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Microdosing with psychedelics: what do we know?

/ LSD, Microdosing, Mushrooms / Psilocybin, Papers, Psychology, Publications / /

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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LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors

/ LSD, Neuroscience, Papers, Psychology / Leave a Comment / / , , , ,

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), 12181. https://doi.org/10.1038/s41598-020-68899-y

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LSD-induced increases in social adaptation to opinions similar to one’s own are associated with stimulation of serotonin receptors

/ LSD, Papers, Psychology, Publications / / , , , ,

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

/ Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Publications /

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

/ Anthropology & Sociology, Iboga / Ibogaine, Papers, Psychology, Publications / / , , ,

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

/ Anthropology & Sociology, Mushrooms / Psilocybin, Papers, Publications / / , , , ,

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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Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca

/ Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / / , , , , , ,

Abstract

Background: Ayahuasca is a traditional Amazon brew and its potential antidepressant properties have recently been explored in scientific settings. We conducted a double-blind placebo-controlled trial of ayahuasca with treatment-resistant depression patients (n = 28) and healthy controls (n = 45).

Aims: We are evaluating the blood inflammatory biomarkers: C-reactive protein and interleukin 6, as a potential consequence of ayahuasca intake and their correlation with serum cortisol and brain-derived neurotrophic factor levels. Blood samples were collected at pre-treatment and 48 hours after substance ingestion to assess the concentration of inflammatory biomarkers, together with administration of the Montgomery-Åsberg Depression Rating Scale.

Results: At pre-treatment, patients showed higher C-reactive protein levels than healthy controls and a significant negative correlation between C-reactive protein and serum cortisol levels was revealed (rho = -0.40, n = 14). C-reactive protein in those patients was not correlated with Montgomery-Åsberg Depression Rating Scale scores. We observed a significant reduction of C-reactive protein levels across time in both patients and controls treated with ayahuasca, but not with placebo. Patients treated with ayahuasca showed a significant correlation (rho = + 0.57) between larger reductions of C-reactive protein and lower depressive symptoms at 48 hours after substance ingestion (Montgomery-Åsberg Depression Rating Scale). No significant result with respect to interleukin 6 and brain-derived neurotrophic factor was found. Furthermore, these biomarkers did not predict the antidepressant response or remission rates observed.

Conclusions: These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca and encourage further clinical trials in adults with depression.

Galvão-Coelho, N. L., de Menezes Galvão, A. C., de Almeida, R. N., Palhano-Fontes, F., Campos Braga, I., Lobão Soares, B., … & de Araujo, D. B. (2020). Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca. Journal of Psychopharmacology, 34(10), 1125-1133; 10.1177/0269881120936486
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Psychedelic Treatment for Trauma-Related Psychological and Cognitive Impairment Among US Special Operations Forces Veterans

/ Anxiety Disorders / PTSD, Depressive Disorders, DMT, Iboga / Ibogaine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Psychotic Disorders, Publications / / , , , ,

Abstract

Background

U.S. Special Operations Forces Veterans are at increased risk for a variety of mental health problems and cognitive impairment associated with military service. Current treatments are lacking in effectiveness and adherence. Therefore, this study examined psychedelic treatment with ibogaine and 5-methoxy-N,N-dimethyltryptamine for trauma-related psychological and cognitive impairment among U.S. Special Operations Forces Veterans.

Method

We conducted a survey of Veterans who completed a specific psychedelic clinical program in Mexico between 2017 and 2019. Questions probed retrospective reports of mental health and cognitive functioning during the 30 days before and 30 days after treatment. A total of 65 people completed treatment during this time frame and were eligible for contact. Of these, 51 (78%) completed the survey and were included in data analyses (mean age = 40; male = 96%; married = 55%; Caucasian/White = 92%; Operation Enduring Freedom/Operation Iraqi Freedom Service = 96%).

Results

Results indicated significant and very large reductions in retrospective report of suicidal ideation (p < .001; d = −1.9), cognitive impairment (p < .001; d = −2.8), and symptoms of posttraumatic stress disorder (p < .001; d = −3.6), depression (p < .001; d = −3.7), and anxiety (p < .001; d = −3.1). Results also showed a significant and large increase in retrospective report of psychological flexibility (p < .001; d = 2.9) from before-to-after the psychedelic treatment. Increases in the retrospective report of psychological flexibility were strongly associated with retrospective report of reductions in cognitive impairment, and symptoms of posttraumatic stress disorder, depression, and anxiety (rs range −0.61 to −0.75; p < .001). Additionally, most participants rated the psychedelic experiences as one of the top five personally meaningful (84%), spiritually significant (88%), and psychologically insightful (86%) experiences of their lives.
Limitations: Several limitations should be considered including the retrospective, self-report, survey design of the study, and the lack of randomization and blinding, thus making these finding preliminary.

Conclusion

U.S. Special Operations Forces Veterans may have unique treatment needs because of the sequela of problems associated with repeated trauma exposure and the nature of the exposure. Psychedelic-assisted therapy with these under-researched psychedelics may hold unique promise for this population. However, controlled studies are needed to determine whether this treatment is efficacious in relieving mental health and cognitive impairment among U.S. Special Operations Forces Veterans.

Davis, A. K., Averill, L. A., Sepeda, N. D., Barsuglia, J. P., & Amoroso, T. (2020). Psychedelic Treatment for Trauma-Related Psychological and Cognitive Impairment Among US Special Operations Forces Veterans. Chronic Stress, 4, 2470547020939564; 10.1177/2470547020939564
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In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor

/ Papers, Pharmacology & Chemistry, Publications / / , ,

Abstract

Serotonergic psychedelics, substances exerting their effects primarily through the serotonin 2A receptor (5-HT2AR), continue to comprise a substantial portion of reported new psychoactive substances (NPS). The exact mechanisms of action of psychedelics still remain to be elucidated further, and certain pathways remain largely unexplored on a molecular level for this group of compounds. A systematic comparison of substances belonging to different subclasses, monitoring the receptor-proximal β-arrestin 2 recruitment, is lacking. Based on a previously reported in vitro bioassay employing functional complementation of a split nanoluciferase to monitor β-arrestin 2 recruitment to the 5-HT2AR, we here report on the setup of a stable HEK 293 T cell-based bioassay. Following verification of the performance of this new stable cell system as compared to a system based on transient transfection, the stable expression system was deemed suitable for the pharmacological characterization of psychedelic NPS. Subsequently, it was applied for the in vitro assessment of the structure-activity relationship of a set of 30 substances, representing different subclasses of phenylalkylamine psychedelics, among which 12 phenethylamine derivatives (2C-X), 7 phenylisopropylamines (DOx) and 11 N-benzylderivatives (25X-NB). The resulting potency and efficacy values provide insights into the structure-activity relationship of the tested compounds, overall confirm findings observed with other reported in vitro assays, and even show a significant correlation with estimated common doses. This approach, in which a large series of psychedelic NPS belonging to different subclasses is comparatively tested, using a same assay setup, monitoring a receptor-proximal event, not only gives pharmacological insights, but may also allow prioritization of legal actions related to the most potent -and potentially dangerous- compounds.

Pottie, E., Cannaert, A., & Stove, C. P. (2020). In vitro structure–activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor. Archives of Toxicology, 94(10), 3449-3460; 10.1007/s00204-020-02836-w
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3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil

/ Anxiety Disorders / PTSD, MDMA, Papers, Psychiatry & Medicine, Psychology, Publications / / , , , , , ,

Abstract

Objective: To conduct Brazil’s first clinical trial employing 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder (PTSD), given its high prevalence resulting from epidemic violence.

Methods: Of 60 volunteers, four matched the inclusion & exclusion criteria. Three patients with PTSD secondary to sexual abuse (diagnosed by the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale for DSMV-4 [CAPS 4]) completed enrollment and treatment, following a standardized Multidisciplinary Association for Psychedelic Studies protocol consisting of 15 weekly therapy sessions: three with orally administered MDMA with concurrent psychotherapy and music, spaced approximately 1 month apart. CAPS-4 scores two months after the final MDMA session were the primary outcome.

Results: No serious adverse events occurred. The most frequent adverse events were somatic pains and anguish. CAPS-4 reductions were always greater than 25 points. The final scores were 61, 27, and 8, down from baseline scores of 90, 78, and 72, respectively. All reductions were greater than 30%, which is indicative of clinically significant improvement. Secondary outcomes included lower Beck Depressive Inventory scores and higher Post-Traumatic Growth Inventory and Global Assessment of Functioning scores.

Conclusions: Considering the current limitations in safe and efficacious treatments for PTSD and recent studies abroad with larger patient samples, MDMA-assisted psychotherapy could become a viable treatment in Brazil.

Jardim, A. V., Jardim, D. V., Chaves, B. R., Steglich, M., Ot’alora G, M., Mithoefer, M. C., … & Doblin, R. (2020). 3, 4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil. Brazilian Journal of Psychiatry, (AHEAD); 10.1590/1516-4446-2020-0980
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Healing culture and its somewhat humorous discontents - July 22

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