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The rise, fall, and possible rise of LSD

August 1, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Humanities & Art, LSD, Papers, Publications, Substance Use Disorder / By / ,

Abstract

LSD and other hallucinogens or psychedelics have been therapeutically used in psychiatry in the period between the Second World War and the late 1980s. In the past years renewed interest in the medical sciences for research and therapeutic use of these substances has evolved. AIM: A discussion of contemporary lsd research in the context of earlier research. METHOD: A systematic survey of the literature on the psychiatric use of lsd and the reactions towards lsd use in society. RESULTS: Since 1947 lsd has been therapeutically used in the treatment of anxiety, depression, addiction, post traumatic disorders, and other conditions. Since the early 1960s this use has been criticized because of the danger of evoking psychoses in patients, and because of the rise of a widespread non-medical use. However, there is no consolidated evidence-base for either the positive or the negative outcomes of lsd therapy. CONCLUSION: At this moment it is unpredictable whether lsd will make a comeback in psychiatry. Contemporary research attempts to evade all public controversy and to build up a solid evidence-base. Nevertheless it demonstrates a direct continuity with earlier research.

Snelders, S., & Pieters, T. (2020). The rise, fall, and possible rise of LSD. Tijdschrift Voor Psychiatrie, 62(8), 707-712.
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[Psychedelics in the treatment of substance use disorders and psychosis]

August 1, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, Papers, Psychology, Psychotic Disorders, Publications, Substance Use Disorder / By / , , ,

Abstract

After psychedelics were banned in 1968, the flourishing research on the use of psychedelics in patients with a mental disorder stopped abruptly. Recently, we see a renaissance of this research.<br/> AIM: To present an overview of what is known about the treatment of addiction and psychosis with psychedelics.<br/> METHOD: Literature study based on Medline en PubMed publications till December 2019.<br/> RESULTS: Studies on the effectiveness of psychedelics in the treatment of addiction and psychosis is still very limited in size and methodological quality. Nevertheless, most studies show positive effects of both classical and atypical psychedelics in a variety of addictions on motivation, craving, reduced consumption, and abstinence often following a single dose and with long-lasting benefits (3-24 months). Use of ketamine in patients with a psychosis stabilized on an antipsychotic might reduce negative symptoms.<br/> CONCLUSION: Before psychedelics can be used in standard clinical practice for the treatment of patients with an addiction or a psychosis, larger and methodologically better studies are needed. The use of psychedelics also creates an opportunity to better understand the shared underlying pathology of many different mental disorders.
van den Brink, W., Breeksema, J. J., Vermetten, E., & Schoevers, R. A. (2020). Psychedelics in the treatment of substance use disorders and psychosis. Tijdschrift Voor Psychiatrie, 62(8), 650-658., https://pubmed.ncbi.nlm.nih.gov/32816293/
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[Psychedelics for existential distress in terminally ill patients]

August 1, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Existential distress in patients with a terminal illness is often associated with (symptoms of) anxiety and depression. Psychotherapeutic interventions seem effective but effects are short-lived. There are no proven effective pharmacological interventions.<br/> AIM: To present an overview of literature on psychedelic treatment of existential distress in patients with terminal illness.<br/> METHOD: Literature research in PubMed/Medline databases, supplemented with cross-references.<br/> RESULTS: 14 clinical studies have been conducted: 6 with classic psychedelics between 1960 and 1980, and 8 with classic psychedelics and ketamine after 2000. Results of early pre-post studies are promising but have serious methodological limitations. Recent clinical research with LSD, psilocybin and ketamine are also promising although limited in terms of research design and generalizability. Overall, studies show a positive effect on existential and spiritual well-being, quality of life, acceptance and (symptoms of) anxiety and depression. Mystical experiences are correlated with positive outcomes. Few adverse effects are reported.<br/> CONCLUSION: Treatment of existential distress using classical psychedelics or ketamine in patients with terminal illness seems auspicious. Larger clinical studies in a more diverse patient population with fewer methodological limitations are needed to draw conclusions about efficacy and generalizability.
Schimmel, N., Breeksema, J. J., Veraart, J. K. E., van den Brink, W., & Schoevers, R. A. (2020). Psychedelics for existential distress in terminally ill patients. Tijdschrift Voor Psychiatrie, 62(8), 659-668., https://europepmc.org/article/med/32816294
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Microdosing with psychedelics: what do we know?

August 1, 2020 / LSD, Microdosing, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

The repeated use of small doses of psychedelics such as psilocybin and lsd over a period of time (microdosing, md) has gained popularity and scientific attention in recent years. Retrospective reports from users suggest clinical potential.<br/> AIM: To answer the question whether md with psychedelics could theoretically provide symptom relief for people with psychiatric disorders. <br/> METHOD: Investigate what the current evidence is about the effects of md with psychedelics on the behavioral level, psychological functioning and mental well-being. A search for relevant articles in PubMed and Medline databases (on January 10, 2020), which resulted in a total of 28 hits. After de-duplication, removal of irrelevant and addition of relevant articles, 23 articles were included.<br/> RESULTS: Most of the knowledge we have so far comes from uncontrolled online questionnaire studies in which users report retrospectively or keep diaries of the effects they experience during md. According to users, it leads to positive effects on mood, concentration, focus and productivity. Negative effects, including physical discomfort and increased fear, also seem to occur. The limited number of experimental studies in healthy people revealed that md has subtle effects on cognitive processes and brain connectivity.<br/> CONCLUSION: The findings of experimental studies in combination with the reports from users give cause for further investigation into the clinical potential of low-dose psychedelics in combating certain symptoms. More placebo-controlled studies are needed to provide clarity for who (age, diagnosis) md can be effective and for which (cognitive, emotional) processes.
Kuypers, K. P. C. (2020). Microdosing with psychedelics: what do we know?. Tijdschrift Voor Psychiatrie, 62(8), 669-676., https://pubmed.ncbi.nlm.nih.gov/32816295/

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[Psychedelics in the treatment of PTSD]

August 1, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Ketamine, LSD, MDMA, Papers, Psychology, Publications / By / , , , , ,

Abstract

Posttraumatic stress disorder (PTSD) is often a chronic condition, despite the availability of various evidence-based treatment options. Psychedelics offer new treatment opportunities.<br/> AIM: An overview of the current evidence, therapeutic context, and possible mechanisms of action of different types of psychedelics in the treatment of PTSD.<br/> METHOD: A scoping review of the available literature.<br/> RESULTS: MDMA-assisted psychotherapy has shown to produce lasting reductions in PTSD symptoms in multiple RCTs. Based on a small number of studies, ketamine administration appears to lead to temporary symptom relief. Current studies are investigating whether the use of ketamine in combination with psychotherapy can lead to lasting reductions in PTSD symptoms. Classical psychedelics (such as psilocybin and LSD) induce psychoactive effects (on behavior or experience) that could contribute to the psychotherapeutic treatment of PTSD but have not yet been investigated in controlled studies. Reported positive effects extend beyond PTSD symptoms only.<br/> CONCLUSION: Psychedelics may have potential to serve as a catalyst for the psychotherapeutic treatment of PTSD. Most evidence exists for MDMA-supported psychotherapy; relatively little research is available on ketamine and classical psychedelics. Future research needs to show whether the use of psychedelics can be integrated into available treatment options for PTSD.
Vermetten, E., Krediet, E., Bostoen, T., Breeksema, J. J., Schoevers, R. A., & van den Brink, W. (2020). Psychedelics in the treatment of PTSD. Tijdschrift Voor Psychiatrie, 62(8), 640-649., https://pubmed.ncbi.nlm.nih.gov/32816292/

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The Current Status of Psychedelics in Psychiatry

July 29, 2020 / Humanities & Art, LSD, Papers, Publications / By / ,

Abstract

In the 1950s, the Swiss pharmaceutical company Sandoz, which employed the chemist Albert Hofmann, who discovered lysergic acid diethylamide (LSD) and the similar serotonergic psychedelic psilocybin, made these drugs available to the psychiatric research community as the products Delysid and Indocybin, respectively. By the 1960s, these drugs had caused a revolution in brain science and psychiatry because of their widespread use by researchers and clinicians in many Western countries, especially the US. Before LSD was banned, the US National Institutes of Health funded more than 130 studies exploring its clinical utility, with positive results in a range of disorders but particularly anxiety, depression, and alcoholism. However, the displacement of LSD into recreational use and eventual association with the anti-Vietnam war movement led to all psychedelics being banned in the US. This ban became ratified globally under the 1971 UN Convention on narcotics. Since then, research funding, drug production, and the study of psychedelics as clinical agents has been virtually stopped. Until very recently, no companies would manufacture medical-grade psychedelics, which made getting regulatory approval for clinical research—especially clinical trials—very difficult and in some countries (eg, Germany) impossible.

Nutt, D., & Carhart-Harris, R. (2021). The current status of psychedelics in psychiatry. JAMA psychiatry, 78(2), 121-122.; 10.1001/jamapsychiatry.2020.2171
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LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors

July 22, 2020 / LSD, Papers, Psychology, Publications / By / , , , ,

Abstract

Adapting one’s attitudes and behaviors to group norms is essential for successful social interaction and, thus, participation in society. Yet, despite its importance for societal and individual functioning, the underlying neuropharmacology is poorly understood. We therefore investigated its neurochemical and neural correlates in a pharmacological functional magnetic resonance imaging study. Lysergic acid diethylamide (LSD) has been shown to alter social processing and therefore provides the unique opportunity to investigate the role of the 5-HT2A receptor in social influence processing. Twenty-four healthy human volunteers received either (1) placebo + placebo, (2) placebo + LSD (100 µg), or (3) the 5-HT2A receptor antagonist ketanserin (40 mg) + LSD (100 µg) at three different occasions in a double-blind, randomized, counterbalanced, cross-over design. LSD increases social adaptation but only if the opinions of others are similar to the individual’s own. These increases were associated with increased activity in the medial prefrontal cortex while participants received social feedback. Furthermore, pretreatment with the 5-HT2A antagonist ketanserin fully blocked LSD-induced changes during feedback processing, indicating a key role of the 5-HT2A system in social feedback processing. Our results highlight the crucial role of the 5-HT-system in social influence and, thus, provide important insight into the neuropharmacological basis of social cognition and behavior.
Duerler, P., Schilbach, L., Stämpfli, P., Vollenweider, F. X., & Preller, K. H. (2020). LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors. Scientific reports, 10(1), 1-11., https://doi.org/10.1038/s41598-020-68899-y
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Immunochemical monitoring of psilocybin and psilocin to identify hallucinogenic mushrooms

July 21, 2020 / Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Publications / By

Abstract

Development of rapid and reliable immunochemical methods for monitoring psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine; Pyb) and psilocin (dephosphorylated metabolite; Psi), the psychoactive compounds contained within hallucinogenic mushrooms (magic mushrooms), is desirable in order to identify these mushrooms and regulate their illicit use. Because no antibody was publicly available for this purpose, we generated two independent monoclonal antibodies (mAbs) against Pyb or Psi, and then developed enzyme-linked immunosorbent assays (ELISAs) by using them. To generate the specific antibodies, novel immunogenic conjugates were prepared by linking Pyb or Psi molecules to carrier proteins by modifying their 2-(N,N-dimethylamino)ethyl side chains. Spleen cells from mice immunized with these conjugates were fused with P3/NS1/1-Ag4-1 myeloma cells, and hybridoma clones secreting anti-Pyb and anti-Psi mAbs were established. These mAbs were characterized for their biochemical features and then applied to competitive ELISAs, which used microplates coated with Pyb or Psi linked with albumin. These ELISAs enabled the determination of Pyb or Psi with measurable ranges of ca. 0.20-20 or 0.040-2.0 μg/assay (limit of detection was 0.14 or 0.029 μg/assay), respectively. The related tryptamines were satisfactorily discriminated as exemplified by the cross-reactivity of the ELISA to determine Pyb (or Psi) with Psi (or Pyb) that were found to be 2.8 % (or <0.5 %), respectively. The Pyb and Psi contents in a dried powder of the hallucinogenic mushroom, Psilocybe cubensis, were determined to be 0.39 and 0.32 (w/w)%, respectively. The ELISAs developed using the current mAbs are promising tools for identifying illegal hallucinogenic mushrooms.

Morita, I., Oyama, H., Kiguchi, Y., Oguri, A., Fujimoto, N., Takeuchi, A., … & Kobayashi, N. (2020). Immunochemical monitoring of psilocybin and psilocin to identify hallucinogenic mushrooms. Journal of Pharmaceutical and Biomedical Analysis, 190, 113485; 10.1016/j.jpba.2020.113485

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Ibogaine therapy for addiction: Consumer views from online fora

July 18, 2020 / Anthropology & Sociology, Iboga / Ibogaine, Papers, Psychology, Publications / By / , , ,

Abstract

Background Ibogaine is a psychedelic drug used by for-profit clinics and lay-people to treat addiction, despite some reported fatalities and a lack of rigorous clinical research. Little is known about ibogaine therapy from a consumer perspective. Online discussions generate and disseminate information about ibogaine therapy and provide a window into how people understand ibogaine’s risks and uses. We examined views expressed in online fora in order to describe a consumer perspective of ibogaine therapy for addiction, and to elucidate the role of online fora in mediating people’s understanding of, and engagement with ibogaine. Methods We thematically analysed 40 threads comprising posts from 101 individual contributors from two popular online fora; Reddit (n = 20) and Drugs Forum (n = 20). Results Our analysis identified three primary themes: (1) online fora as a resource for do-it-yourself research; (2) the therapeutic interaction in ibogaine therapy, and; (3) therapeutic mechanisms of ibogaine. Online fora were a key resource for information about ibogaine therapy, where personal experiences and evidence-based information were valued. Treatment arrangements, risks, and harm reduction were discussed at length by forum participants. Discussions of therapeutic effects focused on pharmacological mechanisms but positive psychological changes resulting from the psychedelic experience were also reported. Clinic-based treatment was preferred by many forum participants due to safety concerns, but money and time and treatment intent sometimes necessitated lay-administration of ibogaine. Microdosing of ibogaine was also frequently discussed. Conclusion: Online fora appear to have facilitated a sense of community where individuals are held to account for the success of ibogaine therapy. Fora discussions illustrate that neuroscientific explanations of addiction and behaviour have explanatory salience for people involved in ibogaine therapy. Online fora could be used as a platform for clinician and peer-led support and harm-reduction interventions, and for further research monitoring treatment practices and long-term outcomes.

Barber, M., Gardner, J., Savic, M., & Carter, A. (2020). Ibogaine therapy for addiction: Consumer views from online fora. International Journal of Drug Policy, 83, 102857.; 10.1016/j.drugpo.2020.102857

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Perceived harm, motivations for use and subjective experiences of recreational psychedelic 'magic' mushroom use

July 17, 2020 / Anthropology & Sociology, Mushrooms / Psilocybin, Papers, Publications / By / , , , ,

Abstract

Background: Data on actual harm of magic mushrooms suggest that toxicity and abuse potential is low, however, their legal status suggests otherwise. We aimed to gauge perception of harm of magic mushrooms in both users and mushroom-naïve participants. We also aimed to observe differences in expectations of effects between users and mushroom-naïve participants, and whether motivations for use predicted their expected effects.

Method: In total, 73 polydrug users with experience of using magic mushrooms and 78 mushroom-naïve participants completed an online survey. We asked participants to rank a list of 10 substances from most dangerous to least dangerous and questioned them about expectation of effect using a modified magic mushroom expectation questionnaire. Users were asked about their motivations for using magic mushrooms.

Results: Both groups perceive mushrooms to be safer than heroin, cocaine, prescription painkillers, gamma-hydroxybutyrate (GHB), ecstasy, tobacco and alcohol. However, the mushroom-naïve group ranked mushrooms as significantly more dangerous than the user group. Non-users reported greater expectancy for negative intoxication. Users reported greater expected entactogenic, prosocial, aesthetic and mood effects, and perceptual alterations. Finally, expectant effects of mushroom use were associated with different motivations for use, for example using for personal psychotherapy was associated with expectation of increased entactogenic effects and decreased negative effects.

Conclusion: Our data suggest a general perception of harm that is in line with data on actual harm, but at odds with current legal classifications. Future clinical investigations may require management of negative intoxication expectation of participants with no prior experience of psilocybin.

Roberts, C. A., Osborne-Miller, I., Cole, J., Gage, S. H., & Christiansen, P. (2020). Perceived harm, motivations for use and subjective experiences of recreational psychedelic ‘magic’mushroom use. Journal of Psychopharmacology, 34(9), 999-1007; 10.1177/0269881120936508
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