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MDMA for the treatment of mood disorder: all talk no substance?

Abstract

Background: Unipolar depression is the third highest contributor to the global burden of disease, yet current pharmacotherapies typically take about 6 weeks to have an effect. A rapid-onset agent is an attractive prospect, not only to alleviate symptoms before first-line antidepressants display therapeutic action, but as a further treatment option in nonresponsive cases. It has been suggested that 3,4-methylene-dioxymethamphetamine (MDMA) could play a part in the treatment of depression, either as a rapid-onset pharmacological agent or as an adjunct to psychotherapy. Whilst these hypotheses are in keeping with the monoamine theory of depression and the principles surrounding psychotherapy, explicit experimental evidence of an antidepressant effect of MDMA has rarely been established.

Aims: To address the hypothesis surrounding MDMA as a rapid-onset antidepressant by examining pharmacological, psychological and behavioural studies. We consider whether this therapy could be safe by looking at the translation of neurotoxicity data from animals to humans.

Method: A literature review of the evidence supporting this hypothesis was performed.

Conclusions: The pharmacology of MDMA offers a promising target as a rapid-onset agent and MDMA is currently being investigated for use in psychotherapy in anxiety disorders; translation from these studies for use in depression may be possible. However, experimental evidence and safety analysis are insufficient to confirm or reject this theory at present.

Patel, R., & Titheradge, D. (2015). MDMA for the treatment of mood disorder: all talk no substance?. Therapeutic Advances in Psychopharmacology, 2045125315583786. https://dx.doi.org/

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Xenolinguistics – Psychedelics, Language, and the Evolution of Consciousness

xenolinguisticsXenolinguistics – Psychedelics, Language, and the Evolution of Consciousness by Diana Reed Slattery, with a foreword by Allyson Grey. Evolver Editions, 2015.

Psychedelic research always in some way evokes what David Chalmers has called the “hard problem of consciousness”. How does experience arise from physical activity in the brain and, to apply this problem to psychedelics, how does the alteration of the chemistry of the brain alter this experience? Most published research into psychedelics does not address this question directly. Diana Reed Slattery, however, combines both her subjective experiences, those of several other people, with scientific insights from linguistics, biology and psychology. The result is a richly illustrated philosophical work rather than a scientific attempt at proof and explanation. Her work opens up new avenues for further scientific and philosophical inquiries.

The focus of the book is xenolinguistics, which is defined as the study of alien (i.e. strange) languages. Slattery further limits the scope to previously non-existing languages that have been “received” during psychedelic experiences. Although this is a fringe phenomenon even within , understanding it might shed light on other aspects of the psychedelic experience and consciousness in general. Slattery’s aim is twofold. On the one hand she wants to show how psychedelic practices, the use of psychedelics within a certain ritualistic (secular, spiritual or religious) context, can be a “powerful means of gathering knowledge about consciousness”. On the other hand, she examines the results of her own and others’ psychedelic practice in the light of theories of the evolutionfrom a variety of disciplines, with a continuous focus on languages learned during the psychedelic experience.

The book is divided into three parts. The first deals with the practices used for xenolinguistics. The discussion of rituals and the philosophical segments on what can be considered “self” and “other” are among the most interesting of the book, as they pose questions about the way psychedelic experiences are interpreted; is the thing one communicates with the Self, subconscious, Other or even alien? Slattery argues that psychedelic practice hinges upon the setting of a clear intent, controlling the set and setting and the focus that one brings to the experience. Her practice is simple in the sense that no elaborate ritual or belief system accompanies the expglidemazeerience. The idea is to ingest the psychedelic (Slattery mostly uses psilocybin mushrooms, 2C-B, MDMA and cannabis) in solitude, experience and report as fully as possible. She got a “download” of the language she calls Glide quite early on in her practice and continued to explore the details in the years that followed. Glide is an aesthetically pleasing and purely visual language that meanders in all directions. It consists of glyphs, each comprising three rounded strokes. Combining these glyphs results in a ‘Maze’, where glyphs flow into each other. Meaning is multidimensional and reverberates throughout the field of meaning that is created. The result is non-linear and unbounded, much like the psychedelic experience. It is interesting to note that here, the focus on healing that we find in much research on psychedelics is largely absent, in order to focus on knowledge acquisition and creativity. This perspective is very welcome in a field that has become focused on one or just a few aspects of the psychedelic experience, namely the therapeutical applications and the neurobiological effects of psychedelics.

The second part of the book is more theoretical, as Slattery frames xenolinguistics within some scientific theories. This evaluation is far from complete and theories that do not support the possibility of xenolinguistics are not considered. The mere fact that people sometimes receive or develop strange languages under the influence of psychedelics disqualifies any theory that precludes this possibility. In this sense, a more dialectical approach would perhaps have been more beneficial. As it stands, however, it is a collection of fascinating scientific theories that all somehow fit in with the practice of xenolinguistics. Slattery refers to many key actors in psychedelic research; the extensive 16-page bibliography stands witness to this achievement and provides a wealth of information for those who want to dig further into the material. The theoretical ideas are interwoven with notes from her personal journal that support or illustrate the hypotheses about how perception, reality, language and consciousness are, to use one of the beautiful key concepts of the book, intertwingled.

The third part focuses on language, natural and unnatural, constructed and living. Slattery gives examples from a variety of xenolinguists of how meaning is put into language in the psychedelic experience. The role of language in society is also elaborated upon. Strange languages serve many purposes, according to Slattery: they help us express new ideas, new emotions; they enable us to convey these to others or alternatively to keep them private while still being expressed; and they allow us to experience reality in a different way, showing how the creative use of language can alter the way we see the world. Slattery refers to the idea put forth by Richard Doyle that the psychedelic experience is an ecodelic experience, which gives us the opportunity to see ourselves as part of nature and to see how things are interconnected.

Xenolinguistics is a book for those interested in the interplay between psychedelics, language and consciousness. The overall picture that emerges shows that psychedelics can shed light on the way in which language and consciousness interact and co-evolve, by providing us with new languages that stretch our awareness beyond that which we are accustomed to. While the scientific theories in the book are interesting and support the ideas put forth by the author, those looking for pure science will probably be disappointed. The strength of the book lies in its exploration of new ideas and their synthesis into an overarching worldview that invites the reader to think along. The role language plays in our ongoing search for meaning and connection needs further study. This book is an inspiring and inspired attempt to open up this new field.

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[Boekrecensie] Xenolinguistics – Psychedelics, Language, and the Evolution of Consciousness

xenolinguisticsXenolinguistics – Psychedelics, Language, and the Evolution of Consciousness, door Diana Reed Slattery, met een voorwoord van Allyson Grey. Evolver Editions, 2015

Psychedelisch onderzoek roept altijd op een bepaalde manier wat David Chalmers het “moeilijke probleem van bewustzijn” noemt op. Op welke manier vloeit ervaring voort uit fysieke activiteit in het brein en, om dit probleem op psychedelica toe te passen, op welke manier verandert een wijziging in de chemie van het brein deze ervaring? Het meeste gepubliceerde psychedelische onderzoek richt zich niet direct op deze vraag. Maar Diana Reed Slattery combineert zowel haar eigen persoonlijke ervaringen als die van een aantal anderen met wetenschappelijke inzichten uit de taalkunde, biologie en psychologie. Het resultaat is eerder een rijkelijk geïllustreerd filosofisch werk dan een wetenschappelijke poging tot bewijsvoering en uitleg. Haar werk opent nieuwe deuren voor verdere wetenschappelijke en filosofische vraagstukken.

Het boek focust op xenolinguïstiek, wat wordt gedefinieerd als het onderzoek naar vreemde (d.w.z. rare) talen. Slattery beperkt het onderwerp verder tot talen die voorheen nog niet bestonden en die zijn “ontvangen” tijdens psychedelische ervaringen. Ook al is dit zelfs binnen de psychedelische gemeenschap een randverschijnsel, het begrijpen ervan zou licht kunnen werpen op andere aspecten van de psychedelische ervaring en op bewustzijn in het algemeen. Slattery heeft twee doelen. Aan de ene kant wil ze laten zien hoe psychedelische praktijken, het gebruik van psychedelica binnen een bepaald ritueel kader (seculier, spiritueel of religieus) erg “krachtige middelen om kennis over bewustzijn te verkrijgen” kunnen zijn. Aan de andere kant onderzoekt ze de resultaten van haar eigen psychedelische praktijk en die van anderen aan de hand van theorieën over de evolutie van bewustzijn vanuit een verscheidenheid aan disciplines, met een voortdurende focus op talen die tijdens de psychedelische ervaring zijn aangeleerd.

Het boek is opgedeeld in drie delen. Het eerste deel gaat over de praktijken die gepaard gaan met xenolinguïstiek. De discussies over rituelen en de filosofische passages over wat als “zelf” en “ander” zou kunnen worden gezien vallen onder de meest interessante in het boek, omdat ze vragen stellen over de manier waarop psychedelische ervaringen worden geïnterpreteerd; is datgene waarmee men communiceert het Zelf, het onderbewuste, het Andere of zelfs totaal uitheems? Slattery stelt dat het gebruik van psychedelica draait om het stellen van een duidelijke intentie, het onder controle houden van set en setting en de focus die men meeneemt in de ervaring. Haar handelen is simpel in die zin dat er geen uitgedacht ritueel of geloofssysteem is dat de ervaring begeleidt. Het idee is om in je eentje het psychedelicum in te nemen (Slattery gebruikt voornamelijk paddo’s, 2C-B, MDMA en cannabis) om vervolgens de ervaring te beleven en haar zo volledig mogelijk te rapporteren. Ze heeft vrij vroeg tijdens haar praktijk een “download” van een taal die ze Glide noemt ontvangen en heeft in de jaren daarna de details hierglidemazevan steeds verder verkend. Glide is een puur visuele taal die een lust is voor het oog en alle richtingen uit kronkelt. Het bestaat uit tekens die ieder uit drie ronde lijnen bestaan. Het combineren van deze tekens resulteert in een ‘Maze’, waar ze in elkaar vloeien. Betekenis is multidimensionaal en weergalmt door het veld van betekenis dat gecreëerd wordt. Het resultaat is niet-lineair en onbegrensd, en lijkt daarmee erg op de psychedelische ervaring. Het is interessant om op te merken dat de focus op genezing die we terugvinden in veel psychedelisch onderzoek hier grotendeels ontbreekt, zodat er meer kan worden gekeken naar het verkrijgen van kennis en naar creativiteit. Dit perspectief is erg welkom in een gebied dat zich is gaan focussen op een enkele of slechts een paar aspecten van de psychedelische ervaring, zoals de therapeutische toepassingen en de neurobiologische effecten van psychedelica.

Het tweede deel van het boek is theoretischer, omdat Slattery de xenolinguïstiek binnen enkele wetenschappelijke theorieën plaatst. Deze evaluatie is verre van compleet en theorieën die de mogelijkheid tot xenolinguistiek niet steunen worden niet genoemd. Het enkele feit dat mensen soms vreemde talen ontvangen of ontwikkelen onder invloed van psychedelica zorgt ervoor dat iedere theorie die deze mogelijkheid uitsluit wordt gediskwalificeerd. In die zin was een meer dialectische benadering misschien voordeliger geweest. Maar zoals het er voor staat, is het een verzameling van fascinerende wetenschappelijke theorieën die allemaal op een of andere wijze binnen het veld van de xenolinguïstiek passen. Slattery verwijst naar veel sleutelfiguren binnen het psychedelisch onderzoek; de uitgebreide, 16 pagina’s tellende bibliografie is het bewijs van deze prestatie en biedt een rijke bron aan informatie voor diegenen die zich verder in de stof willen verdiepen. De theoretische ideeën zijn verweven met aantekeningen uit haar persoonlijke verslagen die ter ondersteuning of illustratie dienen van de hypotheses over hoe perceptie, de realiteit, taal en bewustzijn onderling zijn verstrengeld.

Het derde deel richt zich op de taal: natuurlijke en onnatuurlijke, geconstrueerde en levende taal. Slattery geeft voorbeelden van een aantal xenolinguïsten over hoe betekenis tot taal wordt tijdens een psychedelische ervaring. De rol van de taal binnen de maatschappij wordt ook uitgewerkt. Vreemde talen dienen vele doelen volgens Slattery: ze helpen ons om nieuwe ideeën en nieuwe emoties te uiten; ze maken het mogelijk om deze naar anderen over te brengen of ze privé te houden terwijl ze toch worden uitgedrukt; ze kunnen ons de realiteit op een andere manier laten ervaren, en laten daarmee zien hoe het creatief gebruik van taal de manier waarop we de wereld zien kan veranderen. Slattery verwijst naar het idee van Richard Doyle dat de psychedelische ervaring een ecodelische ervaring is, die ons de mogelijkheid geeft om onszelf als deel van de natuur te zien en te zien hoe dingen met elkaar verbonden zijn.

Xenolinguistics is een boek voor diegenen die geïnteresseerd zijn in de wisselwerking tussen psychedelica, taal en bewustzijn. Het totaalplaatje laat zien dat psychedelica licht kunnen werpen op de manier waarop taal en bewustzijn op elkaar inwerken en co-evolueren, door ons te voorzien van nieuwe talen die ons bewustzijn kunnen uitrekken tot verder dan we gewend zijn. Terwijl de wetenschappelijke theorieën in het boek interessant zijn en de ideeën van auteur ondersteunen, zullen diegenen die op zoek naar zijn pure wetenschap waarschijnlijk teleurgesteld zijn. De kracht van het boek ligt in zijn verkenning van nieuwe ideeën en hun synthese in een overkoepelend wereldbeeld dat de lezer uitnodigt om mee te denken. De rol die taal speelt in onze permanente zoektocht naar betekenis en verbondenheid heeft verder onderzoek nodig. Dit boek is een inspirerende en geïnspireerde poging om dit nieuwe gebied toegankelijk te maken.

Koop dit boek via bookdepository.com en ondersteun daarmee Stichting OPEN

Ibogan, Tacaman, and Cytotoxic Bisindole Alkaloids from Tabernaemontana. Cononusine, an Iboga Alkaloid with Unusual Incorporation of a Pyrrolidone Moiety

Abstract

Abstract Image

Six new indole alkaloids, viz., cononusine (1, a rare example of an iboga–pyrrolidone conjugate), ervaluteine (2), vincamajicine (3), tacamonidine (4), 6-oxoibogaine (5), and N4-chloromethylnorfluorocurarine chloride (6), and two new vobasinyl-iboga bisindole alkaloids, ervatensines A (7) and B (8), in addition to other known alkaloids, were isolated from the stem-bark extract of the Malayan Tabernaemontana corymbosa. The structures of these alkaloids were established on the basis of NMR and MS analyses and, in one instance (7), confirmed by X-ray diffraction analysis. Vincamajicine (3) showed appreciable activity in reversing multidrug resistance in vincristine-resistant KB cells (IC50 2.62 μM), while ervatensines A (7) and B (8) and two other known bisindoles displayed pronounced in vitro growth inhibitory activity against human KB cells (IC50 < 2 μM). Compounds 7 and 8 also showed good growth inhibitory activity against A549, MCF-7, MDA-468, HCT-116, and HT-29 cells (IC50 0.70–4.19 μM). Cell cycle and annexin V-FITC apoptosis assays indicated that compounds 7 and 8 inhibited proliferation of HCT-116 and MDA-468 cells, evoking apoptotic and necrotic cell death.

Lim, K. H., Raja, V. J., Bradshaw, T. D., Lim, S. H., Low, Y. Y., & Kam, T. S. (2015). Ibogan, Tacaman, and Cytotoxic Bisindole Alkaloids from Tabernaemontana. Cononusine, an Iboga Alkaloid with Unusual Incorporation of a Pyrrolidone Moiety. Journal of natural products. http://dx.doi.org/10.1021/acs.jnatprod.5b00117

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Intimate insight: MDMA changes how people talk about significant others

Abstract

Rationale: ±3,4-methylenedioxymethamphetamine (MDMA) is widely believed to increase sociability. The drug alters speech production and fluency, and may influence speech content. Here, we investigated the effect of MDMA on speech content, which may reveal how this drug affects social interactions.

Method: Thirty-five healthy volunteers with prior MDMA experience completed this two-session, within-subjects, double-blind study during which they received 1.5 mg/kg oral MDMA and placebo. Participants completed a five-minute standardized talking task during which they discussed a close personal relationship (e.g. a friend or family member) with a research assistant. The conversations were analyzed for selected content categories (e.g. words pertaining to affect, social interaction, and cognition), using both a standard dictionary method (Pennebaker’s Linguistic Inquiry and Word Count: LIWC) and a machine learning method using random forest classifiers.

Results: Both analytic methods revealed that MDMA altered speech content relative to placebo. Using LIWC scores, the drug increased use of social and sexual words, consistent with reports that MDMA increases willingness to disclose. Using the machine learning algorithm, we found that MDMA increased use of social words and words relating to both positive and negative emotions.

Conclusions: These findings are consistent with reports that MDMA acutely alters speech content, specifically increasing emotional and social content during a brief semistructured dyadic interaction. Studying effects of psychoactive drugs on speech content may offer new insights into drug effects on mental states, and on emotional and psychosocial interaction.

Baggott, M. J., Kirkpatrick, M. G., Bedi, G., & de Wit, H. (2015). Intimate insight: MDMA changes how people talk about significant others. Journal of Psychopharmacology, 0269881115581962. https://dx.doi.org/
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Fatty acid constituents of Peganum harmala plant using Gas Chromatography–Mass Spectroscopy

Abstract

Fatty acid contents of the Peganum harmala plant as a result of hexane extraction were analyzed using GC–MS. The saturated fatty acid composition of the harmal plant was tetradecanoic, pentadecanoic, tridecanoic, hexadecanoic, heptadecanoic and octadecanoic acids, while the saturated fatty acid derivatives were 12-methyl tetradecanoic, 5,9,13-trimethyl tetradecanoic and 2-methyl octadecanoic acids. The most abundant fatty acid was hexadecanoic with concentration 48.13% followed by octadecanoic with concentration 13.80%. There are four unsaturated fatty acids called (E)-9-dodecenoic, (Z)-9-hexadecenoic, (Z,Z)-9,12-octadecadienoic and (Z,Z,Z)-9,12,15-octadecatrienoic. The most abundant unsaturated fatty acid was (Z,Z,Z)-9,12,15-octadecatrienoic with concentration 14.79% followed by (Z,Z)-9,12-octadecadienoic with concentration 10.61%. Also, there are eight non-fatty acid compounds 1-octadecene, 6,10,14-trimethyl-2-pentadecanone, (E)-15-heptadecenal, oxacyclohexadecan-2 one, 1,2,2,6,8-pentamethyl-7-oxabicyclo[4.3.1]dec-8-en-10-one, hexadecane-1,2-diol, n-heneicosane and eicosan-3-ol.

Moussa, T. A., & Almaghrabi, O. A. (2015). Fatty acid constituents of Peganum harmala plant using Gas Chromatography–Mass Spectroscopy. Saudi Journal of Biological Sciences. https://dx.doi.org/10.1016/j.sjbs.2015.04.013
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Lecture University of Groningen: The comeback of psychedelic science

At Monday May 18th, there will be a lecture by Joost Breeksema, the president of OPEN, at the University of Groningen. This lecture is organized by the English lecture committee of student society VIP (Psychology University of Groningen), in collaboration with the OPEN Foundation.
VIP created a Facebook event with more information on this lecture.
THE COMEBACK OF PSYCHEDELIC SCIENCE
Discussing the therapeutic and mystical potential of psychedelics
When LSD was discovered in 1943, it was initially seen as a tool to mimic and understand psychosis. In the following years, psychedelics would be regarded as valuable instruments that could provide insight into otherwise inaccessible realms of the human mind. Pioneering Czech psychiatrist Stanislav Grof thought that ‘psychedelics, used responsibly and with proper caution, would be for psychiatry what the microscope is for medicine or the telescope for astronomy.’ Shortly after, however, psychedelics and related research were outlawed.
Recently a ‘psychedelic renaissance’ took off, ushering in a whole new phase of scientific investigation. Can psilocybin really help people overcome their fear of death? How does MDMA interact with the brain to heal heavily traumatized patients? Can psychedelics be used to treat addiction? And what role do mystical experiences play in all this?
In this lecture Joost Breeksema discusses past, present and future research directions, the latest scientific results and whether we really need science to understand the potential that psychedelic experiences offer.
This lecture will be in English

Lezing Universiteit van Groningen: The comeback of psychedelic science

Op maandag 18 mei zal Joost Breeksema, de voorzitter van Stichting OPEN, een lezing geven aan de Universiteit van Groningen. Deze lezing wordt georganiseerd door het English lecture committee van studievereniging VIP (Psychologie Universiteit van Groningen), in samenwerking met Stichting OPEN.
VIP heeft een Facebook event gecreeërd met meer informatie over deze lezing.
THE COMEBACK OF PSYCHEDELIC SCIENCE
Discussing the therapeutic and mystical potential of psychedelics
When LSD was discovered in 1943, it was initially seen as a tool to mimic and understand psychosis. In the following years, psychedelics would be regarded as valuable instruments that could provide insight into otherwise inaccessible realms of the human mind. Pioneering Czech psychiatrist Stanislav Grof thought that ‘psychedelics, used responsibly and with proper caution, would be for psychiatry what the microscope is for medicine or the telescope for astronomy.’ Shortly after, however, psychedelics and related research were outlawed.
Recently a ‘psychedelic renaissance’ took off, ushering in a whole new phase of scientific investigation. Can psilocybin really help people overcome their fear of death? How does MDMA interact with the brain to heal heavily traumatized patients? Can psychedelics be used to treat addiction? And what role do mystical experiences play in all this?
In this lecture Joost Breeksema discusses past, present and future research directions, the latest scientific results and whether we really need science to understand the potential that psychedelic experiences offer.

Ketamine-A Narrative Review of Its Uses in Medicine

Abstract

One of the most fascinating drugs in the anesthesiologist’s armament is ketamine, an N-methyl-D-aspartate receptor antagonist with a myriad of uses. The drug is a dissociative anesthetic and has been used more often as an analgesic in numerous hospital units, outpatient pain clinics, and in the prehospital realm. It has been used to treat postoperative pain, chronic pain, complex regional pain syndrome, phantom limb pain, and other neuropathic conditions requiring analgesia. Research has also demonstrated its efficacy as an adjunct in psychotherapy, as a treatment for both depression and posttraumatic stress disorder, as a procedural sedative, and as a treatment for respiratory and neurologic conditions. Ketamine is not without its adverse effects, some of which can be mitigated with certain efforts. Such effects make it necessary for the clinician to use the drug only in situations where it will provide the greatest benefit with the fewest adverse effects. To the best of our knowledge, none of the reviews regarding ketamine have taken a comprehensive look at the drug’s uses in all territories of medicine. This review will serve to touch on its chemical data, pharmacokinetics and pharmacodynamics, medical uses, and adverse effects while focusing specifically on the drugs usage in anesthesia and analgesia.

Radvansky, B. M., Puri, S., Sifonios, A. N., Eloy, J. D., & Le, V. (2015). Ketamine-A Narrative Review of Its Uses in Medicine. American journal of therapeutics. https://dx.doi.org/10.1097/MJT.0000000000000257
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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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