Pb(II) Monoamides with -NH2 Ligands.

The synthesis and characterization of the first divalent germanium, tin, and lead monoamide derivatives of the parent amide group -NH(2) are presented. They have the general formula (ArMNH(2))(2) (M = Ge, Ar = Ar'(C(6)H(3)-2,6-Pr(i)(2)) or Ar* (C(6)H(3)-2,6(C(6)H(2)-2,4,6-Pr(i)(3))); M = Sn, Ar = Ar*; M = Pb, Ar = Ar*). For germanium and tin, they were obtained by reacting the corresponding terphenyl halides of the group 14 elements with liquid ammonia in diethyl ether. The lead amide derivative (Ar*PbNH(2))(2) was synthesized by reaction of LiNH(2) with Ar*PbBr in diethyl ether. The compounds were characterized by IR and multinuclear NMR spectroscopies and by X-ray crystallography in the case of the (Ar'GeNH(2))(2) or (Ar*SnNH(2))(2) derivatives. They possess dimeric structures with two -NH(2) groups bridging the germanium and tin centers. For lead, the reaction with ammonia led to isolation of a stable ammine complex of formula Ar*PbBr(NH(3)) which was characterized by IR and NMR spectroscopies and by X-ray crystallography. It is the first structural characterization of a divalent lead ammine complex.

Characterization of Ar'Sn(micro-Br)Sn(Ar')CH2C6H4-4-Pri (Ar' = C6H3-2,6-Dipp2; Dipp = C6H3-2,6-Pri2): a stable structural analogue for a heavier group 14 element monobridged alkene isomer HM(micro-H)MH2 (M = Sn or Pb).

The title compound is the first stable structural analogue for the monobridged isomer of a heavier group 14 alkene analogue.