How does ayahuasca work from a psychiatric perspective? Pros and cons of the entheogenic therapy.

OBJECTIVE: Ayahuasca is a hallucinogenic plant preparation, traditionally consumed in sacred ceremonies by indigenous North-Westerner Amazonian countries like Colombia, Peru, Brazil, and Ecuador. It is fundamental to carefully balance benefits/risks related to the ayahuasca intake, both during ceremonies and experimental settings. The aim is at evaluating and comparing the potential therapeutic benefits versus health risks related to ayahuasca intake (both acutely and chronically), focusing on its application in psychedelic psychiatry. DESIGN: A comprehensive mini overview focusing on psychiatric outcomes following ayahuasca intake both in healthy volunteers and in clinical samples. RESULTS: Preclinical, observational, and experimental studies in healthy volunteers as well as in clinical samples suggest that ayahuasca may be beneficial as an antidepressant, emotional regulator, anxiolytic, and antiaddictive drug, by exerting fast-acting and enduring clinical effects. Ayahuasca appears to be safe and well tolerated, nausea and emesis being the most reported and transient side effects. Some findings suggest not to use ayahuasca in bipolar or psychotic patients because of an increased risk of manic switch and/or psychotic onset. CONCLUSIONS: Further research should be carried out in randomized, double-blind, placebo-controlled trials, by implementing neuroimaging studies, in order to better evaluate therapeutic potential of ayahuasca in mental disorders.

An insight into the deep web; why it matters for addiction psychiatry?

OBJECTIVE: Nowadays, the web is rapidly spreading, playing a significant role in the marketing or sale or distribution of "quasi" legal drugs, hence facilitating continuous changes in drug scenarios. The easily renewable and anarchic online drug-market is gradually transforming indeed the drug market itself, from a "street" to a "virtual" one, with customers being able to shop with a relative anonymity in a 24-hr marketplace. The hidden "deep web" is facilitating this phenomenon. The paper aims at providing an overview to mental health's and addiction's professionals on current knowledge about prodrug activities on the deep web. METHODS: A nonparticipant netnographic qualitative study of a list of prodrug websites (blogs, fora, and drug marketplaces) located into the surface web was here carried out. A systematic Internet search was conducted on Duckduckgo® and Google® whilst including the following keywords: "drugs" or "legal highs" or "Novel Psychoactive Substances" or "NPS" combined with the word deep web. RESULTS: Four themes (e.g., "How to access into the deepweb"; "Darknet and the online drug trading sites"; "Grams-search engine for the deep web"; and "Cryptocurrencies") and 14 categories were here generated and properly discussed. CONCLUSIONS: This paper represents a complete or systematical guideline about the deep web, specifically focusing on practical information on online drug marketplaces, useful for addiction's professionals.

From concept(ion) to life after death/the grave: The 'natural' history and life cycle(s) of novel psychoactive substances (NPS).

A range of information needs should be met in order to better understand and predict the longevity/existence of novel psychoactive substances (NPS). This conceptual paper argues that one way of assessing how long a molecule may be around is to document how the life cycles or natural histories of 'traditional' drugs and NPS evolve. The earliest indication of the possible appearance of a new substance might be evidenced on the DeepWeb. However, this means they are less visible, in line with the clandestine nature of drug use and supply. Therefore, monitoring discussion groups/fora needs the development of new methods compared to those used in the Surface Net. Issues needing consideration in establishing NPS life cycles are outlined here, together with the probable outcomes that could result. The approach advocated means that it should be easier to identify which NPS are likely to come up or are emerging in real time, and, therefore, pre-empt/prevent their supply.

Is there a potential of misuse for Magnolia officinalis compounds/metabolites?

OBJECTIVE: Magnolia bark contains magnolol, metabolized to tetrahydromagnolol and honokiol, with both GABA-ergic/cannabimimetic activities, hence of possible attraction to vulnerable individuals/recreational misusers. METHODS: A literature review, assessment of related anecdotal online Magnolia misuse's reports and an overview of Magnolia products' online acquisition possibilities has been here described. RESULTS: No peer-reviewed papers about Magnolia abuse/misuse/dependence/addiction were identified. Conversely, from a range of websites emerged potentially 3 groups of Magnolia misusers: (a) subjects with a psychiatric history already treated with benzodiazepines, being attracted to Magnolia bark as a "natural sedative"; (b) polydrug misusers, ingesting Magnolia with a range of other herbs/plants, attracted by the GABA-ergic/cannabimimetic activities; (c) subjects naive to the misusing drugs' scenario, perceiving Magnolia as a natural dietary supplement/weight-control compound. CONCLUSIONS: To the best of our knowledge, this is the first paper commenting on the possible Magnolia derivatives' potential of misuse. Magnolia's recent increase in popularity, mainly as a sedative, may be arguably due to its peculiar pharmacological properties/acceptable affordability levels/virtually worldwide favorable legal status and customers' attraction to a product being perceived as "natural" and hence somehow "safe." Future/potent/synthetic magnolol and honokiol structural analogues could however contribute to increasing the number of synthetic GABA-ergic/cannabimimetic misusing compounds.

Substance-related psychopathology and aggressiveness in a nightlife holiday resort: Results from a pilot study in a psychiatric inpatient unit in Ibiza.

OBJECTIVES: We aimed to describe a sample of subjects admitted to a psychiatric unit after the intake of psychoactive substances for recreational purposes. METHODS: Between June and September 2015, 49 subjects were included. Sociodemographic characteristics and psychopathological aspects were investigated, and urine samples for further analysis were collected. Three subgroups (cannabinoids, stimulants, and depressors users) were identified, according to the structured interview regarding substance use and urinalysis. RESULTS: Level of aggressiveness was found to be significantly higher (p < .05) in the cannabinoids subgroup. Self-reported symptom severity was comparable among groups, but trends could be identified: SCL-90 results showed a prevalence of anxiety symptoms among depressors users, hostility or aggression in the tetrahydrocannabinol subgroup, and psychoticism in the stimulants subgroup. CONCLUSIONS: The use of psychoactive substances was be characterised by poly-use of both traditional and novel substances. The presence of aggressiveness emerged as a main feature associated with the use of cannabis and other cannabinoids. Binge drinking and sleep deprivation also represented a relevant component in almost all the evaluated subjects.

Profiling online recreational/prescription drugs' customers and overview of drug vending virtual marketplaces.

OBJECTIVES: Internet and social networking sites play a significant role in the marketing and distribution of recreational/prescription drugs without restrictions. We aimed here at reviewing data relating to the profile of the online drug customer and at describing drug vending websites. METHODS: The PubMed, Google Scholar, and Scopus databases were searched here in order to elicit data on the socio-demographic characteristics of the recreational marketplaces/online pharmacies' customers and the determinants relating to online drug purchasing activities. RESULTS: Typical online recreational drugs' customers seem to be Caucasian, men, in their 20s, highly educated, and using the web to impact as minimally as possible on their existing work/professional status. Conversely, people without any health insurance seemed to look at the web as a source of more affordable prescription medicines. Drug vending websites are typically presented here with a "no prescription required" approach, together with aggressive marketing strategies. CONCLUSIONS: The online availability of recreational/prescriptions drugs remains a public health concern. A more precise understanding of online vending sites' customers may well facilitate the drafting and implementation of proper prevention campaigns aimed at counteracting the increasing levels of online drug acquisition and hence intake activities.

Venlafaxine as the 'baby ecstasy'? Literature overview and analysis of web-based misusers' experiences.

INTRODUCTION: Venlafaxine is one of the most frequently prescribed antidepressants worldwide, despite its toxicity risk in overdose. Furthermore, the molecule has been recently identified at the EU-wide level as one of the novel psychoactive substances. This paper aims at investigating the potential of misuse, taking into account both the existing literature and the analysis of the misusers' experiences as described in venlafaxine misuse web reports. METHODS: A literature search was performed using PubMed, Embase, and Medline. Posts/threads relating to venlafaxine misuse issues were identified through Google® and Yahoo® English-language searches. Resulting websites' data were then qualitatively assessed, and information was collected on a range of issues, including dosage, drug intake modalities, untoward drug effects, and association with other recreational drugs. RESULTS: A few literature case reports focusing on venlafaxine as a misusing drug were here identified. The molecule was here typically ingested or snorted at dosages up to 10-15 times higher than those clinically advised, obtaining MDMA/amphetamine-like stimulant and psychedelic effects. Polydrug misuse was commonly reported. Venlafaxine appeared to be widely available online for sale. CONCLUSIONS: Physicians should carefully evaluate patients for history of drug dependence and observe them for signs of venlafaxine misuse.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial.

BACKGROUND: Data on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH. METHODS/DESIGN: We will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events. DISCUSSION: The results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

"Spiceophrenia": a systematic overview of "spice"-related psychopathological issues and a case report.

OBJECTIVES: The use of synthetic cannabimimetics (SC; "spice" drugs) is increasing, especially among teenagers and young adults. In parallel with this, the number of studies describing intoxication episodes associated with psychotic symptoms in SC users is growing. We present both a systematic review of the related literature and a case report, which seems to highlight the existence of a possible association between SC use and psychosis. METHODS: Some 223 relevant studies were here identified and reviewed. Out of these, 120 full text articles were assessed for eligibility, and 41 were finally included in the systematic review. RESULTS: According to the available data from the studies here identified, SC's average age of users was 22.97 years, and the male/female ratio was 3.16:1. SC compounds most often reported in studies using biological specimen analysis were JWH-018, JWH-073, JWH-122, CP-47,497, and JWH-250. Mounting evidence seemed to suggest that psychotic symptoms such as hallucinations and delusions may occur in acute/chronic SC users. CONCLUSIONS: Although a clear causal link may not be here identified, the available evidence suggests that SC can trigger the onset of acute psychosis in vulnerable individuals and/or the exacerbation of psychotic episodes in those with a previous psychiatric history.

'New/Designer Benzodiazepines': An Analysis of the Literature and Psychonauts' Trip Reports.

BACKGROUND: NPS belonging to the benzodiazepine (BZD) class, e.g., 'legal/designer BZDs'/'research chemicals', have recently emerged in the drug (mainly online/virtual) market. OBJECTIVE: While certain NPS belonging to the BZD class possess pharmacological profiles similar to controlled pharmaceutical BZDs, clinical and pharmacological profiles of current emerging BZDs are still not well-described. Therefore, there is a need to increase clinicians'/public health knowledge/awareness, to incentive harm reduction strategies. METHOD: A comprehensive overview was carried out by using the EMCDDA/EDND database regularly monitored by our research team, by specifically looking at the 'new BZDs' so far notified. Furthermore, given the limitation of peer-reviewed data published so far, a nonparticipant multilingual qualitative netnographic study was conducted to obtain further clinical/pharmacological/ toxicological data, including psychonauts' online trip reports. RESULTS: First designer BZDs appeared as NPS around 2007. So far, 29 designer BZDs have been notified to the EMCDDA, being some of them extremely powerful, also at lower dosages. They are sold as tablets/powder/pellets/capsules/blotters/liquids, at very affordable prices, and variably administered. Some are also sold on the illicit drugmarket as counterfeit forms of traditional BZDs or as either adulterants or diluents in heroin or other synthetic opioids/cannabinoids. Nowadays, there is no guarantee of the quality of designer BZDs composition/purification and, hence, most NPS consumers may be inadvertently exposed to unsafe and harmful compounds. CONCLUSION: Given the limited information on their pharmacology/toxicity, variations in dosage, onset of effects, combination of substances, potency, and general patient or individual variability, the concomitant use of these substances with other drugs entails several and unpredictable risks.

Closing the gap between training needs and training provision in addiction medicine.

Substance use disorders pose a significant global social and economic burden. Although effective interventions exist, treatment coverage remains limited. The lack of an adequately trained workforce is one of the prominent reasons. Recent initiatives have been taken worldwide to improve training, but further efforts are required to build curricula that are internationally applicable. We believe that the training needs of professionals in the area have not yet been explored in sufficient detail. We propose that a peer-led survey to assess those needs, using a standardised structured tool, would help to overcome this deficiency. The findings from such a survey could be used to develop a core set of competencies which is sufficiently flexible in its implementation to address the specific needs of the wide range of professionals working in addiction medicine worldwide.

The use of new psychoactive substances (NPS) in young people and their role in mental health care: a systematic review.

Introduction: Over the past 10 years, a large number of New Psychoactive Substances (NPS) have entered the recreational drug scenario. NPS intake has been associated with health-related risks, and especially so for vulnerable populations such as the youngsters. Currently, most knowledge on the NPS health effects is learnt from both a range of users' reports, made available through the psychonauts' web fora, and from the few published, related toxicity, clinical observations.Areas covered: This paper aims at providing an overview of NPS effects on youngsters' mental health, whilst performing a systematic review of the current related knowledge.Expert opinion: NPS consumption poses serious health risks, due to both a range of unpredictable clinical pharmacological properties and the typical concomitant use of other psychoactive molecules; overall, this can lead to near misses and fatalities. In comparison with adults, the central nervous system of children/adolescents may be more vulnerable to the activity of these molecules, hence raising even further the levels of health-related concerns. More research is needed to provide evidence of both short- and long-term effects of NPS, related health risks, and their addiction potential.

The Bridge Between Classical and "Synthetic"/Chemical Psychoses: Towards a Clinical, Psychopathological, and Therapeutic Perspective.

The critical spread and dissemination of novel psychoactive substances (NPS), particularly among the most vulnerable youngsters, may pose a further concern about the psychotic trajectories related to the intake of new synthetic drugs. The psychopathological pattern of the "new psychoses" appears to be extremely different from the classical presentation. Therefore, clinicians need more data on these new synthetic psychoses and recommendations on how to manage them. The present mini-review aims at deepening both the clinical, psychopathological features of synthetic/chemical NPS-induced psychoses and their therapeutic strategies, according to the different NPS classes implicated, by underlining the main differences with the "classical" psychoses. A comprehensive review was conducted using the PubMed/Medline database by combining the search strategy of free-text terms and exploding a range of MESH headings relating to the topics of novel psychoactive substances and synthetic/chemical psychoses as follows: {(Novel Psychoactive Substances[Title/Abstract]) AND Psychosis[Title/Abstract])} and for each NPS categories as well, focusing on synthetic cannabinoids and cathinones, without time and/or language restrictions. Finally, an overview of the main clinical and psychopathological features between classical versus NPS-induced chemical/synthetic psychoses is provided for clinicians working with dual disorders and addiction psychiatry. Further insight is given here on therapeutic strategies and practical guidelines for managing patients affected with synthetic/chemical NPS-induced psychoses.

Characteristics of deaths associated with kratom use.

BACKGROUND: Kratom (Mitragyna speciosa Korth) use has increased in Western countries, with a rising number of associated deaths. There is growing debate about the involvement of kratom in these events. AIMS: This study details the characteristics of such fatalities and provides a 'state-of-the-art' review. METHODS: UK cases were identified from mortality registers by searching with the terms 'kratom', 'mitragynine', etc. Databases and online media were searched using these terms and 'death', 'fatal*', 'overdose', 'poisoning', etc. to identify additional cases; details were obtained from relevant officials. Case characteristics were extracted into an Excel spreadsheet, and analysed employing descriptive statistics and thematic analysis. RESULTS: Typical case characteristics (n = 156): male (80%), mean age 32.3 years, White (100%), drug abuse history (95%); reasons for use included self-medication, recreation, relaxation, bodybuilding, and avoiding positive drug tests. Mitragynine alone was identified/implicated in 23% of cases. Poly substance use was common (87%), typically controlled/recreational drugs, therapeutic drugs, and alcohol. Death cause(s) included toxic effects of kratom ± other substances; underlying health issues. CONCLUSIONS: These findings add substantially to the knowledge base on kratom-associated deaths; these need systematic, accurate recording. Kratom's safety profile remains only partially understood; toxic and fatal levels require quantification.

Psychedelic Fauna for Psychonaut Hunters: A Mini-Review.

Currently different classes of psychoactive substances are easily available for abuse, including several hundred novel psychoactive substances (NPS). Some of these drugs occur naturally in plants and animals or are chemically modified from plant or animal compounds and have been abused by humans over millennia. Recently, the occurrence of a new "drug culture" (e.g., psychonauts) who consume a great variety of NPS with hallucinogenic/psychedelic properties, facilitated the development of a new "psychedelic trend" toward the consumption of substances contained in some species of animals ("psychedelic fauna"). The present review aims at providing an overview of the most commonly abused "psychedelic animals," by combining a dual search strategy coming from online psychonauts' experiences and English literature searches on the PubMed/Medline Google Scholar databases. A multilingual qualitative assessment on a range of websites and online resources was performed in order to identify a list of animals who possess some psychoactive properties and could be abused by humans for recreational purposes. Several species are implicated (i.e., ants, amphibians, fish). Routes of administration depend on the animal, substance included, metabolism, toxicity and individual, social and cultural variability. Online purchase and access are easy through tourism-related search strategies ("frog trip," "help of charmer snake," "religious trip").

NPS: Medical Consequences Associated with Their Intake.

Over the last decade, the 'traditional' drug scene has been supplemented - but not replaced - by the emergence of a range of novel psychoactive substances (NPS), which are either newly created or existing drugs, including medications, now being used in novel ways. By the end of 2014, in excess of 500 NPS had been reported by a large number of countries in the world. Most recent data show, however, that synthetic cathinones, synthetic cannabinoids, and psychedelics/phenethylamines account for the largest number of NPS.The present chapter aims at providing an overview of the clinical and pharmacological issues relating to these most popular NPS categories. Given the vast range of medical and psychopathological issues associated with the molecules here described, it is crucial for health professionals to be aware of the effects and toxicity of NPS. A general overview of the acute management of NPS adverse events is provided as well, although further studies are required to identify a range of evidence-based, index molecule-focused, treatment strategies. The rapid pace of change in the NPS online market constitutes a major challenge to the provision of current and reliable scientific knowledge on these substances.

Synthetic Cannabinoids: Psychopharmacology, Clinical Aspects, Psychotic Onset.

BACKGROUND: Synthetic Cannabinoids (SC) are the widest and most diffused class of Novel Psychoactive Substances. The short- and long- term health risks associated with the consumption of SC are often unknown to both users and health professionals. This review aims to provide a synthesis of the most recent and relevant insights on the pharmacology, clinical and psychopathological aspects of SC. METHOD: A structured search of two bibliographic databases (PubMed and Scopus) was undertaken according to inclusion/exclusion criteria. The following terms "synthetic cannabinoid*", "synthetic cannabimimetic*", "synthetic cannabis", "synthetic marijuana" and "Spice AND cannabinoid*" were used as search strings. RESULTS: 162 relevant results, mainly published in the past two years were revealed. Most results emerged for the keyword "synthetic cannabinoid*", followed by the combination "Spice* AND "cannabinoid*". Most papers were epidemiological, forensic, toxicologic, or analytical. The results of studies were systematized according their contribution to the comprehension of pharmacological, clinical and psychopathological effects of SC. Fifteen SC-related fatality cases were reviewed according to their histories, pathology and toxicology findings. CONCLUSION: The findings of this review confirm the importance of prompt and reliable information available for health professionals More specific analytic techniques and designed preventive strategies are required to face unprecedented SC challenge.

Evolutionary Considerations on the Emerging Subculture of the E-psychonauts and the Novel Psychoactive Substances: A Comeback to the Shamanism?

BACKGROUND: Evolutionary research on drug abuse has hitherto been restricted to proximate studies, considering aetiology, mechanism, and ontogeny. However, in order to explain the recent emergency of a new behavioral pattern (e.g. 'the e-psychonaut style') of novel psychoactive substances' (NPS) intake, a complementary evolutionary model may be needed. OBJECTIVE: A range of evolutionary interpretations on the 'psychonaut style' and the recent emergency of NPS were here considered. METHOD: The PubMed database was searched in order to elicit evolutionary theory-based documents commenting on NPS/NPS users/e-psychonauts. RESULTS: The traditional 'shamanic style' use of entheogens/plant-derived compounds may present with a range of similarities with the 'e-psychonauts' use of mostly of hallucinogen/psychedelic NPS. These users consider themselves as 'new/technological' shamans. CONCLUSION: Indeed, a range of evolutionary mechanisms, such as: optimal foraging, costly signaling, and reproduction at the expense of health may all cooperate to explain the recent spread and diffusion of the NPS market, and this may represent a reason of concern.

Is there a Teratogenicity Risk Associated with Cannabis and Synthetic Cannabimimetics' ('Spice') Intake?

BACKGROUND: Substance use, including cannabis, has been documented amongst women both in the pre-conception period and during pregnancy, particularly during the 1st trimester, which is clearly the most critical period in the organogenesis. The recent emergence on the drug market of synthetic cannabimimetics/SC ('spice') may represent a new challenge for clinicians. OBJECTIVE: A literature overview on the teratogenicity profile of both cannabis and synthetic cannabimimetics was here carried out. METHOD: The PubMed database was searched in order to collect all relevant cases and data regarding the possible evidence of teratogenicity issues associated with cannabis and SC intake. RESULTS: The use of cannabis in pregnant women has been associated with a plethora of both obstetrical/ gestational complications and neurobehavioral/neurological effects on newborns. Conversely, only few and conflicting data are related to SC misuse issues. CONCLUSION: Although cannabis use may be considered a risk factor for the occurrence of pregnancyrelated morbidity issues, many studies relied on self-reports and showed inconsistent results when controlling for potential confounders, including tobacco use. Given the role of the endocannabinoid system in both pregnancy and delivery, SC potency at interacting with the endocannabinoid system may be a reason of concern. Clinicians should carefully assess each woman planning a pregnancy, or who is pregnant already, and who is at risk of persisting in her current cannabis and/or SC intake. A nonjudgmental approach, aiming at collecting both a history of drug/alcohol use and at providing information regarding the risks associated with cannabis/SC intake during pregnancy is here advised.

Cannabis; Epidemiological, Neurobiological and Psychopathological Issues: An Update.

BACKGROUND: Cannabis is the illicit drug with both the largest current levels of consumption and the highest reported lifetime prevalence levels in the world. Across different countries, the prevalence of cannabis use varies according to the individual income, with the highest use being reported in North America, Australia and Europe. Despite its 'soft drug' reputation, cannabis misuse may be associated with several acute and chronic adverse effects. OBJECTIVE: The present article aims at reviewing several papers on epidemiological, neurobiological and psychopathological aspects of the use of cannabis. The PubMed database was here examined in order to collect and discuss a range of identified papers. DISCUSSION: Cannabis intake usually starts during late adolescence/early adulthood (15-24 years) and drastically decreases in adulthood with the acquisition of working, familiar and social responsibilities. Clinical evidence supports the current socio-epidemiological alarm concerning the increased consumption among youngsters and the risks related to the onset of psychotic disorders. The mechanism of action of cannabis presents some analogies with other abused drugs, e.g. opiates. Furthermore, it has been well demonstrated that cannabis intake in adolescence may facilitate the transition to the use and/or abuse of other psychotropic drugs, hence properly being considered a 'gateway drug'. Some considerations on synthetic cannabimimetics are provided here as well. CONCLUSION: In conclusion, the highest prevalence of cannabis use and the social perception of a relatively low associated risk are in contrast with current knowledge based on biological and clinical evidence. Indeed, there are concerns relating to cannabis intake association with detrimental effects on both cognitive impairment and mental health.