OPEN Foundation

Psychiatry & Medicine

The use of illicit drugs as self-medication in the treatment of cluster headache: Results from an Italian online survey

Abstract

BACKGROUND:

Cluster headache (CH) patients often receive unsatisfactory treatment and may explore illicit substances as alternatives. We aimed to explore this use of illicit drugs for CH treatment.

METHODS:

We invited CH patients from an Internet-based self-help group to complete a questionnaire regarding their therapeutic use of illicit substances.

RESULTS:

Of the 54 respondents, 29 were classified as chronic and 39 were drug-resistant cases. Fifty patients had previously tried subcutaneous sumatriptan, 40 had tried O2, and 48 had tried at least one prophylactic treatment. All 54 patients specified that they were dissatisfied with conventional treatments. Thirty-four patients had used cannabinoids, 13 cocaine, 8 heroin, 18 psilocybin, 12 lysergic acid amide (LSA), and 4 lysergic acid diethylamide (LSD).

DISCUSSION:

Some patients with intractable CH decided to try illicit drugs concomitantly with cessation of medical care. Most of these patients found suggestions for illicit drug use on the Internet. Many patients seemed to underestimate the judicial consequences of, and had an overestimated confidence in the safety of, such illicit treatments. Physicians are often not informed by patients of their choice to use illicit drugs. This leads to questions regarding the true nature of the physician-patient relationship among dissatisfied CH patients.

Di Lorenzo, C., Coppola, G., Di Lorenzo, G., Bracaglia, M., Rossi, P., & Pierelli, F. (2015). The use of illicit drugs as self-medication in the treatment of cluster headache: Results from an Italian online survey. Cephalalgia. https://dx.doi.org/10.1177/0333102415583145
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A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication

Abstract

Types 1 and 2 diabetes affect some 380 million people worldwide. Both ultimately result from a deficiency of functional pancreatic insulin-producing beta cells. Beta cells proliferate in humans during a brief temporal window beginning around the time of birth, with a peak percentage (~2%) engaged in the cell cycle in the first year of life. In embryonic life and after early childhood, beta cell replication is barely detectable. Whereas beta cell expansion seems an obvious therapeutic approach to beta cell deficiency, adult human beta cells have proven recalcitrant to such efforts. Hence, there remains an urgent need for antidiabetic therapeutic agents that can induce regeneration and expansion of adult human beta cells in vivo or ex vivo. Here, using a high-throughput small-molecule screen (HTS), we find that analogs of the small molecule harmine function as a new class of human beta cell mitogenic compounds. We also define dual-specificity tyrosine-regulated kinase-1a (DYRK1A) as the likely target of harmine and the nuclear factors of activated T cells (NFAT) family of transcription factors as likely mediators of human beta cell proliferation and differentiation. Using three different mouse and human islet in vivo–based models, we show that harmine is able to induce beta cell proliferation, increase islet mass and improve glycemic control. These observations suggest that harmine analogs may have unique therapeutic promise for human diabetes therapy. Enhancing the potency and beta cell specificity of these compounds are important future challenges.

Wang, P., Alvarez-Perez, J. C., Felsenfeld, D. P., Liu, H., Sivendran, S., Bender, A., … & Stewart, A. F. (2015). A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication. Nature medicine. https://dx.doi.org/doi:10.1038/nm.3820
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Ex vivo effects of ibogaine on the activity of antioxidative enzymes in human erythrocytes

Abstract

Ethnopharmacological relevance

Ibogaine is a naturally occurring alkaloid with psychotropic and metabotropic effects, derived from the bark of the root of the West African Tabernanthe iboga plant. The tribes of Kongo basin have been using iboga as a stimulant, for medicinal purposes, and in rite of passage ceremonies, for centuries. Besides, it has been found that this drug has anti-addictive effects.

Aim of the study

Previous studies have demonstrated that ibogaine changed the quantity of ATP and energy related enzymes as well as the activity of antioxidant enzymes in cells thus altering redox equilibrium in a time manner. In this work, the mechanism of its action was further studied by measuring the effects of ibogaine in human erythrocytes in vitro on ATP liberation, membrane fluidity and antioxidant enzymes activity.

Materials and methods

Heparinized human blood samples were incubated with ibogaine (10 and 20 μM) at 37°C for 1 h. Blood plasma was separated by centrifugation and the levels of ATP and uric acid were measured 10 min after the addition of ibogaine using standard kits. The activity of copper–zinc superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were measured in erythrocytes after incubation period. The stability of SOD1 activity was further tested through in vitro incubation with H2O2 and scanning of its electrophoretic profiles. Membrane fluidity was determined using an electron paramagnetic resonance spin-labelling method.

Results

Results showed that ibogaine treatment of erythrocytes in vitro increased ATP concentration in the blood plasma without changes in neither erythrocytes membrane fluidity nor uric acid concentration. Ibogaine also increased SOD1 activity in erythrocytes at both doses applied here. Treatment with 20 μM also elevated GR activity after in vitro incubation at 37 °C. Electrophoretic profiles revealed that incubation with ibogaine mitigates H2O2 mediated suppression of SOD1 activity.

Conclusion

Some of the effects of ibogaine seem to be mediated through its influence on energy metabolism, redox active processes and the effects of discrete fluctuations of individual reactive oxygen species on different levels of enzyme activities. Overall, ibogaine acts as a pro-antioxidant by increasing activity of antioxidative enzymes and as an adaptagene in oxidative distress.

Nikolić-Kokić, A., Oreščanin-Dušić, Z., Spasojević, I., Slavić, M., Mijušković, A., Paškulin, R., … & Blagojević, D. P. (2015). Ex vivo effects of ibogaine on the activity of antioxidative enzymes in Human erythrocytes. Journal of ethnopharmacology. http://dx.doi.org/10.1016/j.jep.2015.01.037
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Editorial (Thematic Issue: Introduction to 'Beneficial Effects of Psychedelics with a Special Focus on Addictions')

Editorial

Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’

We are witnessing a revival of psychedelic research. An increasing number of studies investigating the therapeutic use of psychedelics are currently underway at some of the most renowned universities. Dedicating a second issue of ‘Current Drug Abuse Reviews’ to psychedelics aims to keep up with this blossoming field. With the availability of modern scientific instruments, psychedelic research is once again gaining a firm foothold in academia.

The idea of this special issue originated at the Interdisciplinary Conference on Psychedelic Research, organised by the OPEN Foundation in 2012. OPEN was founded in 2007 in the Netherlands, in order to stimulate and advance scientific research into psychedelics. This special issue of CDAR takes an interdisciplinary approach to the topic of psychedelics and mental health, while maintaining a particular focus on applications of psychedelics in the fields of substance abuse and addiction. This special issue also takes a critical look at some widespread assumptions about psychedelics, introduces new ideas and suggests novel directions for future research.

Kortekaas, R., & Breeksema, J. J. (2015). Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’. Current Drug Abuse Reviews, 7(2), 69-70. https://dx.doi.org/10.2174/1874473708666150120114604

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Articles in this special issue:

Editorial (Thematic Issue: Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’)
Ayahuasca, Psychedelic Studies and Health Sciences: The Politics of Knowledge and Inquiry into an Amazonian Plant Brew
Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings – Evaluating the Kosmicare Project at Boom Festival
Psychedelics as Medicines for Substance Abuse Rehabilitation: Evaluating Treatments with LSD, Peyote, Ibogaine and Ayahuasca
A Qualitative Report on the Subjective Experience of Intravenous Psilocybin Administered in an fMRI Environment
Salvinorin A and Related Compounds as Therapeutic Drugs for Psychostimulant-Related Disorders

Editorial (Thematic Issue: Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’)

Editorial

Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’

We are witnessing a revival of psychedelic research. An increasing number of studies investigating the therapeutic use of psychedelics are currently underway at some of the most renowned universities. Dedicating a second issue of ‘Current Drug Abuse Reviews’ to psychedelics aims to keep up with this blossoming field. With the availability of modern scientific instruments, psychedelic research is once again gaining a firm foothold in academia.

The idea of this special issue originated at the Interdisciplinary Conference on Psychedelic Research, organised by the OPEN Foundation in 2012. OPEN was founded in 2007 in the Netherlands, in order to stimulate and advance scientific research into psychedelics. This special issue of CDAR takes an interdisciplinary approach to the topic of psychedelics and mental health, while maintaining a particular focus on applications of psychedelics in the fields of substance abuse and addiction. This special issue also takes a critical look at some widespread assumptions about psychedelics, introduces new ideas and suggests novel directions for future research.

Kortekaas, R., & Breeksema, J. J. (2015). Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’. Current Drug Abuse Reviews, 7(2), 69-70. https://dx.doi.org/10.2174/1874473708666150120114604

Link to full text

Articles in this special issue:

Editorial (Thematic Issue: Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’)
Ayahuasca, Psychedelic Studies and Health Sciences: The Politics of Knowledge and Inquiry into an Amazonian Plant Brew
Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings – Evaluating the Kosmicare Project at Boom Festival
Psychedelics as Medicines for Substance Abuse Rehabilitation: Evaluating Treatments with LSD, Peyote, Ibogaine and Ayahuasca
A Qualitative Report on the Subjective Experience of Intravenous Psilocybin Administered in an fMRI Environment
Salvinorin A and Related Compounds as Therapeutic Drugs for Psychostimulant-Related Disorders

Ayahuasca, Psychedelic Studies and Health Sciences: The Politics of Knowledge and Inquiry into an Amazonian Plant Brew

Abstract

This article offers critical sociological and philosophical reflections on ayahuasca and other psychedelics as objects of research in medicine, health and human sciences. It situates 21st century scientific inquiry on ayahuasca in the broader context of how early modern European social trends and intellectual pursuits translated into new forms of empiricism and experimental philosophy, but later evolved into a form of dogmatism that convenienced the political suppression of academic inquiry into psychedelics. Applying ideas from the field of science and technology studies, we consider how ayahuasca’s myriad ontological representations in the 21st century — for example, plant teacher, traditional medicine, religious sacrament, material commodity, cognitive tool, illicit drug — influence our understanding of it as an object of inquiry. We then explore epistemological issues related to ayahuasca studies, including how the indigenous and mestizo concept of “plant teacher” or the more instrumental notion of psychedelics as “cognitive tools” may impact understanding of knowledge. This leads to questions about whether scientists engaged in ayahuasca research should be expected to have personal experiences with the brew, and how these may be perceived to help or hinder the objectivity of their pursuits. We conclude with some brief reflections on the politics of psychedelic research and impediments to academic knowledge production in the field of psychedelic studies.

Tupper, K. W., & Labate, B. C. (2015). Ayahuasca, Psychedelic Studies and Health Sciences: The Politics of Knowledge and Inquiry into an Amazonian Plant Brew. Current Drug Abuse Reviews, 7(2), 71-80. https://dx.doi.org/10.2174/1874473708666150107155042
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Serotonin 5-HT₂ receptor activation prevents allergic asthma in a mouse model.

Abstract

Asthma is an inflammatory disease of the lung characterized by airways hyper-responsiveness (AHR), inflammation, and mucus hyperproduction. Current mainstream therapies include bronchodilators that relieve bronchoconstriction and inhaled glucocorticoids to reduce inflammation. The small molecule hormone and neurotransmitter serotonin has long been known to be involved in inflammatory processes; however, its precise role in asthma is unknown. We have previously established that activation of serotonin 5-hydroxytryptamine (5-HT)(2A) receptors has potent anti-inflammatory activity in primary cultures of vascular tissues and in the whole animal in vasculature and gut tissues. The 5-HT(2A) receptor agonist, (R)-2,5-dimethoxy-4-iodoamphetamine [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][(R)-DOI] is especially potent. In this work, we have examined the effect of (R)-DOI in an established mouse model of allergic asthma. In the ovalbumin mouse model of allergic inflammation, we demonstrate that inhalation of (R)-DOI prevents the development of many key features of allergic asthma, including AHR, mucus hyperproduction, airways inflammation, and pulmonary eosinophil recruitment. Our results highlight a likely role of the 5-HT2 receptors in allergic airways disease and suggest that 5-HT2 receptor agonists may represent an effective and novel small molecule-based therapy for asthma.

Nau, F., Miller, J., Saravia, J., Ahlert, T., Yu, B., Happel, K. I., … & Nichols, C. D. (2015). Serotonin 5-HT2 receptor activation prevents allergic asthma in a mouse model. American Journal of Physiology-Lung Cellular and Molecular Physiology, 308(2), L191-L198.
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Development and validation of a rapid turboflow LC-MS/MS method for the quantification of LSD and 2-oxo-3-hydroxy LSD in serum and urine samples of emergency toxicological cases

Abstract

Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of the present study is to develop a quantitative turboflow LC-MS/MS method that can be used for rapid quantification of LSD and its main metabolite 2-oxo-3-hydroxy LSD (O-H-LSD) in serum and urine in emergency toxicological cases without time-consuming extraction steps. The method was developed on an ion-trap LC-MS/MS instrument coupled to a turbulent-flow extraction system. The validation data showed no significant matrix effects and no ion suppression has been observed in serum and urine. Mean intraday accuracy and precision for LSD were 101 and 6.84 %, in urine samples and 97.40 and 5.89 % in serum, respectively. For O-H-LSD, the respective values were 97.50 and 4.99 % in urine and 107 and 4.70 % in serum. Mean interday accuracy and precision for LSD were 100 and 8.26 % in urine and 101 and 6.56 % in serum, respectively. For O-H-LSD, the respective values were 101 and 8.11 % in urine and 99.8 and 8.35 % in serum, respectively. The lower limit of quantification for LSD was determined to be 0.1 ng/ml. LSD concentrations in serum were expected to be up to 8 ng/ml. 2-Oxo-3-hydroxy LSD concentrations in urine up to 250 ng/ml. The new method was accurate and precise in the range of expected serum and urine concentrations in patients with a suspected LSD intoxication. Until now, the method has been applied in five cases with suspected LSD intoxication where the intake of the drug has been verified four times with LSD concentrations in serum in the range of 1.80–14.70 ng/ml and once with a LSD concentration of 1.25 ng/ml in urine. In serum of two patients, the O-H-LSD concentration was determined to be 0.99 and 0.45 ng/ml. In the urine of a third patient, the O-H-LSD concentration was 9.70 ng/ml.

Dolder, P. C., Liechti, M. E., & Rentsch, K. M. (2015). Development and validation of a rapid turboflow LC-MS/MS method for the quantification of LSD and 2-oxo-3-hydroxy LSD in serum and urine samples of emergency toxicological cases. Analytical and bioanalytical chemistry, 407(6), 1577-1584. http://dx.doi.org/10.1007/s00216-014-8388-1

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Medical Drug or Shamanic Power Plant: The Uses of Kambô in Brazil

Abstract

The secretion from the frog Phyllomedusa bicolor, known in Portuguese as kambô, has traditionally been used as a stimulant and an invigorating agent for hunting by indigenous groups such as the Katukina, Yawanawa, and the Kaxinawa in the southeast Amazon. Since the mid 90s, its use has expanded to large cities in Brazil and, since the late 2000s, abroad to Europe and the US. The urban diffusion of the use of kambô has taken place via healing clinics offering alternative therapies, by way of members of the Brazilian ayahuasca religions, and through travel, mainly by Amazonian rubber tappers, the Katukina, and the Kawinawa Indians. In this article, we present an ethnography of the expansion and reinvention of the use of kambô. We describe the individuals who apply the substance, who are a diverse group, including indigenous healers, ex-rubber tappers, holistic therapists, and doctors. We argue that the frog secretion has a double appeal among this new urban clientele: as a “remedy of science,” in which its biochemical properties are stressed; and as a “remedy of spirit,” in which its “indigenous origin” is more valued, as if kambô was a kind of shamanic power plant analogous to peyote and ayahuasca.

Labate, B. C., & Lima, E. C. D. (2014). Medical Drug or Shamanic Power Plant: The Uses of Kambô in Brazil. Ponto Urbe. Revista do núcleo de antropologia urbana da USP, (15).
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Immunological Effects of Ayahuasca in Humans

Abstract

Ayahuasca is a botanical hallucinogen traditionally used by indigenous groups of the northwest Amazon. In the last decade, the use of ayahuasca has spread from Brazil, Colombia, Ecuador, and Peru to the U.S., Europe, Asia, and Africa. Despite acute and long-term evidence of good tolerability and safety for ayahuasca administered in the laboratory or ritually consumed in religious contexts, little is known about the immunological impact of ayahuasca on humans. Since ayahuasca is used by an increasing number of consumers, and considering its therapeutic potential, more information is needed regarding ayahuasca potential risks. This article presents a brief overview of the available data regarding the immunological impact of ayahuasca in humans.

dos Santos, R. G. (2014). Immunological Effects of Ayahuasca in Humans. Journal of psychoactive drugs, 46(5), 383-388. https://dx.doi.org/10.1080/02791072.2014.960113

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