A systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans.

INTRODUCTION: Kratom (Mitragyna speciosa) is a tropical plant traditionally used as an ethnomedicinal remedy for several conditions in South East Asia. Despite the increased interest in its therapeutical benefits in Western countries, little scientific evidence is available to support such claims, and existing data remain limited to kratom's chronic consumption. OBJECTIVE: Our study aims to investigate (pre)clinical evidence on the efficacy of kratom as a therapeutic aid and its safety profile in humans. METHODS: A systematic literature search using PubMed and the Medline database was conducted between April and November 2020. RESULTS: Both preclinical (N = 57) and clinical (N = 18) studies emerged from our search. Preclinical data indicated a therapeutic value in terms of acute/chronic pain (N = 23), morphine/ethanol withdrawal, and dependence (N = 14), among other medical conditions (N = 26). Clinical data included interventional studies (N = 2) reporting reduced pain sensitivity, and observational studies (N = 9) describing the association between kratom's chronic (daily/frequent) use and safety issues, in terms of health consequences (e.g., learning impairment, high cholesterol level, dependence/withdrawal). CONCLUSIONS: Although the initial (pre)clinical evidence on kratom's therapeutic potential and its safety profile in humans is encouraging, further validation in large, controlled clinical trials is required.

Inverse correlation between plasma 2-arachidonoylglycerol levels and subjective severity of depression.

OBJECTIVE: Endocannabinoids have been implicated in the pathophysiology of Major Depressive Disorder (MDD) and might represent potential targets for therapeutic intervention. Objectives of the study were: (1) to measure plasma levels of endocannabinoids in a group of antidepressant-free depressed outpatients; (2) to explore their relationship with the severity of depressive symptoms as subjectively perceived by the patients; and (3) to investigate the effect of the selective serotonin reuptake inhibitor escitalopram on endocannabinoid levels. METHODS: We measured plasma levels of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anadamide), in 12 drug-free outpatients diagnosed with MDD and in 12 matched healthy controls. In the patient group, endocannabinoids plasma levels were assessed at baseline and after 2 months of treatment with escitalopram. RESULTS: Baseline plasma levels of the two endocannabinoids did not differ between depressed patients and healthy controls. However, there was a significant inverse correlation between 2-arachidonoylglycerol levels and the severity of subjectively perceived depressive symptoms. Treatment with escitalopram did not change endocannabinoid levels in depressed patients, although it caused the expected improvement of depressive symptoms. CONCLUSIONS: Our results suggest that 2-arachidonylglycerol, the most abundant endocannabinoid in the central nervous system, might act to mitigate depressive symptoms, and raise the interesting possibility that 2-arachidonylglycerol and anandamide are differentially regulated in patients affected by MDD. Also, our data suggest but do not prove that the endocannabinoid system is not regulated by serotonergic transmission, at least in depressed patients.

The rise of new psychoactive substances and psychiatric implications: A wide-ranging, multifaceted challenge that needs far-reaching common legislative strategies.

The ever-growing number of novel psychoactive substances (NPS) that have been surfacing globally, as well as related changes in drug abuse trends, undoubtedly constitute a difficult and multifaceted challenge for psychiatry. The intake and abuse of such substances has been linked to a risk of psychopathological disturbances, which stem from imbalances of a range of neurotransmitter pathways and receptors. Through an analysis of relevant research articles and reviews (particularly those outlining NPS neurological and cerebral mechanisms of action and psychopathological consequences arising from NPS abuse; research papers more closely focused on chemical/pharmacological aspects have been ruled out), through a systematic analysis of Pubmed, Medline, PsycLIT and EMBASE literature, as well as data released by health care institutions and drug enforcement agencies (among which the World Health Organization, the United Nations Office on Drugs and Crime, the European Monitoring Centre for Drugs and Drug Addiction, Eurojust, the Novel Psychoactive Treatment UK Network, the Court of Justice of the European Union), the authors aimed to elaborate on the most relevant data relative to NPS-related psychiatric effects, focusing on the conceptual and definition-related complexities inherent to NPS, clinical management and motivations for NPS use; moreover, an effort has been made to highlight the possible measures in order to tackle the unremitting rise of such elusive and potentially harmful substances.

'Delusional' consent in somatic treatment: the emblematic case of electroconvulsive therapy.

Even more than for other treatments, great importance must be given to informed consent in the case of electroconvulsive therapy (ECT). In a percentage of cases, the symbolic connotation of the treatment, even if mostly and intrinsically negative, may actually be a determining factor in the patient's motives for giving consent. On an ethical and medicolegal level, the most critical point is that concerning consent to the treatment by a psychotic subject with a severely compromised ability to comprehend the nature and objective of the proposed therapy, but who nonetheless expresses his consent, for reasons derived from delusional thoughts. In fact, this situation necessarily brings to light the contradiction between an explicit expression of consent, a necessary formality for the commencement of therapy, and the validity of this consent, which may be severely compromised due to the patient's inability to comprehend reality and therefore to accept the proposal of treatment, which is intrinsic to this reality. With the use of an electric current, the symbolic experience associated with anaesthesia, and the connection to convulsions, ECT enters the collective consciousness. In relation to this, ECT is symbolic of these three factors and hooks on to the thoughts, fears, feelings and expectations of delusional patients. These are often exemplified in the violent intervention of the persecutor in the patient with schizophrenia, the expected punishment for the 'error' committed for which the depressed patient blames himself and the social repression of the maniacal patient's affirmation of his inflated self-esteem.

Novel psychoactive substances (NPS) use in severe mental illness (SMI) patients: Potential changes in the phenomenology of psychiatric diseases.

OBJECTIVE: Literature is quite poor about the clinical effects of novel psychoactive substances (NPS) and the long-term consequences of NPS use in psychiatric patients. Consequently, it is of the greatest interest to examine which effects NPS can exert in patients with previous severe mental illness (SMI), such as psychotic patients. The aim of this work was a comprehensive review about NPS use in patients with SMI. METHODS: We searched Medline or PubMed for relevant English-language citations and reviews describing relationships between NPS use and mental disorders, as well as for the main groups of substances and associated psychiatric manifestations. All studies reporting single case or case series of patients were selected. RESULTS: The NPS use in patients with SMI is probably underestimated. The one existing systematic review considers only 14 studies, 12 of which are case reports. Most clinical results report acute symptom exacerbation of preexisting psychosis. Paranoid, mood, and aggression symptoms occur more frequently. CONCLUSIONS: NPS use could modify clinical features of SMI, but these conclusions cannot be generalizable. More evidence is needed to establish the causal and effective connection between NPS use and course of illness, type of psychiatric symptoms, and outcome of treatment in terms of adherence or response.

Can mobile phone technology support a rapid sharing of information on novel psychoactive substances among health and other professionals internationally?

BACKGROUND: The diffusion of novel psychoactive substances (NPSs), combined with the ability of the Internet to act as an online marketplace, has led to unprecedented challenges for governments, health agencies, and substance misuse services. Despite increasing research, there is a paucity of reliable information available to professionals working in the field. The paper will present the pilot results of the first mobile application (SMAIL) for rapid information sharing on NPSs among health professionals. METHODS: The development of SMAIL was divided into 2 parts: (a) the creation of the application for registered users, enabling them to send an SMS or email with the name or "street name" of an NPS and receive within seconds emails or SMS with the information, when available and (b) the development of a database to support the incoming requests. RESULTS: One hundred twenty-two professionals based in 22 countries used the service over the pilot period of 16 months (from May 2012 to September 2013). Five hundred fifty-seven enquires were made. Users received rapid information on NPSs, and 61% of them rated the service as excellent. CONCLUSIONS: This is the right time to use mobile phone technologies for rapid information sharing and prevention activities on NPSs.

Hair analysis for the detection of drug use-is there potential for evasion?

BACKGROUND: Hair analysis for illicit substances is widely used to detect chronic drug consumption or abstention from drugs. Testees are increasingly seeking ways to avoid detection by using a variety of untested adulterant products (e.g., shampoos, cleansers) widely sold online. This study aims to investigate adulteration of hair samples and to assess effectiveness of such methods. METHODS: The literature on hair test evasion was searched for on PubMed or MEDLINE, Psycinfo, and Google Scholar. Given the sparse nature of peer-reviewed data on this subject, results were integrated with a qualitative assessment of online sources, including user-orientated information or commercial websites, drug fora and "chat rooms". Over four million web sources were identified in a Google search by using "beat hair drug test" and the first 86 were monitored on regular basis and considered for further analysis. RESULTS: Attempts to influence hair test results are widespread. Various "shampoos," and "cleansers" among other products, were found for sale, which claim to remove analytes. Often advertised with aggressive marketing strategies, which include discounts, testimonials, and unsupported claims of efficacy. However, these products may pose serious health hazards and are also potentially toxic. In addition, many anecdotal reports suggest that Novel Psychoactive Substances are also consumed as an evasion technique, as these are not easily detectable via standard drug test. Recent changes on Novel Psychoactive Substances legislations such as New Psychoactive Bill in the UK might further challenge the testing process. CONCLUSION: Further research is needed by way of chemical analysis and trial of the adulterant products sold online and their effects as well as the development of more sophisticated hair testing techniques.

Captagon: use and trade in the Middle East.

BACKGROUND: Fenetheylline, a psychostimulant drug, often branded as Captagon, is a combination of amphetamine and theophylline. Since the cessation of its legal production in 1986, counterfeited products have been produced illicitly in south-east Europe and far-east Asia. Its profitable trade has been linked to terrorist organizations, including Islamic State of Iraq and the Levant. This study aims to reach up-to-date data, concerning the Captagon e-commerce and use in the Middle East. METHODS: A multi-staged and multi-lingual literature search was carried out. A list of prespecified keywords was applied across medical and paramedical databases, web and Dark web, search engines, social communication media, electronic commerce websites, media networks, and the Global Public Health Intelligence Network database. RESULTS: The use of Captagon as a stimulant in terrorist settings has been marginally covered in the literature. Data can widely be retrieved from Google and AOL search engines, YouTube, and Amazon e-commerce websites, and to a lesser extent from Alibaba and eBay. On the contrary, Middle Eastern e-commerce websites yielded almost no results. Interestingly, the Dark web generated original data for Captagon e-commerce in the Middle East. CONCLUSION: Further investigations are needed on the role that psychoactive drugs play in terrorist attacks and civil war zones. Unless a comprehensive methodological strategy, inclusive of unconventional methods of research, is implemented, it will not be feasible to face such a threat to humanity.

Potential neuroprotective effect of lithium in bipolar patients evaluated by neuropsychological assessment: preliminary results.

OBJECTIVE: Accumulating evidence is delineating a neuroprotective/neurotrophic role for lithium. However, its primary effects on cognition remain ambiguous. We sought to investigate the profile of cognitive impairment in patients with bipolar disorder and to determine whether continued treatment with lithium preserves cognitive functioning. METHODS: In this cross-sectional study, we tested 15 euthymic patients with bipolar I disorder undergoing long-term clinical maintenance treatment with lithium (for at least 12 months), 15 matched patients treated with other mood-stabilizing drugs and who had never received lithium, and 15 matched healthy subjects on the Cambridge Neuropsychological Test Automated Battery. Investigated cognitive domains were visual memory, executive functions, attention, decision-making/impulsivity, and response inhibition. We controlled for age, gender, intelligence, and residual psychiatric symptomatology. RESULTS: Taken together, bipolar patients demonstrated robust deficits in visual memory and executive functions. Once subdivided in treatment subgroups, only non-lithium bipolar patients demonstrated impairments in visual memory. Attention, decision-making, and response inhibition were preserved in both groups. No correlation emerged between neuropsychological tests performance, clinical, and psychological variables. CONCLUSIONS: This study is the first to our knowledge to have demonstrated, by means of a highly sensitive test of visual memory, a potential hippocampus neuroprotective effect of lithium in patients with bipolar disorder. Besides, it confirms prior findings of cognitive deficits in euthymic bipolar patients.

Olanzapine as the ideal "trip terminator"? Analysis of online reports relating to antipsychotics' use and misuse following occurrence of novel psychoactive substance-related psychotic symptoms.

OBJECTIVE: The pharmacological self-management of novel psychoactive substance (NPS)-induced psychopathological consequences represents a fast growing phenomenon. This is facilitated by the frequent sharing of NPS intake experiences online and by the ease of access to a range of psychotropic medications from both the online and street market. Olanzapine is anecdotally reported by Web users to be the most frequent self-prescribed medication to cope with NPS-induced psychoses. Hence, we aimed here at better assessing olanzapine use/misuse for this purpose. METHODS: Exploratory qualitative searches of 163 discussion fora/specialized websites have been carried out in four languages (English, German, Spanish, and Italian) in the time frame November 2012-2013. RESULTS: Most NPS-users allegedly self administer with olanzapine to manage related psychotic crises/"bad trips". This may be typically taken only for a few days, at a dosage range of 5-50 mg/day. CONCLUSIONS: Only a few research studies have formally assessed the effectiveness of olanzapine and indeed of other second-generation antipsychotics to treat NPS-induced psychosis. Olanzapine was suggested here from a range of pro drug websites as being the "ideal" molecule to terminate "bad trips". Health professionals should be informed about the risks related to olanzapine misuse.

Generalized and specific emotion impairments as potential markers of severity in Obsessive-Compulsive Disorder: a preliminary study using Facial Action Coding System (FACS).

BACKGROUND: The role of emotional deficits in the poor outcomes of patients with Obsessive-Compulsive Disorder (OCD) has been emphasized. Generalized and specific emotional abnormalities have been reported, often related to OCD severity and functional disabilities. The objective of the present study was to assess the abilities of experiencing and displaying emotions in OCD patients in response to specific stimuli in relation with the severity of their clinical condition. SUBJECTS AND METHODS: Thirty-six individuals participated in the study: 10 OCD patients with severe symptoms, 11 with mild-moderate symptoms, and 15 healthy controls. All participants watched emotion-eliciting video clips while their facial activity was videotaped. The congruent/incongruent feeling of emotions and the facial expression in reaction to emotions were evaluated. RESULTS: The two subgroups of OCD patients presented similarly incongruent emotive feelings and facial expressions (significantly worse than healthy participants). Moreover, OCD patients with severe symptoms expressed the emotion of happiness and disgust significantly less appropriately than OCD patients with mild-moderate symptoms. CONCLUSIONS: The present data support the hypothesis that impaired emotional processing may: (i) represent a potential contributor to poor outcome in OCD; (ii) constitute a warning sign for clinicians to establish a more comprehensive protocol for more severe cases; (iii) influence therapeutic strategies used to treat this disorder.

"Spice," "kryptonite," "black mamba": an overview of brand names and marketing strategies of novel psychoactive substances on the web.

UNLABELLED: Abstract Introduction: Novel Psychoactive Substances (NPSs) are often sold online as "legal" and "safer" alternatives to International Controlled Drugs (ICDs) with captivating marketing strategies. Our aim was to review and summarize such strategies in terms of the appearance of the products, the brand names, and the latest trends in the illicit online marketplaces. METHODS: Scientific data were searched in PsychInfo and Pubmed databases; results were integrated with an extensive monitoring of Internet (websites, online shops, chat rooms, fora, social networks) and media sources in nine languages (English, French, Farsi, Portuguese, Arabic, Russian, Spanish, and Chinese simplified/traditional) available from secure databases of the Global Public Health Intelligence Network. RESULTS: Evolving strategies for the online diffusion and the retail of NPSs have been identified, including discounts and periodic offers on chosen products. Advertisements and new brand names have been designed to attract customers, especially young people. An increased number of retailers have been recorded as well as new Web platforms and privacy systems. DISCUSSION: NPSs represent an unprecedented challenge in the field of public health with social, cultural, legal, and political implications. Web monitoring activities are essential for mapping the diffusion of NPSs and for supporting innovative Web-based prevention programmes.

Problematic use of Internet in a sample of psychiatric outpatients: preliminary observations from the "real world".

OBJECTIVE: This study aims to explore the prevalence, characteristics, and psychopathology related to Problematic Use of Internet (PUI), including Internet Addiction (IA), within a sample of psychiatric outpatients. METHODS: 143 psychiatric stable outpatients (18-65, mean age: 49; F=84) were included in this study, regardless of their categorical diagnosis. Socio-demographic, clinical, psychopathological, and Internet use-related data (PIU-Scale, Internet Addiction Test, devices, use, activities) were collected across the sample. RESULTS: The prevalence of PUI ranged between 1% (IAT) and 25% (PIU-S), with a homogeneous distribution of PUI symptoms' severity among the four main psychopathological areas (depressive, bipolar, anxiety, and psychotic disorders). PUI was correlated with age and was higher in students as in the general population. Significant associations were found between PUI symptoms and both personality and eating disorders; PUI was also positively correlated with the presence of other addictions (e.g., alcohol and/or substances). A greater proportion of patients with PUI presented other forms of behavioural addiction compared to non-symptomatic patients. Social media and online shopping, as well as video-streaming, resulted to be the main forms of PUI among patients with problematic use of the Internet. DISCUSSION: More studies are required among students diagnosed with eating and personality disorders. The association between PUI and other addictive disorders would support the hypothesis of their common shared pathophysiology. CONCLUSION: Healthcare providers and educators should be made aware of such risks. More studies are needed to confirm such preliminary findings.

Deep transcranial magnetic stimulation for treatment-resistant bipolar depression: a case report of acute and maintenance efficacy.

Deep Transcranial Magnetic Stimulation (dTMS) is currently being evaluated as a possible treatment for several neuropsychiatric disorders and has been demonstrated as a safe and effective procedure. This case presents a patient with bipolar depression that has been treated with 20 daily consecutive dTMS sessions and with one dTMS session every 2 weeks for the following 3 months. Depressive symptoms improved rapidly and response was maintained during the next 6 months; cognitive performances also improved. This report suggests that add-on dTMS may help overcoming drug-resistance in bipolar depression and protect from subsequent bipolar episodes of any polarity.

The case of Geneviève Lhermitte's euthanasia between psychiatric evaluation, legal aspects and ethical reflection.

A recent euthanasia case in Belgium has garnered attention due to its particularly dramatic aspects, sparking clinical and ethical questions about end-of-life choices in cases of mental suffering. A 56-year-old woman, convicted of the murder of her five minor children and sentenced to life imprisonment, has been granted euthanasia for "irreversible psychological suffering". The clinical and psychodynamic aspects of the case, primarily deduced from press reports, are highly complex and give rise to numerous clinical, medico-legal, and bioethical questions. These include inquiries into the true nature of psychopathology, its actual irreversibility, its impact on the ability to express a euthanasia request with adequate awareness, the preserved capacity for self-determination, and broader issues related to end-of-life requests from patients with mental disorders. These aspects are considered in the context of the legislation in various European countries. The unique details of this case underscore the critical challenges associated with these complex issues.

The Interaction Between Optimism and Pessimism Predicted the Perceived Risk of Infection During the Covid-19 Pandemic: An Exploratory Cross-Sectional Study.

In this study, we examined the relationship between optimism and pessimism associated with the Covid-19 pandemic, mental health, and perceived risk of infection. In particular, we tested the hypothesis that, when optimism and pessimism were high during the pandemic period, a worse mental health and a higher perception of risk would be reported. To this end, a convenience sample of 374 Italian adults was enrolled. Measures included perceived stress, optimism, and pessimism associated with the development of the pandemic situation, as well as the perceived risk of Covid-19 infection. The results showed that optimism and pessimism were associated with perceived stress and Covid-19 risk perception while controlling for demographic variables. Optimism and stress were negatively related, while pessimism was positively related to both stress and risk perception. Furthermore, the interaction between optimism and optimism was significant, with a higher perception of risk in the presence of both high optimism and pessimism, and a lower perception of risk with high optimism and low pessimism. These results support the hypothesis that optimism and pessimism interacted in predicting Covid-19 risk perception and show that they should be measured as partially correlated but independent constructs in future investigations.

A preliminary study on similarities and dissimilarities of Neurological Soft Signs in schizophrenic and obsessive-compulsive disorders suggests a common maldevelopmental model.

AIM: Neurological Soft Signs (NSS) represent minor neurological signs related to non-specific cerebral alterations. They have been documented in many psychiatric disorders including schizophrenia (SCZ) and obsessive-compulsive disorder (OCD). Aim of this study was to determine and compare the incidence and severity of NSS in patients with SCZ, in patients with OCD, and healthy control subjects (HCs). METHODS: Using the Neurological Evaluation Scale (NES), this study investigated NSS in 15 SCZ patients, 14 OCD patients, and 15 HCs. PANSS and Y-BOCS were used to evaluate clinical picture in both groups. RESULTS: Patients with SCZ showed significantly higher scores compared to HCs in the NES total and each of the three NES subscales (Integrative Sensory Function, Motor Coordination, and Sequencing of Complex Motor Acts). Patients with OCD also showed significantly higher scores compared to HCs in the NES total, Motor Coordination and Sequencing of Complex Motor Acts, but not in Integrative Sensory Function. No significant differences emerged in the NES total and the various subscales scores between the two patients' groups. CONCLUSIONS: Our results seem to confirm the presence of NSS in both SCZ and OCD. The different types of NSS presented by the two patients' groups versus HCs further supports the findings of widespread cerebral alterations in SCZ, on the other hand, with a preferential involvement of prefrontal and frontal cortex in OCD.

Psychiatric advance directives (Ulysses Contract): the need for a specific law and a criteria proposal for its introduction.

AIM: Advance healthcare directives in the psychiatric field raise more concerns and controversies compared to their use in other medical branches. We discuss the role of advance directives in this field and suggest a criteria proposal for the settlement of a comprehensive regulation on the matter. METHODS: We analyse the existing law and discuss the ethical points in the Italian context and, in comparison, with the United Kingdom context. RESULTS: Numerous studies have highlighted that psychiatric patients experience advance directives as an instrument to participate in therapeutic decision-making. Regarding the usefulness of advance directives, Italy and the United Kingdom did not approve deontological rules or laws. The United Nations Commission states that, based on the principles of the Convention on the Rights of Persons with Disabilities, it is necessary to respect the spatient's will, even if it is biased by psychic disorders. CONCLUSIONS: The Convention does not consider advance directives; instead, they just suggest using some support to have the patient regain their competence. In case this is unsuccessful, it is necessary to appoint a substitute decision-maker to express, even in the light of the advance directives, the will that the patient would have expressed if he had been competent.

Sleep and biorythm disturbances in schizophrenia, mood and anxiety disorders: a review.

Sleep problems and circadian rhythms disturbances are common in many psychiatric disorders, with the most often-reported sleep problem in most cases being insomnia. In this paper, the main findings about sleep disturbances(features and therapy) and other biorhythm disturbances (biological timekeepers, CLOCK genes, GSK3, melatonin, hypothalamo-pituitary-adrenal axis, body temperature) are reviewed in relation to schizophrenia, mood and anxiety disorders.