OPEN Foundation

Author name: OPEN Foundation

Embracing Neurodiversity in Psychedelic Science: A Mixed-Methods Inquiry into the MDMA Experiences of Autistic Adults

Abstract

This exploratory inquiry analyzed subjective experiences autistic adults reported after they took the drug 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy, in nonclinical settings. Using a secure, globally available website, this study collected data from participants in 13 countries who were experienced with MDMA (n = 100). A subset of survey respondents (n = 24) were then invited to participate in qualitative interviews. The researcher applied thematic content analysis of interview transcripts to create a comprehensive account of emergent themes. MDMA has well-documented acute effects that promote pro-social attitudes such as caring and trust in neurotypical, or typically developing, populations. Findings from this study suggested that MDMA-assisted therapy may be an effective catalyst in autistic adults for intra- and interpersonal change. In addition, participants reported accounts of lasting transformation and healing from conditions such as trauma and social anxiety that are common in autistic populations. No participants reported long-term adverse outcomes as a result of using MDMA/ecstasy. Qualitative findings support a case for future clinical trials of MDMA-assisted therapy with autistic adults who present with social adaptability challenges.

Danforth, A. L. (2019). Embracing neurodiversity in psychedelic science: A mixed-methods inquiry into the MDMA experiences of autistic adults. Journal of psychoactive drugs51(2), 146-154., 10.1080/02791072.2019.1587116
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Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action

Abstract

Salvia divinorum is a herbal plant native to the southwest region of Mexico. Traditional preparations of this plant have been used in illness treatments that converge with inflammatory conditions and pain. Currently, S. divinorum extracts have become popular in several countries as a recreational drug due to its hallucinogenic effects. Its main active component is a diterpene named salvinorin A (SA), a potent naturally occurring hallucinogen with a great affinity to the κ opioid receptors and with allosteric modulation of cannabinoid type 1 receptors. Recent biochemical research has revealed the mechanism of action of the anti-inflammatory and analgesic effect of SA at the cellular and molecular level. Nevertheless, because of their short-lasting and hallucinogenic effect, the research has focused on discovering a new analogue of SA that is able to induce analgesia and reduce inflammation with a long-lasting effect but without the hallucinatory component. In this review, we explore the role of S. divinorum, SA and its analogues. We focus mainly on their analgesic and anti-inflammatory roles but also mention their psychoactive properties.

Coffeen, U., & Pellicer, F. (2019). Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action. Journal of pain research12, 1069., 10.2147/JPR.S188619

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A Review of 3,4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy.

Abstract

This paper provides a brief review of the history, proposed pharmacological mechanisms, safety issues, and clinical applications of the medicine 3,4-methylenedioxymethamphetamine (MDMA). Most clinical MDMA research in patients to date has focused on MDMA-assisted psychotherapy to treat posttraumatic stress disorder (PTSD). In this review paper other potential therapeutic applications for MDMA therapy are described, including contemporary studies treating anxiety associated with autism and the authors’ ongoing study exploring the potential role for MDMA-assisted psychotherapy to treat alcohol use disorder. MDMA therapy for PTSD is now entering the final Phase 3 stage of drug development, with a target set for licensing by the FDA and EMA in 2021. This means that if clinical efficacy criteria are achieved, MDMA would become a medicine.
Sessa, B., Higbed, L., & Nutt, D. (2019). A Review of 3, 4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy. Frontiers in Psychiatry10, 138., https://doi.org/10.3389/fpsyt.2019.00138
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Combining Cognitive-Behavioral Conjoint Therapy for PTSD with 3,4-Methylenedioxymethamphetamine (MDMA): A Case Example.

Abstract

Treatments for posttraumatic stress disorder (PTSD) have evolved significantly in the past 35 years. From what was historically viewed as a pervasive, intractable condition have emerged multiple evidence-based intervention options. These treatments, predominantly cognitive behavioral in orientation, provide significant symptom improvement in 50-60% of recipients. The treatment of PTSD with MDMA-assisted psychotherapy using a supportive, non-directive approach has yielded promising results. It is unknown, however, how different therapeutic modalities could impact or improve outcomes. Therefore, to capitalize on the strengths of both approaches, Cognitive Behavioral Conjoint Therapy for PTSD (CBCT) was combined with MDMA in a small pilot trial. The current article provides a case study of one couple involved in the trial, chosen to provide a demographically representative example of the study participants and a case with a severe trauma history, to offer a detailed account of the methodology and choices made to integrate CBCT and MDMA, as well as an account of their experience through the treatment and their treatment gains. This article offers a description of the combination of CBCT for PTSD and MDMA, and demonstrates that it can produce reductions in PTSD symptoms and improvements in relationship satisfaction.
Wagner, A. C., Mithoefer, M. C., Mithoefer, A. T., & Monson, C. M. (2019). Combining cognitive-behavioral conjoint therapy for PTSD with 3, 4-methylenedioxymethamphetamine (MDMA): A case example. Journal of psychoactive drugs51(2), 166-173., https://doi.org/10.1080/02791072.2019.1589028
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Beyond LSD: A Broader Psychedelic Zeitgeist during the Early to Mid-20 th Century

Abstract

During the 1950s and 1960s, there was a tremendous surge in research into the effects of psychedelic drugs. When discussing this period of research, the discovery of the psychoactive properties of LSD in 1943 is often presented as the main, and sometimes only, driving force of the boom in research. This “Great Person,” or “Great Chemical,” historiographical lens fails to acknowledge other factors that were fundamental in setting the stage for the research. In particular, other psychedelic drugs, such as mescaline, were already being probed for their uses in psychotherapy and as models for psychosis before the effects of LSD had been discovered. Psilocybin and other classical psychedelics had also been discovered by Western researchers around the same time as the synthesis of LSD. Additionally, many of the dominant zeitgeists (e.g., pharmacological, psychoanalytic, and humanistic) in psychology during this period were congruent with psychedelic research. This article argues that while the discovery of LSD may have been a catalyst for psychedelic research in the 1950s and ’60s, there was a broader psychedelic zeitgeist that deserves acknowledgement for setting the stage.
Aday, J. S., Bloesch, E. K., & Davoli, C. C. (2019). Beyond LSD: A broader psychedelic zeitgeist during the early to mid-20th century. Journal of psychoactive drugs51(3), 210-217., https://doi.org/10.1080/02791072.2019.1581961
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Ketamine: A Paradigm Shift for Depression Research and Treatment

Abstract

Ketamine is the first exemplar of a rapid-acting antidepressant with efficacy for treatment-resistant symptoms of mood disorders. Its discovery emerged from a reconceptualization of the biology of depression. Neurobiological insights into ketamine efficacy shed new light on the mechanisms underlying antidepressant efficacy.
Krystal, J. H., Abdallah, C. G., Sanacora, G., Charney, D. S., & Duman, R. S. (2019). Ketamine: A Paradigm Shift for Depression Research and Treatment. Neuron101(5), 774-778., 10.1016/j.neuron.2019.02.005
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Beyond LSD: A Broader Psychedelic Zeitgeist during the Early to Mid-20th Century.

Abstract

During the 1950s and 1960s, there was a tremendous surge in research into the effects of psychedelic drugs. When discussing this period of research, the discovery of the psychoactive properties of LSD in 1943 is often presented as the main, and sometimes only, driving force of the boom in research. This “Great Person,” or “Great Chemical,” historiographical lens fails to acknowledge other factors that were fundamental in setting the stage for the research. In particular, other psychedelic drugs, such as mescaline, were already being probed for their uses in psychotherapy and as models for psychosis before the effects of LSD had been discovered. Psilocybin and other classical psychedelics had also been discovered by Western researchers around the same time as the synthesis of LSD. Additionally, many of the dominant zeitgeists (e.g., pharmacological, psychoanalytic, and humanistic) in psychology during this period were congruent with psychedelic research. This article argues that while the discovery of LSD may have been a catalyst for psychedelic research in the 1950s and ’60s, there was a broader psychedelic zeitgeist that deserves acknowledgement for setting the stage.
Aday, J. S., Bloesch, E. K., & Davoli, C. C. (2019). Beyond LSD: A Broader Psychedelic Zeitgeist during the Early to Mid-20th Century. Journal of psychoactive drugs, 1-8., https://doi.org/10.1080/02791072.2019.1581961
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Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits.

Abstract

Ibogaine is an atypical psychedelic alkaloid, which has been subject of research due to its reported ability to attenuate drug-seeking behavior. Recent work has suggested that ibogaine effects on alcohol self-administration in rats are related to the release of Glial cell Derived Neurotrophic Factor (GDNF) in the Ventral Tegmental Area (VTA), a mesencephalic region which hosts the soma of dopaminergic neurons. Although previous reports have shown ibogaine’s ability to induce GDNF expression in rat midbrain, there are no studies addressing its effect on the expression of GDNF and other neurotrophic factors (NFs) such as Brain Derived Neurotrophic Factor (BDNF) or Nerve Growth Factor (NGF) in distinct brain regions containing dopaminergic neurons. In this work, we examined the effect of ibogaine acute administration on the expression of these NFs in the VTA, Prefrontal Cortex (PFC), Nucleus Accumbens (NAcc) and the Substantia Nigra (SN). Rats were i.p. treated with ibogaine 20 mg/kg (I20), 40 mg/kg (I40) or vehicle, and NFs expression was analyzed after 3 and 24 h. At 24 h an increase of the expression of the NFs transcripts was observed in a site and dose dependent manner. Only for I40, GDNF was selectively upregulated in the VTA and SN. Both doses elicited a large increase in the expression of BDNF transcripts in the NAcc, SN and PFC, while in the VTA a significant effect was found only for I40. Finally, NGF mRNA was upregulated in all regions after I40, while I20 showed a selective upregulation in PFC and VTA. Regarding protein levels, an increase of GDNF was observed in the VTA only for I40 but no significant increase for BDNF was found in all the studied areas. Interestingly, an increase of proBDNF was detected in the NAcc for both doses. These results show for the first time a selective increase of GDNF specifically in the VTA for I40 but not for I20 after 24 h of administration, which agrees with the effective dose found in previous self-administration studies in rodents. Further research is needed to understand the contribution of these changes to ibogaine’s ability to attenuate drug-seeking behavior.
Marton, S., González, B., Rodríguez, S., Miquel, E., Martínez-Palma, L., Pazos, M., … & Scorza, C. (2019). Ibogaine administration modifies GDNF and BDNF expression in brain regions involved in mesocorticolimbic and nigral dopaminergic circuits. Frontiers in pharmacology10, 193., https://doi.org/10.3389/fphar.2019.00193
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Chronic, Intermittent Microdoses of the Psychedelic N,N-Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents

Abstract

Drugs capable of ameliorating symptoms of depression and anxiety while also improving cognitive function and sociability are highly desirable. Anecdotal reports have suggested that serotonergic psychedelics administered in low doses on a chronic, intermittent schedule, so-called “microdosing”, might produce beneficial effects on mood, anxiety, cognition, and social interaction. Here, we test this hypothesis by subjecting male and female Sprague Dawley rats to behavioral testing following the chronic, intermittent administration of low doses of the psychedelic N,N-dimethyltryptamine (DMT). The behavioral and cellular effects of this dosing regimen were distinct from those induced following a single high dose of the drug. We found that chronic, intermittent, low doses of DMT produced an antidepressant-like phenotype and enhanced fear extinction learning without impacting working memory or social interaction. Additionally, male rats treated with DMT on this schedule gained a significant amount of body weight during the course of the study. Taken together, our results suggest that psychedelic microdosing may alleviate symptoms of mood and anxiety disorders, though the potential hazards of this practice warrant further investigation.
Cameron, L. P., Benson, C. J., DeFelice, B. C., Fiehn, O., & Olson, D. E. (2019). Chronic, Intermittent Microdoses of the Psychedelic N, N-Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents. ACS chemical neuroscience., 10.1021/acschemneuro.8b00692
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5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety

Abstract

BACKGROUND:

A recent epidemiological study suggested that 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used for spiritual and recreational reasons is associated with subjective improvement in depression and anxiety. Further exploration of the potential psychotherapeutic effects of 5-MeO-DMT could inform future clinical trials.

OBJECTIVES:

We examined self-reported improvement in depression and anxiety among people who use 5-MeO-DMT in a group setting with structured procedures guiding dose and administration of 5-MeO-DMT. Such procedures also include activities for the preparation of, and support during/following sessions, which are similar to procedures used in clinical trials of hallucinogen administration. Next, we examined whether depression or anxiety were improved following use, and whether the acute subjective effects (mystical/challenging) or beliefs about the 5-MeO-DMT experience were associated with improvements in these conditions.

METHODS:

Respondents (n = 362; Mage = 47.7; Male = 55%; White/Caucasian = 84%) completed an anonymous web-based survey.

RESULTS:

Of those reporting having been diagnosed with depression (41%) or anxiety (48%), most reported these conditions were improved (depression = 80%; anxiety = 79%) following 5-MeO-DMT use, and fewer reported they were unchanged (depression = 17%; anxiety = 19%) or worsened (depression = 3%; anxiety = 2%). Improvement in depression/anxiety conditions were associated with greater intensity of mystical experiences and higher ratings of the spiritual significance and personal meaning of the 5-MeO-DMT experience. There were no associations between depression or anxiety improvement and the intensity of acute challenging physical/psychological effects during the 5-MeO-DMT experience.

CONCLUSIONS:

Future prospective controlled clinical pharmacology studies should examine the safety and efficacy of 5-MeO-DMT administration for relieving depression and anxiety.

Davis, A. K., So, S., Lancelotta, R., Barsuglia, J. P., & Griffiths, R. R. (2018). 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. The American journal of drug and alcohol abuse, 1-9., 10.1080/00952990.2018.1545024
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Online Community Meet-Up with Janis Phelps - Online Event - June 26