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Symposium Universiteit Utrecht: Psychedelics – Novel Applications for Depression

SymposiumUnitas

 Psychedelics – Novel Applications for Depression

An evening symposium dedicated to recent research into the potential anti-depressant effects and mechanisms of action of psychedelic drugs. Organized in collaboration with U.P.S.V. “Unitas Pharmaceuticorum”.

There’s a recognized need among therapists for more effective interventions for depression. The currently available psychopharmaceutical medications don’t work for everyone. What do we know about the effectiveness of psychedelics? To discuss these topics, we invited three young researchers, from three countries and three related disciplines. All presentations will be in English.

  • Tobias Buchborn is a German neuropsychologist, doing research at the Otto van Guericke University in Magdeburg. He studied the antidepressant potential of LSD in animals and will present his findings and implications for the clinical practice.
  • Mendel Kaelen is a Dutch neuroscientist working at Imperial College London. His talk will cover neuroimaging studies concerning the brain mechanisms of psychedelics and music, and their role in psychedelic-assisted therapy for treatment-resistant depression. You can read about his most recent publication here.
  • Tharcila Chaves is a Brazilian pharmacist, who is currently studying the effects of orally administered ketamine for therapy resistant severely depressed patients at the Medical Centre of the University of Groningen (UMCG).

There will be time for a plenary discussion and Q&A with the researchers afterwards. Please be on time!

Date: September 15th, 2015
Time: 19:00 – 22:00
Location: Marinus Ruppertgebouw (blue lecture hall), Leuvenlaan 21, Utrecht.
Tickets: €2,- for members Unitas Pharmaceuticorum / €7,50 for non-members. Sold on location.
Reserve your ticket(s) by sending an email to assessor1@upsv.nl (Unitas Pharmaceuticorum)
Also see the Facebook event page for updates and more information.

Symposium Universiteit Utrecht: Psychedelics – Novel Applications for Depression Read More »

Symposium Utrecht University: Psychedelics – Novel Applications for Depression

Unitassymposium

Psychedelics – Novel Applications for Depression

An evening symposium dedicated to recent research into the potential anti-depressant effects and mechanisms of action of psychedelic drugs. Organized in collaboration with U.P.S.V. “Unitas Pharmaceuticorum”.

There’s a recognized need among therapists for more effective interventions for depression. The currently available psychopharmaceutical medications don’t work for everyone. What do we know about the effectiveness of psychedelics? To discuss these topics, we invited three young researchers, from three countries and three related disciplines. All presentations will be in English.

  • Tobias Buchborn is a German neuropsychologist, doing research at the Otto van Guericke University in Magdeburg. He studied the antidepressant potential of LSD in animals and will present his findings and implications for the clinical practice.
  • Mendel Kaelen is a Dutch neuroscientist working at Imperial College London. His talk will cover neuroimaging studies concerning the brain mechanisms of psychedelics and music, and their role in psychedelic-assisted therapy for treatment-resistant depression. You can read about his most recent publication here.
  • Tharcila Chaves is a Brazilian pharmacist, who is currently studying the effects of orally administered ketamine for therapy resistant severely depressed patients at the Medical Centre of the University of Groningen (UMCG).

There will be time for a plenary discussion and Q&A with the researchers afterwards. Please be on time!

Date: September 15th, 2015
Time: 19:00 – 22:00
Location: Marinus Ruppertgebouw (blue lecture hall), Leuvenlaan 21, Utrecht.
Tickets: €2,- for members Unitas Pharmaceuticorum / €7,50 for non-members. Sold on location.
Reserve your ticket(s) by sending an email to assessor1@upsv.nl (Unitas Pharmaceuticorum)

Also see the Facebook event page for updates and more information.

Symposium Utrecht University: Psychedelics – Novel Applications for Depression Read More »

Does LSD enhance the emotional response to music?

Aside from its hallucinogenic properties, LSD is known to have noticeable effects on emotion. This is one of the reasons why psychedelics were used in psychotherapy in the 1950s and 60s, hypothesizing that they facilitate emotional release and insight  [1][2]. Similarly, music can evoke emotion and was also a component in psychedelic-assisted psychotherapy, for aiding emotional arousal and release, and in promoting the occurrence of peak or spiritual-type experiences [3][4]. Working at Imperial College, London, neuroscientist and OPEN board member Mendel Kaelen and colleagues conducted a study [5] aiming to explore the significance of music in psychedelic-assisted psychotherapy. Using a placebo-controlled setup, the study sought to test the hypothesis that the emotional response to music is enhanced on LSD. The research team also investigated the role of music in occasioning peak or spiritual-type experiences.

Ten participants attended two study days. During one such day, they received a placebo (10ml saline), while on the other day they were given between 40 and 80 μg of LSD, with roughly a week in between. The design was single-blind, which means participants were blind to which condition they were in, but researchers were not. Participants listened to a playlist of five different (mostly neo-classical and ambient) instrumental tracks on each of the two study days, with the order of the playlist counterbalanced across participants. In order to assess the emotional response to the music, participants were asked how emotionally affected they were by the music, which served as the primary outcome. Furthermore, the Geneva Emotional Music Scale (GEMS-9) was used to investigate the specific factors of the participants’ emotional experiences, consisting of nine subcategories of emotion (wonder, transcendence, power, tenderness, nostalgia, peacefulness, joyful activation, and tension). The results showed that the mean scores for the emotional response to music were significantly higher for the LSD condition than for the placebo. Additionally, all nine factors on the GEMS-9 scored higher in the LSD condition than in the placebo, with significant increases for the items “wonder”, “transcendence”, “power” and “tenderness”. Correlational analyses showed a significant positive relationship between ratings of intensity of drug effects and emotional arousal to music.

The finding that LSD enhances the emotional response to music supports the popular assumption that music has more significance under the influence of psychedelic drugs. Emotions of transcendence and wonder are traditionally thought of as core constituents of peak and spiritual experiences [6][7]. This led the authors to infer that the combination of LSD and music may increase the likelihood of having spiritual-type or peak experiences. Moreover, these experiences have been shown to correlate with sustained improvements in well-being and life satisfaction [8] and also with increases in the personality trait of openness [9], which supports the view that music is an important element in psychedelic-assisted therapy.

Due to this being a pilot study, it does come with its limitations. Small sample size and musical genre selection mean that results cannot be generalised to a larger population. Also, participants could have guessed the purpose of the study, meaning the results could reflect their own or the researchers’ expectations. Additionally, results could be attributed to the effect of LSD alone, rather than the specific effect of music in combination with the drug.

When asked about the implications of his study for future research, Mr. Kaelen told us these are just humble first steps in helping build an evidence-based approach to psychedelic therapy. “It’s important to start a discussion on the role of music and the importance of the setting in general within psychedelic therapy,” Kaelen said. “Due to the study’s limitations, future studies have to come up with different designs and more detailed research questions.” Kaelen also mentioned research already underway at Imperial College, including brain imaging studies with FMRI and MEG, which aim to investigate which brain mechanisms are involved. He also emphasised the importance of translating elements into clinical work. “A clinical trial, now in progress at Imperial, uses psilocybin for treatment-resistant depression. Part of this study looks at the role of music, which will hopefully further our understanding of how music and psychedelic therapy work together.”


[1] Busch AK, Johnson WC (1950) L.S.D. 25 as an aid in psychotherapy; preliminary report of a new drug. Diseases of the nervous system 11: 241-243

[2] Leuner HC (1983) Psycholytic therapy: Hallucinogenics as an aid in psychodynamically oriented psychotherapy In Psychedelic Reflections, ed. Grinspoon L & Bakalar JB, pp. 177-192: Human Science Press

[3] Bonny HL, Pahnke WN (1972) The use of music in psychedelic (LSD) psychotherapy. Journal of music therapy: 64-87

[4] Grof S (1980) LSD Psychotherapy. Hunter House Publishers, US.

[5] Kaelen et al. (2015) LSD enhances the emotional response to music . Psychopharmacology [Abstract]

[6] Maslow AH (1993) The Farther Reaches of Human Nature. Arkana

[7] Richards WA (2009) The rebirth of research with entheogens: lessons from the past and hypotheses for the future. The Journal of Transpersonal Psychology Vol. 41: 139-150

[8] Griffiths RR, Richards W, Johnson MW, McCann U, Jesse R (2008) Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. Journal of psychopharmacology 22: 621-632

[9] MacLean KA, Johnson MW, Griffiths RR (2011) Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. Journal of psychopharmacology 25: 1453-1461

Does LSD enhance the emotional response to music? Read More »

Versterkt LSD de emotionele reactie op muziek?

Music_Psychedelic_pictureNaast zijn hallucinogene eigenschappen staat LSD erom bekend merkbare effecten te hebben op emotie. Dit is een van de redenen waarom psychedelica in de jaren vijftig en zestig werden gebruikt bij psychotherapie, onder de hypothese dat ze emotionele bevrijding en inzichten helpen bereiken [1][2]. Muziek kan op soortgelijke manier emoties oproepen en was ook een onderdeel van psychedelica-ondersteunde psychotherapie, ter bevordering van emotionele prikkeling en verlossing, en om te helpen ‘piek’- of spirituele ervaringen op te roepen [3][4]. Mendel Kaelen, als neurowetenschapper werkzaam bij het Imperial College te Londen en OPEN bestuurslid, en zijn collega’s, voerden een onderzoek [5] uit met als doel de significantie van muziek bij psychedelica-ondersteunde psychotherapie te verkennen. Het onderzoek richtte zich op het toetsen van de hypothese dat de emotionele reactie op muziek wordt versterkt door LSD, gebruikmakend van een placebo-gecontroleerde opstelling. Het onderzoeksteam onderzocht ook de rol van muziek bij het opwekken van piek- of spirituele ervaringen.

Tien deelnemers woonden twee onderzoeksdagen bij. Op een van die dagen kregen ze een placebo (10ml zoutoplossing), terwijl ze op de andere dag tussen 40 en 80 μg LSD kregen, met ongeveer een week ertussen. Het ontwerp was enkelblind, wat betekent dat de deelnemers niet wisten in welke toestand ze verkeerden, maar de onderzoekers wel. Deelnemers luisterden naar een afspeellijst van vijf verschillende instrumentele nummers (voornamelijk neoklassiek en ambient) op beide onderzoeksdagen, waarbij de volgorde van de nummers door de deelnemersgroep heen evenredig werd verdeeld. Om de emotionele reactie op de muziek vast te stellen, werden deelnemers gevraagd hoezeer ze emotioneel werden beïnvloed door de muziek. Hun antwoorden vormden de hoofdzakelijke uitkomst van het onderzoek. Verder werd de Geneva Emotional Music Scale (GEMS-9) gebruikt om de specifieke factoren van de emotionele ervaringen van de deelnemers te onderzoeken, bestaande uit 9 subcategorieën van emotie (verwondering, transcendentie, kracht, zachtheid, nostalgie, vredigheid, speelse activering en spanning). De resultaten lieten zien dat de gemiddelde scores voor emotionele respons op muziek significant hoger waren voor de LSD-toestand dan voor de placebo. Daar bovenop bleek dat alle negen factoren van de GEMS-9 hoger scoorden bij de LSD-toestand dan bij de placebo, met significante toenames bij de aspecten “verwondering”, “transcendentie”, “kracht” en “zachtheid”. Verbandzoekende analyses lieten een significante positieve relatie zien tussen de aangegeven intensiteit van de effecten van de toegediende middelen en de emotionele prikkeling door de muziek.

De bevinding dat LSD de emotionele reactie op muziek versterkt ondersteunt de populaire aanname dat muziek meer betekenis heeft onder invloed van psychedelica. Overstijgings-emoties (transcendentie) en gevoelens van verwondering worden van oudsher gezien als kernelementen van spirituele of piekervaringen [6][7]. Hieruit leidden de onderzoekers af dat de combinatie van LSD en muziek de kans op het hebben van spirituele of piekervaringen kan vergroten. Bovendien is van deze ervaringen in het verleden aangetoond dat ze in verband kunnen worden gebracht met blijvende verbeteringen in gevoelens van welzijn en levensblijheid [8] en ook met toenames in de persoonlijkheidseigenschap van openheid [9], wat de opvatting ondersteunt dat muziek een belangrijk element in psychedelisch-ondersteunde therapie is.

Aangezien dit een pilot-onderzoek is, zijn er beperkingen aan verbonden. Een kleine populatievertegenwoordiging en de selectie van muziekgenres betekenen dat de resultaten niet kunnen worden gegeneraliseerd voor een grotere bevolkingsgroep. Ook kunnen de deelnemers hebben geraden wat het doel van het onderzoek was, wat betekent dat de resultaten zouden kunnen voortkomen uit hun eigen verwachtingen, of die van de onderzoekers. Daarbij zouden de resultaten ook alleen aan het effect van LSD kunnen worden toegeschreven, in plaats van aan het specifieke effect van muziek in combinatie met het middel.

Op de vraag naar de implicaties van zijn onderzoek voor toekomstige studies, zei dhr. Kaelen ons dat dit slechts bescheiden eerste stapjes zijn in het bijdragen aan een door bewijs geschraagde aanpak van psychedelische therapie. “Het is belangrijk om de discussie aan te gaan over de rol van muziek, en meer algemeen over het belang van de juiste setting, bij psychedelische therapie,” zegt Kaelen. “Vanwege de beperkingen van dit onderzoek moeten toekomstige studies andere ontwerpen en meer gedetailleerde onderzoeksvragen bedenken.” Kaelen noemde ook reeds aangevangen onderzoeken door het Imperial College, waarbij onder andere gebruik wordt gemaakt van hersenscans zoals fMRI en MEG, en die zich richten op de vraag welke hersenmechanismen hierbij betrokken zijn. Hij legde ook de nadruk op het belang van het vertalen van elementen naar klinisch werk. “Een klinisch onderzoek, dat momenteel aan het Imperial College gaande is, maakt gebruik van psilocybine voor behandelings-resistente depressie. Een deel van dit onderzoek kijkt naar de rol van muziek, wat hopelijk zal bijdragen aan een dieper inzicht in hoe muziek en psychedelische therapie samenwerken.”


[1] Busch AK, Johnson WC (1950) L.S.D. 25 as an aid in psychotherapy; preliminary report of a new drug. Diseases of the nervous system 11: 241-243

[2] Leuner HC (1983) Psycholytic therapy: Hallucinogenics as an aid in psychodynamically oriented psychotherapy In Psychedelic Reflections, ed. Grinspoon L & Bakalar JB, pp. 177-192: Human Science Press

[3] Bonny HL, Pahnke WN (1972) The use of music in psychedelic (LSD) psychotherapy. Journal of music therapy: 64-87

[4] Grof S (1980) LSD Psychotherapy. Hunter House Publishers, US

[5] Kaelen et al. (2015) LSD enhances the emotional response to music . Journal of Psychopharmacology

[6] Maslow AH (1993) The Farther Reaches of Human Nature. Arkana

[7] Richards WA (2009) The rebirth of research with entheogens: lessons from the past and hypotheses for the future. The Journal of Transpersonal Psychology Vol. 41: 139-150

[8] Griffiths RR, Richards W, Johnson MW, McCann U, Jesse R (2008) Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. Journal of psychopharmacology 22: 621-632

[9] MacLean KA, Johnson MW, Griffiths RR (2011) Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. Journal of psychopharmacology 25: 1453-1461

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Noribogaine is a G-Protein Biased κ-Opioid Receptor Agonist

Abstract

Noribogaine is the long-lived human metabolite of the anti-addictive substance ibogaine. Noribogaine efficaciously reaches the brain with concentrations up to 20 μM after acute therapeutic dose of 40 mg/kg ibogaine in animals. Noribogaine displays atypical opioid-like components in vivo, anti-addictive effects and potent modulatory properties of the tolerance to opiates for which the mode of action remained uncharacterized thus far. Our binding experiments and computational simulations indicates that noribogaine may bind to the orthosteric morphinan binding site of the opioid receptors. Functional activities of noribogaine at G-protein and non G-protein pathways of the mu and kappa opioid receptors were characterized. Noribogaine was a weak mu antagonist with a functional inhibition constants (Ke) of 20 μM at the G-protein and β-arrestin signaling pathways. Conversely, noribogaine was a G-protein biased kappa agonist 75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50 = 9 μM) but only 12% as efficacious at recruiting β-arrestin, which could contribute to the lack of dysphoric effects of noribogaine. In turn, noribogaine functionally inhibited dynorphin-induced kappa β-arrestin recruitment and was more potent than its G-protein agonistic activity with an IC50 of 1 μM. This biased agonist/antagonist pharmacology is unique to noribogaine in comparison to various other ligands including ibogaine, 18-MC, nalmefene, and 6’-GNTI. We predict noribogaine to promote certain analgesic effects as well as anti-addictive effects at effective concentrations >1 μM in the brain. Because elevated levels of dynorphins are commonly observed and correlated with anxiety, dysphoric effects, and decreased dopaminergic tone, a therapeutically relevant functional inhibition bias to endogenously released dynorphins by noribogaine might be worthy of consideration for treating anxiety and substance related disorders.

Maillet, E. L., Milon, N., Heghinian, M. D., Fishback, J., Schürer, S. C., Garamszegi, N., & Mash, D. C. (2015). Noribogaine is a G-Protein Biased κ-Opioid Receptor Agonist. Neuropharmacology. https://dx.doi.org/10.1016/j.neuropharm.2015.08.032
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5-HT2A and mGlu2/3 receptor interactions: on their relevance to cognitive function and psychosis

Abstract

Serotonin [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”][5-hydroxytryptamine (5-HT)] and glutamate have both been implicated in the pathophysiology of neuropsychiatric disorders but also in the mechanism of antipsychotic and hallucinogenic drug actions. Furthermore, close antagonistic interactions between 5-HT2A and metabotropic glutamate (mGlu)2/3 receptors have been established over the last decades on the basis of numerous electrophysiological, biochemical, and behavioral studies. Besides synaptic mechanisms, more recent findings suggested that heterodimeric 5-HT2A-mGlu2 receptor complexes in the prefrontal cortex may account for the functional crosstalk between these two receptor subtypes. In this review, we focus on in-vitro and in-vivo studies documenting the important relationship between 5-HT2A and mGlu2/3 receptors, with relevance to both normal behavioral function and psychosis.

Wischhof, L., & Koch, M. (2015). 5-HT2A and mGlu2/3 receptor interactions: on their relevance to cognitive function and psychosis. Behavioural pharmacology. https://dx.doi.org/10.1097/FBP.0000000000000183
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Mathematics and mysticism

Abstract

Is there a world of mathematics above and beyond ordinary reality, as Plato proposed? Or is mathematics a cultural construct? In this short article we speculate on the place of mathematical reality from the perspective of the mystical cosmologies of the ancient traditions of meditation, psychedelics, and divination.

Abraham, R. (2015). Mathematics and Mysticism. Progress in biophysics and molecular biology. https://dx.doi.org/10.1016/j.pbiomolbio.2015.08.016
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LSD enhances the emotional response to music

Abstract

RATIONALE:

There is renewed interest in the therapeutic potential of psychedelic drugs such as lysergic acid diethylamide (LSD). LSD was used extensively in the 1950s and 1960s as an adjunct in psychotherapy, reportedly enhancing emotionality. Music is an effective tool to evoke and study emotion and is considered an important element in psychedelic-assisted psychotherapy; however, the hypothesis that psychedelics enhance the emotional response to music has yet to be investigated in a modern placebo-controlled study.

OBJECTIVES:

The present study sought to test the hypothesis that music-evoked emotions are enhanced under LSD.

METHODS:

Ten healthy volunteers listened to five different tracks of instrumental music during each of two study days, a placebo day followed by an LSD day, separated by 5-7 days. Subjective ratings were completed after each music track and included a visual analogue scale (VAS) and the nine-item Geneva Emotional Music Scale (GEMS-9).

RESULTS:

Results demonstrated that the emotional response to music is enhanced by LSD, especially the emotions “wonder”, “transcendence”, “power” and “tenderness”.

CONCLUSIONS:

These findings reinforce the long-held assumption that psychedelics enhance music-evoked emotion, and provide tentative and indirect support for the notion that this effect can be harnessed in the context of psychedelic-assisted psychotherapy. Further research is required to test this link directly.

Kaelen, M., Barrett, F. S., Roseman, L., Lorenz, R., Family, N., Bolstridge, M., … & Carhart-Harris, R. L. (2015). LSD enhances the emotional response to music. Psychopharmacology, 1-8. https://dx.doi.org/10.1007/s00213-015-4014-y
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Lysergic Acid Diethylamide and Psilocybin Revisited

Abstract

The past decade brought the beginnings of a renaissance in research on psychedelic drugs. Two articles in this issue of Biological Psychiatry signify that the resurrection of this long-ignored topic has begun to mature and bear at least the promise of fruit. In the early 1970s, the onset of the “War on Drugs” brought with it a near-total hiatus in serious research on psychedelic drugs, especially in the United States. The resumption of credible work in this area has come from Switzerland, where many of the original pioneering studies were initiated in the 1950s and 1960s.

Geyer, M. A. (2015). Lysergic Acid Diethylamide and Psilocybin Revisited. Biological psychiatry, 78(8), 516-518. http://dx.doi.org/10.1016/j.biopsych.2015.08.003
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[Interview] Michael Bogenschutz likens psilocybin treatment to ‘reverse PTSD’

Addiction psychologist Michael P. Bogenschutz currently works at the Department of Psychiatry at NYU. Prior to New York, he worked at the Department of Psychiatry and Behavioral Sciences, University of New Mexico.

Much of Bogenschutz’s work has involved searching for new applications of existing treatments for addictions. The OPEN Foundation talked to him to learn more about his research on psilocybin-assisted treatment for alcohol dependence, the first trial of its kind.

Could you briefly describe your career, and what led you to pursue psychedelic research?

My career has focused on clinical treatment and, particularly in the last 10-15 years, clinical research on treating addictions. I have always been deeply interested in how people change and how we can facilitate change in problematic behaviours.

Working with patients, you’ll find people who will tell you they came to a point where they just quit suddenly, while some gradually become abstinent or the problem diminished over time, and others have relapse episodes for years, never improve, or get worse. There is a very real and not uncommon phenomenon of sudden and categorical change in behaviour, which is not unique to addiction. I find that interesting scientifically, psychologically and clinically. Why does this happen to some people and not to others?

I really became interested in research with psychedelics shortly after joining the faculty at the University of New Mexico (UNM) in 1994. At that time, Rick Strassman was doing work with the intravenous administration of DMT. Dr. Strassman left UNM not long afterwards and as I was a junior faculty member, it didn’t seem realistic to pursue my own research in that area. I didn’t think much about it again until I saw Roland Griffiths’ 2006 paper on the effects of psilocybin on healthy volunteers.

I was immensely impressed with both the findings and the fact that it was possible to do these kinds of studies. In that paper, the authors describe the acute effects of psilocybin in volunteers and the relatively high frequency of mystical types of experiences. More importantly, from a clinical perspective, there was a report of the persisting change in attitudes, emotional states and relationships. The follow-up paper two years later documented the persistence of these effects on the basis of a single experience with relatively high doses. I found it immensely interesting and it made sense to start investigating the clinical potential of these types of drugs myself.

Addiction obviously has a huge public health impact. Why are you interested in alcohol-related issues and treatments in particular?

I’m interested in addiction in general but for me alcohol, which is a very common, devastating addiction throughout the world, was a logical place to start. As I learned when I started investigating the topic, a considerable amount of research on the use of psychedelic treatment (mainly LSD) and alcohol had already been conducted in the late 1950s.

In the United States, the Alcoholics Anonymous (AA) philosophy is prevalent in addiction treatment. It’s a philosophy that emphasizes the spiritual component of the addiction process and the importance of becoming healthier spiritually in order to recover. This also interests me.

What are the benefits of using psilocybin over LSD in a study?

Psilocybin has two practical advantages. For one, the duration of action is significantly shorter, in the order of six hours instead of ten with LSD. This makes psilocybin easier to use in an outpatient model. In other words, you can administer it in the course of a normal workday, whereas LSD sessions could easily continue late into the evening. Another important reason is that there is much more stigma attached to LSD. Many people think of LSD as a very dangerous and frightening drug. Certainly in the 1960s, there were many adverse reactions to LSD. Much of this had to do with taking extremely high doses of a substance with unknown potency, as well as a lack of understanding at the time about how important setting was in determining an experience’s outcome. Clinically speaking, both LSD and psilocybin appear to be very safe when used under carefully controlled research conditions. Also, even though the psilocybin we administer is actually a synthetic version, people often think of the substance as “mushrooms” or a naturally occurring compound, which is reassuring to some people.

Could you generalise about what types of persons were interested in joining this trial?

We recruited from the community, using advertisements aimed specifically at people who were not engaged in treatment. We wanted this to be a stand-alone treatment. We required people to be alcohol dependent, in general good health, and not suffering from any serious psychiatric illness. In our Albuquerque study, participants were working and had some intact social structure or support. They had been alcohol-dependent for an average of 15 years, the mean age was 40, and there were six men and four women. Some had limited amounts of experience with psychedelics in the past, but we excluded those with extensive use.

One concern was that people might volunteer because they wanted a psilocybin experience. We wanted to attract those seriously interested in changing their drinking and open to the possibility of novel treatments.

Can you describe the setting you provided for your patients?

The outpatient clinic was set up to look as much as possible like a comfortable living room with a large couch. We asked participants for most of the session to wear eyeshades and headphones – there was a standard program of music – and instructions were to focus on their internal experience, to accept and explore whatever came up. We prepared them for what they might experience during sessions, what the possible range of experiences could be, and advised them to manage those experiences in order to make the most of them. We believed that setting an intention was important. In this context, the general intention might have been to use the session to learn or experience something to help them make a positive change in drinking or other issues related to drinking they wanted to explore. There was very little direct intervention. Two therapists provided support and were available to intervene when needed, otherwise they checked in every 30 minutes to an hour to make sure the participant was doing okay. At the end of that session, the participants could start talking about what they had experienced. (The volunteers received psilocybin in one or two supervised sessions; this was in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions, ed.)

In some of the initial LSD trials, the therapists’ aim was to recreate an experience akin to delirium tremens (DT), a severe withdrawal symptom sometimes experienced by alcohol-dependent patients. These DTs were often a turning point for alcoholics, and they felt LSD could have similar consequences. What they found was that some participants had mystical, transcendent experiences that affected their long-term behaviour. Could you describe how peak experiences affected the patients in your study?

On a psychological and biological level, we don’t have theories, let alone data to explain these phenomena. In the context of a person trying to address a problem and make a kind of change, what we’ve seen is that participants often have an experience of oneness, the hallmark of a mystical experience. They have a sense of unity with all of creation or the universe or God, and they also have a very powerful experience of love and connection on a deep emotional level. This includes self-love and self-compassion, that feeling of being okay. This sounds almost trivial, but for some of these folks who’ve experienced a lifetime of feeling unloved, it’s a very powerful experience. In some cases, they told us their drinking had been motivated by the lack of feeling loved or lovable, and that this experience made them feel less like they needed to drink for that reason.

Other changes accompany this kind of experience. People emerge with a sense of optimism that change is possible, that life can be different because they have experienced something that is so different from anything they could have imagined. We’ve seen people spend a lot of time during sessions thinking about family and relationships, about the grief, guilt and harm their drinking has brought to others, as well as themselves. People emerge from sessions talking about pro-social values like being a good parent or contributing to society. We’ve measured significant decreases in craving and an increase in confidence that they will be able to make a change in their drinking.

How can taking a drug once or twice cause lasting behaviour change? What evidence speaks to this question?

I don’t really have an answer. Clearly things are going on in the brain and we are beginning to conduct studies that look at brain function using MRI scans before and after the psilocybin sessions. But we can’t say yet why a single acute experience can produce such lasting changes.

The best analogy we have come up with is Post Traumatic Stress Disorder (PTSD), in which a single traumatic event can impact someone’s day-to-day experience. These traumas can be of a purely psychological nature, though they often involve physical violence as well. PTSD is an example of how an acute event can cause persistent psychological and measurable biological changes in brain function and structure. Maybe what we are seeing with psilocybin is something like the opposite of PTSD—an experience so powerfully positive it can actually make lasting impact on one’s psyche and brain.

Addiction is a misguided search for spirituality. Can you comment on this or elaborate?

Carl Jung is really the person who expanded on this idea, which was that through intoxicants people (in some limited way) were able to experience connection, unity, a sense of wellness and being loved. You can think of it as a misguided search for mystical or human connection, a way to experience a reliable emotional attachment to something external in order to receive comfort. This can be a useful way of understanding and reframing people’s struggle with addictive substances as not simply seeking hedonistic pleasure, but a genuine desire for wholeness. Though if this isn’t found in healthier ways, it can readily become a trap.

The outcome of your study seems to be very promising: all of the patients experienced a definite improvement. However it was a small sample. Do you have plans to do another clinical trial?

This was a small trial without a control group, done to demonstrate the feasibility of conducting such a study. We were able to demonstrate clinical improvement, and the degree of improvement correlated with the strength of the subject’s experience during sessions. It is suggestive and by no means conclusive or convincing evidence. We need to do much larger controlled trials. Our current trial aims to recruit 180 alcohol-dependent patients, which will provide a much more rigorous test of efficacy. This will take a few years—we estimate five—to complete the trial.

Do you think there may be obstacles other than scientific that might bring psychedelic research to a halt all over again? Or do you think it will evolve into standard practice?

We understand these drugs better scientifically than we did in the 1960s, in terms of effects, potential dangers, and how to minimise those dangers in a clinical research setting. The people doing clinical research with psychedelics now are serious, experienced scientists who approach their work cautiously and with scientific rigour. The general public also has a much better understanding of psychedelics than it did 50 years ago. We need to stay balanced in our approach and avoid extrapolating beyond the data, guard against exaggerated claims and expectations, and remind people of the significant risks that exist with these drugs when used outside of structured and controlled settings.

While I and others in the field are hopeful that what we discover will lead to important advances in addiction treatment, no drug is a magic cure. There are limitations to any treatment. Addiction is a complex, chronic disorder and you cannot cure everyone in one or two sessions, nor reduce the risks to zero. But it’s reasonable to hope that we will be able to demonstrate reproducible benefits, and learn a lot about the psychology and biology of behaviour change in the process.

[Interview] Michael Bogenschutz likens psilocybin treatment to ‘reverse PTSD’ Read More »

In-Person Psychedelic Community Picnic (Amsterdam) - July 29