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Background: Ayahuasca is a serotoninergic hallucinogen that plays a central role in the Amazonian traditional medicine. Its psychoactive effects are associated with the presence of N,N-dimethyltryptamine (DMT), and monoamine oxidase inhibitors (MAO-A). Advances in neuroimaging investigations have provided insight into ayahuasca’s neurobiological mechanisms of action. Methods: Selecting only studies with neuroimaging results related to human ayahuasca consumption, we included six articles from a previous systematic review of serotoninergic hallucinogen neuroimaging studies up to 2016. Furthermore, we updated the data with a new systematic search from 2016 to 2022. We searched the PubMed, SciELO, and LILACS databases using the search terms “(ayahuasca OR DMT) AND (MRI OR fMRI OR PET OR SPECT OR imaging OR neuroimaging)”. Results: Our updated search provided five new articles for a total of 11 included in this review. The results on the Default Mode Network (DMN) are evident and may indicate a path to short term neuromodulation. Acutely, local neural networks appeared to become expanded, while overall brain connectivity declined. On chronic consumers, anatomical changes were reported, most notably related to cingulate cortex. Conclusion: Ayahuasca seems to change acute brain connectivity similarly to other psychedelics. The results are preliminary and further studies are warranted.

Background: Despite the benefits that synthetic pesticides have provided in terms of pest and disease control, they cause serious long-term consequences for both the environment and living organisms. Interest in ecofriendly products has subsequently increased in recent years. Methods: This article briefly analyzes the available ethnobotanical evidence regarding the use of Cannabis sativa as a pesticide and offers a systematic review of experimental studies. Results: Our findings indicate that both ethnobotanical and experimental procedures support the use of C. sativa as a pesticide, as remarkable toxicity has been observed against pest organisms. The results included in the systematic review of experimental studies (n = 30) show a high degree of heterogeneity, but certain conclusions can be extracted to guide further research. For instance, promising pesticide properties were reported for most of the groups of species tested, especially Arachnida and Insecta; the efficacy of C. sativa as a pesticide can be derived from a wide variety of compounds that it contains and possible synergistic effects; it is crucial to standardize the phytochemical profile of C. sativa plants used as well as to obtain easily reproducible results; appropriate extraction methods should be explored; and upper inflorescences of the plant may be preferred for the production of the essential oil, but further studies should explore better other parts of the plant. Conclusion: In the coming years, as new findings are produced, the promising potential of C. sativa as a pesticide will be elucidated, and reviews such as the present one constitute useful basic tools to make these processes easier

The Global Mental Health (GMH) movement aims to provide urgently needed treatment to those with mental illness, especially in low- and middle-income countries. Due to the complexity of providing mental health services to people from various cultures, there is much debate among GMH advocates regarding the best way to proceed. While biomedical interventions offer some degree of help, complementary approaches should focus on the social/community aspects. Many cultures conduct traditional rituals involving the communal use of psychoactive plants. We propose that these practices should be respected, protected, and promoted as valuable tools with regard to mental health care at the community level. The traditional use of psychoactive plants promotes community engagement and participation, and they are relatively affordable. Furthermore, the worldviews and meaning-making systems of local population are respected. The medical systems surrounding the use of psychoactive plants can be explained in biomedical terms, and many recently published clinical trials have demonstrated their therapeutic potential. Psychoactive plants and associated rituals offer potential benefits as complementary aspects of mental health services. They should be considered as such by international practitioners and advocates of the GMH movement.

Ibogaine is one of the alkaloids naturally found in plants such as Tabernanthe iboga, which has been traditionally used by members of the Bwiti culture. Since the discovery of its anti-addictive properties by Howard S. Lotsof in 1962, ibogaine has been used experimentally to treat substance use disorders (SUD), especially those involving opioids. We aim to provide a detailed understanding of the underlying psychological aspects of underground ibogaine use for the treatment of SUD.Semi-structured interviews were carried out with 13 participants with SUD, which motivated their self-treatment with ibogaine. The data were analysed using the grounded theory approach and considered the context of the treatment, and the nature of the occurring hallucinogenic and cognitive phenomena during the treatment experience.We identified several psychological effects that the study respondents experienced, which seem to play a substantial role in the therapeutic process concerning SUD. The evoking of interpersonal and transpersonal experiences, autobiographical memories, and preparation, integration and motivation for a lifestyle change are important components that participants reported during and after ibogaine intake.Ibogaine is increasingly being used for the treatment of SUD, due in part to the limited treatment options currently available. Its beneficial effects seem to be related not only to its complex pharmacology but also to the subjective experience that ibogaine induces. The main aspects of this experience are related to autobiographical memories and valuable personal insights, which together appear to help individuals cope with their SUD.

Context Ibogaine is the main alkaloid of the African shrub Tabernanthe iboga. It produces hallucinogenic and psychostimulant effects, but it is currently known for the anti-addictive properties. Despite the potential therapeutic effects, several cases of fatalities and serious adverse events related to ibogaine/noribogaine use can be found in the literature. Most studies consist in case reports or were conducted under non-controlled settings, so causation cannot be clearly established. Objectives To update (2015-2020) the literature on the adverse events and fatalities associated with ibogaine/noribogaine administration. Methods Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results Eighteen studies were included in the final selection. Highly heterogeneous results were found in terms of kind of product used or the known dosages. The adverse events were classified in acute effects ( 24 h), mainly persistent cardiac alterations, psychiatric, and neurological signs. Conclusions There is a high need of phase I clinical trials that can describe the safety of different dosages of ibogaine with standardized products. Further research should perform clinical profiling of vulnerable populations, and design effective screening methods and clinical procedures.

BACKGROUND In recent decades, ritualistic use of ayahuasca has spread throughout the world. Retrospective studies have suggested a good psychological safety profile, but prospective studies involving ceremony ayahuasca-naive participants are lacking. METHODS We conducted the study using a subsample from a previous study, for which first-time ceremony ayahuasca participants were recruited. The subsample consisted of 7 subjects who experienced acute and challenging psychological reactions. The semistructured Mini-International Neuropsychiatric Interview and psychometric questionnaires were administered before participants attended the ayahuasca ceremony and at 1 and 6 months after exposure. Subjective experiences were also recorded. RESULTS Seven subjects from a sample of 40 reported having experienced intense challenging psychological effects during the ayahuasca ceremony. Four of those 7 subjects met the diagnostic criteria for 1 or more psychiatric disorder before the ayahuasca ceremony. One month after the ceremony, 2 of those subjects no longer showed psychiatric symptoms, whereas the symptoms of the other 2 were reduced considerably. Those results persisted at the 6-month follow-up. Inappropriate setting/context (poor guiding skills and screening) contributed to some of the challenging reactions. Most of the participants (6 of 7) did not take ayahuasca again during the study period. CONCLUSIONS Based on the cases reported here, we suggest that although it is possible that participating in ayahuasca ceremonies may entail acute psychological negative reactions, those challenging experiences can also have positive long-term effects. Prospective research on the safety profile of ayahuasca and how it is affected by the context of different practices and safety strategies is therefore necessary.

Can the emerging field of psychedelic research benefit from natural product research? We believe it can. In this manuscript we delineate certain topics of research with hallucinogens that directly connect with research on natural products in general.

In the drug development, the formation of highly selective ligands has been unsuccessful in the treatment of central nervous system disorders. Multi-target ligands, from the polypharmacology paradigm, are being proposed as treatments for these complex disorders, since they offer enhanced efficacy and a strong safety profile. Natural products are the best examples of multi-target compounds, so they are of high interest within this paradigm. Additionally, recent research on psychoactive drugs of natural origin, such as ayahuasca and cannabis, has demonstrated the promising therapeutic potential for the treatment of some psychiatric and neurological disorders. In this text, we describe how research on psychoactive drugs can be effectively combined with the polypharmacology paradigm, providing ayahuasca and cannabis research as examples. The advantages and disadvantages are also discussed.

Ayahuasca is a plant decoction in traditional Amazonian medicine. Its ritual use has been internationalized, leading to policy challenges that countries should address. This study evaluates the impact of regular ayahuasca ceremony participation on health by assessing the health status of 377 participants in ayahuasca ceremonies in the Netherlands using validated health indicators. A questionnaire was developed and administered to study participants. The questionnaire included several health indicators with public health relevance (e.g., BMI, diet, physical activity) and psychometrically validated questionnaires (ELS and COPE-easy). The data retrieved through health indicators was compared to normative Dutch data. Participants (50.1% women) were mostly Dutch (84.6%) with a mean age of 48.8 years (SD = 11.6). Compared to normative Dutch data, regular participants in ayahuasca ceremonies showed better general well-being, fewer chronic or lifestyle-related diseases, more physical activity, and a more balanced diet. Participants also used less alcohol during the COVID-19 pandemic, and although they used more illegal drugs than the general population, they did not report associated harms. Our findings suggest that regular participation in ayahuasca ceremonies is not linked to relevant health harms. This data could help drug policymakers to develop and implement evidence-based public policies.

To assess endocannabinoid (anandamide, AEA; 2-arachidonoylglycerol, 2-AG) plasma levels in healthy volunteers and in volunteers with social anxiety disorder (SAD) after a single oral dose of ayahuasca or placebo.Post hoc analysis of endocannabinoid plasma levels (baseline, 90 and 240 min after drug intake) from two parallel-group, randomized, placebo-controlled trials. In Study 1, 20 healthy volunteers ingested ayahuasca (average 1.58 mg/ml dimethyltryptamine (DMT)) or placebo, and in Study 2, 17 volunteers with SAD received ayahuasca (average 0.680 mg/ml DMT) or placebo.A significant difference was observed in AEA concentrations in Study 2 after ayahuasca intake (ΧAlthough our findings suggest that ayahuasca could modulate AEA levels in SAD patients, the high interindividual variability in both trials and the small samples preclude definitive conclusions. More research with larger samples is needed to better understand the effects of ayahuasca and other hallucinogens in the endocannabinoid system.

The COVID-19 pandemic has made evident the need to develop effective strategies to cushion the psychological consequences of social catastrophes. Preliminary evidence suggests that the use of hallucinogens is a protective factor that mitigates against such stressors. However, the underlying mechanisms must be further explored. This study specifically focused on the potential role of coping strategies in this regard, analyzing them through an online survey completed by a total of 2971 subjects who were followed up with from the beginning of the COVID-19 pandemic until six months after baseline. The survey was published in three different cultures (English, Spanish, and Portuguese), allowing for the collection of data from three different cultural contexts. The results show that coping strategies were generally more related to psychological well-being and psychopathology than to hallucinogenic drug use. However, regarding the latter, users of hallucinogens had higher scores on problem-focused engagement and disengagement and lower scores on wishful thinking than non-users. Longitudinally, while most baseline coping scores were associated with psychological distress and the severity of psychological symptoms, some coping strategies were related to the use of hallucinogens. These results show an adaptive pattern of coping strategies among hallucinogen users. Further research should take into account that coping strategies are only marginally associated with hallucinogenic drug use. Other underlying mechanisms explaining the better adjustment of users of hallucinogens to pandemics should be explored.

The number of patients using cannabis for therapeutic purposes is growing worldwide. While research regarding the treatment of certain diseases/disorders with cannabis and cannabinoids is also expanding, only a few longitudinal studies have assessed the mid-term impacts of medical cannabis use on psychological variables and quality of life (QoL). The aim of the study was to assess the psychological safety and QoL of patients with chronic diseases who self-medicate with cannabis over time. We recruited patients with various chronic diseases who use cannabis and collected data regarding patterns of cannabis use as well as mental health, personality and QoL. Participants were followed-up at baseline, 4, 8 and 12 months. Hair analysis was conducted to confirm the presence of cannabinoids. Personality assessment showed a consistent decrease in self-transcendence and self-directedness scores. Neither cognitive nor psychopathological deterioration was found. There were also no variations in QoL. Mid-term use of medical cannabis seems to show adequate tolerability regarding cognitive and psychopathological abilities, and it may help patients with chronic diseases to maintain an acceptable QoL.

In recent years, the use of natural psychoactive drugs (NPDs) has grown rapidly. They are classified as new psychoactive substances (NPSs), despite the reality that they have been used for centurie...

Background and aimsPain is the most prevalent symptom of a health condition, and it is inappropriately treated in many cases. Here, we present a case report in which we observe a long-lasting analg...

The volume of research on the therapeutic use of psychedelic drugs has been increasing during the last decades. Partly because of the need of innovative treatments in psychiatry, several studies have assessed the safety and efficacy of drugs like psilocybin or ayahuasca for a wide range of mental disorders, including major depression. The first section of this chapter will offer an introduction to psychedelic research, including a brief historical overview and discussions about appropriate terminology. In the second section, the recently published clinical trials in which psychedelic drugs were administered to patients will be analysed in detail. Then, in the third section, the main neurobiological mechanisms of these drugs will be described, noting that while some of these mechanisms could be potentially associated with their therapeutic properties, they are commonly used as adjuvants in psychotherapeutic processes. The last section suggests future challenges for this groundbreaking field of research and therapy.

Background The mechanisms through which kappa opioid receptor (KOR) agonists induce psychotomimetic effects are largely unknown, although the modulation of this receptor has attracted attention for its clinical use. In this work, we characterize the neuropharmacological effects of salvinorin-A, a highly selective KOR agonist. Methods Changes in multimodal electroencephalography, single-photon emission computed tomography, and subjective effects following the acute administration of salvinorin-A are reported. The study included 2 sub-studies that employed a double-blind, crossover, randomized, placebo-controlled design. Results The electroencephalography measures showed a marked increase in delta and gamma waves and a decrease in alpha waves while subjects were under the effect of salvinorin-A. Regarding single-photon emission computed tomography measures, significant decreases in regional cerebral blood flow were detected in multiple regions of the frontal, temporal, parietal, and occipital cortices. Significant regional cerebral blood flow increases were observed in some regions of the medial temporal lobe, including the amygdala, the hippocampal gyrus, and the cerebellum. The pattern of subjective effects induced by salvinorin-A was similar to those observed in relation to other psychotomimetic drugs but with an evidently dissociative nature. No dysphoric effects were reported. Conclusion The salvinorin-A–mediated KOR agonism induced dramatic psychotomimetic effects along with a generalized decrease in cerebral blood flow and electric activity within the cerebral cortex.

Ibogaine is the main alkaloid of the African shrub Tabernanthe iboga. It produces hallucinogenic and psychostimulant effects, but it is currently known for the anti-addictive properties. Despite the potential therapeutic effects, several cases of fatalities and serious adverse events related to ibogaine/noribogaine use can be found in the literature. Most studies consist in case reports or were conducted under non-controlled settings, so causation cannot be clearly established.To update (2015-2020) the literature on the adverse events and fatalities associated with ibogaine/noribogaine administration.Systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).Eighteen studies were included in the final selection. Highly heterogeneous results were found in terms of kind of product used or the known dosages. The adverse events were classified in acute effects ( 24 h), mainly cardiac (the most common was QTc prolongation), gastrointestinal, neurological, and clinical alterations, and long-lasting effects ( 24 h), mainly persistent cardiac alterations, psychiatric, and neurological signs.There is a high need of phase I clinical trials that can describe the safety of different dosages of ibogaine with standardized products. Further research should perform clinical profiling of vulnerable populations, and design effective screening methods and clinical procedures.

The volume of research on the therapeutic use of psychedelic drugs has been increasing during the last decades. Partly because of the need of innovative treatments in psychiatry, several studies have assessed the safety and efficacy of drugs like psilocybin or ayahuasca for a wide range of mental disorders, including major depression. The first section of this chapter will offer an introduction to psychedelic research, including a brief historical overview and discussions about appropriate terminology. In the second section, the recently published clinical trials in which psychedelic drugs were administered to patients will be analysed in detail. Then, in the third section, the main neurobiological mechanisms of these drugs will be described, noting that while some of these mechanisms could be potentially associated with their therapeutic properties, they are commonly used as adjuvants in psychotherapeutic processes. The last section suggests future challenges for this groundbreaking field of research and therapy.

ObjectiveThis study aimed to clarify the influence of extra-pharmacological factors in the etiology of bad trips, a common adverse reaction related to the consumption of psychedelic drugs.MethodsA ...

Ayahuasca is a hallucinogenic decoction used as a traditional medicine in several Amazonian regions. The ritualistic use of ayahuasca has spread throughout many countries, making it necessary to study its risks and benefits. Two sub-studies were designed for this investigation. In sub-study 1, a psychiatric interview and a battery of questionnaires were administered to subjects (n = 40) before their first ayahuasca use. Two follow-ups were conducted at 1 and 6 months. In sub-study 2, the same interview and battery of questionnaires were administered to long-term ayahuasca users (n = 23) and their scores were compared with those of the ayahuasca-naïve group. In the first assessment, nearly half (45%) of the naïve users were found to meet the diagnostic criteria for a psychiatric disorder. After the ayahuasca use, more than 80% of those subjects showed clinical improvements that persisted at 6 months. The questionnaires showed significant reductions in depression and psychopathology. Regarding sub-study 2, long-term users showed lower depression scores, and higher scores for self-transcendence and quality of life, as compared to their peers in sub-study 1. Further controlled and observational naturalistic studies assessing the eventual risks and potential benefits of ayahuasca are warranted.

The current crisis in psychopharmacology has a long history and needs to be addressed with innovative and effective strategies. Here we discuss some of the roots of this crisis and suggest that the therapeutic use of psychedelic drugs represents a promising and integrative treatment with enduring effects for mental health problems.

Assessing the health status of ayahuasca users has been challenging due to the limitations involved in randomized clinical trials and psychometric approaches. The main objective of this study is the implementation of an approach based on public health indicators. We developed a self-administered questionnaire that was administered to long-term ayahuasca users around Spain. The questionnaire was administrated face-to-face to participants (