OPEN Foundation

Day: 1 August 2020

The impact of 3,4-methylendioxymetamphetamine (MDMA) abstinence on seeking behavior and the expression of the D 2-like and mGlu 5 receptors in the rat brain using saturation binding analyses

January 27, 2022 / Addiction, MDMA, Neuroscience, Papers, Psychopharmacology / Leave a Comment / By / , , , , , ,

Abstract

The abundance of research indicates that enriched environment acts as a beneficial factor reducing the risks of relapse in substance use disorder. There is also strong evidence showing the engagement of brain dopaminergic and glutamatergic signaling through the dopamine D2-like and metabotropic glutamate type 5 (mGlu5) receptors, respectively, that has a direct impact on drug reward and drug abstinence. The present study involved 3,4-methylendioxymethamphetamine (MDMA) self-administration with the yoked-triad procedure in rats kept under different housing conditions during abstinence – enriched environment (EE) or isolation cage (IC) conditions – aimed at evaluating changes in brain receptors affecting drug-seeking behavior as well as density and affinity of the D2-like and mGlu5 receptors in several regions of the animal brain. Our results show that exposure to EE conditions strongly reduced active lever presses during cue-induced drug-seeking. At the neurochemical level, we demonstrated marked decreases of D2-like receptor affinity in the dorsal striatum in rats previously self-administering MDMA under EE and increases in density under IC conditions. Moreover, we found the increases in the density and decreases in the affinity of the D2-like receptor in the prefrontal cortex and nucleus accumbens provoked by IC conditions. The mGlu5 receptor density decreased only in the prefrontal cortex after IC and EE abstinence. Moreover, our study has revealed a clear decrease in mGlu5 receptor density in the nucleus accumbens in the group actively administering MDMA only under EE conditions. This study demonstrates that housing conditions have impact on drug-seeking behavior in rats during abstinence from MDMA self-administration. The observed changes in the dopamine D2-like and mGlu5 receptor Bmax and/or Kd values were brain-region specific and related to either pharmacological and/or motivational features of MDMA.

Frankowska, M., Miszkiel, J., Pomierny-Chamiolo, L., Pomierny, B., Celeste Borelli, A., Suder, A., & Filip, M. (2020). The impact of 3,4-methylendioxymetamphetamine (MDMA) abstinence on seeking behavior and the expression of the D2-like and mGlu5 receptors in the rat brain using saturation binding analyses. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 71(4), 10.26402/jpp.2020.4.09. https://doi.org/10.26402/jpp.2020.4.09

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The rise, fall, and possible rise of LSD

August 1, 2020 / Addiction, Anxiety disorders / PTSD, Depression, History, LSD, Other subjects, Papers, Psychopharmacology, Publications, Sociology / 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 / Addiction, Anxiety disorders / PTSD, Depression, Ketamine, Papers, Psychiatry, Psychology, Psychopharmacology, Psychosis, Psychotherapy, Publications / 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, Depression, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychiatry, Psychology, Psychopharmacology, 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, Psychiatry, Psychology, Psychopharmacology, 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, Depression, Ketamine, LSD, MDMA, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, 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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30 April - Q&A with Rick Strassman

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