OPEN Foundation

Anthropology

Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison

Abstract

The recent renaissance of psychedelic science has reignited interest in the similarity of drug-induced experiences to those more commonly observed in psychiatric contexts such as the schizophrenia-spectrum. This report from a multidisciplinary working group of the International Consortium on Hallucinations Research (ICHR) addresses this issue, putting special emphasis on hallucinatory experiences. We review evidence collected at different scales of understanding, from pharmacology to brain-imaging, phenomenology and anthropology, highlighting similarities and differences between hallucinations under psychedelics and in the schizophrenia-spectrum disorders. Finally, we attempt to integrate these findings using computational approaches and conclude with recommendations for future research.

Leptourgos, P., Fortier-Davy, M., Carhart-Harris, R., Corlett, P. R., Dupuis, D., Halberstadt, A. L., Kometer, M., Kozakova, E., LarØi, F., Noorani, T. N., Preller, K. H., Waters, F., Zaytseva, Y., & Jardri, R. (2020). Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison. Schizophrenia bulletin, 46(6), 1396–1408. https://doi.org/10.1093/schbul/sbaa117

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Chemical Composition of Traditional and Analog Ayahuasca

Abstract

Traditional ayahuasca can be defined as a brew made from Amazonian vine Banisteriopsis caapi and Amazonian admixture plants. Ayahuasca is used by indigenous groups in Amazonia, as a sacrament in syncretic Brazilian religions, and in healing and spiritual ceremonies internationally. The study aimed to determine concentrations of the main bio- and psychoactive components of ayahuasca used in different locations and traditions. We collected 102 samples of brews from ayahuasca-using communities. Concentrations of N,N-dimethyltryptamine (DMT), tetrahydroharmine, harmine, and harmaline were determined by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Qualitative analyses for non-traditional additives (moclobemide, psilocin, yuremamine) were performed by high resolution mass spectrometry. Higher and more variable concentrations of DMT in neoshamanic ayahuasca samples compared to indigenous samples may indicate use of higher and more variable proportions of DMT-containing admixture plants. From European samples, we found two related samples of analog ayahuasca containing moclobemide, psilocin, DMT, yuremamine, and very low concentrations of B. caapi alkaloids. Some analogs of ayahuasca (Peganum harmala, Mimosa tenuiflora) were used in Europe. No analogs were found from Brazil or Santo Daime ceremonies in Europe. We recommend awareness about the constituents of the brew and ethical self-regulation among practitioners of ayahuasca ceremonies.

Kaasik, H., Souza, R., Zandonadi, F. S., Tófoli, L. F., & Sussulini, A. (2021). Chemical Composition of Traditional and Analog Ayahuasca. Journal of psychoactive drugs, 53(1), 65–75. https://doi.org/10.1080/02791072.2020.1815911

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Ibogaine therapy for addiction: Consumer views from online fora

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 Policy83, 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

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 Psychopharmacology34(9), 999-1007; 10.1177/0269881120936508
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Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains

Abstract

Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers investigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity. While the concept of criticality is of central importance to this theory, few of the published studies on psychedelics investigate it directly, testing instead related measures such as algorithmic complexity or Shannon entropy. We propose using the fractal dimension of functional activity in the brain as a measure of complexity since findings from physics suggest that as a system organizes towards criticality, it tends to take on a fractal structure. We tested two different measures of fractal dimension, one spatial and one temporal, using fMRI data from volunteers under the influence of both LSD and psilocybin. The first was the fractal dimension of cortical functional connectivity networks and the second was the fractal dimension of BOLD time-series. In addition to the fractal measures, we used a well-established, non-fractal measure of signal complexity and show that they behave similarly. We were able to show that both psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. With both LSD and psilocybin, we were able to localize changes in the fractal dimension of BOLD signals to brain areas assigned to the dorsal-attenion network. These results show that psychedelic drugs increase the fractal dimension of activity in the brain and we see this as an indicator that the changes in consciousness triggered by psychedelics are associated with evolution towards a critical zone.

Varley, T. F., Carhart-Harris, R., Roseman, L., Menon, D. K., & Stamatakis, E. A. (2020). Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains. NeuroImage220, 117049; 10.1016/j.neuroimage.2020.117049
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Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains

Abstract

Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers investigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity. While the concept of criticality is of central importance to this theory, few of the published studies on psychedelics investigate it directly, testing instead related measures such as algorithmic complexity or Shannon entropy. We propose using the fractal dimension of functional activity in the brain as a measure of complexity since findings from physics suggest that as a system organizes towards criticality, it tends to take on a fractal structure. We tested two different measures of fractal dimension, one spatial and one temporal, using fMRI data from volunteers under the influence of both LSD and psilocybin. The first was the fractal dimension of cortical functional connectivity networks and the second was the fractal dimension of BOLD time-series. In addition to the fractal measures, we used a well-established, non-fractal measure of signal complexity and show that they behave similarly. We were able to show that both psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. With both LSD and psilocybin, we were able to localize changes in the fractal dimension of BOLD signals to brain areas assigned to the dorsal-attenion network. These results show that psychedelic drugs increase the fractal dimension of activity in the brain and we see this as an indicator that the changes in consciousness triggered by psychedelics are associated with evolution towards a critical zone.

Varley, T. F., Carhart-Harris, R., Roseman, L., Menon, D. K., & Stamatakis, E. A. (2020). Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains. NeuroImage220, 117049; 10.1016/j.neuroimage.2020.117049
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Psilocybin: from ancient magic to modern medicine

Abstract

Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is an indole-based secondary metabolite produced by numerous species of mushrooms. South American Aztec Indians referred to them as teonanacatl, meaning “god’s flesh,” and they were used in religious and healing rituals. Spanish missionaries in the 1500s attempted to destroy all records and evidence of the use of these mushrooms. Nevertheless, a 16th century Spanish Franciscan friar and historian mentioned teonanacatl in his extensive writings, intriguing 20th century ethnopharmacologists and leading to a decades-long search for the identity of teonanacatl. Their search ultimately led to a 1957 photo-essay in a popular magazine, describing for the Western world the use of these mushrooms. Specimens were ultimately obtained, and their active principle identified and chemically synthesized. In the past 10–15 years several FDA-approved clinical studies have indicated potential medical value for psilocybin-assisted psychotherapy in treating depression, anxiety, and certain addictions. At present, assuming that the early clinical studies can be validated by larger studies, psilocybin is poised to make a significant impact on treatments available to psychiatric medicine.

Nichols, D. E. (2020). Psilocybin: from ancient magic to modern medicine. The Journal of Antibiotics, 1-8., doi.org/10.1038/s41429-020-0311-8
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Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance

Abstract

The efficacy of psychedelic-assisted therapies for mental disorders has been attributed to the lasting change from experiential avoidance to acceptance that these treatments appear to facilitate. This article presents a conceptual model that specifies potential psychological mechanisms underlying such change, and that shows substantial parallels between psychedelic therapy and cognitive behavioral therapy: We propose that in the carefully controlled context of psychedelic therapy as applied in contemporary clinical research, psychedelic-induced belief relaxation can increase motivation for acceptance via operant conditioning, thus engendering episodes of relatively avoidance-free exposure to greatly intensified private events. Under these unique learning conditions, relaxed avoidance-related beliefs can be exposed to corrective information and become revised accordingly, which may explain long-term increases in acceptance and corresponding reductions in psychopathology. Open research questions and implications for clinical practice are discussed.

Wolff, M., Evens, R., Mertens, L. J., Koslowski, M., Betzler, F., Gründer, G., & Jungaberle, H. (2020). Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance. Frontiers in Psychiatry11, 5.; 10.3389/fpsyt.2020.00005
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Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey.

Abstract

Background: Observational data and preliminary studies suggest serotonin 2A agonist psychedelics may hold potential in treating a variety of substance use disorders (SUDs), including opioid use disorder (OUD).

Aims: The study aim was to describe and analyze self-reported cases in which naturalistic psychedelic use was followed by cessation or reduction in other substance use.

Methods: An anonymous online survey of individuals reporting cessation or reduction in cannabis, opioid, or stimulant use following psychedelic use in non-clinical settings.

Results: Four hundred forty-four respondents, mostly in the USA (67%) completed the survey. Participants reported 4.5 years of problematic substance use on average before the psychedelic experience to which they attributed a reduction in drug consumption, with 79% meeting retrospective criteria for severe SUD. Most reported taking a moderate or high dose of LSD (43%) or psilocybin-containing mushrooms (29%), followed by significant reduction in drug consumption. Before the psychedelic experience 96% met SUD criteria, whereas only 27% met SUD criteria afterward. Participants rated their psychedelic experience as highly meaningful and insightful, with 28% endorsing psychedelic-associated changes in life priorities or values as facilitating reduced substance misuse. Greater psychedelic dose, insight, mystical-type effects, and personal meaning of experiences were associated with greater reduction in drug consumption.

Conclusions: While these cross-sectional and self-report methods cannot determine whether psychedelics caused changes in drug use, results suggest the potential that psychedelics cause reductions in problematic substance use, and support additional clinical research on psychedelic-assisted treatment for SUD.

Garcia-Romeu, A., Davis, A. K., Erowid, E., Griffiths, R. R., & Johnson, M. W. (2020). Persisting reductions in cannabis, opioid, and stimulant misuse after naturalistic psychedelic use: An online survey. Frontiers in psychiatry10, 955; 10.3389/fpsyt.2019.00955
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Self-Rated Effectiveness of Microdosing With Psychedelics for Mental and Physical Health Problems Among Microdosers

Abstract

Background: There is a growing interest in the use of psychedelic substances for health related purposes, including symptom relief for disorders like anxiety, depression, and pain. Although the focus of recent clinical trials has been on high doses of these substances, anecdotal evidence suggests that low (micro) doses are also effective, and may be more suitable for certain conditions. Nonetheless, empirical evidence regarding the efficacy of microdosing with psychedelics for symptomatic relief is lacking. The present study aimed to investigate, by means of an online questionnaire, the self-rated effectiveness (SRE) of microdosing with psychedelics (MDP) for mental and physiological disorders compared to the conventional prescribed treatment and to regular doses of psychedelics. Methods: An online questionnaire was launched on several websites and fora between March and July 2018. Respondents who had consented, were 18 years of age or older, had experience with microdosing and were diagnosed with at least one mental or physiological disorder by a medical doctor or therapist (N = 410; 7.2%) were included in the analyses. Odds ratio were calculated to compare the SRE of MDP with conventional treatment, and regular psychedelic doses for mental and physiological diagnoses for each of the three effectiveness questions (“Did it work,” “Symptom disappear,” “Quality of life improved”). Results: Odds ratio showed that SRE of MDP was significantly higher compared to that of conventional treatments for both mental and physiological diagnoses; and that these effects were specific for ADHD/ADD and anxiety disorders. In contrast, SRE of MDP was lower compared to that of higher, regular psychedelic doses for mental disorders such as anxiety and depression, while for physiological disorders no difference was shown. Conclusion: This study demonstrates that SRE of MDP to alleviate symptoms of a range of mental or physiological diagnoses is higher compared to conventionally offered treatment options, and lower than regular (‘full’) psychedelic doses. Future RCTs in patient populations should objectively assess the effectivity claims of psychedelics, and whether these are dose related, disorder specific, and superior to conventional treatments.

Hutten, N. R., Mason, N. L., Dolder, P. C., & Kuypers, K. P. (2019). Self-rated effectiveness of microdosing with psychedelics for mental and physical health problems amongst microdosers. Frontiers in psychiatry10, 672. 10.3389/fpsyt.2019.00672

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