Monoamine Oxidase Inhibition by Plant-Derived β-Carbolines; Implications for the Psychopharmacology of Tobacco and Ayahuasca

The monoamine oxidases (MAOs) are flavin-containing amine oxidoreductases responsible for metabolism of many biogenic amine molecules in the brain and peripheral tissues. Whereas serotonin is the preferred substrate of MAO-A, phenylethylamine is metabolized by MAO-B, and dopamine and tyramine are nearly ambivalent with respect to the two isozymes. β-Carboline alkaloids such as harmine, harman(e), and norharman(e) are MAO inhibitors present in many plant materials, including foodstuffs, medicinal plants, and intoxicants, notably in tobacco (Nicotiana spp.) and in Banisteriopsis caapi, a vine used in the Amazonian ayahuasca brew. The β-carbolines present in B. caapi may have effects on neurogenesis and intrinsic antidepressant properties, in addition to potentiating the bioavailability of the hallucinogen N,N-dimethyltryptamine (DMT), which is often present in admixture plants of ayahuasca such as Psychotria viridis. Tobacco also contains physiologically relevant concentrations of β-carbolines, which potentially contribute to its psychopharmacology. However, in both cases, the threshold of MAO inhibition sufficient to interact with biogenic amine neurotransmission remains to be established. An important class of antidepressant medications provoke a complete and irreversible inhibition of MAO-A/B, and such complete inhibition is almost unattainable with reversible and competitive inhibitors such as β-carbolines. However, the preclinical and clinical observations with synthetic MAO inhibitors present a background for obtaining a better understanding of the polypharmacologies of tobacco and ayahuasca. Furthermore, MAO inhibitors of diverse structures are present in a wide variety of medicinal plants, but their pharmacological relevance in many instances remains to be established. Keywords: Banisteriopsis caapi; Nicotiana; ayahuasca; dimethyltryptamine (DMT); harmine; monoamine oxidase (MAO); tobacco; β-carbolines

Monoamine Oxidase Inhibition by Plant-Derived β-Carbolines; Implications for the Psychopharmacology of Tobacco and Ayahuasca.

The monoamine oxidases (MAOs) are flavin-containing amine oxidoreductases responsible for metabolism of many biogenic amine molecules in the brain and peripheral tissues. Whereas serotonin is the preferred substrate of MAO-A, phenylethylamine is metabolized by MAO-B, and dopamine and tyramine are nearly ambivalent with respect to the two isozymes. β-Carboline alkaloids such as harmine, harman(e), and norharman(e) are MAO inhibitors present in many plant materials, including foodstuffs, medicinal plants, and intoxicants, notably in tobacco (Nicotiana spp.) and in Banisteriopsis caapi, a vine used in the Amazonian ayahuasca brew. The β-carbolines present in B. caapi may have effects on neurogenesis and intrinsic antidepressant properties, in addition to potentiating the bioavailability of the hallucinogen N,N-dimethyltryptamine (DMT), which is often present in admixture plants of ayahuasca such as Psychotria viridis. Tobacco also contains physiologically relevant concentrations of β-carbolines, which potentially contribute to its psychopharmacology. However, in both cases, the threshold of MAO inhibition sufficient to interact with biogenic amine neurotransmission remains to be established. An important class of antidepressant medications provoke a complete and irreversible inhibition of MAO-A/B, and such complete inhibition is almost unattainable with reversible and competitive inhibitors such as β-carbolines. However, the preclinical and clinical observations with synthetic MAO inhibitors present a background for obtaining a better understanding of the polypharmacologies of tobacco and ayahuasca. Furthermore, MAO inhibitors of diverse structures are present in a wide variety of medicinal plants, but their pharmacological relevance in many instances remains to be established

Within-treatment changes in a novel addiction treatment program using traditional Amazonian medicine

Aims: The therapeutic use of psychedelics is regaining scientific momentum, but similarly psychoactive ethnobotanical substances have a long history of medical (and other) uses in indigenous contexts. Here we aimed to evaluate patient outcomes in a residential addiction treatment center that employs a novel combination of Western and traditional Amazonian methods. Methods: The study was observational, with repeated measures applied throughout treatment. All tests were administered in the center, which is located in Tarapoto, Peru. Data were collected between 2014 and 2015, and the study sample consisted of 36 male inpatients who were motivated to seek treatment and who entered into treatment voluntarily. Around 58% of the sample was from South America, 28% from Europe, and the remaining 14% from North America. We primarily employed repeated measures on a psychological test battery administered throughout treatment, measuring perceived stress, craving frequency, mental illness symptoms, spiritual well-being, and physical and emotional health. Addiction severity was measured on intake, and neuropsychological performance was assessed in a subsample from intake to at least 2 months into treatment. Results: Statistically significant and clinically positive changes were found across all repeated measures. These changes appeared early in the treatment and were maintained over time. Significant improvements were also found for neuropsychological functioning. Conclusion: These results provide evidence for treatment safety in a highly novel addiction treatment setting, while also suggesting positive therapeutic effects

Indigenous-Amazonian Traditional Medicine's Usage of the Tobacco Plant: A Transdisciplinary Ethnopsychological Mixed-Methods Case Study

Harmful usage of tobacco is a global public health problem associated with adverse health effects and addiction. Yet, in the Peruvian Amazon, the native region of Nicotiana rustica L., this plant is used in remarkably different manners: it is considered a potent medicinal plant, applied in liquid form for oral ingestion to treat mental health problems, a common and ancient healing practice in this region. Using a transdisciplinary field research approach with mixed ethnopsychological methods, this work aimed to report for the first time a case study in this context. The intervention took place in the Peruvian Amazon (Loreto) and involved ritual tobacco ingestion in a weeklong retreat-like frame, administered by a specialized traditional Amazonian healer. The patient was a 37-year-old woman with diagnosed mood, anxiety, and attention deficit disorders, as well as a chronic somatic condition. We applied qualitative experience-sampling during and quantitative symptom assessments pre- and post-treatment. Our findings offer a detailed description of the experiential therapeutic process during the treatment week and suggest clinically relevant improvements in patient well-being. This work is significant in view of the globally prevalent harmful uses of tobacco and the current scientific trend of revisiting herbal psychoactives (e.g., cannabis, psilocybin) for their therapeutic potentials

Amazonian Medicine and the Psychedelic Revival: Considering the "Dieta"

Background: In Peruvian Amazonian medicine, plant diets (dietas) are a fundamental and highly flexible technique with a variety of uses: from treating and preventing illness, to increasing strength and resilience, to rites of passage, to learning even medicine itself. Many of the plants used in diets are psychoactive; for example, one now well-known plant that can be dieted is Banisteriopsis caapi-the vine also used in the psychoactive brew ayahuasca. The use of ayahuasca has attracted increasing clinical attention towards Amazonian medicine in recent decades, and much work has focused on the potent DMT-containing ayahuasca brew, thus placing the tradition within the purview of psychedelic science. Aims: In comparison to ayahuasca, the properties of diets have been studied less often. Our work draws on data from Amazonian healers to examine plant diets as medical practices, while also considering their fit within the "set and setting framework" that is central to psychedelic research. We argue that the framework is not sufficiently broad for understanding diets, and thus the investigation aimed to expand the conceptual field of Amazonian medicine, particularly in the context of a renewed psychedelic science and its theoretical concepts. Design: We used qualitative data from interviews with Amazonian healers, applying a thematic analysis and contrasting findings with the available literature. Setting: Interviews were conducted in various locations in the San Martín province of Peru between 2015 and 2017. Participants: We selected and interviewed eight healers who had been extensively trained in traditional Amazonian medicine. Measures: Semi-structured interviews were used to gain insight into the healers' personal experiences with plant diets. Conclusions: Diets are complex but understudied medical practices that should not be explained by reference to pharmacology or psychology only. Intercultural and interdisciplinary research programmes are called for in order to not only better understand plant diets, but traditional Amazonian medicine on the whole

Traditional Amazonian Medicine Adapted To Treat Substance Use Disorder

Pathological substance use is amongst the most persistent and costly ills of global modern society. In spite of advances made in therapeutic possibilities over the past decades, long-term treatment responses remain relatively discouraging, with relapse rates higher than for most other psychiatric disorders. The chronic disease course of substance use disorder (SUD) has led to debate whether illness management strategies from somatic chronic care may also be suitable for SUD. In particular, traditional or alternative medicines, a common present-day adjunct to conventional somatic chronic care, may offer benefits for SUDs as well. The current work consists of three empirical studies exploring the therapeutic potential of traditional Amazonian medicine as applied in an integrative addiction treatment program, using a multimodal and cross-disciplinary research approach. The investigation was conducted at the Takiwasi Center for Addiction Treatment and Rehabilitation in the Peruvian Amazon, an integrative healthcare center that implements a combination of traditional Amazonian medicine and conventional psychotherapy. As a first step, Study 1 aimed to investigate how SUD is understood in traditional Amazonian medicine and which kinds of treatment methods are used in this context, also aiming to identify the main therapeutic technique used for SUD. For this purpose, we conducted interviews with 13 practicing experts of Amazonian medicine, asking them about their underlying conceptions of disease etiology and treatment of SUD. A qualitative content analytic approach was adopted for data analysis, which revealed an array of conceptual categories. Some of the concepts regarding disease etiology showed similarity to Western scientific views proposing a biopsychosocial model for SUD. Amazonian treatment concepts however differed markedly from Western ones. Instead of identifying a main treatment constituent, the experts emphasized the importance of an integral, combined application of Amazonian methods. Study 2 then aimed to investigate who the people are that seek out the Amazonian medicine based treatment for SUDs, assessing clinical and socio- demographic characteristics of 50 SUD-diagnosed patients enrolling in the Takiwasi treatment by means of structured clinical interviews and psychological self-report measures. We additionally were interested to know the participants' motivations for selecting this particular therapy program, which we assessed via qualitative analysis of patient motivation letters. Our results showed that most Takiwasi patients were young or middle-aged, unmarried males living with their relatives in urban areas in Peru or other Latin American countries. Polydrug use was the most common diagnosis, with cannabis, alcohol, cocaine and cocaine base paste as the most prevalent substances. Common comorbid psychopathologies included anxiety and mood disorders as well as antisocial personality disorder. Compared to norms from patients entering conventional psychiatric treatment, severity was elevated in the Takiwasi sample on several addiction and well-being indicators. The motives behind individuals' choices to initiate treatment at this center are described. Finally, Study 3 aimed to explore short-term treatment effects of the overall Takiwasi therapy program. About one-third of the initial sample abandoned treatment prematurely, which resulted in a final sample of n = 36 SUD-diagnosed patients that completed the treatment. We found significant improvements of addiction severity from baseline assessment to treatment completion on indicators of drug use, alcohol use, psychiatric status, and social and familial relationships. Overall substance craving decreased significantly after treatment, as did overall emotional distress. Quality of life scores increased significantly at treatment completion. Taken together, these findings point to a substantial improvement of key symptomatic features of SUD after completing this alternative SUD treatment. At the same time it is important to note that these results are preliminary and need to be confirmed by further, randomized-controlled studies including follow up assessments. In summary, findings from this research point to a promising novel treatment approach for SUD, which invites further investigation. We propose two parallel lines of research to be followed: One is qualitative, involving a detailed and systematic inquiry into the conceptual underpinnings of Amazonian medicine, and a thorough analysis of its characteristics and specifics for safe and efficacious application. The second line of research should involve quantitative studies on treatment effects, using progressively more controlled research designs adapted to a traditional medicines paradigm, while also assessing the transferability of Amazonian therapeutic methods to other cultural contexts. Results from the current work serve as a basis for future research and may in the long term open new treatment possibilities for SUD on a large scale.Schädlicher Substanzgebrauch gilt als eines der wesentlichsten Gesundheitsprobleme weltweit, welches auf individueller sowie gesellschaftlicher Ebene mit erheblichen Kosten und Leidensdruck verbunden ist. Substanzgebrauchsstörungen gelten heute als chronische Erkrankung, für deren Versorgung noch nach langfristig wirksamen Lösungen gesucht wird. Heutzutage wird für die Behandlung somatischer chronischer Erkrankungen zunehmend zu alternativ- bzw. traditionell-medizinischen Verfahren gegriffen, oftmals zusätzlich zu herkömmlichen medizinischen Behandlungen. Eine solche Behandlungsstrategie könnte auch für Substanzgebrauchsstörungen Chancen bergen. Die vorliegende Arbeit untersucht in drei empirischen Studien mittels multimodalem Forschungsdesign, interdisziplinärem Rahmen und kulturübergreifender Perspektive die therapeutischen Potentiale einer spezifischen alternativen Suchtbehandlung, welche auf traditionellen Heilmethoden aus dem Peruanischen Amazonasgebiet basiert. Die Untersuchung wurde im Takiwasi Center (Tarapoto, Peru) durchgeführt, ein Suchtbehandlungszentrum, dessen Therapieangebot westliche psychotherapeutische Methoden mit traditioneller Amazonasmedizin kombiniert. Studie 1 ermittelte Krankheits- und Behandlungskonzepte aus traditionell- medizinischer Sicht mittels qualitativer Forschungsmethoden. Es wurden halbstrukturierte Interviews mit 13 praktizierenden Experten/innen der traditionellen Amazonasmedizin durchgeführt und inhaltsanalytisch ausgewertet. Die Ergebnisse wiesen auf ein vielschichtiges Krankheitsverständnis hin. Der Experten ätiologische Erklärungen zeigten Ähnlichkeit mit aktuellen wissenschaftlichen Ansätzen welche ein biopsychosoziales Modell für Substanzgebrauchsstörungen postulieren. Die traditionellen Behandlungsmethoden hingegen, welche die komplexe Anwendung von Medizinalpflanzen mittels rituellen Techniken umfassen, sind mit westlichen Therapien schwer vergleichbar. Die Experten betonten in diesem Zusammenhang die Bedeutsamkeit der traditionellen Techniken und des ganzheitlichen Einsatzes der verschiedenen Interventionen. In Studie 2 wurden die Merkmale der Patienten, die das peruanische integrative Therapiezentrum aufsuchen, untersucht. Zu diesem Zweck wurden soziodemographische sowie klinische Merkmale von 50 Patienten anhand von klinischen Interviews und psychologischen Fragebogen erfasst. Zusätzlich wurde der motivationsbezogene Hintergrund der Entscheidung, sich in dieser Klinik behandeln zu lassen, mittels qualitativem Verfahren erfasst. Ergebnisse zeigten, dass die meisten Takiwasi-Patienten unverheiratete Männer jungen oder mittleren Alters sind, welche in städtischen Regionen Perus und anderer lateinamerikanischen Länder leben. Die meisten Patienten wiesen einen Mischkonsum auf, wobei Cannabis und Alkohol die meistgebrauchten Substanzen waren, gefolgt von Kokain und deren Vorläuferprodukt (Kokainbasispaste). Komorbide psychische Störungen umfassten insbesondere affektive und Angststörungen sowie antisoziale Persönlichkeitsstörung. Vergleiche mit Normwerten wiesen bei einigen klinischen Indikatoren auf einen stärkeren Beeinträchtigungsgrad der Stichprobe hin. Ergebnisse bezüglich Behandlungsmotivation werden im Detail beschrieben. Studie 3 ermittelte anhand eines naturalistischen Forschungsdesigns die Kurzzeiteffekte der Takiwasi-Therapie insgesamt. Die Baseline-Messung klinischer und soziodemographischer Merkmalen erfolgte bei Eintritt vor Beginn der Behandlung(T1). Die Indikatoren die als Outcome-Kriterien dienten wurden nach Beendigung der Therapie erneut gemessen (T2). Etwa ein Drittel der Studienteilnehmer verliess die Behandlung frühzeitig, so dass die finale Stichprobe aus 36 Teilnehmenden bestand. Es konnten signifikante Verbesserungen des Schweregrads bei folgenden klinischen Indikatoren festgestellt werden: Drogenkonsum, Alkoholkonsum, psychiatrische Beeinträchtigung, soziale/familiäre Beeinträchtigung, Substanzcraving, allgemeine emotionale Beeinträchtigung sowie Lebensqualität. Aufgrund des naturalistischen Designs und der fehlenden Kontrollgruppenbedingung sollten diese Ergebnisse allerdings als präliminär verstanden werden; sie stellen erste Hinweise für positive Outcomes dieser Therapie dar. Insgesamt deuten die Ergebnisse der vorliegenden Untersuchung auf einen vielversprechenden integrativen Behandlungsansatz für Substanzgebrauchsstörungen hin. Weitere vertiefende wissenschaftliche Studien sind notwendig, um endgültige Aussagen machen zu können. Hierfür sollten zwei Forschungsrichtungen weiterverfolgt werden: Zum einen sollte durch weitere qualitative Studien ein vertieftes Verständnis der Therapiemethoden und der Amazonasmedizin zugrundeliegender Konzepte erarbeitet werden. Zum anderen sollte weitere quantitative Forschung mittels kontrollierter randomisierter Studien die Langzeiteffekte der Behandlung untersuchen und deren Anwendung in verschiedenen Kulturen erproben. Die vorliegenden Befunde bilden die Grundlage für weiterführende Studien, welche längerfristig zu neuen Behandlungsmöglichkeiten für Substanzgebrauchsstörungen auf internationaler Ebene führen könnten

"Tobacco Is the Chief Medicinal Plant in My Work": Therapeutic Uses of Tobacco in Peruvian Amazonian Medicine Exemplified by the Work of a Maestro Tabaquero

Introduction Harmful usage of tobacco is a public health problem of global concern and, in many countries, the main risk factor for non-communicable diseases. Yet, in the Peruvian Amazon, the geographical region believed to be tobacco's historical birthplace, this plant is associated with a strikingly different usage and repute: Tobacco (especially Nicotiana rustica L.) in this area is described as a potent medicinal plant, used topically or via ingestion to treat a variety of health conditions. The goal of this transdisciplinary field study was to investigate clinical applications of the tobacco plant as per Amazonian medicine exemplified in the practice of a reputed Maestro Tabaquero, an Amazonian traditional healer whose medical specialization focuses on tobacco-based treatments. Methods Using a transdisciplinary clinical approach, we conducted in-depth interviews with the tabaquero applying the systematizing expert interview method, in order to map modes of preparation and administration, indications, contraindications, effects, risks, adverse effects, and systemic aspects of tobacco-based remedies. Results The informant's descriptions revealed refined knowledge on this plant's therapeutic properties and scope, safety profile, and application techniques. The main indications mentioned included "problems of the mind," of the respiratory system, parasitic illnesses (intestinal/skin), gout, and Amazonian epistemic conditions described as spiritual-energetic in nature. A liquid remedy taken orally was his most commonly used preparation, with acute/sub-acute effects involving a pronounced psychoactive component (altered state of consciousness) and physiological response (emesis, nausea). A skilled tabaquero that knows how to dose, administer, and intervene in case of adverse effects was considered imperative for safe treatment delivery. Conclusions To our knowledge, this is the first study employing a transdisciplinary clinical approach to examine therapeutic applications of tobacco by an Amazonian tabaquero. Our findings significantly contribute to the growing research literature on Amazonian medicine and emergent psychedelic-assisted therapies and could, in the long-term, open new treatment avenues in several domains. Forthcoming studies should assess toxicity/safety and clinical outcomes of patients receiving Amazonian tobacco-based treatment

Teacher plants — Indigenous Peruvian-Amazonian dietary practices as a method for using psychoactives

Ethnopharmacological relevance: Indigenous groups of the Amazon have developed intricate methods for the application of psychoactives, among which particularly the dieta or diet method of Peruvian-Amazonian traditional medicine stands out. It is a retreat-like intervention involving lengthy periods of social, behavioural, and alimentary restrictions, while ingesting specially prepared plant substances. The interplay of the dietary conditions and plants ingested sensitizes the dieter to receive healing, strength, guidance, and knowledge. From a clinical scientific point of view, the method has remained largely underexplored, but seems more pertinent than ever given the increasing interest in Amazonian psychoactive preparations including ayahuasca (Banisteriopsis caapi) and the burgeoning field of psychedelic-assisted therapies in general. Aim of the study: This study offers a descriptive account and emic interpretation of the Peruvian-Amazonian dieta. More specifically we document in detail the procedure, its context and purpose of application, effects, modes of action, adverse effects, and risks, from the perspectives of a sample of Peruvian traditional healers. The Peruvian-Amazonian dieta is a multi-purpose method for making use of medicinal plants, many of which (but not all), are psychoactive; the current work especially focuses on its therapeutic applications in conjunction with psychoactives. Methods: We interviewed 16 healers working in the Ucayali, San Martín, and Loreto provinces of Peru using a semi-structured interview approach. Interviews were audio-recorded and transcribed verbatim. The extensive data derived from these interviews were analysed by means of computer-assisted manifest qualitative content analysis using a theory-advancing approach. Over 500 coded text segments were categorized, resulting in 7 main theme clusters and corresponding sub-themes. Results: The interviewed healers described a complex intervention with multifaceted applications (treatment, prevention, training) and effects in various domains (body, mind, spirit, energy). The process was portrayed as transformative, with benefits attributed to the effects of the so-called teacher plants in conjunction with the diet's conditions, along with the skill of the healer guiding the intervention. Further, a detailed risk assessment revealed sophisticated safety measures and tools designed to address adverse responses. The importance of adequate training of the healer that administers the diet was particularly highlighted in this context. Conclusions: The dieta is a central therapeutic concept and tool in Peruvian-Amazonian traditional medicine and a unique method for using psychoactive plants. Multidisciplinary health research that includes traditional treatment methods from Indigenous cultures, Amazonian and other, should not be neglected in the current global interest in psychedelic therapies; such research may in the long-term contribute to a more inclusive psychedelic research paradigm as well as healthcare practice in countries where rich traditional healing systems exist, and perhaps beyond. It may also contribute to the recognition of the Indigenous healers as not only historical forerunners, but also current leading experts in psychedelic medicine

Conceptions and practices of an integrative treatment for substance use disorders involving Amazonian medicine: traditional healers’ perspectives

Objective: The harmful use of psychoactive substances represents one of today’s largest public health problems. Yet, in spite of its global relevance, current treatment for substance use disorders (SUDs) is still not entirely successful. The purpose of this study was to investigate alternative treatments and conceptions from traditional Amazonian medicine adapted to SUDs. Methods: We conducted semi-structured interviews with 13 practicing experts at a well-established addiction treatment center in the Peruvian Amazon and performed qualitative content analysis on the collected data. Main categories were deductively defined and corresponding subcategories inductively developed. Results: Our findings revealed characteristic features and consequences, causes and antecedents, and treatment methods of SUDs as the main categories. Overall, concepts of disease etiology bore resemblance with contemporary biopsychosocial models of SUDs. The Amazonian therapeutic means however differed markedly from current Western ones. The main methods involved dietary retreats, healing ceremonies, and purging rituals. The integral application of Amazonian methods, as well as their traditional implementation according to prescribed ritual protocols, were emphasized by the experts as crucial for efficacy and safety of treatment delivery. Conclusion: We suggest further scientific attention to these therapies, including clinical studies, for which our results provide conceptual underpinnings. Findings from this research expand the cross-cultural understanding of SUDs and, in the long run, may enhance its treatment options

Indigenous-Amazonian Traditional Medicine’s Usage of the Tobacco Plant: A Transdisciplinary Ethnopsychological Mixed-Methods Case Study

Harmful usage of tobacco is a global public health problem associated with adverse health effects and addiction. Yet, in the Peruvian Amazon, the native region of Nicotiana rustica L., this plant is used in remarkably different manners: it is considered a potent medicinal plant, applied in liquid form for oral ingestion to treat mental health problems, a common and ancient healing practice in this region. Using a transdisciplinary field research approach with mixed ethnopsychological methods, this work aimed to report for the first time a case study in this context. The intervention took place in the Peruvian Amazon (Loreto) and involved ritual tobacco ingestion in a weeklong retreat-like frame, administered by a specialized traditional Amazonian healer. The patient was a 37-year-old woman with diagnosed mood, anxiety, and attention deficit disorders, as well as a chronic somatic condition. We applied qualitative experience-sampling during and quantitative symptom assessments pre- and post-treatment. Our findings offer a detailed description of the experiential therapeutic process during the treatment week and suggest clinically relevant improvements in patient well-being. This work is significant in view of the globally prevalent harmful uses of tobacco and the current scientific trend of revisiting herbal psychoactives (e.g., cannabis, psilocybin) for their therapeutic potentials